iridoids and loganin

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti-diabetic, antiinflammatory, neuroprotective, and anti-tumor activities, etc. Studies have shown that these underlying mechanisms include anti-oxidation, antiinflammation and anti-apoptosis by regulating a variety of signaling pathways, such as STAT3/NF-κB, JAK/STAT3, TLR4/NF-κB, PI3K/Akt, MCP-1/CCR2, and RAGE/Nox4/p65 NF-κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.

Topics: Cornus; Humans; Iridoids; NF-kappa B; Phosphatidylinositol 3-Kinases; Signal Transduction

Secologanin, a secoiridoid glucoside, is a pivotal terpenoid intermediate in the biosynthesis of biologically active monoterpenoid indole alkaloids such as reserpine, ajmaline, and vinblastine which are biosynthesized via strictosidine, an alkaloidal glucoside, formed from secologanin and tryptamine. In secologanin biosynthesis, the oxidative cleavage process of loganin to secologanin and the hydroxylation of 7-deoxyloganin to loganin have remained unknown enzymologically and mechanistically. Cornoside is a unique glucoside with 4-hydroxy-2,5-cyclohexadien-1-one (benzoquinol) ring and is widespread in families such as Cornaceae, Oleaceae, and Scrophulariaceae but its biosynthesis, especially the oxidative process, remain to be investigated. Shikonin is a red naphthazarin pigment derived from the roots of Lithospermum erythorhizon and produced biotechnologically by cell cultures. Its biosynthesis including the production regulation mechanism has been investigated in detail. However, the naphthazarin ring formation process, probably starting with the hydroxylation of the side chain of geranylhydroquinone, a key intermediate at the late stage of shikonin biosynthesis, remained unknown. In the present review, cytochrome P450 monooxygenases involved in the biosyntheses of three structurally and biosynthetically interesting compounds, secologanin, cornoside, and shikonin, a described together with the results of previous and recent biosynthetic studies. The biosyntheses of related compounds are also discussed.

Topics: Cyclohexanones; Cytochrome P-450 Enzyme System; Glucosides; Indole Alkaloids; Iridoid Glucosides; Iridoids; Naphthoquinones; Oxidation-Reduction; Plants; Secologanin Tryptamine Alkaloids; Tryptamines; Vinca Alkaloids

Divergent total syntheses of the hetero-oligomeric iridoid glycosides mainly found in

Topics: Glycosides; Iridoid Glycosides; Iridoids

Corni Fructus is a traditional Chinese herb and widely applied for treatment of age-related disorders in China. Iridoid glycoside was considered as the active ingredient of Corni Fructus. Loganin is one of the major iridoid glycosides and quality control components of Corni Fructus. Emerging evidence emphasized the beneficial effect of loganin on neurodegenerative disorders, such as Alzheimer's disease (AD). However, the detailed mechanism underlying the neuroprotective action of loganin remains to be unraveled.. To explore the improvement of loganin on cognitive impairment in 3 × Tg-AD mice and reveal the potential mechanism.. Eight-month 3 × Tg-AD male mice were intraperitoneally injected with loganin (20 and 40 mg/kg) for consecutive 21 days. Behavioral tests were used to evaluated the cognition-enhancing effects of loganin, and Nissl staining and thioflavine S staining were performed to analyze neuronal survival and Aβ pathology. Western blot analysis, transmission electron microscopy and immunofluorescence were utilized to explore the molecular mechanism of loganin in AD mice involved mitochondrial dynamics and mitophagy. Aβ. Loganin significantly mitigated the learning and memory deficit and amyloid β-protein (Aβ) deposition, and recovered synaptic ultrastructure in 3 × Tg-AD mice. Perturbed mitochondrial dynamics characterized by excessive fission and insufficient fusion were restored after loganin treatment. Meanwhile, loganin reversed the increase of mitophagy markers (LC3II, p62, PINK1 and Parkin) and mitochondrial markers (TOM20 and COXIV) in hippocampus of AD mice, and enhanced the location of optineurin (OPTN, a well-known mitophagy receptor) to mitochondria. Accumulated PINK1, Parkin, p62 and LC3II were also revealed in Aβ. Our observations confirmed that loganin enhanced cognitive function and alleviated AD pathology probably by promoting OPTN-mediated mitophagy,. Loganin might be a potential drug candidate for AD therapy via targeting mitophagy.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cognitive Dysfunction; Humans; Iridoids; Male; Mice; Mitophagy; Molecular Docking Simulation; Neuroblastoma; Protein Kinases; Ubiquitin-Protein Ligases

Loganin is an iridoid with potent pharmacological effects. Loganin contains a hemiacetal structure and can convert to dialdehyde intermediates after deglycosylation. We hypothesized that the metabolites of loganin with hemiacetal can generate reactive dialdehyde intermediates. This study aims to characterize the metabolic profiling of loganin and especially for the unstable dialdehyde intermediates by using ultra-performance liquid chromatograph-quadrupole orbitrap mass spectrometry. In this study, a total of 26 stable metabolites were identified in loganin-treated rats. Loganin underwent different metabolism in the intestine and liver, which was confirmed mainly by the metabolites in the hepatic portal vein. In the intestine, the major metabolic pathways were ester hydrolysis and deglycosylation, followed by methylation and dehydrogenation. The hepatic metabolism pathways were hydrogenation, hydroxylation, glucuronidation, and sulfonation. The circulating metabolites with high abundance were mainly derived from intestinal metabolism. Importantly, 11 unstable dialdehyde intermediates of loganin were identified and described for the first time. The dialdehyde intermediates were identified by their dihydropyridine conjugates with amino acids. The dialdehyde intermediates were mainly produced in the intestine. The dialdehyde intermediates enable covalent modification of intestinal proteins. Loganin can up-regulate the activity of intestinal bile salt hydrolase (BSH), catalyzing bile acid metabolism. The level of protein adducts was positively associated with BSH activity, indicating dialdehyde intermediates played a key role in the up-regulation of BSH activities. In conclusion, this study not only demonstrates the characteristic metabolic fate of loganin but also facilitates the understanding of the pharmacologic effects of dialdehyde intermediates.

Topics: Activation, Metabolic; Animals; Intestines; Iridoids; Rats

Inflammation plays a crucial part in osteoarthritis (OA) development. This work aimed to explore loganin's role and molecular mechanism in inflammation and clarify its anti-inflammatory effects in OA treatment.. Chondrocytes were stimulated using interleukin (IL)-1β and loganin at two concentrations (1 μM and 10 μM). Nitric oxide (NO) and prostaglandin E2 (PGE2) expression was assessed. Real-time polymerase chain reaction was used to evaluate inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-6, and tumor necrosis factor (TNF)-α mRNA levels. Western blot was used to investigate TLR4, MyD88, p-p65, and IκB-α expression. p65 nuclear translocation, synovial inflammatory response, and cartilage degeneration were also assessed.. Loganin significantly reduced IL-1β-mediated PGE2, NO, iNOS, and COX-2 expression compared with that of the IL-1β stimulation group. The TLR4/MyD88/NF-κB pathway was suppressed by loganin, which decreased inflammatory cytokine (TNF-α and IL-6) levels compared with those of the IL-1β stimulation group. Loganin inhibited IL-1β-mediated NF-κB p65 nuclear translocation compared with that of the IL-1β stimulation group. Loganin partially suppressed cartilage degeneration and the synovial inflammatory response. This work demonstrated that loganin inhibited IL-1β-mediated inflammation in rat chondrocytes through TLR4/MyD88/NF-κB pathway regulation, thereby reducing rat cartilage degeneration and the synovial inflammatory response.

Topics: Animals; Cartilage; Chondrocytes; Cyclooxygenase 2; Dinoprostone; Inflammation; Interleukin-1beta; Interleukin-6; Iridoids; Myeloid Differentiation Factor 88; NF-kappa B; Nitric Oxide; Osteoarthritis; Rats; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Topics: Animals; Female; Iridoids; Mice; Osteoblasts; Osteogenesis; Osteoporosis

To investigate the role of loganin in hypoxia/reperfusion (H/R)-induced renal tubular epithelial cells and ischemia/reperfusion-induced acute kidney injury (AKI). Cells were received H/R treatment and cultured with different concentrations of loganin. The cell activity and apoptosis were detected. The expressions of apoptosis-related proteins, inflammatory factors, oxidative stress related molecules, and related molecules of JAK2/STAT3 and Nrf2/HO-1 signaling pathways were measured. AKI model of mice was established by I/R procedure, and the kidney was collected for hematoxylin and eosin (HE) staining. H/R treatment inhibited cell activity and apoptosis, but loganin attenuated the effect of H/R. Moreover, loganin inhibited H/R-induced inflammatory response and oxidative stress in tubular epithelial cells. Loganin down-regulated the expression of apoptosis-related proteins, suppressed JAK2/STAT3 pathway, and activated Nrf2/HO-1 pathway. In animal experiment, loganin reduced tubular injury in AKI mice.Loganin had anti-apoptotic, anti-inflammatory, and anti-oxidative stress effects on H/R-induced tubular epithelial cells, and could improve AKI in mice induced by I/R. This effect might be achieved by inhibiting JAK2/STAT3 and activating the Nrf2/HO-1 signaling pathway.

Topics: Acute Kidney Injury; Animals; Apoptosis; Heme Oxygenase-1; Iridoids; Ischemia; Kidney; Mice; NF-E2-Related Factor 2; Oxidative Stress; Reperfusion; Reperfusion Injury; Signal Transduction

Neuropathic pain has been shown to be modulated by the activation of the chemokine C-X-C motif ligand 12 (CXCL12)/chemokine CXC receptor 4 (CXCR4) dependent nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. Loganin, an iridoid glycoside, was proven to prevent neuropathic pain, but its underlying mechanisms related to NLRP3 activation are still unknown.. This study investigated the underlying mechanisms of loganin's effect on chronic constriction injury (CCI)-induced NLRP3 inflammasome activation in the spinal cord.. Sprague-Dawley rats were randomly divided into four groups: sham, CCI, sham + loganin, and CCI + loganin. Loganin (5 mg/kg/day) was administered intraperitoneally starting the day after surgery. Paw withdrawal threshold (PWT) and latency (PWL) were assessed before CCI and on days 1, 3, 7 and 14 after CCI. Spinal cords were collected for western blots and immunofluorescence studies.. Loganin prevented CCI-attenuated PWT and PWL, suggesting improved mechanical allodynia and thermal hyperalgesia. The expression of CXCL12, CXCR4, thioredoxin-interacting protein (TXNIP), NLRP3 inflammasome (NLRP3, ASC, and caspase-1), IL-1β, and IL-18 were enhanced on day 7 after CCI, and all were reduced after loganin treatment. Dual immunofluorescence also showed that increased CXCL12, CXCR4, and NLRP3 were colocalized with NeuN (neuronal marker), GFAP (astrocyte marker), and Iba1 (microglial marker) on day 7 in the ipsilateral spinal dorsal horn (SDH). These immunoreactivities were attenuated in loganin-treated rats. Moreover, loganin decreased the assembly of NLRP3/ASC inflammasome after CCI in the ipsilateral SDH. Loganin appears to attenuate CCI-induced neuropathic pain by suppressing CXCL12/CXCR4-mediated NLRP3 inflammasome.. Our findings suggest that loganin might be a suitable candidate for managing CCI-provoked neuropathic pain.

Topics: Animals; Cell Cycle Proteins; Hyperalgesia; Inflammasomes; Iridoids; Neuralgia; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Receptors, Chemokine; Receptors, CXCR4; Spinal Cord

Loganin is an iridoid glycoside with antioxidant, anti-inflammatory, glucose-lowering activities which may address the pathological mechanisms of painful diabetic neuropathy (PDN) related to inflammation, oxidative stress, and hyperglycemia. This study investigated the underlying mechanisms of action of loganin on PDN. The in vivo model of PDN was established by streptozotocin-nicotinamide (STZ-NA) induction in Sprague Dawley (SD) rats. Subsequently, loganin (5 mg/kg) was administered by daily intraperitoneal injection. High-glucose stimulated human SH-SY5Y cells co-incubated with loganin were used to mimic the in vitro model of PDN. Loganin improved PDN rats' associated pain behaviors (allodynia and hyperalgesia), insulin resistance index (HOMA-IR), and serum levels of superoxide dismutase (SOD), catalase and glutathione. Loganin also reduced pain-associated channel protein Ca

Topics: Animals; Antioxidants; Behavior, Animal; Blood Glucose; Body Weight; Calcitonin Gene-Related Peptide; Calcium Channels, T-Type; Cell Line, Tumor; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Fasting; Humans; Hyperglycemia; Inflammation; Inflammation Mediators; Insulin; Insulin Resistance; Iridoids; Male; Neuralgia; Neuroglia; NF-kappa B; Niacinamide; Oxidative Stress; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Dorsal Horn; Streptozocin

Topics: Alzheimer Disease; Animals; Cognitive Dysfunction; Disease Models, Animal; Female; Hippocampus; Iridoids; Mice; Mice, Transgenic; Morris Water Maze Test; Neuroprotective Agents; Proteome

The theory of inflammation is one of the important theories in the pathogenesis of diabetic nephropathy (DN). We herein aimed to explore whether loganin affected macrophage infiltration and activation upon diabetic nephropathy (DN) by a spontaneous DN mice and a co-culture system of glomerular mesangial cells (GMCs) and macrophage cells (RAW264.7) which was induced by advanced glycation end products (AGEs).. Loganin showed remarkable capacity on protecting renal from damage by mitigating diabetic symptoms, improving the histomorphology of the kidney, decreasing the expression of extracellular matrix such as FN, COL-IV and TGF-β, reversing the production of IL-12 and IL-10 and decreasing the number of infiltrating macrophages in the kidney. Moreover, loganin showed markedly effects by suppressing iNOS and CD16/32 expressions (M1 markers), increasing Arg-1 and CD206 expressions (M2 markers), which were the phenotypic transformation of macrophage. These effects may be attributed to the inhibition of the receptor for AGEs (RAGE) /monocyte chemotactic protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2) signaling pathway, with significantly down-regulated expressions of RAGE, MCP-1 and CCR2 by loganin. Loganin further decreased MCP-1 secretion when RAGE was silenced, which means other target was involved in regulating the MCP-1 expression. While loganin combinated with the inhibitor of CCR2 exerted stronger anti-inhibition effects of iNOS expression, suggesting that CCR2 was the target of loganin in regulating the activation of macrophages.. Loganin could ameliorate DN kidney damage by inhibiting macrophage infiltration and activation via the MCP-1/CCR2 signaling pathway in DN.

Topics: Animals; Chemokine CCL2; Chemokine CCL8; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Fibronectins; Glycation End Products, Advanced; Iridoids; Kidney; Macrophage Activation; Macrophages; Male; Mesangial Cells; Mice; Mice, Inbred C57BL; RAW 264.7 Cells; Receptors, CCR1; Receptors, CCR2; Signal Transduction; Transforming Growth Factor beta1

Cisplatin is the most widely used chemotherapeutic agent. However, it often causes nephrotoxicity, which results in acute kidney injury (AKI). Therefore, we urgently need a drug that can reduce the nephrotoxicity induced by cisplatin. Loganin is a major iridoid glycoside isolated from Corni fructus that has been used as an anti-inflammatory agent in various pathological models. However, the renal protective activity of loganin remains unclear. In this study, to examine the protective effect of loganin on cisplatin-induced AKI, male C57BL/6 mice were orally administered with loganin (1, 10, and 20 mg/kg) 1 h before intraperitoneal injection of cisplatin (10 mg/kg) and sacrificed at three days after the injection. The administration of loganin inhibited the elevation of blood urea nitrogen (BUN) and creatinine (CREA) in serum, which are used as biomarkers of AKI. Moreover, histological kidney injury, proximal tubule damages, and renal cell death, such as apoptosis and ferroptosis, were reduced by loganin treatment. Also, pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, reduced by loganin treatment. Furthermore, loganin deactivated the extracellular signal-regulated kinases (ERK) 1 and 2 during AKI. Taken together, our results suggest that loganin may attenuate cisplatin-induced AKI through the inhibition of ERK1/2.

Topics: Acute Kidney Injury; Animals; Apoptosis; Blood Urea Nitrogen; Cell Death; Cisplatin; Creatinine; Cytokines; Iridoids; Kidney; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL

Sepsis, a destructive inflammatory response syndrome, is the principal reason to induce death in the intensive care unit. Loganin has been proved to possess the property of anti-inflammation, antioxidant, neuroprotection, and sedation. The primary aim of this study was to evaluate whether Loganin could alleviate acute kidney injury (AKI) during sepsis and investigate the latent mechanisms.. Septic AKI models were established by cecal ligation and puncture (CLP) surgery in mice and given Loganin (20, 40, 80 mg/kg) by gavage. Lipopolysaccharides (LPS)-stimulated human kidney proximal tubular (HK2) cells incubated in Loganin (5, 10, 20 μ M) were used to explore the accurate mechanisms. Survival rate, renal function (creatinine and blood urea nitrogen), and renal pathological changes were detected in septic mice. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), mitochondrial membrane potential, mitochondrial calcium overload, and nuclear factor E2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway activation in vivo and in vitro were determined by commercial kits and Western blot. Cell apoptosis, apoptotic-related protein (cleaved caspase-3, Bcl-2, and Bax) expression and protein kinase B (AKT) phosphorylation in vivo and in vitro were measured by TUNEL staining and Western blot. Finally, AKT blockage by 10 μM LY294002 or Nrf2 inhibition by10 μ M ML385 were utilized to prove the involvement of AKT and Nrf2/HO-1 pathway in AKI during sepsis.. We found Loganin treatment (20, 40, 80 mg/kg) mitigated septic AKI reflected by elevated renal function and palliative pathological changes. Oxidative stress and apoptosis in the kidney and LPS-treated HK2 cells were also inhibited by Loganin administration, which was accompanied by AKT and Nrf2/HO-1 pathway activation. Besides, the protective effects of Loganin could be diminished by AKT or Nrf2 blockage, indicating the involvement of AKT and Nrf2/HO-1 pathway.. The results suggested that the protective effects of Loganin on AKI during sepsis might be mediated by AKT and Nrf2/HO-1 pathway signaling activation in kidney proximal tubular cells.

Topics: Acute Kidney Injury; Animals; Cell Line; Cornus; Dose-Response Relationship, Drug; Heme Oxygenase-1; Iridoids; Lipopolysaccharides; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Molecular Structure; NF-E2-Related Factor 2; Protective Agents; Proto-Oncogene Proteins c-akt; Sepsis; Signal Transduction; Structure-Activity Relationship

Gout is a type of inflammatory arthritis caused by the deposition of monosodium uric acid (MSU) crystals in tissues. The etiology of gout is directly linked to the NLRP3 inflammasome, since MSU crystals are NLRP3 inflammasome activators. Therefore, we decided to search for a small-molecule inhibitor of the NLRP3 inflammasome for the prevention of gout inflammation. We found that loganin suppressed MSU crystals-induced caspase-1 (p20) and interleukin (IL)-1β production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks formation in mouse primary macrophages, showing its ability to inhibit the NLRP3 inflammasome. In an air pouch inflammation model, oral administration of loganin to mice prevented MSU crystals-induced production of mature IL-1β and IL-18 in air pouch exudates, resulting in decreased neutrophil recruitment. Furthermore, oral administration of loganin suppressed MSU crystals-induced gout inflammation in a mouse foot gout model, which was accompanied by the inhibition of the NLRP3 inflammasome. Loganin blocked de novo synthesis of mitochondrial DNA in air pouches and foot tissues injected with MSU crystals. Consistently, loganin prevented MSU crystals-induced mitochondrial damage in macrophages, as it increased mitochondrial membrane potential and decreased the amount of mitochondrial reactive oxygen species. These data demonstrate that loganin suppresses NLRP3 inflammasome activation by inhibiting mitochondrial stress. These results suggest a novel pharmacological strategy to prevent gout inflammation by blocking NLRP3 inflammasome activation and mitochondrial dysfunction.

