iridoids and monotropein

As a glycoside iridoid, monotropein (MON) has a wide range of pharmacological properties, including anti-inflammatory, antioxidant, and anti-apoptotic effects. However, few studies have investigated MON's cardiovascular protective effects. Therefore, this study aimed to explore the role of MON in doxorubicin (DOX)-induced cardiotoxicity. To establish the myocardial toxicity model, mice were intraperitoneally injected with DOX. After admimistration of DOX, myocardial injury markers were increased, cardiac function was reduced, and pathological changes were observed in the myocardium, indicating successful construction of the myocardial injury model. Our study showed that MON treatment mitigated DOX-induced myocardial damage and improved cardiac dysfunction. In addition, DOX-treated mice displayed higher levels of inflammation and oxidative stress, while MON treatment also reversed these pathological changes. Moreover, DOX-treated mice were more susceptible to ventricular fibrillation, whereas MON reduced ventricular fibrillation incidence. Further studies have shown that MON could reverse DOX-induced inhibition of the AKT signaling pathway. Besides, the application of AKT inhibitor could partially abolish MON's cardioprotective effects. To conclude, this study demonstrated the ability of MON to reduce DOX-induced myocardial damage, cardiac dysfunction, inflammation, and oxidative stress, as well as ventricular fibrillation risk. These may attributable to the activation of the AKT pathway.

Topics: Animals; Apoptosis; Arrhythmias, Cardiac; Doxorubicin; Inflammation; Iridoids; Mice; Myocytes, Cardiac; Oxidative Stress; Proto-Oncogene Proteins c-akt; Signal Transduction; Ventricular Fibrillation

The present study aimed to investigate the effects of monotropein (MON) on improving dexamethasone (DEX)-induced muscle atrophy in mice and C2C12 mouse skeletal muscle cells. The body weights, grip strengths, and muscle weights of mice were assessed. The histological change in the gastrocnemius tissues was also observed through H&E staining. The expression of myosin heavy chain (MyHC), muscle ring finger 1 (MuRF1), and muscle atrophy F-box (Atrogin1) and the phosphorylation of AKT, mTOR, and FOXO3a in the muscle tissues of mice and C2C12 myotubes were analyzed using Western blotting. MON improved muscle atrophy in mice and C2C12 myotubes by regulating catabolic states via the AKT/mTOR/FOXO3a signaling pathways, and enhanced muscle function by the increases of muscle mass and strength in mice. This suggests that MON could be used for the prevention and treatment of muscle atrophy in patients.

Topics: Dexamethasone; Humans; Iridoids; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases

Monotropein (Mon) is a kind of iridoid glycoside plant secondary metabolite primarily present in some edible and medicinal plants. The aim of this study was to investigate the effect of Mon on lipopolysaccharide (LPS)-induced inflammatory bone loss in mice and osteoclasts (OCs) derived from bone marrow-derived macrophages (BMMs), and explore the mechanisms underlying the effect of Mon on LPS-induced osteoclastogenesis. It was found that Mon markedly attenuated deterioration of the bone micro-architecture, enhanced tissue mineral content (TMC) and bone volume/total volume (BV/TV), reduced structure model index (SMI) and trabecular separation/spacing (Tb.Sp) in the bone tissue and decreased the activities of tartrate resistant acid phosphatase-5b (TRACP-5b), receptor activator NF-κB (RANK), and receptor activator NF-κB ligand (RANKL) as well as the serum levels of interleukin 6 (IL-6) and interleukin 1β (IL-1β) in LPS-treated mice. In addition, Mon treatment reduced the number of TRAP positive OCs in the bone tissue of LPS-treated mice and also exerted a stronger inhibitory effect on formation, differentiation, and F-actin ring construction of OCs derived from BMMs. Mon significantly inhibited the expression of the nuclear factor of activated T-cells c1 (NFATc1) and the immediate early gene (C-Fos) and nuclear translocation of NFATc1 in LPS-treated OCs, thereby inhibiting the expression of matrix metalloproteinase-9 (MMP-9), cathepsin K (CtsK), and TRAP. Mon significantly inhibited the expression of TRAF6, phosphorylation of P65, and degradation of IKBα, thus inhibiting the activation of NF-κB pathway in LPS-induced inflammatory mice and OCs derived from BMMs, and also inhibited LPS-induced phosphorylation of protein kinase B (Akt) and Glycogen synthase kinase 3β (GSK-3β) in OCs derived from BMMs. In conclusion, these results suggested that Mon could effectively inhibit osteoclastogenesis both in vitro and in vivo and therefore may prove to be potential option for prevention and treatment of osteoclastic bone resorption-related diseases.