Topics: Administration, Oral; Animals; Cells, Cultured; Disease Models, Animal; DNA, Mitochondrial; Gout; Inflammasomes; Inflammation; Iridoids; Macrophages; Male; Mice, Inbred C57BL; Mitochondria; NLR Family, Pyrin Domain-Containing 3 Protein; Uric Acid

Sepsis is a systemic inflammatory response syndrome resulted from severe infection. Excessive inflammation response plays an important role in sepsis-induced acute lung injury (ALI). Loganin is an iridoid glycoside isolated from Corni fructus and exerts an anti-inflammatory effect in multiple inflammatory diseases; however, the role of loganin in sepsis-induced ALI remains unknown. In the current study, the cecal ligation and puncture (CLP)-induced murine sepsis model was constructed to investigate the anti-inflammatory property of loganin in sepsis-induced ALI. Lipopolysaccharide (LPS)-treated Raw 264.7 cells and primary murine peritoneal macrophages were established to further explore underlying mechanism of loganin. Results showed that intragastrical administration of loganin significantly increased murine survival, reduced the alveolar structure damage and inflammatory cell infiltration. Loganin suppressed the release of the M1 macrophage-associated pro-inflammatory cytokines and induced the activation of M2-type anti-inflammatory cytokines. Besides, loganin dramatically inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent IL-1β secretion. Further in vitro studies confirmed that loganin efficiently inhibited M1 macrophage polarization and NLRP3 inflammasome activation by blocking the extra-cellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways. Taken together, the anti-inflammatory effect of loganin in sepsis-induced ALI was associated with the ERK and NF-κB pathway-mediated macrophage polarization and NLRP3 inflammasome activation. Our study offers a favorable mechanistic basis to support the therapeutic potential of loganin in anti-inflammatory diseases, such as sepsis-induced ALI.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Caspase 1; Inflammasomes; Interleukin-1beta; Iridoids; Lung; Macrophages; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; RAW 264.7 Cells; Sepsis

Topics: Animals; Anti-Inflammatory Agents; Cell Proliferation; Cell Survival; Dinoprostone; Heme Oxygenase-1; Inflammation; Iridoids; Lipopolysaccharides; Membrane Proteins; Mice; NF-E2-Related Factor 2; Nitric Oxide; Oxidative Stress; Phagocytosis; RAW 264.7 Cells; Reactive Oxygen Species; Signal Transduction

Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression.. To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process.. We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively.. Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST.. Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Depression; Iridoids; Mice; Motor Activity; Serotonin

Loganin, an iridoid glycoside, is one of the quality control indexes of Cornus officinalis Sieb. et Zucc. Increasing evidence emphasize the important role of inflammation in the pathology of depression, which links depression with other chronic diseases. Loganin prevents inflammatory response in multiple diseases and reverses depressive-like behaviors. However, the mechanisms underlying antidepressant-like effects of loganin for the treatment of inflammation-associated depression are not utterly understood.. The present study was designed to predict the potential targets of loganin against inflammation-associated depression using a network pharmacology approach.. Pharmmapper and Uniport were used to predict loganin-related targets. Targets of inflammation were identified through GeneCards databases and Online Mendelian Inheritance in Man (OMIM). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to identify the potential mechanism. Finally, qRT-PCR and ELISA were used to confirm the role of loganin on these targets.. There were 15 nodes in the loganin-inflammation-depression intersection targets network. In the network, the degree value of CTNNB1 was above 3. Among top ten pathways identified by KEGG analysis, Th1/Th2 cell differentiation and IL-17 signaling pathways were related with both inflammation and depression. As indicated by qRT-PCR results, loganin increased CTNNB1 mRNA level. Moreover, loganin elevated M2 markers of microglia but decreased M1 markers of microglia against lipopolysaccharide (LPS), indicated by qRT-PCR results and ELISA results.. CTNNB1 was the main target of loganin. Loganin alleviated LPS-induced inflammation through inhibiting M1 polarization of microglia. Our results provide a better understanding of loganin-induced antidepressant-like effects for the treatment of inflammation-associated depression.

Topics: Animals; Antidepressive Agents; beta Catenin; Cell Line; Cell Survival; Depression; Inflammation; Iridoids; Lipopolysaccharides; Mice; Microglia; Network Pharmacology; Protein Interaction Maps; Reproducibility of Results; Tumor Necrosis Factor-alpha

Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Loganin is a major iridoid glycoside and one of the quality control indexes of CF. In TCM clinical practice, prescription containing CF is commonly used to treat osteoarthritis (OA), but the underlying mechanisms of loganin are not yet utterly understood.. The aims of the present study are to confirm the therapeutic effects of loganin in an OA mouse model and to determine the mechanisms involved in the OA protective effects.. The destabilization of the medial meniscus (DMM) procedure was performed on the right knee of 8-week-old C57BL/6 male mice. 30 or 100 μg/ml of loganin was then injected into articular space twice a week for 8 and 12-week. Safranin O/Fast green staining, H&E staining, micro-CT analysis were performed to analyze structural and morphological changes. The protein expression of collagen type II (Col2), metalloproteinase-3 (Mmp3), matrix metalloproteinase 13 (Mmp13) collagen type X (Col10), cryopyrin and caspase-1 were detected by immunochemistry staining. Immuno-fluorescence assay was performed to assess changes in expression of CD31, endomucin, p65 and p-I-κB.. Results of histomorphometry showed that loganin delays the progression of OA in the DMM model. In cartilage, loganin decreased the OARSI score, increasing hyaline cartilage (HC) thickness and decreasing calcified cartilage (CC) thickness. Moreover, loganin inhibited osteophyte formation, reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th) and increased trabecular separation (Tb.Sp) in subchondral bone. Mechanistically, loganin increased the expressions of Col2, decreases the expression of Mmp3, Mmp13, Col10, cryopyrin and caspase-1 in cartilage. In parallel, loganin inhibited the expression of CD31 and endomucin in subchondral bone. Furthermore, loganin suppressed nuclear translocation of p65 protein, and decreased the amount of p-I-κB in chondrocytes.. In summary, these results uncovered that loganin inhibits NF-κB signaling and attenuates cartilage matrix catabolism and pyroptosis of chondrocytes in articular cartilage. Loganin may serve as a potential therapeutic agent for OA treatment.

Topics: Animals; Chondrocytes; Collagen Type II; Collagen Type X; Cornus; Disease Models, Animal; Fruit; Humans; Iridoids; Male; Menisci, Tibial; Mice; NF-kappa B; Osteoarthritis, Knee; Pyroptosis; Signal Transduction

Inflammatory bowel disease (IBD) is a chronic, recurrent gastrointestinal inflammation that affects millions of people around the world. Loganin, an iridoid glycoside, has shown the anti-inflammatory effects. However, the effect of loganin on IBD and its underlying molecular mechanism are not clear. The present study aimed to investigate whether loganin could alleviate IBD and its mechanisms. The intestinal epithelial Caco-2 cell line was treated with lipopolysaccharide (LPS) to establish an in vitro IBD model. MTT assay was used to detect cell viability. The expression and release level of inflammatory factors were determined by both real-time-PCR and ELISA. Western blotting was used to assess the NF-κB and JAK/STAT3 pathway-related protein levels. The results showed that loganin repressed the expression and release of IL-6, TNF-α, and IL-1β, and inhibited TLR4/NF-κB and JAK/STAT3 signaling pathways in a concentration-dependent manner. Overexpression of TLR4 could reverse the effect of loganin, leading to activation of NF-κB signaling and production of inflammatory factors. Meanwhile, IGF-1, a JAK/STAT3 signaling activator, could also reverse the anti-inflammation effect of loganin. In conclusion, loganin inhibited LPS-activated intestinal epithelial inflammation by repressing TLR4/NF-κB and JAK/STAT3 signaling pathway.

Topics: Caco-2 Cells; Cell Survival; Cytokines; Humans; Inflammation; Inflammation Mediators; Insulin-Like Growth Factor I; Intestinal Mucosa; Iridoids; Janus Kinases; Lipopolysaccharides; NF-kappa B; Signal Transduction; STAT3 Transcription Factor; Toll-Like Receptor 4

Peripheral nerve injury can produce chronic and ultimately neuropathic pain. The chronic constriction injury (CCI) model has provided a deeper understanding of nociception and chronic pain. Loganin is a well-known herbal medicine with glucose-lowering action and neuroprotective activity.. This study investigated the molecular mechanisms by which loganin reduced CCI-induced neuropathic pain.. Sprague-Dawley rats were randomly divided into four groups: sham, sham+loganin, CCI and CCI+loganin. Loganin (1 or 5 mg/kg/day) was injected intraperitoneally once daily for 14 days, starting the day after CCI. For behavioral testing, mechanical and thermal responses were assessed before surgery and on d1, d3, d7 and d14 after surgery. Sciatic nerves (SNs) were collected to measure proinflammatory cytokines. Proximal and distal SNs were collected separately for Western blotting and immunofluorescence studies.. Thermal hyperalgesia and mechanical allodynia were reduced in the loganin-treated group as compared to the CCI group. Loganin (5 mg/kg/day) prevented CCI from inducing proinflammatory cytokines (TNF-α, IL-1β), inflammatory proteins (TNF-α, IL-1β, pNFκB, pIκB/IκB, iNOS) and receptor (TNFR1, IL-1R), adaptor protein (TRAF2) of TNF-α, and Schwann cell demyelination and axonal damage. Loganin also blocked IκB phosphorylation (p-IκB). Double immunofluorescent staining further demonstrated that pNFκB/pIκB protein was reduced by loganin in Schwann cells on d7 after CCI. In the distal stumps of injured SN, Schwann cell demyelination was correlated with pain behaviors in CCI rats.. Our findings indicate that loganin improves CCI-induced neuroinflammation and pain behavior by downregulating TNF-α/IL-1β-dependent NF-κB activation.

Topics: Analgesics, Non-Narcotic; Animals; Chronic Pain; Constriction; Cytokines; Hyperalgesia; Interleukin-1beta; Iridoids; Male; Neuralgia; NF-kappa B; Rats, Sprague-Dawley; Schwann Cells; Sciatic Nerve; Tumor Necrosis Factor-alpha

Morroniside and loganin are iridoid glycosides extracted from Cornus officinalis, a plant species widely used in traditional Chinese medicine. However, the anti-inflammatory effects of morroniside and loganin in colitis are barely understood. The aim of the present study was to explore the effects of morroniside and loganin on the dextran sodium sulfate (DSS)-induced murine model of colitis and an LPS-induced colorectal cancer (CRC) cell inflammation model, and to clarify the underlying mechanisms. We found that morroniside and loganin were able to ameliorate clinical features, including disease activity index (DAI), histological inflammation score and periodic acid-Schiff staining (PAS). In the mouse model, morroniside and loganin treatment increased expression of tight junction proteins (TJs) and decreased pro-inflammatory cytokine production. Moreover, our findings showed that the expression of p-STAT3 and p-p65 were suppressed compared to the disease group. In in vitro experiments, treatment with morroniside and loganin had no obvious effects on proliferative activity in HCT116 cells and HIEC-6 cells. Expression of pro-inflammatory cytokines was inhibited by morroniside and loganin treatment in comparison with the LPS-treated group. Taken together, morroniside and loganin have beneficial effects on colitis in vivo and are anti-inflammatory in vitro. Possible mechanisms of the anti-inflammatory response may include blockade of the STAT3/NF-κB pathway.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Colitis; Colitis, Ulcerative; Cornus; Dextran Sulfate; Disease Models, Animal; Glycosides; Humans; Iridoid Glycosides; Iridoids; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; NF-kappa B; Phosphorylation; Signal Transduction; STAT3 Transcription Factor

Rehmanniae Radix (RR) and Cornus officinalis (CO) are a typical herbal pair used to treat diabetic nephropathy (DN) in clinical practice. DN can be effectively treated by catalpol (Cat) and loganin (Log), the main active components of RR and CO respectively, through combating apoptosis, oxidative stress and inflammation. Herein, a spontaneous DN and podocyte injury model induced by advanced glycation end products (AGEs), i.e. KK-Ay mice, was used to explore the cooperative effects of Log and Cat on DN and the mechanism targeting the AGEs-RAGE (receptor for AGE) pathway.. Log and Cat alone or in combination mitigated diabetic symptoms, decreased the level of fasting blood glucose, and increased that of serum insulin. The two drugs alone or in combination protected renal function from damage, prevented extracellular matrix hyperplasia and glycogen deposition, as well as alleviated the loss of podocytes detected by histological assay and immunohistochemistry. Flow cytometry revealed that Log and Cat alone or in combination relieved the apoptosis of AGEs-induced podocytes in vitro. Silencing RAGE by RNA interference played a protective role in podocyte apoptosis, whereas overexpression of it worked oppositely. Western blot exhibited that Log and Cat alone or in combination inhibited the activation of RAGE/p38 MAPK/p65 NF-κB and RAGE/Nox4/p65 NF-κB pathways in podocytes. The inhibitory effects of drug combination were more evident than those of individual treatments.. Log and Cat cooperatively resisted the apoptosis of podocytes upon DN by targeting AGEs-RAGE and its downstream pathways p38 MAPK and Nox4.

Topics: Animals; Apoptosis; Diabetic Nephropathies; Drug Therapy, Combination; Glycation End Products, Advanced; Iridoid Glucosides; Iridoids; Male; Mice; Mice, Inbred C57BL; NADPH Oxidase 4; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Podocytes; Receptor for Advanced Glycation End Products; Signal Transduction

Diabetes mellitus (DM) damages male reproduction at multiple levels, such as endocrine secretion, spermatogenesis and penile erection. We herein investigated the protective effects and mechanism of loganin targeting the advanced glycation end products (AGEs)/receptor for AGEs (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/NF-κB signalling pathway. Loganin relieved the general DM symptoms and decreased the blood glucose level of KK-Ay DM mice. Haematoxylin-eosin staining demonstrated that loganin ameliorated testicular histology and function and enhanced the activities of testis-specific markers lactate dehydrogenase (LDH), acid phosphatase (ACP) and gamma-glutamyl transferase (γ-GT). Loganin also showed evident anti-oxidative stress, anti-apoptotic and anti-inflammatory effects on DM-induced reproductive damage by restoring glutathione (GSH) level and superoxide dismutase (SOD) activity, as well as reducing reactive oxygen species (ROS) level and Bax/Bcl-2 ratio in vivo and in vitro. Western blotting exhibited that loganin significantly inhibited the AGEs/RAGE/p38MAPK/NF-κB signalling pathway. Acridine orange and ethidium bromide staining (AOEB) and Western blotting showed that loganin in combination with inhibitors of RAGE, p38MAPK and NF-κB exerted stronger anti-apoptotic effects on AGE-induced GC-2 cell damage compared with loganin alone. In conclusion, loganin can protect against DM-induced reproductive damage, probably by suppressing the AGEs/RAGE/p38MAPK/NF-κB pathway.

Topics: Animals; Apoptosis; Cell Line; Diabetes Mellitus, Experimental; Down-Regulation; Glycation End Products, Advanced; Inflammation; Iridoids; Kidney; Male; Mice; NF-kappa B; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Protective Agents; Receptor for Advanced Glycation End Products; Signal Transduction; Spermatozoa; Testis

A wide variety of plant raw materials thought to promote health are used as herbal medicines as well as foods. However, there is no legal maximum or minimum concentration limit on any herbal compound when these plant raw materials are used in processed foods. Legally, these processed foods are regulated only for harmful substances, and there is no other guarantee of their contents. Therefore, the objective of this study was to determine the concentrations of 12 herbal compounds (nodakenin, decursin, decursinol angelate, morroniside, loganin, glycyrrhizic acid, liquiritigenin, puerarin, daidzin, schisandrin, gomisin A, gomisin N) in commonly used plant raw materials, such as "Angelica Gigas root", "Cornus Fruit", "Liquorice Root", "Pueraria Root", and "Schisandra Fruit"; and also in 45 processed foods, using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method validation was performed successfully using the parameters of specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, matrix effect, extraction recovery, and stability. The 12 herbal compounds were determined to be present in all the foods advertised as containing each ingredient, although in very low concentrations in some cases. Three solid samples labelled as 100% pure material from one herbal species also contained herbal compounds found in others, so that intentional or unintentional adulteration was suspected.

Topics: Benzopyrans; Butyrates; Chromatography, Liquid; Coumarins; Cyclooctanes; Dioxoles; Flavanones; Food Analysis; Fruit; Glucosides; Glycosides; Glycyrrhizic Acid; Herbal Medicine; Iridoids; Isoflavones; Lignans; Plant Roots; Plants, Medicinal; Polycyclic Compounds; Tandem Mass Spectrometry

Diabetic peripheral neuropathy (DPN) is caused by hyperglycemia, which induces oxidative stress and inflammatory responses that damage nerve tissue. Excessive generation of reactive oxygen species (ROS) and NOD-like receptor protein 3 (NLRP3) inflammasome activation trigger the inflammation and pyroptosis in diabetes. Schwann cell dysfunction further promotes DPN progression. Loganin has been shown to have antioxidant and anti-inflammatory neuroprotective activities. This study evaluated the neuroprotective effect of loganin on high-glucose (25 mM)-induced rat Schwann cell line RSC96 injury, a recognized in vitro cell model of DPN. RSC96 cells were pretreated with loganin (0.1, 1, 10, 25, 50 μM) before exposure to high glucose. Loganin's effects were examined by CCK-8 assay, ROS assay, cell death assay, immunofluorescence staining, quantitative RT-PCR and western blot. High-glucose-treated RSC96 cells sustained cell viability loss, ROS generation, NF-κB nuclear translocation, P2 × 7 purinergic receptor and TXNIP (thioredoxin-interacting protein) expression, NLRP3 inflammasome (NLRP3, ASC, caspase-1) activation, IL-1β and IL-18 maturation and gasdermin D cleavage. Those effects were reduced by loganin pretreatment. In conclusion, we found that loganin's antioxidant effects prevent RSC96 Schwann cell pyroptosis by inhibiting ROS generation and suppressing NLRP3 inflammasome activation.

Topics: Animals; Glucose; Humans; Inflammasomes; Iridoids; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Rats; Schwann Cells

Loganin, a major bioactive iridoid glycoside derived from Cornus officinalis, exerts different beneficial biological properties. Recently, loganin has been reported to exhibit potential anti-inflammatory effects in the intestinal tissues, while the detailed mechanisms remain elusive. This study aimed to investigate whether loganin could inhibit the inflammatory response in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and to explore possible molecular mechanisms involved in this process. Results showed that oral administration of loganin significantly decreased body weight loss, disease activity index, colon shortening, myeloperoxidase (MPO) activity and pathologic abnormalities in UC mice. Loganin obviously inhibited the mRNA and protein levels of IL-6, TNF-α and IL-1β in colon tissues from UC mice. Furthermore, loganin remarkably reduced macrophage M1 polarization in UC mice evidenced by reduced the number of F4/80 and iNOS dual-stained M1 macrophages, and the expression of M1 macrophage-related pro-inflammatory chemokines/cytokines including MCP-1, CXCL10 as well as COX-2. Further investigation showed that loganin upregulated the mRNA and protein levels of Sirt1, with the inhibition of NF-κB-p65 acetylation in colon tissues from UC mice. Moreover, Sirt1-specific inhibitor Ex527 administration abolished the anti-inflammatory and anti-macrophage M1 polarization effects of loganin in UC. Thus, loganin could inhibit M1 macrophage-mediated inflammation and modulate Sirt1/NF-κB signaling pathway to attenuate DSS-induced UC. Loganin was considered as a viable natural strategy in the treatment of UC.[Figure: see text].

Topics: Animals; Blotting, Western; Colitis, Ulcerative; Cytokines; Iridoids; Macrophages; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Real-Time Polymerase Chain Reaction; Signal Transduction; Sirtuin 1

Alzheimer's disease (AD), also defined as a tauopathology, is a common neurodegenerative disease. Hyper-phosphorylation, cleavage or truncation, and aggregation of tau contribute to AD. Thus, targeting the post-translational modifications on tau may be a therapeutic strategy to treat AD. This study understood how cornel iridoid glycoside (CIG) affects tau post-translational modifications and synaptic abnormalities. The 10-month old P301S tau transgenic mice were given CIG at 100 and 200 mg/kg every day orally for 1 month. Hyperphosphorylated and truncated tau, synapse-associated proteins and glutamatergic receptors were all detected using Western blotting. The interactions between Morroniside (MOR) or Loganin (LOG) and tau were detected using Autodock and Surface Plasmon Resonance (SPR). The effects of CIG on the aggregation of tau were investigated using a cell-free system. CIG attenuated tau hyperphosphorylation at Thr205, Ser212, Ser262, Thr231 and Ser235 (AT180), but had no effect on tau truncation in the brains of 10-month old P301S mice. Binding free energies and interactions revealed that MOR and LOG bound with tau. We also found that CIG upregulated synapse-associated proteins such as PSD-95, syntaxin1A and synaptotagmin. In addition, CIG restored N-methyl-D-aspartic acid receptor and glutamate receptor levels. CIG improves post-translational modification of tau as well as synaptic abnormalities. The data presented here reveal that CIG may be used in the treatment of AD.

Topics: Administration, Oral; Animals; Brain; Cell-Free System; Disease Models, Animal; Female; Glycosides; Humans; Iridoids; Male; Mice; Mice, Transgenic; Models, Molecular; Molecular Docking Simulation; Mutation; Phenotype; Protein Binding; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; tau Proteins; Tauopathies; Treatment Outcome

Qiangshen tablet, an important prescription consisting of 14 kinds of Chinese herbal medicines, has been used for decades to treat kidney yang deficiency syndrome (KYDS) in China. Qiangshen tablet has been recorded in ChP (2015 edition) and possesses the effect of strengthening yang, invigorating qi and tonifying kidneys. In this research, a simple, reliable and specific method was established for simultaneous determination of stachydrine, psoralen, isopsoralen, morroniside, paeoniflorin and loganin in normal and KYDS rat plasma after intragastric administration of a Qiangshen tablet suspension by UPLC-MS/MS. Protein precipitation (PP) by acetonitrile and liquid-liquid extraction (LLE) by ethyl acetate - n-butanol (1: 1, v/v) were used for pretreatment of plasma samples. Chromatographic separation of two IS (Internal Standard) and six analytes was achieved using an ACQUITY UPLC® BEH C

Topics: Animals; Chromatography, High Pressure Liquid; Drug Monitoring; Drugs, Chinese Herbal; Ficusin; Furocoumarins; Glucosides; Glycosides; Iridoids; Male; Metabolome; Monoterpenes; Proline; Rats; Rats, Sprague-Dawley; Tablets; Tandem Mass Spectrometry; Yang Deficiency

BACKGROUND Chondrocyte apoptosis and catabolism are 2 major factors that contribute to the progression of osteoarthritis (OA). Loganin, an iridoid glycoside present in several herbs, including Flos lonicerae, Cornus mas L, and Strychnos nux vomica, is a valuable medication with anti-inflammatory and anti-apoptotic effects. Our study examines these effects and explores the potential benefits of loganin in the OA treatment. MATERIAL AND METHODS To clarify the roles of loganin in OA and its specific signaling pathway, chondrocytes were administrated with IL-1ß and supplemented with or without LY294002 (a classic PI3K/Akt inhibitor). The apoptotic level, catabolic factors (MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5), extracellular matrix (ECM) degradation, and activation of the PI3K/Akt pathway were evaluated using western blotting, PCR, and an immunofluorescent assay. The degenerative condition of the cartilage was evaluated using the Safranin O assay in vivo. The expression of cleaved-caspase-3 (C-caspase-3) was measured using immunochemistry. RESULTS The data suggested that loganin suppressed the apoptotic level, reduced the release of catabolic enzymes, and decreased the ECM degradation of IL-1ß-induced chondrocytes. However, suppressing PI3K/Akt signaling using LY294002 alleviated the therapeutic effects of loganin in chondrocytes. Our in vivo experiment showed that loganin partially attenuated cartilage degradation while inhibiting the apoptotic level. CONCLUSIONS This work revealed that loganin treatment attenuated IL-1ß-treated apoptosis and ECM catabolism in rat chondrocytes via regulation of the PI3K/Akt signaling, revealing that loganin is a potentially useful treatment for OA.

Topics: Animals; Apoptosis; China; Chondrocytes; Inflammation; Interleukin-1beta; Iridoids; Male; Osteoarthritis; Phosphatidylinositol 3-Kinases; Primary Cell Culture; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

The chemical investigation of the methanol extract of Hymenodictyon orixense bark, a Thai medicinal herb, provided five compounds. Their structures were identified on the basis of 1D NMR and MS data, as well as by comparison of the data with published values, as an iridoid glycoside: loganin (1), four coumarins: scopoletin (2), scopolin (3), hymexelsin (4) and scopoletin 7-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside (5). Compounds 1-5 showed acetylcholinesterase (AChE) inhibitory activity in the range of 13.92-34.18% at a concentration of 100 μg/mL. In addition, compounds 1 and 5 are reported for the first time from this genus.

Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Coumarins; Iridoid Glycosides; Iridoids; Phytochemicals; Plant Bark; Plants, Medicinal; Rubiaceae

Herbal medicines are widely used as therapeutic products in many countries. Fructus Corni, a traditional herb medicine, has been clinically used to cure chronic nephropathy for thousands of years. It could be converted by gut microflora in vivo to shape its pharmacological profiles. Thus, metabolic profiles of major active constituents in Fructus Corni extracts by gut microflora from rats in healthy and nephropathy state were firstly investigated in vitro by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) in this study. According to the features of protonated ions, five metabolites (M1, M2, M3, M5 and M6) were found and preliminarily authenticated. Intestinal bacteria were capable of converting N0 (loganin) to its aglycone M1 (loganetin). The latter was further hydrogenated to the corresponding M2 (hydrogenated loganetin) and subsequently to M3 (hydrogenated and demethylated loganetin) by demethylation; While M5 (demethylated morronisid aglycone) and M6 (dehydroxylated morronisid aglycone) were identified as the two metabolites of N4 (morronisid) through demethylation and dehydroxylation. Gut microflora from healthy and nephropathy rats could degrade loganin and morronisid to the above metabolites. However, healthy rat intestinal bacteria showed more powerful degradation and much more amounts of M1 and M6 were obtained in their samples. Additionally, this work demonstrated that UPLC-Q-TOF/MS approach connected with MetaboLynx™ analysis software was rapid and reliable for screening and authentication of natural product metabolites.

Topics: Animals; Chromatography, High Pressure Liquid; Cornus; Gastrointestinal Microbiome; Glycosides; Iridoids; Mass Spectrometry; Plant Extracts; Rats; Renal Insufficiency, Chronic

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Topics: Animals; Anxiety; Behavior, Animal; Cytokines; Depression; Diabetes Mellitus, Experimental; Iridoids; Male; Rats; Rats, Wistar

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Topics: Animals; Anxiety; Behavior, Animal; Cytokines; Depression; Diabetes Mellitus, Experimental; Interleukin-6; Iridoids; Male; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Cornus officinalis-Rehmannia glutinosa herb couple is widely used herb medicine in clinical practice to treat chronic kidney disease (CKD). However, the in vivo integrated metabolism of its main bioactive components in CKD rats remains unknown. In this study, UPLC-Q-TOF/MS technique combined with Metabolynx

Topics: Administration, Oral; Animals; Case-Control Studies; Chromatography, High Pressure Liquid; Cornus; Feces; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Male; Phenols; Plant Extracts; Rats; Rehmannia; Renal Insufficiency, Chronic; Tandem Mass Spectrometry

Topics: Amyloid beta-Peptides; Animals; Dinoprostone; Inflammation; Iridoids; Mice; Microglia; NF-kappa B; Nitric Oxide; Peptide Fragments; Signal Transduction; TNF Receptor-Associated Factor 6; Toll-Like Receptor 4

Parkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with a dosage of 30 mg/kg daily for 5 days to establish a subacute PD model and treated with loganin. Locomotor activity was assessed by a pole test, then mice were euthanized at 1 and 3 days after the last treatment, and brain tissue was prepared for subsequent assays. Loganin rescued decrease of dopamine levels and tyrosine hydroxylase (TH) expression in the striatum, and shortened total locomotor activity (TLA) time of mice. Furthermore, loganin alleviated microglia and astrocyte activation, and suppressed TNF-α and caspase-3 expression through a c-Abl-p38-NFκB pathway. Loganin also downregulated LC3-II and Drp1 expression, and decreased the level of acidic vesicular organelles (AVOs). Loganin exerts neuroprotective effects on MPTP-induced PD mice by decreasing inflammation, autophagy, and apoptosis, suggesting that loganin could serve as a therapeutic drug to ameliorate PD. J. Cell. Biochem. 118: 3495-3510, 2017. © 2017 Wiley Periodicals, Inc.

Topics: Animals; Astrocytes; Corpus Striatum; Dopamine; Iridoids; Male; Mice; Microglia; MPTP Poisoning; Parkinson Disease, Secondary; Tyrosine 3-Monooxygenase

Wine-processing, which is sauteing with rice wine, will change the inclination and direction of herbs' actions. After being wine-processed, the effects of nourishing liver and kidney of Dipsacus asper will be strengthened. However, the underlying mechanism remains elusive. The following study is to establish and validate an UHPLC-MS/MS approach to determine six bioactive constituents in tissue samples, including loganin, loganic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid and asperosaponin VI and apply the approach to a comparative tissue distribution study of raw and wine-processed Dipsacus asper in rats. A Shimadzu UHPLC system coupled with triple quadrupole mass spectrometer was employed for analysis of the six analytes using multiple reaction monitoring (MRM) mode. A one-step protein precipitation by methanol was employed to extract the six analytes from tissues. Chloramphenicol and glycyrrhetinic acid were selected as internal standards. The proposed approach was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery. Our results revealed that all of the calibration curves displayed good linear regression (r

Topics: Animals; Chlorogenic Acid; Chromatography, High Pressure Liquid; Dipsacaceae; Iridoids; Male; Plant Extracts; Plants, Medicinal; Quinic Acid; Rats; Rats, Sprague-Dawley; Saponins; Tandem Mass Spectrometry; Tissue Distribution; Wine

The activity of Schwann cells (SWCs) is very important in trauma-induced nerve repair, and tumour necrosis factor-α (TNF-α) produced during tissue injury inhibits the viability of SWCs, which delays the repair of peripheral nerves. Loganin is an iridoid glycoside that has been shown to alleviate a variety of cytotoxic effects. In the current study, we evaluated the potential efficacy and the mechanism of action of loganin in TNF-α-induced cytotoxicity in SW10 cells. The experimental results indicated that loganin blocked TNF-α-mediated Smad2 activation, downregulated the expression of the G1 phase cell cycle inhibitor p15IN4KB, and upregulated the expression of the G1 phase cell cycle activator cyclin D1-CDK4/6, which upregulated E2F-1-dependent survivin expression and relieved TNF-α-induced apoptosis in SW10 cells. The protective effect of loganin on SWCs has potential medicinal value in the promotion of peripheral nerve repair and is significant for studies in the field of tissue regeneration.

Topics: Apoptosis; Cell Cycle Checkpoints; Cell Line; E2F1 Transcription Factor; Humans; Inhibitor of Apoptosis Proteins; Iridoids; Real-Time Polymerase Chain Reaction; Signal Transduction; Smad2 Protein; Survivin; Tumor Necrosis Factor-alpha

Fructus Corni has been used for nourishing liver and kidney in clinical practice for many years. However, the in vivo integrated metabolism profile of its bioactive components remains unknown. In the present study, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry coupled with the MetaboLynxTM software was established for screening and identification of the metabolites of the loganin and the morroniside in normal and chronic kidney disease (CKD) rat plasma, urine and feces after oral administration of Fructus Corni extract. The results showed that 11 metabolites including taurine and glucuronide conjugates, deglycosylated, dehydrated, (de)hydroxylated, (de)methylated, acetylated products were tentatively detected in normal rat samples while only eight metabolites were obtained in the model samples. Two parent compounds were both absorbed into the blood circulation of the normal and CKD rats. However, the compounds in the CKD rat showed lower metabolic capability. Few kinds and minor amounts of the metabolites were appeared in the CKD rat plasma, urine and feces. While considerable amounts of the parent compounds were detected in the CKD plasma. This helped maintain a high blood drug concentration which might be beneficial for the treatment of CKD. These results will be helpful for the further investigation of the pharmacokinetic study of Fructus Corni in vivo.

Topics: Administration, Oral; Animals; Biomarkers; Chromatography, High Pressure Liquid; Cornus; Glycosides; Iridoids; Male; Metabolome; Metabolomics; Plant Extracts; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Efficient preparation of loganin from Cornus officinalis fruits was investigated. First, effect of extraction conditions on loganin yield was measured. The loganin content in C. officinalis extract was greatly affected by ethanol concentration and extraction time whereas extraction temperature exerted relatively little effect. Response surface methodology with Box-Behnken design suggested optimized extraction condition for maximum loganin yield as ethanol concentration, 32.0%; temperature 46.2 °C and extraction time, 46.7 min, which yielded 10.4 μg loganin/mg dried fruit. Next, the effect of maturation stage of C. officinalis fruits on loganin content was investigated. The loganin content in the extract of C. officinalis fruits was decreased as the maturation process. The loganin content in the unripe fruits was 18.0 μg/mg extract whereas reduced to 13.3 μg/mg extract for ripe fruits. Taken together, our present study suggested the importance of extraction condition and maturation stages for efficient preparation of loganin from C. officinalis fruits.

Topics: Chemical Fractionation; Cornus; Fruit; Iridoids

Monoterpenoid indole alkaloids (MIAs) are plant defense compounds and high-value pharmaceuticals. Biosynthesis of the universal MIA precursor, secologanin, is organized between internal phloem-associated parenchyma (IPAP) and epidermis cells. Transporters for intercellular transport of proposed mobile pathway intermediates have remained elusive. Screening of an Arabidopsis thaliana transporter library expressed in Xenopus oocytes identified AtNPF2.9 as a putative iridoid glucoside importer. Eight orthologs were identified in Catharanthus roseus, of which three, CrNPF2.4, CrNPF2.5 and CrNPF2.6, were capable of transporting the iridoid glucosides 7-deoxyloganic acid, loganic acid, loganin and secologanin into oocytes. Based on enzyme expression data and transporter specificity, we propose that several enzymes of the biosynthetic pathway are present in both IPAP and epidermis cells, and that the three transporters are responsible for transporting not only loganic acid, as previously proposed, but multiple intermediates. Identification of the iridoid glucoside-transporting CrNPFs is an important step toward understanding the complex orchestration of the seco-iridioid pathway.

Topics: Animals; Biological Assay; Biological Transport; Biosynthetic Pathways; Catharanthus; Cell Membrane; Gene Expression Regulation, Plant; Iridoid Glucosides; Iridoids; Kinetics; Membrane Transport Proteins; Models, Biological; Oocytes; Plant Proteins; Protein Transport; Terpenes; Xenopus

1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which induces the pathological characteristics of Parkinson's disease in rodents, also specifically targets dopaminergic neurons in zebrafish embryos and larvae. Loganin, a traditional Chinese drug, was reported to regulate immune function and possess anti-inflammatory and anti-shock effects. Here, we investigate the role of loganin in MPTP-induced Parkinson-like abnormalities in zebrafish. MPTP treatment-induced abnormal development, in larvae, such as pericardium edema, increased yolk color, yolk sac edema, and retarded yolk sac resorption, as well as defects in brain development. Loganin could block MPTP-induced defects, with little toxicity to the eggs. Results of whole mount in situ hybridization showed loganin prevented the loss of both dopaminergic neurons and locomotor activity, exhibited by larvae treated with MPTP. In addition, loganin significantly rescued MPTP-induced neurotoxicity on PC12 cells, possibly through the suppression of PI3K/Akt/mTOR axis and JNK signaling pathways. In conclusion, loganin blocks MPTP-induced neurotoxicity and abnormal development in zebrafish. J. Cell. Biochem. 118: 615-628, 2017. © 2016 Wiley Periodicals, Inc.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Iridoids; MAP Kinase Kinase 4; MPTP Poisoning; Neuroprotective Agents; PC12 Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; TOR Serine-Threonine Kinases; Zebrafish; Zebrafish Proteins

Although the incidence rate of dementia is rapidly growing in the aged population, therapeutic and preventive reagents are still suboptimal. Various model systems are used for the development of such reagents in which scopolamine is one of the favorable pharmacological tools widely applied. Loganin is a major iridoid glycoside obtained from Corni fructus (Cornusofficinalis et Zucc) and demonstrated to have anti-inflammatory, anti-tumor and osteoporosis prevention effects. It has also been found to attenuate Aβ-induced inflammatory reactions and ameliorate memory deficits induced by scopolamine. However, there has been limited information available on how loganin affects learning and memory both electrophysiologically and behaviorally. To assess its effect on learning and memory, we investigated the influence of acute loganin administration on long-term potentiation (LTP) using organotypic cultured hippocampal tissues. In addition, we measured the effects of loganin on the behavior performance related to avoidance memory, short-term spatial navigation memory and long-term spatial learning and memory in the passive avoidance, Y-maze, and Morris water maze learning paradigms, respectively. Loganin dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In accordance with these findings, loganin behaviorally attenuated scopolamine-induced shortening of step-through latency in the passive avoidance test, reduced the percent alternation in the Y-maze, and increased memory retention in the Morris water maze test. These results indicate that loganin can effectively block cholinergic muscarinic receptor blockade -induced deterioration of LTP and memory related behavioral performance. Based on these findings, loganin may aid in the prevention and treatment of Alzheimer's disease and learning and memory-deficit disorders in the future.

Topics: Analysis of Variance; Animals; Avoidance Learning; Biophysics; Cholinergic Antagonists; Electric Stimulation; Hippocampus; In Vitro Techniques; Iridoids; Learning Disabilities; Long-Term Potentiation; Maze Learning; Memory Disorders; Patch-Clamp Techniques; Rats; Recovery of Function; Scopolamine

To study the chemical composition and their anti-inflammatory activities of honeysuckle (Lonicera japonica Thunb.) roots, seventeen compounds were isolated from the roots of L. japonica Thunb. by various chromatography, including silica gel, Sephadex LH-20 and preparative HPLC. Their structures were identified by MS, IR, and nuclear magnetic resonance spectra, as 1-oxo-(1H)-cyclopenta[b]benzofuran-7-carbaldehyde (1), 4-hydroxycinnamic acid (2), chlorogenic acid (3), loganin aglycone (4), caffeic acid (5), secologanin dimethyl acetal (6), korolkoside (7), coniferin (8), sweroside (9), secoxyloganin (10), 5-O-caffeoylquinic acid (11), chlorogenic acid methyl ester (12), chlorogenic acid ethyl ester (13), 3,5-O-dicaffeoylquinic acid (14), 4,5-O-dicaffeoylquinic acid (15), grandifloroside (16), and 4,5-O-dicaffeoylquinic acid (17). Among those, compound 1 is a new compound, and compound 8 is found in L. japonica for the first time. Compounds 1, 3, 14-17 showed significant anti-inflammatory activities against macrophage in zebrafish.