Topics: Actins; Animals; Bone Resorption; Cathepsin K; Glycogen Synthase Kinase 3 beta; Interleukin-1beta; Interleukin-6; Iridoid Glycosides; Iridoids; Ligands; Lipopolysaccharides; Matrix Metalloproteinase 9; Mice; NF-kappa B; NFATC Transcription Factors; Osteoclasts; Proto-Oncogene Proteins c-akt; Tartrate-Resistant Acid Phosphatase; TNF Receptor-Associated Factor 6

Although cisplatin is a common drug in the treatment of malignant tumors, its clinical application is limited due to various side effects, especially acute kidney injury (AKI). Till now, few effective pharmacological strategies can be applied to inhibit cisplatin-induced AKI. Here, we aimed to investigate the protective effects and possible mechanisms of monotropein on cisplatin-induced AKI. In this study, an AKI model was established in cisplatin-treated mice, and serum level of inflammatory cytokines, protein expressions of biochemical indicators and renal pathology were analyzed. Our results showed that our results showed that monotropein could significantly attenuate cisplatin-induced nephrotoxicity and reduce the levels of blood urea nitrogen (BUN) and serum creatinine (CRE). Furthermore, monotropein inhibited cisplatin-induced oxidative stress by reducing MDA level and increasing the activities of GSH, SOD and CAT. The underlying mechanisms of monotropein on alleviating cisplatin-induced AKI were associated with the activation of Nrf2/HO-1 pathway against oxidative stress and the inhibition on NF-κB signaling to suppress inflammation as well as the regulation on the expressions of proteins in apoptosis pathway in this renal injury model. This study firstly provided the evidence that monotropein could significantly attenuate cisplatin-induced AKI and suggested that monotropein might be used as a potential agent to alleviate side effects of cisplatin.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Cisplatin; Disease Models, Animal; Heme Oxygenase-1; Inflammation Mediators; Iridoids; Kidney; Membrane Proteins; Mice, Inbred BALB C; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Signal Transduction

Recently, it has reported that many inflammatory bowel disease (IBD) patients were contracted secondary liver injury. Monotropein (MON), an iridoid glycoside, is demonstrated to possess protective effects on acute colitis mice due to its anti-inflammatory activities. However, it was remained unknown whether MON could inhibit secondary liver injury caused by IBD. The aim of the present study was to investigate the protective roles and mechanisms of MON on secondary liver injury in chronic colitis mice model. In this study, 2% Dextran sodium sulfate (DSS) was used to induce mice model of chronic colitis. The results showed that MON attenuated DSS-induced hepatic pathological damage, liver parameters, infiltration of macrophages and cytokines levels. Furthermore, we found that MON attenuated liver injury through suppressing the activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and down-regulating the activity of NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome. All the data indicated that MON may be an effective therapeutic reagent to attenuate secondary liver injury induced by chronic colitis.

Topics: Animals; Anti-Inflammatory Agents; Chronic Disease; Colitis; Dextran Sulfate; Disease Models, Animal; Inflammasomes; Iridoids; Liver; Liver Diseases; Macrophages; Male; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Toll-Like Receptor 4

Aging is a major risk factor in cardiovascular disease (CVD). Oxidative stress and inflammation are involved in the pathogenesis of CVD, and are closely associated with senescent vascular endothelial cells. Monotropein (Mtp) exerts various bioactive roles, including anti‑inflammatory and antioxidative effects. The aim of the present study was to investigate the function of Mtp in senescent endothelial cells. An MTT assay was performed to evaluate the influence of Mtp on H2O2‑stimulated human umbilical vein endothelial cells (HUVECs). Senescent cells were assessed by determining the expression of senescence‑associated β‑galactosidase, high mobility group AT‑hook 1 and DNA damage marker γ‑H2A.X variant histone. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) and proinflammatory cytokine concentrations were estimated using assay kits to evaluate the levels of oxidative stress and inflammation in HUVECs. The TUNEL assay was performed to identify apoptotic cells. Furthermore, the expression levels of endothelial cell adhesion factors, NF‑κB, activator protein‑1 (AP‑1) and apoptotic proteins were determined via western blotting. Mtp enhanced HUVEC viability following H2O2 stimulation. H2O2‑mediated increases in MDA, proinflammatory cytokine and endothelial cell adhesion factor levels were decreased by Mtp treatment, whereas Mtp reversed H2O2‑mediated downregulation of SOD and GSH‑Px activity. Furthermore, Mtp inhibited cell apoptosis, NF‑κB activation and AP‑1 expression in H2O2‑stimulated HUVECs; however, NF‑κB activator counteracted the anti‑inflammatory, antioxidative and antiapoptotic effects of Mtp. The present study indicated that Mtp ameliorated H2O2‑induced inflammation and oxidative stress potentially by regulating NF‑κB/AP‑1.

Topics: Antioxidants; Apoptosis; Cardiovascular Diseases; Cell Survival; Glutathione Peroxidase; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide; Inflammation; Iridoids; Malondialdehyde; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase; Transcription Factor AP-1

Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS.. Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays.. Parameters such as sperm motility and count, Johnsen's scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio.. This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.