Topics: Animals; Anti-Inflammatory Agents; Chlorogenic Acid; Chromatography, High Pressure Liquid; Iridoid Glucosides; Iridoids; Lonicera; Macrophages; Plant Roots; Quinic Acid; Zebrafish

To isolate and identify the chemical constituents from the seeds of Strychnos nux-vomica.. Chromatographic separation techniques such as silica gel chromatography,ODS chromatography and Sephadex LH-20 chromatography were used for the isolation and purification. The structures of the chemical constituents were identified on the basis of mass spectrometry,NMR spectroscopy and so on.. 16 compounds were isolated and their structures were identified as: α-amyrin( 1), vomicine( 2), stearic acid( 3), β-sitosterol( 4),vanillin( 5), ethyl gallate( 6),methyl gallate( 7),novacine( 8),strychnine( 9), daucosterol( 10),brucine chloromethochloride( 11),loganic acid( 12),strychnine chloromethochloride( 13),brucine( 14),geniposide( 15) and loganin( 16).. Compounds 3,6,7 and 15 are isolated from this genus for the first time.

Topics: Iridoids; Seeds; Strychnine; Strychnos nux-vomica

To study the difference in yield and quality of Gentiana crassicaulis with different transplanting period and transplanting methods, and to determine the optimum transplanting technique of Gentiana crassicaulis in Ludian.. The variation in fresh weight,dry weight,dry discount rate, length, diameter, branches,the content of gentiopicroside,loganin acid,alcohol-soluble extract, total ash were measured, and made a comprehensive evaluation of yield and quality by gray relational distance ideal comprehensive evaluation method.. There was a big difference in yield and quality of Gentiana crassicaulis with different transplanting time and transplanting methods. Gentiana crassicaulis were transplanted in March 10 with the density of 25 cm × 24 cm,and overburden 1 cm and flat transplanting had the best comprehensive evaluation of yield and quality.. The transplanting time of Gentiana crassicaulis in Ludian should begin at the end of early March,and reduce overburden soil on the traditional transplanting methods.

Topics: Gentiana; Iridoid Glucosides; Iridoids

Overt bladder afferent activation may exacerbate endogenous substance P (SP) release to induce intercellular adhesion molecule-1 (ICAM-1)-mediated inflammation and reactive oxygen species (ROS) production leading to hyperactive bladder. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese medicine, has been used to treat lower urinary tract symptoms in patients by undefined mechanisms. We explored the possible mechanisms and the active components of BWDHW on exogenous SP-induced bladder hyperactivity. BWDHW contained six major components: loganin, paeoniflorin, 5-hydroxymethylfurfural, cinnamic acid, cinnamaldehyde, and paeonol by high-performance liquid chromatography. In urethane-anesthetized female Wistar rats, we evaluated transcystometrogram, pelvic afferent nerve activity by electrophysiologic recording techniques, ICAM-1 expression by Western blot and immunohistochemistry, ROS amount by an ultrasensitive chemiluminescence method and possible ROS sources from the different leukocytes by specific stains in SP-treated bladder. BWDHW and its major component loganin dose-dependently inhibited H2 O2 and HOCl activity in vitro. Intragastrical BWDHW (250 mg/kg) and loganin (5 mg/kg) twice daily for 2 weeks did not affect the baseline micturition parameters. Intra-arterial SP (20 µg/rat) through neurokinin-1 receptor activation increased voiding frequency (shortened intercontraction intervals), pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, bladder ROS amount, neutrophils adhesion to venous endothelium, CD68 (monocyte/macrophage), and mast cell infiltration in the inflamed bladder. BWDHW and loganin pretreatment significantly depressed SP-enhanced pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, leukocyte infiltration, and ROS amount, and subsequently improved bladder hyperactivity. In conclusion, our results suggest that BWDHW and its active component loganin improves bladder hyperactivity via inhibiting SP/neurokinin-1 receptor signaling and depressing NF-κB/ICAM-1 mediated oxidative injury and inflammation. Neurourol. Urodynam. 35:771-779, 2016. © 2015 Wiley Periodicals, Inc.

Topics: Animals; Drugs, Chinese Herbal; Female; Intercellular Adhesion Molecule-1; Iridoids; NF-kappa B; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction; Substance P; Urinary Bladder, Overactive; Urination

We propose the cell culture approach to investigate oleuropein (1) biogenesis in Olea europaea L. We suggest employing olive callus cultures to identify the iridoidic precursor of oleuropein. In fact, we confirmed that callus cells from olive shoot explants are able to produce key secoiridoid as 1. To enable this approach, we synthesised and characterised deuterium-labelled iridoidic precursors belonging both to the loganin and the 8-epiloganin series. These iridoids are [7,8-(2)H2]-7-deoxy-8-epi-loganin (2(D)), [8,10-(2)H2]-8-epi-loganin (4(D)) and [7,8-(2)H2]-7-deoxy-loganin (3(D)).

Topics: Deuterium; Iridoid Glucosides; Iridoids; Molecular Structure; Olea; Tissue Culture Techniques

Hypoglycemic activity-guided separation of ethanol extracts from the fruits of Cornus officinalis Sieb. et Zucc (CO) led to the isolation of loganin, morroniside, and ursolic acid. The antidiabetic capacity of CO extracts and related compounds was further investigated in diabetes mellitus mice. The results suggested that both CO extracts and pure compounds could ameliorate diabetes-associated damages and complications. Oral administration of loganin and morroniside decreased fasting blood glucose levels in diabetes mellitus mice. Ursolic acid exhibited the highest reactive oxygen species scavenging activity and α-glucosidase inhibitory activity. Notably, we noticed an interesting synergistic effect between loganin and ursolic acid. Given these favorable hypoglycemic properties, C. officinalis, a food and medicinal plant in China, may be used as a valuable food supplement for the treatment of diabetes mellitus.

Topics: alpha-Glucosidases; Animals; China; Cornus; Diabetes Mellitus, Experimental; Free Radical Scavengers; Fruit; Glycosides; Hep G2 Cells; Humans; Hypoglycemic Agents; Iridoids; Male; Mice; Plant Extracts; Plants, Medicinal; Reactive Oxygen Species; Triterpenes; Ursolic Acid

A sensitive and rapid method for determination of loganin, morroniside, catalpol and acteoside in rat plasma after oral administration of Rehmannia glutinosa Libosch and Cornus officinalis Sieb drug pair based on ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS). Chromatographic separation was achieved using an Acquity UPLC BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the mobile phase A and B. Loganin, morroniside, catalpol, acteoside and the internal standard (chloramphenicol) were detected by selected reaction monitoring in the negative ion mode with the mass transition of m/z 451.0→179.0 (morroniside), m/z 435.0→227.0 (loganin), m/z 407.1→199.1 (catalpol), m/z 623.2→161.0 (acteoside) and m/z 320.8→151.9 (chloramphenicol), respectively. All calibration curves showed good linearity (r>0.991). The precision was evaluated by intra-day and inter-day assays and the RSD% were all within 9.58%. The recovery ranged from 67.62 to 80.14%. The method was successfully applied to pharmacokinetic study of the analytes in normal and doxorubicin-induced chronic kidney disease rat plasma.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Cornus; Drugs, Chinese Herbal; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Limit of Detection; Male; Mass Spectrometry; Phenols; Rats; Rats, Sprague-Dawley; Rehmannia; Renal Insufficiency, Chronic

Starting from a natural cyclopentanoid monoterpene belonging to the class of iridoid glucosides called loganin, we performed the synthesis of a new carbocyclic nucleoside, allowing the preparation of a new lead compound, with a potential HIV antiviral activity as an reverse transcriptase competitive inhibitor that we named LoganVir. The stereocontrol of the coupling reaction was completed utilizing the procedure described by Mitsunobu with a purinic base.

Topics: Adenosine; Anti-HIV Agents; Chemistry Techniques, Synthetic; Cyclopentanes; Iridoids; Nucleosides; Reverse Transcriptase Inhibitors; Vinca

We evaluated the major active components isolated from Corni Fructus: loganin, morroniside, and 7-O-galloyl-D-sedoheptulose as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) for use in Alzheimer's disease treatment. These compounds exhibited predominant cholinesterase (ChEs) inhibitory effects with IC50 values of 0.33, 3.95, and 10.50 ± 1.16 µM, respectively, for AChE, and 33.02, 37.78, and 87.94 ± 4.66 µM, respectively, for BChE. Kinetics studies revealed that loganin and 7-O-galloyl-D-sedoheptulose inhibited AChE with characteristics typical of mixed inhibitors, while morroniside was found to be a noncompetitive inhibitor against AChE and also exerted mixed BChE inhibitory activities. For BACE1, loganin showed noncompetitive type inhibitory effects, while morroniside and 7-O-galloyl-D-sedoheptulose were found to be mixed inhibitors. Furthermore, these compounds exhibited dose-dependent inhibitory activity with ONOO(-)-mediated protein tyrosine nitration. Molecular docking simulation of these compounds demonstrated negative binding energies for ChEs, and BACE1, indicating high affinity and tighter binding capacity for the active site of the enzyme. Loganin was the most potent inhibitor against both ChEs and BACE1. The data suggest that these compounds together can act as a triple inhibitor of AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for Alzheimer's disease treatment.

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases; Butyrylcholinesterase; Cholinesterase Inhibitors; Cornus; Drug Discovery; Glycosides; Heptoses; Iridoids; Kinetics; Molecular Docking Simulation; Protein Binding

Atherosclerosis is a chronic inflammatory disease of the vascular walls. ApoCIII is an independent factor which promotes atherosclerotic processes. This study aimed to investigate whether Loganin administration inhibits the inflammatory response in vitro and in vivo. In the apoCIII-induced mouse adipocytes, the levels of cytokines, including TNF-α, MCP-1 and IL-6 were determined by enzyme-linked immunosorbent assay and their gene expressions were measured through RT-PCR. The phosphorylation of nuclear factor-κB (NF-κB) proteins was analyzed by Western blotting. Our results showed that Loganin markedly decreased TNF-α, MCP-1 and IL-6 concentrations as well as their gene expressions. Western blotting analysis indicated that Loganin suppressed the activation of NF-κB signaling. In the Tyloxapol-treated mouse model, Loganin reduced the contents of TC and TG in mouse serum. The results of Oil Red-O Staining showed that Loganin reduced the production of lipid droplets. So it is suggested that Loganin might be a potential therapeutic agent for preventing the inflammation stress in vitro and in vivo.

Topics: 3T3 Cells; Adipocytes; Animals; Anti-Inflammatory Agents; Atherosclerosis; Chemokine CCL2; Disease Models, Animal; Humans; Inflammation; Interleukin-6; Iridoids; Lipid Metabolism; Mice; NF-kappa B; Phosphorylation; Polyethylene Glycols; Signal Transduction; Tumor Necrosis Factor-alpha

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by motor neurons degeneration and muscular atrophy. There is no effective SMA treatment. Loganin is a botanical candidate with anti-inflammatory, anti-oxidant, glucose-lowering and anti-diabetic nephropathy activities. The aim of this study is to investigate the potential protective effects of loganin on SMA using two cellular models, SMN-deficient NSC34 cells and SMA patient fibroblasts, and an animal disease model, SMAΔ7 mice. In SMN-deficient NSC34 cells, loganin increased cell viability, neurite length, and expressions of SMN, Gemin2, SMN-Gemin2 complex, p-Akt, p-GSK-3β, p-CREB, BDNF and Bcl-2. However, both AG1024 (IGF-1 R antagonist) and IGF-1 R siRNA attenuated the protective effects of loganin on SMN level and cell viability in SMN-deficient NSC34 cells. In SMA patient fibroblasts, loganin up-regulated levels of SMN, FL-SMN2, and Gemins, increased numbers of SMN-containing nuclear gems, modulated splicing factors, and up-regulated p-Akt. Furthermore, in the brain, spinal cord and gastrocnemius muscle of SMAΔ7 mice, loganin up-regulated the expressions of SMN and p-Akt. Results from righting reflex and hind-limb suspension tests indicated loganin improved muscle strength of SMAΔ7 mice; moreover, loganin activated Akt/mTOR signal and inhibited atrogin-1/MuRF-1 signal in gastrocnemius muscle of SMAΔ7 mice. Loganin also increased body weight, but the average lifespan of loganin (20mg/kg/day)-treated SMA mice was 16.80±0.73 days, while saline-treated SMA mice was 10.91±0.96 days. In conclusion, the present results demonstrate that loganin provides benefits to SMA therapeutics via improving SMN restoration, muscle strength and body weight. IGF-1 plays an important role in loganin neuroprotection. Loganin can be therefore a valuable complementary candidate for treatment of neuromuscular diseases via regulation of muscle protein synthesis and neuroprotection.

Topics: Animals; Apoptosis; Cell Line; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Fibroblasts; Genetic Predisposition to Disease; Humans; Insulin-Like Growth Factor I; Iridoids; Mice; Mice, Transgenic; Motor Activity; Motor Neurons; Muscle Proteins; Muscle Strength; Muscle, Skeletal; Muscular Atrophy, Spinal; Mutation; Nerve Degeneration; Neuroprotective Agents; Phenotype; Phosphorylation; Protein Biosynthesis; Proto-Oncogene Proteins c-akt; RNA Interference; Signal Transduction; SKP Cullin F-Box Protein Ligases; Survival of Motor Neuron 1 Protein; Time Factors; TOR Serine-Threonine Kinases; Transfection; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Weight Gain

Aldose reductase (AR) is a key enzyme in the polyol pathway that is strongly implicated in the pathogenesis of diabetic complications. AR inhibitors have been proposed as therapeutic agents for diabetic complications through suppression of sorbitol formation and accumulation. In this study, we evaluated whether two major compounds of Corni Fructus, loganin and 7-O-galloyl-D-sedoheptulose, had an inhibitory effect on diabetic complications through AR inhibition. Because the iridoid glycoside loganin and the low-molecular-weight polyphenol 7-O-galloyl-D-sedoheptulose showed marginal inhibitory activities against rat lens AR (RLAR) and human recombinant AR (HRAR) in inhibition assays, we performed enzyme kinetic analyses and molecular simulation of the interaction of these two compounds with AR to further investigate their potential as inhibitors of diabetic complications. In kinetic analysis using Lineweaver-Burk plots and Dixon plots, loganin and 7-O-galloyl-D-sedoheptulose were both mixed inhibitors of RLAR with inhibition constants (K i) of 27.99 and 128.68 μΜ, respectively. Moreover, molecular docking simulation of both compounds demonstrated negative binding energies (Autodock 4.0 = -6.7; -7.5 kcal/mol; Fred 2.0 = -59.4; -63.2 kcal/mol) indicating a high affinity and tight binding capacity for the active site of the enzyme. Iridoid nucleus and aromatic ring systems and glycoside and sedoheptulose moieties were found to bind tightly to the specificity pocket and the anion binding pocket in RLAR through Phe123, His111, Trp21, Tyr49, His111, and Trp112 residues. Our results clearly indicate that loganin and 7-O-galloyl-D-sedoheptulose have great promise for the treatment of diabetic complications through inhibition of AR.

Topics: Aldehyde Reductase; Binding Sites; Catalytic Domain; Cornus; Diabetes Complications; Enzyme Inhibitors; Heptoses; Humans; Indicators and Reagents; Iridoids; Kinetics; Models, Molecular; Molecular Conformation; Recombinant Proteins

Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of loganin on diabetic nephropathy in vivo.. We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined.. The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney.. Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy.

Topics: Analysis of Variance; Animals; Blood Urea Nitrogen; Blotting, Western; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Disease Models, Animal; DNA Primers; Dose-Response Relationship, Drug; Gene Expression Regulation; Glycation End Products, Advanced; Iridoids; Kidney; Malondialdehyde; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Molecular Structure; Oxidative Stress; Pancreas; Proteinuria; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase

In our continued investigation of plants from the family Oleaceae we have now investigated Picconia azorica endemic to the Azores. Like most species within the family it contains the oleoside-based secoiridoid glucosides ligstroside and oleuropein as the main compounds and in addition verbascoside and echinacoside. As with the previously investigated Picconia excelsa, it also contained the carbocyclic iridoid glucosides involved in the biosynthetic pathway to the oleoside derivatives. However, while P. excelsa contained loganin esterified with some monoterpenoid acids, P. azorica contains similar esters of 7-epi-loganic acid named Picconioside A and B. In addition were found the two 7-O-E/Z-cinnamoyl esters of 7-epi-loganic acid named Picconioside C and D.

Topics: Azores; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Molecular Structure; Oleaceae; Phenols; Pyrans

Amyloid-beta (Aβ) protein, the main constituent of senile plaques, is believed to play a pivotal role in the pathogenesis of Alzheimer's disease (AD). AD is closely associated with inflammatory reactions which are considered to be responses to Aβ deposition. The present study investigated the effect of loganin on Aβ25-35-induced inflammatory damage and the underlying molecular mechanism of its neuroprotective action. Loganin predominantly prevented Aβ25-35-stimulated cell death through suppressing ROS generation, and attenuating apoptosis by inhibiting caspase-3 activity and regulating cell cycle. Furthermore, loganin suppressed the level of TNF-α and protein expression of iNOS and COX-2 in Aβ25-35-injured PC12 cells. These inhibitions appeared to correlate with the suppression of NF-κB activation by loganin, as pre-treating cells with loganin blocked the translocation of NF-κB into the nuclear compartment and degradation of the inhibitory subunit IκB. Loganin substantially inhibited phosphorylation of MAPKs including ERK1/2, p38 and JNK, which are closely related to regulation of NF-κB activation. Taken together, the results implied that loganin attenuated neuroinflammatory responses through the inactivation of NF-κB by NF-κB dependent inflammatory pathways and phosphorylation of MAPK in Aβ25-35-induced PC12 cells.

Topics: Amyloid beta-Peptides; Animals; Apoptosis; Caspase 3; Cell Death; Cyclooxygenase 2; Iridoids; Mitogen-Activated Protein Kinase 3; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; PC12 Cells; Peptide Fragments; Phosphorylation; Rats; Reactive Oxygen Species; Signal Transduction; Tumor Necrosis Factor-alpha

During comparative analysis on Palicourea species from Costa Rica, two unusual loganin derived tryptamine-iridoid alkaloids were isolated from an accession of Palicourea crocea. Besides the already known brachycerine (2), palicroceaine (1) features a novel hexacyclic backbone. A second provenance, however, yielded strictosidinic acid (3), belonging to the more common secologanin derived tryptamine-iridoid alkaloids, such as those found in Palicourea padifolia. From this species, strictosidine (4), lyaloside (5) and its derivative (E)-O-(6')-(4″-hydroxy-3″,5″-dimethoxy)-cinnamoyl lyaloside (6) could be isolated. A herbarium specimen-based screening was performed, indicating some degree of regional differentiation in alkaloid content and biosynthetic pathways within the widespread and variable Pal. crocea. It further shows its differentiation from the related strictosidine containing Palicourea croceoides. The occurrence of loganin derived tryptamine-iridoid alkaloids in Pal. crocea, Psychotria brachyceras and Psychotria brachypoda, all putatively unrelated members of the Palicourea s.l. clade, is a noteworthy exception within the genus, otherwise largely characterized by secologanin-derived tryptamine-iridoid alkaloids.

Topics: Costa Rica; Indole Alkaloids; Iridoid Glucosides; Iridoids; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Rubiaceae; Secologanin Tryptamine Alkaloids

Pharmacokinetic studies on traditional Chinese medicine are useful to evaluate and predict the drug efficacy and safety. The renal impairment may affect drug clearance and other pharmacokinetic processes which can increase toxicity and drug to drug interactions or cause ineffective therapy. Pharmacokinetic studies in pathological status rats might be meaningful for revealing the action mechanism and improving clinical medication of the herb medicine.. A highly sensitive and rapid ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method with multiple-reaction monitoring (MRM) mode was developed and validated for simultaneous quantitation of morroniside and loganin in normal and doxorubicin-induced chronic kidney disease (CKD) rat plasma after oral administration of Shanzhuyu (fruit of Cornus officinalis) extract.. Both calibration curves gave satisfactory linearity (r>0.99) at linear range of 1.96-1962.5ngmL(-1) for morroniside, 1.53-1531.25ngmL(-1) for loganin. The precision and accuracy of the in vivo study were assessed by intra-day and inter-day assays. The percentages of relative standard deviation (RSD) were all within 9.58% and the accuracy (RE) was in the -6.02% to 8.11% range. The extraction recoveries of morroniside, loganin and internal standard (IS) were all >67.62% and the matrix effects ranged from 95.07% to 102.75%.. The pharmacokinetic behavior of morroniside and loganin in normal and CKD rat plasma was determined in this paper. The significant different pharmacokinetic parameters might partly result from the changes of P-glycoprotein and metabolic enzymes in the pathological state. The pharmacokinetic research in the pathological state might provide more useful information to guide the clinical usage of the herb medicine.

Topics: Administration, Oral; Animals; Chromatography, Liquid; Cornus; Fruit; Glycosides; Iridoids; Male; Plant Extracts; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Tandem Mass Spectrometry

Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which, in its most severe form, is associated with multi-organ failure and death. Loganin, a major iridoid glycoside obtained from Corni fructus, has been shown to have anti-inflammatory and anti-shock effects. However, the effects of loganin on AP have not been determined. Pre-treatment of loganin reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by (1) a reduction in several biochemical parameters (pancreatic weight to body weight ratio, myeloperoxidase activity, and level of amylase) and (2) production of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. However, post-treatment of loganin failed to improve pancreatic damage and biochemical parameters of AP, but could inhibit the AP-induced elevation of IL-1β and TNF-α significantly. In addition, cerulein-induced activation of nuclear factor (NF)-κB was inhibited in the pancreas by administration of loganin. In conclusion, these results suggest that loganin exhibits an anti-inflammatory effect in cases of AP and its pulmonary complications through inhibition of NF-κB activation.

Topics: Animals; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Female; Iridoids; Mice; Mice, Inbred C57BL; NF-kappa B; Pancreatitis; Protective Agents

In order to optimize the base fertilizer dosage and root size of Gentiana crassicaulis in Ludian,Yulong, Yunnan,the differences in yield and quality of Gentiana crassicaulis caused by different base fertilizer dosage and root size were investigated.. The variation in fresh weight, dry weight, drying rate, length, diameter, branches as well as the contents of gentiopicroside, loganin acid, alcohol-soluble extract and total ash were determined. The ideal distance grey relational degree comprehensive evaluation method was applied to make a comprehensive evaluation on the quality and yield of Gentiana crassicaulis.. There were big differences in yield and quality of Gentiana crassicaulis among different base fertilizer dosage and root size. 2 000 kg/667 m2 of manure, 20 kg/667 m2 of superphosphate, 100 kg/667 m2 of plant ash and mix size of transplanting roots showed the best comprehensive quality and the highest yield.. 2 000 kg/667 m2 of manure, 20 kg/667 m2 of superphosphate,100 kg/667 m2 of plant ash, high quality transplanting roots and stagger certain depth to transplant are highly recommended to produce high quality and high yield of Gentiana crassicaulis in Ludian, Yulong, Yunnan.

Topics: China; Fertilizers; Gentiana; Iridoid Glucosides; Iridoids; Plant Roots; Plants, Medicinal

To study the pharmacokinetics characteristic of loganin, ferulic acid and stilbene glucoside in rat plasma after oral administration of Bushen Tongluo formula. The plasma samples were treated by using liquid-liquid extraction technique, the concentrations were determined by HPLC-UV. Johnson spherigel C18 column (4.6 mm x 250 mm, 5 μm) was adopted and eluted with the of mobile phase of methanol-water containing 0.01% glacial acetic acid in a gradient mode, with the flow rate at 1.0 mL x min(-1), column temperature at 30 degrees C and injection volume of 10 μL. According to the findings, loganin was determined at 235 nm, ferulic acid and stilbene glucoside were determined at 320 nm, with the sample size of 10 μL. The pharmacokinetic parameters of loganin, ferulic acid and stilbene glucoside were calculated by DAS 2. 0 software as follows: C(max) was (0.369 ± 0.042), (0.387 ± 0.071), (0.233 ± 0.044) mg x L(-1); t(max) was (0.226 ± 0.022), (0.282 ± 0.031), (0.233 ± 0.044) h; t(½β) was (6.89 ± 0.20), (10.73 ± 0.11), (6.93 ± 0.09) h; AUC(0-∞) was (1.91 ± 0.36), (3.22 ± 0.52), (1.52 ± 0.33) mg x h x L(-1); AUCO(0-t) was (1.62 ± 0.33), (2.58 ± 0.43), (1.30 ± 0.30) mg x h x L(-1); CL was (20.2 ± 4.0), (1.39 ± 0.23), (31.7 ± 6.9) L x h(-1) x kg(-1), respectively. The results showed that after the oral administration with Bushen Tongluo formula, loganin, ferulic acid and stilbene glucoside showed concentration-time curves in conformity with the two compartment model, with a rapid absorption, loganin and stilbene glucoside was excreted at a moderate speed, and ferulic acid was excreted slowly (but with the highest bioavailability). Bushen Tongluo formula can main maintain plasma concentration with three administrations everyday and so is suitable to be made into common oral preparation.

Topics: Administration, Oral; Animals; Biological Availability; Coumaric Acids; Drugs, Chinese Herbal; Glucosides; Iridoids; Male; Rats; Rats, Sprague-Dawley; Stilbenes

We recently discovered that the activation of the spinal glucagon-like peptide-1 receptors (GLP-1Rs) by the peptidic agonist exenatide produced antinociception in chronic pain. We suggested that the spinal GLP-1Rs are a potential target molecule for the management of chronic pain. This study evaluated the antinociceptive activities of geniposide, a presumed small molecule GLP-1R agonist. Geniposide produced concentration-dependent, complete protection against hydrogen peroxide-induced oxidative damage in PC12 and HEK293 cells expressing rat and human GLP-1Rs, but not in HEK293T cells that do not express GLP-1Rs. The orthosteric GLP-1R antagonist exendin(9-39) right-shifted the concentration-response curve of geniposide without changing the maximal protection, with identical pA2 values in both cell lines. Subcutaneous and oral geniposide dose-dependently blocked the formalin-induced tonic response but not the acute flinching response. Subcutaneous and oral geniposide had maximum inhibition of 72% and 68%, and ED50s of 13.1 and 52.7 mg/kg, respectively. Seven days of multidaily subcutaneous geniposide and exenatide injections did not induce antinociceptive tolerance. Intrathecal geniposide induced dose-dependent antinociception, which was completely prevented by spinal exendin(9-39), siRNA/GLP-1R and cyclic AMP/PKA pathway inhibitors. The geniposide iridoid analogs geniposidic acid, genipin methyl ether, 1,10-anhydrogenipin, loganin and catalpol effectively inhibited hydrogen peroxide-induced oxidative damage and formalin pain in an exendin(9-39)-reversible manner. Our results suggest that geniposide and its iridoid analogs produce antinociception during persistent pain by activating the spinal GLP-1Rs and that the iridoids represented by geniposide are orthosteric agonists of GLP-1Rs that function similarly in humans and rats and presumably act at the same binding site as exendin(9-39).

Topics: Analgesics; Animals; Central Nervous System Agents; Exenatide; Formaldehyde; Glucagon-Like Peptide-1 Receptor; HEK293 Cells; Heterocyclic Compounds, 3-Ring; Humans; Iridoid Glucosides; Iridoids; Male; Mice; Nociception; PC12 Cells; Peptide Fragments; Peptides; Rats; Rats, Wistar; Receptors, Glucagon; Spinal Cord; Venoms

To investigate the chemical constituents of iridoids from Eucommiae Folium.. The compounds were isolated and purified by various column chromatography, the structures were identified on the basis of physiochemical properties and spectral analysis.. Nine iridoids were isolated and identified as asperuloside (1), daphylloside (2), scandoside methyl ester (3), loganin (4), 8-epi-loganin (5), 7-epi-loganin (6), deacetyl asperulosidic acid methyl ester (7), geniposide (8) and geniposidic acid (9).. Compounds 2 - 7 are isolated from this plant for the first time, compounds 4 - 6 are isolated from this genus for the first time.

Topics: Chromatography, Thin Layer; Coumaric Acids; Eucommiaceae; Iridoids; Molecular Structure; Plant Leaves; Plants, Medicinal

To establish a rapid chromatographic method to separate the iridoid glycosides from Lamioplomis rotata, and to identify the target compounds with PDA and MS.. Methanol-water gradient elution was used to separate and analyze the target compounds. The fluid fractions were gathered according to the chromatogram and dried with the nitrogen airflow. The mass fractions of the target compounds were determined with RP-HPLC and the structures were identified with PDA and MS.. The purity of some compounds exceeded 90% and these 9 compounds were identified as iridoid glycosides, which were Phlorigidoside C (1), Schismoside (2), Sesamoside (3), Shanzhiside methylester (4), 6-O-Acetyl shanzhiside methylester (5), Phloyoside II (6), Penstemoside (7), Loganin (8) and 8-O-Acetyl shanzhiside methylester (9).. The method is simple and practicable with high efficiency. It can be used to qualitative and quantitative analysis of the 9 iridoid glycosides in Lamiphlomis rotata and its preparations.

Topics: Chromatography, High Pressure Liquid; Ethanol; Glucosides; Iridoid Glycosides; Iridoids; Lamiaceae; Molecular Structure; Plant Roots; Plants, Medicinal; Pyrans; Resins, Synthetic; Spectrometry, Mass, Electrospray Ionization; Terpenes

To study the chemical constituents from the flower of Lonicera fragrantissima.. The chemical constituents were isolated and purified by means of several chromatographic techniques, and their structures were elucidated by spectroscopic methods.. Nine compounds were isolated and identified as chlorogenic acid (1), caffeic acid (2), secologanoside (3), secoxyloganin(4), loganin (5), sucrose (6), myo-inositol (7), rutin (8), and chrysoeriol-7-O-β-D-glucoside (9).. Compounds 2-9 are obtained from this plant for the first time.

Topics: Caffeic Acids; Chlorogenic Acid; Flavones; Flowers; Glucosides; Inositol; Iridoid Glucosides; Iridoids; Lonicera; Rutin; Sucrose

Semen Strychni is the seed of Strychnos nux-vomica L. (Loganiaceae). Its quality control procedure remains an issue since previous reports only focused on Strychnos alkaloids. To the best of our knowledge, chlorogenic acid (a phenolic acid) and loganin (an iridoid glycoside) are selected for the first time as marker constituents of quality control for Semen Strychni because of their bioactive activity correlating with therapeutic effects.. This study aimed to develop a simple and comprehensive quantity control method for Semen Strychni.. The optimal ultrasonic extraction procedure was carried out for 45 min using 50% aqueous methanol with 1% formic acid. The satisfactory chromatographic separation was achieved on an Ultimate LP-C18 column with gradient elution using acetonitrile and water containing 30 mmol/L ammonium acetate and 1% formic acid. The high performance liquid chromatography method with diode array detector was validated for linearity, limit of detection and quantification (LOQ), precision, repeatability, accuracy and stability.. All the calibration curves showed good linearity (r(2) ≥ 0.999). The LOQ values for chlorogenic acid, loganin, strychnine, brucine, strychnine N-oxide and brucine N-oxide were 0.54, 0.83, 0.48, 0.50, 0.52 and 0.54 μg/mL, respectively. The method was reproducible with good accuracy in the range 95.6-104.4% and relative standard deviation (RSD) values less than 4.55%. The method was then applied to determine the components of the seed coat, seed leaf, endosperm and whole seed of Semen Strychni.. This newly established method is validated as a simple and practical tool for authentication and quality control of Semen Strychni.

Topics: Buffers; Calibration; Chlorogenic Acid; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Iridoids; Limit of Detection; Linear Models; Loganiaceae; Phytotherapy; Plants, Medicinal; Quality Control; Reference Standards; Reproducibility of Results; Seeds; Solvents; Spectrophotometry, Ultraviolet

This study aimed to determine the effects of different concentrations and combinations of the phytohormones 2,4-dichlorophenoxy acetic acid (2,4-D), kinetin, 6-benzylaminopurine (BAP), and 1-naphthaleneacetic acid (NAA) on callus induction and to demonstrate the role of elicitors and exogenous precursors on the production of mitragynine in a Mitragyna speciosa suspension culture. The best callus induction was achieved from petiole explants cultured on WPM that was supplemented with 4 mg L⁻¹ 2,4-D (70.83%). Calli were transferred to liquid media and agitated on rotary shakers to establish Mitragyna speciosa cell suspension cultures. The optimum settled cell volume was achieved in the presence of WPM that contained 3 mg L⁻¹ 2,4-D and 3% sucrose (9.47 ± 0.4667 mL). The treatment of cultures with different concentrations of yeast extract and salicylic acid for different inoculation periods revealed that the highest mitragynine content as determined by HPLC was achieved from the culture treated with 250 mg L⁻¹ yeast extract (9.275 ± 0.082 mg L⁻¹) that was harvested on day 6 of culturing; salicylic acid showed low mitragynine content in all concentrations used. Tryptophan and loganin were used as exogenous precursors; the highest level of mitragynine production was achieved in cultures treated with 3  μM tryptophan and harvested at 6 days (13.226 ± 1.98 mg L⁻¹).

Topics: 2,4-Dichlorophenoxyacetic Acid; Benzyl Compounds; Iridoids; Kinetin; Mitragyna; Naphthaleneacetic Acids; Plant Growth Regulators; Purines; Secologanin Tryptamine Alkaloids; Tissue Culture Techniques; Tryptophan

In the course of searching for anti-dementia agents from natural products, loganin isolated from EtOAc fraction of Corni fructus possessed specific inhibitory activity against β-secretase (BACE1) with 9.2 × 10⁻⁵  M and K(i) value of 5.5 × 10⁻⁵ M. Loganin exhibited less inhibitory activity to α-secretase (TACE) and other serine proteases exhibiting that it was a relatively specific inhibitor of BACE1. These novel findings suggest that loganin may be used to attenuate the progression and/or prevention of Alzheimer's disease.

Topics: Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases; Cornus; Enzyme Activation; Iridoids

The cytotoxic activity of crude extracts and their fractions from leaves and roots of G. pohliana was assessed against nine human cancer cell lines: melanoma (UACC-62), breast (MCF-7), breast expressing the multidrug resistance phenotype (NCI-ADR), lung (NCI-460), prostate (PCO-3), kidney (786-0), ovarian (OVCAR), colon (HT-29) and leukaemia (K-562). The hexane fraction from leaves (HL) and ethyl acetate (EAR), chloroform (CR) and hydromethanolic (HMR) fractions from roots were the most active fractions against K-562 with GI₅₀ values being lower than 1 μg mL⁻¹. Also, CR and HMR fractions were active against UACC-62 cell line in the same order of magnitude. The phytochemical study of the CR fraction allowed identifying the known iridoids secoxyloganin, sweroside and loganin.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; HT29 Cells; Humans; Iridoid Glucosides; Iridoids; Plant Extracts; Plant Leaves; Plant Roots; Rubiaceae

To study the chemical constituents of Dipsacus asper.. Column chromatography on Silica gel and RP-C18 were applied for isolation and purification of the constituents. Their structures were identified by spectral and chemical methods.. From the crude MeOH fraction of Dipsacus asper, 12 compounds were isolated and identified as Sucrose (1), beta-sitosterol (2), Oleanic acid (3), Triplostoside A (4), Loganin (5), Loganin acid (6), Sweroside (7), Epi-vogeloside ( 8), Vogeloside (9), Akebiasaponin D(10), Cauloside A(11),7-Deoxyloganic acid (12).. Compounds 8, 9, 12 are isolated from this plant for the first time.

Topics: Chromatography, Thin Layer; Dipsacaceae; Iridoids; Plant Roots; Triterpenes

Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Loganin, an iridoid glucoside compound was isolated from Cornus officinalis Sieb. et Zucc. This study was conducted to investigate the efficacy of loganin on DN and to elucidate the potential mechanism. High glucose (HG) stimulated cultured human renal proximal tubular epithelial cells (HK-2) analyzed CTGF expression by Western blotting and investigated whether extracellular signal-regulated kinase (ERK) signaling pathway was involved. Streptozotocin (STZ)-induced experimental DN, randomized to receive intragastric (i.g.) of loganin. Renal tissue, blood and urine samples were collected to determine and analyze. In vitro study, loganin reduced CTGF excretion in HG-induced HK-2 cells through the ERK signaling pathway. In vivo study, I.g. of loganin 5 mg/kg or 10 mg/kg significantly ameliorated renal function and increased body weight. Meanwhile, loganin reduced renal CTGF expression by immunohistochemical staining, reduced serum levels of CTGF. Besides, there were no significant differences in blood sugar levels between the loganin groups compared to the STZ-treated group. Furthermore, loganin ameliorated renal pathology. These results suggested that loganin exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using loganin to treat DN.

Topics: Animals; Blood Glucose; Cell Line; Cell Proliferation; Connective Tissue Growth Factor; Cornus; Cystatin C; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Epithelial Cells; Glucose; Humans; Immunohistochemistry; Iridoids; Kidney; Male; MAP Kinase Signaling System; Rats; Rats, Sprague-Dawley; Weight Gain

The methanolic extract of the fruits of Cornus officinalis S et Z. (Cornaceae) showed the significant neuroprotective activity against glutamate-induced toxicity in HT22 hippocampal cells. Chemical profile of n-BuOH fraction of the methanolic extract of C. officinalis fruits, which showed the most potent activity, was established using HPLC-diode array detector-electrospray-MS (HPLC-DAD-ESI-MS). Through bioactivity-guided isolation, five iridoid glycosides including one new compound, 7-O-butylmorroniside (1), loganin (2), morroniside (3), 7R-O-methylmorroniside (4), 7S-O-methylmorroniside (5) were isolated from the n-BuOH fraction. The protective activities of the isolated compounds, themselves, were not statistically significant. However, the hydrolyzed products of compounds 1, 4 and 5 significantly protected glutamate-injured HT22 cells up to 78±2.2%, 60±3.2% and 59±2.5% of non-treated control, respectively.

Topics: Animals; Cell Line, Transformed; Chemical Fractionation; Chromatography, High Pressure Liquid; Cornus; Fruit; Glutamic Acid; Glycosides; Hippocampus; Hydrolysis; Iridoids; Methanol; Mice; Molecular Structure; Neuroprotective Agents; Plant Extracts; Spectrometry, Mass, Electrospray Ionization

We investigated the mechanisms underlying the protective effects of loganin against hydrogen peroxide (H(2)O(2))-induced neuronal toxicity in SH-SY5Y cells. The neuroprotective effect of loganin was investigated by treating SH-SY5Y cells with H(2)O(2) and then measuring the reduction in H(2)O(2)-induced apoptosis using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. Following H(2)O(2) exposure, Hoechst 33258 staining indicated nuclear condensation in a large proportion of SH-SY5Y cells, along with an increase in reactive oxygen species (ROS) production and an intracellular decrease in mitochondria membrane potential (MMP). Loganin was effective in attenuating all the above-stated phenotypes induced by H(2)O(2). Pretreatment with loganin significantly increased cell viability, reduced H(2)O(2)-induced LDH release and ROS production, and effectively increased intracellular MMP. Pretreatment with loganin also significantly decreased the nuclear condensation induced by H(2)O(2). Western blot data revealed that loganin inhibited the H(2)O(2)-induced up-regulation of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3, increased the H(2)O(2)-induced decrease in the Bcl-2/Bax ratio, and attenuated the H(2)O(2)-induced release of cytochrome c from mitochondria to the cytosol. Furthermore, pretreatment with loganin significantly attenuated the H(2)O(2)-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase 1/2 (ERK 1/2). These results suggest that the protective effects of loganin against H(2)O(2)-induced apoptosis may be due to a decrease in the Bcl-2/Bax ratio expression due to the inhibition of the phosphorylation of JNK, p38, and ERK 1/2 MAPKs. Loganin's neuroprotective properties indicate that this compound may be a potential therapeutic agent for the treatment of neurodegenerative diseases.

Topics: Apoptosis; Blotting, Western; Caspase 3; Cell Line, Tumor; Cytochromes c; Humans; Hydrogen Peroxide; Iridoids; L-Lactate Dehydrogenase; Membrane Potentials; Neuroblastoma; Phosphorylation; Poly(ADP-ribose) Polymerases; Protein Kinases; Reactive Oxygen Species

Allergy-preventive activity of flower buds of Lonicera japonica THUNB. was found in the 35% EtOH extract (LJ) using an in vivo assay, The assay system uses monitoring of a decrease in blood flow (BF) in the tail vein of mice subjected to sensitization with hen-egg white lysozyme (HEL). Bioassay-guided fractionation of the 35% EtOH extract led to isolation of chlorogenic acid (1) and three known iridoid derivatives, loganin (2), secoxyloganin (3) and sweroside (4), all of which inhibited the BF decrease. This suggested that the flower buds of L. japonica and compounds isolated from them have allergy-preventive properties. The structure-activity relationship of iridoid derivatives, morroniside (5), geniposide (6), asperuloside (7), aucubin (8) and catalpol (9), were also tested using the same bioassay method. Compounds 2-5 and 9 having the sp(3) atom at C-8 showed an allergy-preventive effect, while compounds 6, 7 and 8 having a double bond at C-7, C-8 did not.

Topics: Animals; Anti-Allergic Agents; Chickens; Chlorogenic Acid; Female; Flowers; Hypersensitivity; Iridoid Glucosides; Iridoids; Lonicera; Male; Mice; Mice, Inbred Strains; Muramidase; Phytotherapy; Plant Extracts; Structure-Activity Relationship; Veins

To research the chemical constituents from stems and leaves of Lonicera macranthoides.. Various column chromatographies were employed to isolate and purify the constituents. Their structures were elucidated by spectral analysis (IR, MS, 1H-NMR, 13 C-NMR) and chemical evidence.. Nine constituents were obtained and identified as loganin (I), loganic acid (II), morroniside (III),7-O-ethyl-morroniside (IV), scopoletin (V), caffeic acid (VI), chlorogenic acid (VII), beta-sitosterol (VIII), daucosterol (IX).. Compounds I-VI are isolated from the plant for the first time. All the compounds are found for the first time from the stems and leaves of Lonicera macranthoides.

Topics: Caffeic Acids; Glycosides; Iridoids; Lonicera; Molecular Structure; Plant Leaves; Plant Stems; Plants, Medicinal; Scopoletin

Accumulating evidence indicates that uncontrolled diabetes leads to the progression of diabetic complications such as liver disorder. The present study was carried out to elucidate the protective role of loganin extracted from Corni Fructus against hepatic oxidative stress caused by type 2 diabetes. Loganin (20 or 100mg/kg body weight/day, p.o.) was administered every day for 8 weeks to db/db mice, and its effect was assessed on comparison with vehicle-treated db/db and m/m mice. The administration of loganin led to a decrease in glucose and elevation of leptin in serum. The diabetic oxidative stress was attenuated by loganin through inhibitions of reactive oxygen species production and lipid peroxidation in the serum and liver. The expression of proteins induced by oxidative stress was significantly up-regulated in the liver of diabetic db/db mice; however, the expressions of both Nox-4 and p22(phox) were decreased significantly by loganin administration. Loganin showed a crucial effect in the inflammation-activated signaling pathway through the regulation of NF-κB, COX-2, and iNOS. It was also found to regulate the anti-inflammatory factors Nrf-2 and HO-1 in hepatic tissue. Moreover, expression of MCP-1 was significantly down-regulated in the loganin-treated db/db mice. Furthermore, loganin administration showed a protective effect against apoptosis by the regulation of Bcl-2 and cytochrome c. The present study demonstrated that the administration of loganin isolated from Corni Fructus had a protective effect against hepatic oxidative stress under type 2 diabetes through regulations of protein expressions related to oxidative stress, inflammation, and apoptosis.

Topics: Animals; Cornus; Diabetes Mellitus, Type 2; Hyperglycemia; Iridoid Glycosides; Iridoids; Liver; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Protective Agents; Reactive Oxygen Species; Signal Transduction

Fresh first year roots from Dipsacus sylvestris HUDS. were extracted with 70% ethanol, ethyl acetate as well as dichloromethane. Extracts were solubilized in water (lipophilic extracts with addition of polysorbate 80) and tested for their activity against Borrelia burgdorferi sensu stricto in vitro during an eight-day period using amoxicillin as standard. The hydroethanolic extract showed no growth inhibition whereas significant growth inhibiting activity could be shown in the two less polar fractions for the first time. Strongest inhibition was found in the ethyl acetate extract. The effect of polysorbate 80 on bacterial growth was examined and found to be negligible. As the nature of bioactive constituents has not been clarified yet, a micellar electrokinetic capillary chromatography fingerprint analysis for a methanolic extract was applied including loganin, chlorogenic acid, cantleyoside and caffeic acid as marker substances.

Topics: Anti-Bacterial Agents; Borrelia burgdorferi; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Thin Layer; Dipsacaceae; Iridoids; Lipids; Microbial Sensitivity Tests; Plant Extracts; Plant Roots; Solvents; Spectrophotometry, Ultraviolet

NHC catalysed rearrangement of α,β-unsaturated enol esters derived from formyl acetates and cyclopentyl annulated α,β-unsaturated acids provides the cyclopentapyranone core of (-)-7-deoxyloganin (1) with diastereo- and chemoselectivity in 6 steps starting from (-)-citronellal. The elaboration to the natural product has been investigated using two new approaches. The most successful intercepts our previous work on (-)-7-deoxyloganin (1) allowing completion of a formal total synthesis in 10-steps.

Topics: Catalysis; Esters; Glycosylation; Iridoids; Isomerism; Methane; Molecular Structure; Oxidation-Reduction

To establish a method of microwave-assisted extraction and high performance liquid chromatographic (HPLC) for simultaneous determination of three iridoid glycosides including loganin, sweroside and cornuside in Cornus officinalis.. The extraction conditions of microwave power,ethanol concentration, liquid to sample ratio were optimized with a response surface methodology (RSM); Three constituents were separated on an Agilent TC-C18 column by gradient elution using acetonitrile and water as the mobile phase. The flow rate was 1.0 mL/min. The detection wave length was 240 nm.. The optimal conditions of microwave extraction were as follows: microwave power 400 W, ethanol concentration 72%, liquid to sample ratio 15 mL/g, the extraction time 10 min, the extraction times 2; The HPLC peak areas of all the constituents showed good linearity (r>0.9994) in the range of the tested concentration,the average recoveries of the method were 98.68%, 98.24% and 98.29%, respectively.. The established method of microwave-assisted extraction and HPLC simultaneously determination has the advantages of convenient, precision and reliability. It can be used in simultaneous determination of three iridoid glycosides in Cornus officinalis.

Topics: Chromatography, High Pressure Liquid; Cornus; Fruit; Glucosides; Iridoid Glucosides; Iridoids; Microwaves; Pyrans; Quality Control; Reproducibility of Results; Solvents

To analyze the correlation between the quality of Cornus officinalis and the contents of the inorganic elements in the planting soil.. The contents of 11 kinds of inorganic elements including Zn, Mn, K, Fe, Mg, Ca, Cu, Cd, As, Pb and Hg in Cornus officinalis and the planting soil were determined; The contents of loganin, ursolic acid, polysaccharides, tannins, organic acid, water-soluble extractives and ethanol-soluble extractives in Cornus officinalis were determined; The correlation between the quality of Cornus officinalis and the contents of the inorganic elements in the planting soil was analyzed.. There was no significant difference in the content of chemical components of Cornus officinalis produced in the three main areas. The contents of loganin and water-soluble extract complied with pharmacopoeial provisions. Especially, inorganic elements of Fe, Mn and K had significant effects on the quality of Cornus officinalis.. The results provide the foundation for the selection of cultivating area and the reference for standard cultivation of Cornus officinalis.

Topics: China; Cornus; Fruit; Iridoids; Iron; Manganese; Plants, Medicinal; Polysaccharides; Potassium; Quality Control; Soil; Spectrophotometry, Ultraviolet; Trace Elements; Triterpenes; Ursolic Acid

The study on the buds of Jasminum officinale L. var. grandiflorum was carried out to look for anti-HBV constituents. The isolation and purification were performed by HPLC and chromatography on silica gel, polyamide and Sephadex LH-20 column. The structures were elucidated on the basis of physicochemical properties and spectral analysis. Six iridoid glycosides were identified as jasgranoside B (1), 6-O-methy-catalpol (2), deacetyl asperulosidic acid (3), aucubin (4), 8-dehydroxy shanzhiside (5), and loganin (6). Jasgranoside B (1) is a new compound. Compounds 2-6 were isolated from Jasminum officinale L. var. grandiflorum for the first time.

Topics: Antiviral Agents; Flowers; Glucosides; Hep G2 Cells; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Inhibitory Concentration 50; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Jasminum; Molecular Structure; Plants, Medicinal

To develop an HPLC method for determination of loganin in Pterocephalus hookeri.. The analysis was performed on a Welchrom C18 column (4.6 mm x 250 mm, 5 microm) with acetonitrile-water (12:88) as the the mobile phase at a flow rate of 1 mL x min(-1) and the detection wavelength was 240 nm.. The peak areas and injection amounts of loganin had a good linear relationship at the range of 0.06-1.2 microg. The average recovery was 97.0%, and the RSD was 1.4%.. The method is simple, accurate, and can be used for its quality control.

Topics: Chromatography, High Pressure Liquid; Iridoids; Medicine, Tibetan Traditional; Plants, Medicinal

Simultaneous determination method of four marker components, paeoniflorin, loganin, 5-hydroxymethyl-2-furaldehyde and paeonol in traditional herbal medicine, Yukmijihwang tang, was developed to achieve rapidly and systematic quality control by high performance liquid chromatography coupled with diode array detection. To develop this high performance liquid chromatography method, C(18) column (5 microm, 120 A, 4.6 mm x 150 mm) was used with gradient elution of water and methanol as mobile phase. Validation of the chromatography method was evaluated by linearity, recovery, and precision test. Calibration curves of standard components showed excellent linearity with R(2) > 0.9990. Limits of detection and limits of quantification were in the ranges 0.01-0.02 and 0.04-0.07 microg/mL, respectively. The relative standard deviations of data of the intra-day and inter-day experiments were less than 1.15% and 3.76%, respectively. The results of recovery test were found to range from 94.88 to 107.43% with relative standard deviation values 0.07-2.66%. The results of validation suggested that this method was very accurate and stabilized.

Topics: Acetophenones; Benzoates; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Furaldehyde; Glucosides; Iridoids; Medicine, Korean Traditional; Molecular Structure; Monoterpenes; Plant Preparations; Quality Control; Reference Standards; Reproducibility of Results

Previously, we have reported that Corni Fructus possessed hypoglycemic and hypocholesterolemic effects in streptozotocin-induced type 1 diabetic rats and diet-induced hypercholesterolemic rats. Herein, we have focused on the effect and mechanism of loganin, a major iridoid glycoside of Corni Fructus, on the type 2 diabetic db/db mice. Loganin was orally administered to db/db mice at a dose of 20 or 100 mg/kg body weight daily for 8 weeks. The biochemical factors and expressions of protein and mRNA related to lipid metabolism, inflammation, advanced glycation endproducts, and its receptor were measured. In loganin-treated db/db mice, hyperglycemia and dyslipidemia were ameliorated in both the serum and hepatic tissue; however, in the kidney, only triglyceride was reduced. The enhanced oxidative stress was alleviated by loganin through a decrease in thiobarbituric acid-reactive substances (liver and kidney) and reactive oxygen species (serum, liver, and kidney), as well as augmentation of the oxidized to reduced glutathione ratio (liver and kidney). The marked lipid-regulatory effect of loganin was exerted in the liver of type 2 diabetic mice via suppressing mRNA expressions related to lipid synthesis and adjusting the abnormal expression of peroxisome proliferator-activated receptor α and sterol regulatory-element binding protein in the nucleus. Furthermore, loganin inhibited advanced glycation endproduct formation and the expression of its receptor, and nuclear factor-kappa B-induced inflammation in the hepatic tissue of db/db mice. Loganin exhibits protective effects against hepatic injury and other diabetic complications associated with abnormal metabolic states and inflammation caused by oxidative stress and advanced glycation endproduct formation.

Topics: Animals; Biomarkers; Body Weight; Cholesterol; Cornus; Cyclooxygenase 2; Diabetes Mellitus, Type 2; Drinking; Fatty Acids; Gene Expression Regulation, Enzymologic; Glucose; Glycation End Products, Advanced; Hematologic Tests; Inflammation; Iridoids; Kidney; Lipid Metabolism; Liver; Lysine; Male; Mice; Nitric Oxide Synthase Type II; Organ Size; Oxidative Stress; PPAR alpha; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 2; Transcription Factor RelA; Triglycerides

The diastereoselective N-heterocyclic carbene (NHC) catalyzed rearrangement of α,β-unsaturated enol ester (S)-2b has been used to assemble dihydropyranone (S)-3b, a material embodying the bicyclic core of the iridoid family of natural products. Elaboration of this intermediate, by chemoselective reduction followed by stereoselective β-glycosylation, has allowed the total synthesis of (-)-7-deoxyloganin (1) to be achieved in four subsequent steps.

Topics: Catalysis; Esters; Heterocyclic Compounds; Iridoids; Methane; Molecular Structure; Stereoisomerism

The parenteral route has many merits over the oral route, including greater predictability, reproducibility of absorption, and rapid drug action, but injectable phytomedicines are uncommon due to protein precipitating tannin and hemolytic saponin components. In this study, in an effort to develop a safe injectable analgesic phytomedicine, we prepared a tannin and saponin-free Lonicera japonica extract, SKLJI, through fractionation and column purification, and evaluated its anti-inflammatory and analgesic activities in in vivo experimental models of inflammation and pain. The removal of tannin and saponin resulted in loganin and sweroside-enriched SKLJI and it showed reduced hemolysis and protein precipitation. In efficacy tests, SKLJI inhibited croton oil- and arachidonic acid-induced ear edema, acetic acid-induced writhing, and carrageenan-induced rat hind paw hyperalgesia. Inhibition of cylcooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and 5-lipoxyfenase (5-LO) activities by SKLJI appeared to be the mechanism underlying anti-inflammatory and analgesic efficacy. Loganin and sweroside also showed anti-inflammatory and analgesic activities, suggesting that they might be active principles in the efficacy of SKLJI. These results suggest that SKLJI is a viable candidate for a new anti-inflammatory and analgesic phytomedicine that can be administered by the parenteral route.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Cyclooxygenase 2; Enzyme Inhibitors; Hemolysis; Inflammation; Injections, Intravenous; Iridoid Glucosides; Iridoids; Lonicera; Male; Mice; Nitric Oxide Synthase Type II; Plant Extracts; Rats; Rats, Sprague-Dawley

Liuweidihuang wan (LW), initially a well-known formula for curing "wu chi wu ruan", is commonly used nowadays for clinical treatment of postmenopausal osteoporosis (PO), but the identity of the effective substance(s) remains unclear. The present study was designed to evaluate the effects of morroniside and loganin isolated from LW on the proliferation, differentiation and apoptosis of MC3T3-E1 cells, as well as the possible mechanism of action. Morroniside and loganin had no effects on the proliferation of MC3T3-E1 cells, but both susbtances could improve the activity of alkaline phosphatase (ALP), and increase the contents of collagen type I and osteocalcin. Simultaneously, the mRNA expression of caspase-3, capase-9, RANKL was down-regulated and that of bcl-2 was up-regulated, which partially explains the anti-osteoporosis mechanism in MC3T3-E1 cells. In conclusion, morroniside and loganin may directly promote the differentiation and inhibit the apoptosis of MC3T3-E1 cells, and accordingly indirectly reduce bone resorption, which makes them promising natural drugs leads for treating PO in the near future.

Topics: 3T3 Cells; Animals; Cell Proliferation; Drugs, Chinese Herbal; Female; Glycosides; Humans; Iridoids; Male; Mice; Osteoporosis, Postmenopausal

To investigate the effects of four original constituents (Loganin, Morroniside, Peoniflorin, Paeonol) of Liu-wei Di-huang pills on the proliferation and differentiation of rat preadipocyte, and optimize the best concentration by the orthogonal test.. The rat preadipocytes were cultured, then above four original constituents according to 4 factors and 3 levels to make L9 (3(4)) orthogonal test, and the control was performed at the same time. The proliferation of preadipocytes was determined by MTT method, and the accumulation of cellular lipid was determined by Oil Red O staining, the differences between factors and variances were compared by the value of absorbance.. The combination of four original constituents of Liu-wei Di-huang pills could stimulate rat preadipocyte proliferation and inhibited its lipid accumulation. Both the effects were highly significant (P < 0.01) with the combination of A3 B1 C3 D2; Compared with the monosomic group, the effects of the A3 B1 C3 D2 was highly significant (P < 0.01).. Compared with the monosomic group, the effects of the combination of the four original constituents of Liu-wei Di-huang pills on the proliferation and differentiation of rat preadipocyte were highly significant. This combination consists of Loganin, morroniside with high doses, Paeonol, Peoniflorin with mid-dose and low-dose, respectively. Regnesent the overall regulatory role of synergy and officiencg.

Topics: Acetophenones; Adipocytes; Animals; Benzoates; Bridged-Ring Compounds; Cell Differentiation; Cell Proliferation; Cells, Cultured; Drug Combinations; Drug Synergism; Drugs, Chinese Herbal; Fats; Glucosides; Glycosides; Iridoids; Male; Monoterpenes; Plants, Medicinal; Rats; Rats, Wistar

The aim of this study was to investigate the effects of cornel iridoid glycoside (CIG), an ingredient extracted from a traditional Chinese herb Cornus officinalis, on neurological function and neurogenesis after ischemic stroke. CIG was intragastrically administered to rats in doses of 20, 60 and 180 mg/kg/day, starting 3 h after the onset of middle cerebral artery occlusion (MCAO). The behavioral test was performed by using the modified neurological severity score (mNSS). Rats were sacrificed 7, 14, or 28 days after ischemia occurred. Neurogenesis and angiogenesis were detected by using immunofluorescence staining. The messenger ribonucleic acid (mRNA) expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1 was measured by RT-PCR, and the protein expression of VEGF was determined by Western blotting analysis. The treatment with CIG at the doses of 60 and 180 mg/kg/day significantly improved neurological function, and increased the number of bromodeoxyuridine (BrdU)-positive cells and nestin-positive cells in the subventricular zone of rats 7, 14 and 28 days after ischemia. The number of newly mature neurons and blood vessels in striatum, as indicated by BrdU/NeuN and vWF immunoreactivity, respectively, was also increased in CIG-treated rats 28 days after stroke. CIG treatment obviously enhanced the mRNA expression of VEGF and its receptor Flk-1 and the protein expression of VEGF 7 and 28 days after ischemia. The results indicated that CIG promoted neurogenesis and angiogenesis and improved neurological function after ischemia in rats, and the mechanism might be related to CIG's increasing VEGF and Flk-1 in the brain.

Topics: Angiogenesis Inducing Agents; Animals; Brain; Cognition; Cornus; Drugs, Chinese Herbal; Glycosides; Infarction, Middle Cerebral Artery; Iridoids; Male; Neurogenesis; Neurons; Neuroprotective Agents; Neuropsychological Tests; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

We examined anti-amnesic activity of the methanolic extract of Cornus officinalis fruits (COT) and a major constituent, loganin using scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and the Morris water maze tests. Oral treatment of mice with COT (100 mg/kg body weight) and loganin (1 and 2 mg/kg body weight) significantly mitigated scopolamine-induced memory deficits in passive avoidance test. In the Morris water maze test, oral treatment of loganin significantly ameliorated scopolamine-induced memory deficits showing the formation of long-term and/or short-term spatial memory. Moreover, loganin (2 mg/kg body weight) significantly inhibited acetylcholinesterase activity by as much as 45% of control in the mouse hippocampus. These results indicate that loganin may exert antiamnesic activity in in vivo through acetylcholinesterase inhibition.

Topics: Acetylcholinesterase; Administration, Oral; Amnesia; Animals; Avoidance Learning; Behavior, Animal; Cholinesterase Inhibitors; Cognition; Cornus; Disease Models, Animal; Dose-Response Relationship, Drug; Fruit; Hippocampus; Iridoids; Male; Memory, Short-Term; Mice; Mice, Inbred ICR; Nootropic Agents; Scopolamine; Time Factors

Loganin is an iridoid glycoside found in the Flos lonicerae, Fruit cornus, and Strychonos nux vomica. We investigated the effect of loganin on learning and memory impairments induced by scopolamine (0.5mg/kg, i.p.), a muscarinic antagonist, using the Y-maze, passive avoidance, and the Morris water maze tests in mice. In the Y-maze test, loganin (40 mg/kg, p.o.) significantly improved the scopolamine-induced memory impairment. In addition, loganin (20 and 40 mg/kg, p.o.) significantly reversed scopolamine-induced impairments measured by the passive avoidance and the Morris water maze tests. A day after the last trial session of the Morris water maze test (probe trial session), loganin (20 and 40 mg/kg) dose-dependently increased the latency time in the target quadrant. Furthermore, loganin significantly inhibited acetylcholinesterase activity in the hippocampus and frontal cortex. Loganin may have anti-amnesic activity that may hold significant therapeutic value in alleviating certain memory impairments observed in Alzheimer's disease.

Topics: Acetylcholinesterase; Animals; Behavior, Animal; Iridoids; Learning; Male; Maze Learning; Memory Disorders; Mice; Muscarinic Antagonists; Neuroprotective Agents; Scopolamine

Phytochemical study of the aqueous extract of the flowering tops of Lamium album led to identification of the antiviral iridoid isomers lamiridosins A and B (1, 2). These compounds were found to significantly inhibit hepatitis C virus entry (IC(50) 2.31 muM) in vitro. Studies of 14 iridoid analogues showed that, while the parent iridoid glucosides demonstrated no anti-HCV entry activity, the aglycones of shanzhiside methyl ester (4), loganin (5), loganic acid (6), geniposide (10), verbenalin (12), eurostoside (15), and picroside II (17) exhibited significant anti-HCV entry and anti-infectivity activities.

Topics: Antiviral Agents; Hepacivirus; Iridoids; Lamiaceae; Molecular Structure; Plants, Medicinal; Stereoisomerism

A simple and rapid HPLC method was established for simultaneously determining six active components in Fructus Corni. The six components were separated on an Agilent Zorbax Extend C18 column (250 mmx4.6 mm, 5 microm) and detected by diode array detector (DAD). Mobile phase was composed of (A) aqueous phosphoric acid (0.1%, v/v) and (B) acetonitrile phosphoric acid (0.1%, v/v) using a gradient elution. Analyses were performed at 30 degrees C with a flow rate of 1.0 mL/min and UV detection at 218 nm, 240 nm and 284 nm. All calibration curves showed good linear regression (r2>or=0.9999) within tested ranges. The LOD and LOQ were 0.11-1.69 microg/mL and 1.48-16.60 microg/mL, respectively. Overall intra-day and inter-day variations were less than 4.72%, and the average recoveries were 97.97-102.51% for the analytes. The developed method can be applied to the intrinsic quality control of Fructus Corni.

Topics: Biological Assay; Calibration; Chromatography, High Pressure Liquid; Cornus; Drugs, Chinese Herbal; Furaldehyde; Gallic Acid; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Molecular Structure; Pyrans; Reproducibility of Results; Time Factors

To investigate the absorption mechanism of loganin at different intestine segments of rats and the influence of the drug solution concentration, pH, P-gp inductor.. Rats were randomly divided into 10 groups, high, middle and low concentration groups (0.1, 0.025, 0.012 5 mg x mL(-1)), duodenum, jejunum and ileum groups (0.013 mg x mL(-1)), high, middle and low pH groups (0.013 mg x mL(-1)), inducer group (0.013 mg x mL(-1)). The intestine cannulation was performed for in situ recirculation. Loganin concentration in the flux was measured by the reversed phase HPLC.. When the concentration was raised from 0.012 5 to 0.1 mg x mL(-1), the uptake of loganin was linearly increased, and no change of Ka is not found. The pH of flux has no effect on drug absorption. The absorbed dose and Ka sequence (from high to low) of loganin at different intestine segments is ileum, duodenum, jejunum. Furthermore, P-gp inductor RFP has effect on the intestinal absorption.. The absorption of loganin in intestine of rat is a first-order kinetics, the absorption mechanism is probably the passive diffusion. It has specific absorption locus and access to locating administration, meanwhile it's the P-gp substrate, and could increase its fraction of bioavailability by corporation with P-gp inhibitor.

Topics: Animals; Drugs, Chinese Herbal; Duodenum; Hydrogen-Ion Concentration; Ileum; In Vitro Techniques; Intestinal Mucosa; Iridoids; Jejunum; Kinetics; Male; Rats; Rats, Wistar

Similarity analysis based on fingerprints has been commonly used in quality consistency evaluation of herbal medicines. However, very little efforts have been paid in interpreting of the differences in the fingerprints for the purpose of quality control. In this study, a facile and reproducible HPLC-fingerprint of Liuwei Dihuang Pills (LWPs) was developed. Both similarity analysis and Principal Component Analysis (PCA) were employed to evaluate quality consistencies of LWPs produced by five manufacturers. Contribution plots generated by PCA were performed to interpret differences in the chromatograms of samples from different groups and some peaks which importantly contribute to classification were separated and identified. Then, differences in these samples were verified by quantitative analysis and the way to improve quality consistency was discussed. TCM was usually complex in chemical constituents, it is difficult to identify and quantify all of them. Our study demonstrated that the combination of fingerprints of TCM and PCA not only offered a powerful way to quality consistency evaluation of TCM preparations, but also might simplify the process of quality control by quantitation of some important constituents.

Topics: Benzoates; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Evaluation Studies as Topic; Glucosides; Iridoids; Mass Spectrometry; Medicine, Chinese Traditional; Molecular Structure; Molecular Weight; Monoterpenes; Principal Component Analysis; Quality Control; Spectrometry, Mass, Electrospray Ionization

On the base of establishing the fingerprint of JinKui ShenQi pills, the ultraviolet spectra-mass spectrometry/mass spectrometry, method was used to identify the fingerprint. Seperation was performed on the Symmetry Shield RP18 (5 microm, 4. 6 mm X 15 mm) analytical column with mobile phase consisting of 1% acetic acid and acetonitrile with gradient elute at the flow rate of 1.0 mL x min(-1), and the ultraviolet detection wavelength was set at 248 nm. Using the above-mentioned chromatographic condition, the fingerprint of different samples was established and the same fingerprint was defined. The fingerprints of different samples were compared with similarity evaluation software published by Pharmacopeia committee codex (2004A). The mass spectrograph with API-ESI ionization source was used, setting the flow rate at 0.5 mL x min(-1) after splitting stream. The pressure of atomization room was 50 Psi, the flow rate of dry gas was 9.0 L x min(-1), the capillary voltage was 4 kV, and the transmission voltage was 70 V. The negative scanner mode was chosen, scan scope was 100-2000, using ion trap to analyze quasimolecular ion peak and the selected fragment ion, and TIC chromatography and second order mass chromatogram were recorded. The major constituents among in JinKui ShenQi pills from different origins were separated well by HPLC. Although there was difference among different origins, they showed nineteen identical characteristic absorption bands. Three fingerprints chemical compositions such as loganin, cinnamal and paeonol were identified based on the retention time and ultraviolet spectra of standard preparation. According to their ultraviolet spectra, molecular weight and fragmentation information, ten peaks in the fingerprint were identified by ultraviolet spectroscopy-mass, spectrometry/massg spectrometry. They are 1,2,3-tri-O-galloyl-glucose, loganin, paeoniflorin, 1,2,3,6-tetro-O-galloyl-glucose, soya-cerebroside, cornuside, and PGG, benzoyl-oxypaeoniflorin. The result showed that the presented fingerprint of JinKui ShenQi pills contained plenty of information quite valuable for the quality evaluation as well as chemical characterization of JinKui ShenQi pills.

Topics: Acetophenones; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Iridoids; Principal Component Analysis; Spectrophotometry, Ultraviolet; Tandem Mass Spectrometry

To elucidate the promoting effect of the constituents in plasma after oral administration of Liuwei Dihuangwan on proliferation of rat osteoblast.. To add the constituents in plasma after oral administration of Liuwei Dihuangwan with rational concentration into culture solution of rat osteoblast, later using MT method for determining the proliferation rate of rat osteoblast.. The Mixed group including morroniside, sweroside and loganin with different dose all significantly promoted proliferation of rat osteoblast.. This study preliminarily elucidated the constituents such as morroniside, sweroside and loganin in plasma after oral administration of Liuwei Dihuangwan were main biological constituents which contributed to anti-osteoporosis bioactivity of Liuwei Dihuangwan.

Topics: Administration, Oral; Animals; Cell Proliferation; Cells, Cultured; Drugs, Chinese Herbal; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Osteoblasts; Plasma; Rats; Rats, Wistar

To establish a high performance liquid chromatographic (HPLC) amalgamated to double UV waves method for simultaneous determination of loganin and paeonol in Liuwei Dihuang pills.. A HPLC method was developed. The separation was carried out on a Agilent Zorbax SB C18 column (5 microm, 4.6 mm x 250 mm). The mobile phase consisted of water (A) and acetonitrile (B) with linear linear gradient elution [0-8 min, (B) from 1% to 12%; 8-21 min, B keep 12%; 21-40 min, (B) from 12% to 90%; 40-50 min, B keep 90% for 10 min]. The detection was Photodiode Array with the detection wavelengths were at 236 nm and 274 nm. The column temperature being 30 degrees C and the flow rate was 1.0 mL min(-1). Extracting the chromatergraph from 274 nm and 236 nm, we amalgamated the two chromatographs by matlab programmed.. The calibration curves of loganin and paeonol were linear in the ranges of 0.0362-1.09 microg (r =0. 9998) and 0.0450-1.35 microg (r =0.9998), respectively. The average recoveries of loganin and paeonol were 97.3% (RSD 1.4 %) and 103.0% (RSD 1.9%), respectively. Three different batches of Liuwei Dihuang pills were determined with this method.. This is a more convenient, reasonable and credible quality control method for the traditional Chinese medicine.

Topics: Acetophenones; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Iridoids; Reproducibility of Results; Spectrophotometry, Ultraviolet

Loganin is an important constituent of the traditional Chinese medicine Fructus Corni, with several bioactivities. Microbial metabolism of loganin by intestinal bacteria was investigated. Two metabolites (log-1 and log-2) were isolated from anaerobic culture and their structures were identified by means of their ESI-MS, (1)H-NMR, (13)C-NMR and 2D-NMR spectral data. Log-1 was an aglycone of loganin and log-2 was proved to be a new compound. In vivo metabolites of loganin were detected in rat urine, bile and feces after oral administration of loganin and the structures were proved to be identical with that of the microbial metabolites log-1 and log-2 by HPLC-PDA analysis and comparison with the reference standards. Therefore we can prepare metabolites by anaerobic culture with intestinal bacteria.

Topics: Animals; Bacteria; Chromatography, High Pressure Liquid; Intestines; Iridoids; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization

Fructus Corni, the fruits of Cornus officinalis Sieb. et Zucc., is one important ingredient in Quei Fu Di Huang Wan, a Chinese herbal mixture.. In the present study, additional anti-diabetic actions of Fructus Corni on transcriptional regulation of hepatic gluconeogenesis or beta-cell functions were investigated.. Insulin mimetic action of Fructus Corni on dexamethasone and 8-bromo-cAMP induced phosphoenolpyruvate carboxykinase (PEPCK) expression in H4IIE cells was investigated. Besides, BRIN-BD11 cells were used to evaluate both insulinotropic and beta-cell protective effect of Fructus Corni.. Firstly, both methanol extract (CO-W-M) and fraction (CO-W-M2) had potent insulin mimic activity on PEPCK expression. Secondly, possibility of both loganin and ursolic acid as the responsible compounds was excluded. Moreover, indication of the existence of phenolic compounds in CO-W-M2 was noticed. In the presence of CO-W-M2, not only was the viability of BRIN-BD11 cells treated with alloxan, streptozotcin, or cytokine mix all significantly increased but also glucose-stimulated insulin secretion was potentiated.. The ability of CO-W-M2 to reduce gene expression for hepatic gluconeogenesis, to protect beta-cell against toxic challenge, and to enhance insulin secretion strengthen the role of Fructus Corni in diabetes therapy.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Blotting, Western; Cell Death; Cell Survival; Cells, Cultured; Cornus; Dexamethasone; Diabetes Mellitus, Experimental; Electrophoresis, Polyacrylamide Gel; Fruit; Gene Expression; Gluconeogenesis; Glucose; Humans; Insulin; Insulin-Secreting Cells; Iridoids; Liver; Phosphoenolpyruvate Carboxykinase (ATP); Rats; RNA, Messenger; Triterpenes; Ursolic Acid

This study presents a new HPLC method for the simultaneous determination of seven major components, namely chlorogenic acid, caffeic acid, loganin, sweroside, secoxyloganin, rutin and luteolin 7-O-glucoside in Caulis Lonicerae Japonicae, a commonly used traditional Chinese medicinal herb derived from the caulis of Lonicera japonica Thunb. These seven compounds, belonging to the chemical types of phenolic acids, iridoids and flavonoids, were separated on a C18 column (250 x 4.6 mm, 5.0 microm) with the column temperature at 30 degrees C. The mobile phase was composed of (A) aqueous acetic acid (0.4%, v/v) and (B) acetonitrile using a gradient elution of 10% B at 0-12 min, 10-17% B at 12-25 min and 17% B at 25-35 min. The flow rate was 1.0 mL/min and detection wavelength was set at 245 nm. The limit of detection (S/N = 3) ranged from 0.10 to 0.23 microg/mL and the limit of quantification (S/N = 10) ranged from 0.69 to 3.56 microg/mL. All calibration curves showed good linear regression (r2 > 0.9990) within the test ranges. The intra- and inter-day precisions as determined from sample solutions were below 1.24 and 2.28%, respectively. The recoveries for seven compounds were found to range from 94.2 to 103.6%. This verified method has been successfully applied to evaluation of commercial samples of Caulis Lonicerae Japonicae from different markets in China.

Topics: Caffeic Acids; Chlorogenic Acid; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flavonoids; Glucosides; Hydroxybenzoates; Iridoid Glucosides; Iridoids; Linear Models; Lonicera; Luteolin; Molecular Structure; Reproducibility of Results; Rutin; Sensitivity and Specificity; Spectrophotometry, Ultraviolet

A micellar electrokinetic chromatography (MEKC) method for the simultaneous determination of four bioactive constituents (morroniside, loganin, paeoniflorin and paeonal) in the Chinese patent medicine Liuwei Dihuang Pills is established. A carrier composed of 0.2M boric acid, 0.02 M sodium dodecyl sulfate (SDS) and 5% acetonitrile (pH was adjusted to 10.5 with 0.1 M NaOH) is found to be the most suitable electrolyte for this separation. The four constituents in Liuwei Dihuang Pills can be easily determined within 16 min. Optimization of separation is realized with the univariate approach by studying the effects of four factors relevant to run buffer on migration times.

Topics: Acetonitriles; Benzoates; Boric Acids; Bridged-Ring Compounds; Buffers; Chloramphenicol; Chromatography, Micellar Electrokinetic Capillary; Drug Carriers; Drugs, Chinese Herbal; Glucosides; Glycosides; Humans; Hydrogen-Ion Concentration; Iridoids; Molecular Structure; Monoterpenes; Reference Standards; Reproducibility of Results; Sodium Dodecyl Sulfate; Time Factors

To study the chemical constituents from n-BuOH portion of ethanolic extract from the stem of Luculia pinceana.. The column chromatographic techniques were applied to isolate constituents. A combination of IR, FAB-MS, NMR and 2D NMR spectroscopy was used to identify structures.. Seven compounds were isolated from the n-BuOH fraction and their structures were elucidated as vogeloside (1), epi-vogeloside (2), loganoside (3), loganin (4), cincholic acid 28-O-beta-D-glucopyranosyl ester (5), cincholic acid-3-O-beta-D-glucopyranoside, 28-O-beta-D-glucopyranosyl ester (6), cincholic acid-3-O-beta-D-glucopyranoside (7).. Compounds 1-7 were isolated from the genus for the first time.

Topics: Glucosides; Iridoids; Plant Stems; Plants, Medicinal; Rubiaceae; Saponins

Among the pharmacologically important terpenoid indole alkaloids produced by Catharanthus roseus are the anti-cancer drugs vinblastine and vincristine. These two drugs are produced in small yields within the plant, which makes them expensive to produce commercially. Metabolic engineering has focused on increasing flux through this pathway by various means such as elicitation, precursor feeding, and introduction of genes encoding specific metabolic enzymes into the plant. Recently in our lab, a feedback-resistant anthranilate synthase alpha subunit was over-expressed in C. roseus hairy roots under the control of a glucocorticoid inducible promoter system. Upon induction we observed a large increase in the indole precursors, tryptophan, and tryptamine. The current work explores the effects of over-expressing the anthranilate synthase alpha or alpha and beta subunits in combination with feeding with the terpenoid precursors 1-deoxy-D-xylulose, loganin, and secologanin. In feeding 1-deoxy-D-xylulose to the hairy root line expressing the anthranilate synthase alpha subunit, we observed an increase of 125% in hörhammericine levels in the induced samples, while loganin feeding increased catharanthine by 45% in the induced samples. Loganin feeding to the hairy root line expressing anthranilate synthase alpha and beta subunits increases catharanthine by 26%, ajmalicine by 84%, lochnericine by 119%, and tabersonine by 225% in the induced samples. These results suggest that the terpenoid precursors to the terpenoid indole alkaloids are important factors in terpenoid indole alkaloid production.

Topics: Anthranilate Synthase; Catharanthus; Indole Alkaloids; Iridoid Glucosides; Iridoids; Plant Roots; Tryptamines; Tryptophan; Xylulose

Jasmonates enhance the expression of various genes involved in terpenoid indole alkaloid (TIA) biosynthesis in Catharanthus roseus. We applied precursor feeding to our C. roseus suspensions to determine how methyl jasmonate (MJ) alters the precursor availability for TIA biosynthesis. C. roseus suspensions were induced with MJ (100 microM) on day 6 and fed loganin (0.30 mM), tryptamine (0.15 mM), loganin plus tryptamine, or geraniol (0.1-1.0 mM) on day 7. While MJ increased ajmalicine production by 3-fold, induced cultures were still limited by terpenoid precursors. However, both induced and non-induced cultures became tryptamine-limited with excess loganin. Geraniol feeding also increased ajmalicine production in non-induced cultures. But MJ appeared to increase geraniol availability in induced cultures, due presumably to the increased expression of Dxs with MJ addition.

Topics: Acetates; Acyclic Monoterpenes; Catharanthus; Cells, Cultured; Cyclopentanes; Iridoids; Oxylipins; Secologanin Tryptamine Alkaloids; Terpenes; Tryptamines

A rapid, sensitive and selective high performance liquid chromatography (HPLC) method was developed and validated for determination of loganin in rat tissues. Samples were prepared based on a simple protein precipitation. Separation of loganin was achieved on a reversed-phase C(18) column (250 x 4.6 mm, 5 microm) with a mobile phase consisting of acetonitrile and water (16:84, v/v) at a flow rate of 1.0 mL/min. The detection wavelength was set at 236 nm and the temperature of the column was kept at 30 degrees C. The method was applied to study tissue distribution of loganin in rats after a single administration of loganin at a dose of 20 mg/kg. The highest level was observed in kidney, then in stomach, lung and small intestine. The lowest level was found in brain. The peak levels were attained at 90 min in most tissues. It was indicated that kidney was the major distribution tissue of loganin in rats, and that loganin had difficulty in crossing the blood-brain barrier. It was also found there was no long-term accumulation of loganin in rat tissues.

Topics: Animals; Chromatography, High Pressure Liquid; Female; Iridoids; Male; Molecular Structure; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tissue Distribution

To gain a clear idea on function of getting fid of cores of Cornus officinalis Sieb. et Zucc. and elect a suitable processing method and technics of Crnus officinalis Sieb. et Zucc. in producing area.. The contents of loganin and morroniside were determined in the cores and sarocarp of Cornus officinalis Sieb. et Zucc.; Using pathogonal method, the methods which Cornus officinalis sieb. et Zuee. were warmed or poached were isolated by determining quantitively loganin from Cornus officinalis Sieb. et Zucc. by HPLC.. There was a bit loganin and morroniside in the cores of Cornus officinalis Sieb. et Zuecc.; There were three aspects that were marked influence to extracted account of loganin which were hot temperature of poach, adding water and time of warming. The best suitable extracting technology was warmed in 60 degrees C by 10 min and then getted rid of cores.. Clearing the non-medicinal positon is the function of getting rid of cores of Cornus officinalis Sieb. et Zucc. and warming is better than poach.

Topics: Chromatography, High Pressure Liquid; Cornus; Drugs, Chinese Herbal; Fruit; Glycosides; Iridoids; Plants, Medicinal; Quality Control; Technology, Pharmaceutical; Time Factors

To investigate the chemical constituents of water-soluble part of stem of Nauclea officinalis.. The compounds were isolated and purified by resins, silica gel, and Sephadex LH20 column chromatography repeatedly, and their structures were identified by spectral analysis.. Seven compounds were isolated and identified as: naucleamide A-10-O-beta-D-glucopyranoside (I), 5-beta-carboxystrictosidin (II), sweroside (III), loganin (IV), 3,4-dimethoxyphenyl-beta-D-glucopyranoside (V), 3, 4, 5-trimethoxyphenyl-beta-D-glucopyranoside (VI), 2-phenethylrutinoside (VII).. Compound I is a new indole alkaloid glucoside, compounds I-VII were isolated from this plant for the first time.

Topics: Carbolines; Glucosides; Glycosides; Indole Alkaloids; Iridoid Glucosides; Iridoids; Molecular Conformation; Molecular Structure; Plant Stems; Plants, Medicinal; Rubiaceae

Advanced glycation end products (AGE) are involved in the alterations of renal mesangial cell (MCs) growth, a feature of early stages of diabetic nephropathy (DN). We postulate that morroniside and loganin, 2 components extracted from Cornus officinalis, may ameliorate the detrimental effects of AGE-induced MCs proliferation by preventing oxidative stress. Rat MCs cultured in AGE milieu were treated with morroniside and loganin. Results showed that morroniside and loganin inhibited AGE-induced MC proliferation as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Fluorescence microscopy revealed that the morroniside and loganin improved the morphological changes of MCs. Flow cytometric analysis showed that morroniside and loganin inhibited the cell cycle of rat MCs. Furthermore, the level of reactive oxygen species was significantly reduced, and the activities of superoxide dismutase and glutathione peroxidase were markedly increased, whereas the level of malondialdehyde was not significantly reduced. These results suggest that morroniside and loganin regulate MC growth by preventing oxidative stress. Thus, this study provides a molecular basis for the use of morroniside and loganin in the early stages of DN.

Topics: Animals; Antioxidants; Cell Cycle; Cell Line; Cell Proliferation; Cell Shape; Cornus; Diabetic Nephropathies; Flow Cytometry; Glutathione Peroxidase; Glycation End Products, Advanced; Glycosides; Iridoids; Malondialdehyde; Mesangial Cells; Microscopy, Fluorescence; Oxidative Stress; Rats; Reactive Oxygen Species; Superoxide Dismutase

The phytochemical analysis of iridoidic fraction of the aerial parts of Vinca sardoa and Vinca difformis, gave the identification of loganic acid in V. difformis as unique iridoid glucoside, while loganin is also present in V. sardoa. The two taxa highly differ in alkaloids, so the chemotaxonomic classification in two different species is supported.

Topics: Classification; Iridoids; Plant Leaves; Vinca

An efficient micellar electrokinetic capillary chromatography method was developed to analyze three major active components including morroniside, loganin and gallic acid in Fructus corni and its six preparations for the first time. The factors that could affect the separation were studied, such as the pH of the buffer, concentrations of SDS, organic modifier and beta-CD, and the applied voltage. The optimum analysis conditions were 10 mmol/L NaH(2)PO(4)-5 mmol/L Na(2)B(4)O(7) (pH 6.8) buffer containing 140 mmol/L SDS, 1 mmol/L beta-CD, 5% (v/v) methanol and 12.5 kV applied voltage. The linearity between the peak-areas and the concentrations of the analytes were investigated, and they exhibit excellent linear behavior over the concentration ranges (correlation coefficients 0.9953-0.9995). In addition, the pK(a) of gallic acid was determined using capillary zone electrophoresis. The result was consistent with that reported by the literature.

Topics: Buffers; Chromatography, Micellar Electrokinetic Capillary; Drugs, Chinese Herbal; Electrophoresis, Capillary; Gallic Acid; Iridoids; Molecular Structure; Reproducibility of Results; Temperature

Three seco-iridoids 7-methoxydiderroside, 6'-O-acetyldiderroside and 8-O-tigloyldiderroside, were isolated from the wood bark of Calycophyllum spruceanum together with the known iridoids loganetin, loganin and the seco-iridoids secoxyloganin, kingiside and diderroside. Their structures were elucidated by means of NMR and MS spectral data analysis. Using NOE correlations and coupling constants, the relative stereochemistry of the new derivatives was established. 7-Methoxydiderroside, 6'-O-acetyldiderroside and the known secoxyloganin and diderroside showed in vitro activity against trypomastigote forms of Trypanosoma cruzi, with IC(50) values of 59.0, 90.2, 74,2 and 84.9 microg/mL, respectively and were compared to the standard gentian violet (IC(50) 7.5 microg/ml).

Topics: Animals; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Magnetic Resonance Spectroscopy; Molecular Structure; Rubiaceae; Stereoisomerism; Trypanocidal Agents; Trypanosoma cruzi

To establish a revered-phase HPLC method for the study of pharmacokinetics of loganin and morroniside in Cornus officinalis injectionin mice after a single oral and intravenous administrations.. The Diamonsil C18 column (4.6 mm x 250 mm, 5 microns) was used as the analytical column and the mobile phase consisted of acetonitrile-methanol-0.2% formic acid (12:8:80) with the flow rate at 1.0 mL.min-1. The UV detection was set at 237 nm.. The calibration curves of loganin and morroniside were linear in the range from 0.38 to 68.25 mg.L-1(r = 0.9999), and from 0.66 to 117.22 mg.L-1(r = 0.9999), respectively. The lowest determination concentrations of loganin and morroniside were 0.10 and 0.16 mg.L-1, respectively. The recoveries and relative standard deviations of loganin were 99.6% (2.0%), 102.0% (1.0%), 87.9% (7.2%), and those of morroniside were 99.2% (2.5%), 104.1% (1.2%), 92.7% (4.2%), respectively. The relative standard deviations of within-day and between-day precision for the method were all less than 6.8%. After a single intravenous administration of Cornus officinalis injection to mice, the mean plasma concentration-time courses were found to fit a two-compartment open model, the main pharmacokinetic parameters of loganin were as follows: T1/2(alpha), T1/2(beta), K21, K12, K10, V(c), AUC, CL were 3.2 min, 25.1 min, 5.997 h-1, 4.981 h-1, 3.564 h-1, 0.551 L.kg-1, 13.59 mg.L-1.h, 1.965 L.kg-1.h-1, respectively and those of morroniside were 3.6 min, 21.5 min, 5.926 h-1, 3.833 h-1, 3.797 h-1, 0.647 L.kg-1, 27.15 mg.L-1.h, 2.457 L.kg-1.h-1, respectively.. It is the first time to establish the revered-phase HPLC method to determine concentrations of loganin and morroniside in plasma and to obtain their pharmacokinetic parameters and characteristics.

Topics: Administration, Oral; Animals; Area Under Curve; Chromatography, High Pressure Liquid; Cornus; Drugs, Chinese Herbal; Female; Injections, Intravenous; Iridoids; Male; Mice; Plants, Medicinal

To establish a RP-HPLC method for determination of glycosides in Traditional Chinese Medicine Liu-wei Di-huang.. The samples were analyzed on an ODS column at 30 degrees C, with mobile phase of methanol/water (33:67) at flow rate 1.0 mL.min and detection at wavelength of 236 nm.. Three major components reached base-line separation and were identified to be mononiside, loganin, paeoniflorin. Respectively for the three components, linear correlations were found between peak areas and concentrations in the ranges of 7.4-60, 7.7-62 mg.L-1 and 8.5-68 mg.L-1, and the recoveries were 98.8%, 98.3%, 99.6%.. The established method is proved to be suitable for simultaneous quantification of three major glycosidic components in Liuwei Dihuang decoction and can be used for evaluation of the quality of Liuwei Dihuang preparations.

Topics: Benzoates; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Cornus; Dioscorea; Drug Combinations; Drugs, Chinese Herbal; Glucosides; Iridoids; Monoterpenes; Plants, Medicinal; Quality Control; Rehmannia

To develop a method for determination of loganin in mouse plasma by using high-performance liquid chromatography. The method was employed to study pharmacokinetics of loganin.. An RP-C18 was used as the stationary phase. The mobile phase consisted of methanol-water (30:70), at the flow-rate of 0.8 mL.min-1. The UV absorbance detector was set at 240 nm. Plasma samples were treated with solid phase extraction.. The recovery of loganin in mouse plasma was 86.0%-91.5%. The calibration curve in plasma was linear over the range of 0.01-5.00 micrograms.mL-1. The limit of quantitation was 10 ng.mL-1. The RSDs of intra-day and inter-day (n = 5) were less than 15%. The pharmacokinetic parameters were Cmax = 6.8 micrograms.mL-1, Tmax = 30 min, T1/2 alpha = 26.1 min, T1/2 beta = 29.01 min.. The method is accurate, sensitive and suitable for pharmcokinetic study of loganin. The absorption and elimination of loganin were rapid after ig in mice.

Topics: Adjuvants, Immunologic; Animals; Area Under Curve; Chromatography, High Pressure Liquid; Iridoids; Male; Mice

A new iridoid glucoside dimer, coelobillardin (1), was isolated from the aerial parts of Coelospermum billardieri. Its structure has been elucidated on the basis of MS and NMR data. From a biogenetic point of view, this compound, which includes a cyclobutane basic core, should be considered as a [2+2] dimerization product of (E)-10-(4-hydroxycinnamoyloxy)loganin, which is the major iridoid isolated from the plant.

Topics: Acylation; Chromatography; Cyclobutanes; Dimerization; Glucose; Hydrolysis; Iridoids; Methanol; New Caledonia; Nuclear Magnetic Resonance, Biomolecular; Plant Extracts; Rubiaceae; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Stereoisomerism

A fast and easy method was sought for determination of the iridoid glycosides catalpol, ketologanin, verbenalin, loganin, 8-epi-loganic acid, geniposidic acid and 10-cinnamoyl catalpol in plant samples. The method involved micellar electrokinetic capillary chromatography (MEKC) coupled on-line to mass spectrometry. The partial filling technique and electrospray ionization were used. Seven iridoid glycosides could be separated with use of MEKC under basic conditions. However, 8-epi-loganic acid and geniposidic acid could not be detected simultaneously with the five neutral iridoid glycosides by mass spectrometry. Therefore, only the neutral iridoid glycosides were screened from plant samples. Catalpol, verbenalin, loganin and possibly 10-cinnamoyl catalpol were found in an examination of seven plant species in the genera Plantago, Veronica, Melampyrum, Succisa, and Valeriana. Aucubin, which was not included in the sample mixture used in method development because of overlapping with catalpol in MEKC, was also detected. The limits of detection for the iridoid glycosides, both at the UV and at the mass spectrometer, are given.

Topics: Chromatography, Micellar Electrokinetic Capillary; Glucosides; Hydrogen-Ion Concentration; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Mass Spectrometry; Molecular Structure; Molecular Weight; Plantago; Plants, Medicinal; Pyrans; Scrophulariaceae; Species Specificity; Spectrophotometry, Ultraviolet; Valerianaceae

The activity of 7-deoxyloganin 7-hydroxylase, an enzyme catalyzing the conversion of 7-deoxyloganin into loganin, was detected in a microsomal preparation from the cell suspension cultures of Lonicera japonica. It was dependent on NADPH and molecular oxygen. The enzymatic reaction was inhibited by carbon monoxide as well as by several cytochrome P450 inhibitors, especially ketoconazole, indicating that the reaction was mediated by cytochrome P450. The enzyme showed substrate specificity for 7-deoxyloganin. The K(m) values for 7-deoxyloganin and NADPH were estimated as 170 and 18 microM, respectively, from Lineweaver-Burk plots.

Topics: Carbon Monoxide; Cells, Cultured; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Glucosides; Iridoids; Ketoconazole; Magnoliopsida; Metyrapone; Miconazole; Microsomes; Mixed Function Oxygenases; NADP; Oxygen; Oxygen Consumption; Pyrans

Secologanin synthase, an enzyme catalyzing the oxidative cleavage of the cyclopentane ring in loganin to form secologanin, was detected in microsomal preparations from cell suspension cultures of Lonicera japonica. The reaction required NADPH and molecular oxygen, and was blocked by carbon monoxide as well as by several other cytochrome P450 inhibitors, indicating that the reaction was mediated by cytochrome P450. Of the substrates examined, only specificity for loganin was demonstrated. A possible reaction mechanism is described.

Topics: Carbon Monoxide; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Glucosides; Iridoid Glucosides; Iridoids; Magnoliopsida; Microsomes; NADP; Oxidoreductases Acting on CH-CH Group Donors; Oxygen; Pyrans; Substrate Specificity

A new iridoid glycoside 6'-O-beta-apiofuranosylsweroside was isolated from the ethanolic extract of the roots of Lonicera quinquelocularis along with the known compounds loganin and sweroside.

Topics: Disaccharides; Glucosides; Glycosides; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Magnetic Resonance Spectroscopy; Plant Extracts; Plant Roots; Plant Shoots; Plants, Medicinal; Pyrans; Pyrones

The molecular characterization of CYP72A1 from Catharanthus roseus (Madagascar periwinkle) was described nearly a decade ago, but the enzyme function remained unknown. We now show by in situ hybridization and immunohistochemistry that the expression in immature leaves is epidermis-specific. It thus follows the pattern previously established for early enzymes in the pathway to indole alkaloids, suggesting that CYP72A1 may be involved in their biosynthesis. The early reactions in that pathway, i.e. from geraniol to strictosidine, contain several candidates for P450 activities. We investigated in this work two reactions, the conversion of 7-deoxyloganin to loganin (deoxyloganin 7-hydroxylase, DL7H) and the oxidative ring cleavage converting loganin into secologanin (secologanin synthase, SLS). The action of DL7H has not been demonstrated in vitro previously, and SLS has only recently been identified as P450 activity in one other plant. We show for the first time that both enzyme activities are present in microsomes from C. roseus cell cultures. We then tested whether CYP72A1 expressed in E. coli as a translational fusion with the C. roseus P450 reductase (P450Red) has one or both of these activities. The results show that CYP72A1 converts loganin into secologanin.

Topics: Asteraceae; Cells, Cultured; Cloning, Molecular; Cytochrome P-450 Enzyme System; Escherichia coli; Glucosides; Iridoid Glucosides; Iridoids; Molecular Sequence Data; Oxidoreductases Acting on CH-CH Group Donors; Pyrans; Vinca Alkaloids

A high performance liquid chromatographic method has been developed for the determination of loganin in the fruit of Cornus of ficinalis. The method is rapid, accurate and sensitive.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Fruit; Glucosides; Iridoids; Magnoliopsida; Pyrans

The content of loganin extracted from Cornus of ficinalis was determined directly on a CS-930 TLC scanner. The method is simple and sensitive, and can serve as an index for checking the quality of C. of ficinalis.

Topics: Chromatography, Thin Layer; Densitometry; Drugs, Chinese Herbal; Glucosides; Iridoids; Pyrans; Quality Control

Omission of 2,4-D from culture medium during one subculture of Catharanthus roseus cells, strain C20, resulted in an increased alkaloid accumulation, without effect on growth. Alkaloid accumulation, rather than growth, seemed to be more sensitive to 2,4-D. 2,4-D inhibited alkaloid accumulation essentially during growth phase, but its inhibitory effect during this period was partially reversible. As this reversibility was underlined only during the stationary phase, this suggested that this action could be situated upstream in a terpenoid non-specific pathway. 2,4-D feeding showed that inhibition is weaker and weaker as the alkaloid accumulation period proceeds. Auxin action during this period could take place downstream in specific alkaloid pathways. The lower alkaloid accumulation obtained after loganic acid feeding compared to that obtained with secologanin and loganin could indicate that loganic acid methylation should be one of the 2,4-D target(s).

Topics: 2,4-Dichlorophenoxyacetic Acid; Cells, Cultured; Glucosides; Iridoid Glucosides; Iridoids; Plants, Medicinal; Pyrans; Secologanin Tryptamine Alkaloids; Vinca Alkaloids; Yohimbine

A reinvestigation of the roots of Guettarda platypoda afforded in addition to morronoside and sweroside isolated previously further two iridoids, loganic acid and loganin and a rare secoiridoid, secoxyloganin. The structures were elucidated by NMR techniques. This is the first report of the isolation of such compounds from G.platypoda. Some chemotaxonomic conclusion can be drawn.

Topics: Chemical Phenomena; Chemistry; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Plants, Medicinal; Pyrans

Topics: Iridoids; Strychnine