Topics: Animals; Antioxidants; Body Weight; Disease Models, Animal; Endoplasmic Reticulum Stress; Iridoids; Kaempferols; Male; Mitochondria; Organ Size; Oxidative Stress; Quercetin; Rats; Rats, Sprague-Dawley; Signal Transduction; Testis; Varicocele

Attenuating oxidative stress-induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress-induced mitochondrial dysfunction and stimulate bone marrow-derived EPC (BM-EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM-EPCs and prevented tert-butyl hydroperoxide (TBHP)-induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation. Moreover, Mtp accelerated wound healing in rats, as indicated by reduced healing times, decreased macrophage infiltration and increased blood vessel formation. In summary, Mtp promoted mobilization and differentiation of BM-EPCs and protected against apoptosis and autophagy by suppressing the AMPK/mTOR pathway, improving wound healing in vivo. This study revealed that Mtp is a potential therapeutic for endothelial injury-related wounds.

Topics: AMP-Activated Protein Kinases; Angiogenesis Inducing Agents; Animals; Antioxidants; Apoptosis; Autophagy; Bone Marrow Cells; Carrier Proteins; Cell Movement; Cell Proliferation; Endothelial Progenitor Cells; Gene Expression Regulation; Intracellular Signaling Peptides and Proteins; Iridoids; Male; Neovascularization, Physiologic; Oxidative Stress; Phosphoproteins; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Surgical Wound; tert-Butylhydroperoxide; TOR Serine-Threonine Kinases; Wound Healing

Estrogen deficiency and inflammation are known to play important roles in bone metabolism and occurrence of osteoporosis. Monotropein as an iridoid glycoside is reported to decrease estrogen deficiency-induced bone loss and inhibit inflammatory response in LPS-induced RAW 264.7 macrophages. However, the effect of monotropein on bone loss in chronic inflammatory conditions remains unclear. It was found in the present study that monotropein significantly inhibited bone mass reduction and improved bone micro-architectures by enhancing bone formation and blocking increased secretion of inflammatory cytokines in osteoporotic mice induced by combined ovariectomy and LPS. Our in vitro experiment further demonstrated that monotropein was able to increase the proliferation and activity of alkaline phosphatase (ALP), bone matrix mineralization and the expression of bone matrix protein osteopontin (OPN) in osteoblastic MC3T3-E1 cells injured by LPS. In addition, monotropein significantly decreased the production of IL-6 and IL-1β, inhibited the nuclear translocation of p65 and NF-κB P50, and down-regulated the phosphorylation of NF-κB p65 and IKK, indicating that monotropein could attenuate inflammatory impairment to MC3T3-E1 cells by suppressing the activation of NF-κB pathway. All these results suggest that monotropein may prove to be a promising candidate for the prevention and treatment of inflammatory bone loss.

Topics: Alkaline Phosphatase; Animals; Bone Density; Bone Matrix; Bone Resorption; Calcification, Physiologic; Cell Cycle; Cell Line; Cell Proliferation; Female; Femur; Inflammation; Interleukin-1beta; Interleukin-6; Iridoids; Lipopolysaccharides; Mice, Inbred C57BL; NF-kappa B; Osteoblasts; Osteocalcin; Osteoporosis; Ovariectomy; Signal Transduction; X-Ray Microtomography

Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO.. An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods.. Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC. The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.

Topics: Administration, Oral; Animals; Drugs, Chinese Herbal; Female; Glycosides; Iridoid Glycosides; Iridoids; Male; Molecular Structure; Morinda; Plant Roots; Rats; Rats, Wistar; Tandem Mass Spectrometry; Tissue Distribution

Cultivated blueberry (Vaccinium corymbosum, Vaccinium angustifolium, Vaccinium darrowii, and Vaccinium virgatum) is an economically important fruit crop native to North America and a member of the Ericaceae family. Several species in the Ericaceae family including cranberry, lignonberry, bilberry, and neotropical blueberry species have been shown to produce iridoids, a class of pharmacologically important compounds present in over 15 plant families demonstrated to have a wide range of biological activities in humans including anti-cancer, anti-bacterial, and anti-inflammatory. While the antioxidant capacity of cultivated blueberry has been well studied, surveys of iridoid production in blueberry have been restricted to fruit of a very limited number of accessions of V. corymbosum, V. angustifolium and V. virgatum; none of these analyses have detected iridoids. To provide a broader survey of iridoid biosynthesis in cultivated blueberry, we constructed a panel of 84 accessions representing a wide range of cultivated market classes, as well as wild blueberry species, and surveyed these for the presence of iridoids. We identified the iridoid glycoside monotropein in fruits and leaves of all 13 wild Vaccinium species, yet only five of the 71 cultivars. Monotropein positive cultivars all had recent introgressions from wild species, suggesting that iridoid production can be targeted through breeding efforts that incorporate wild germplasm. A series of diverse developmental tissues was also surveyed in the diversity panel, demonstrating a wide range in iridoid content across tissues. Taken together, this data provides the foundation to dissect the molecular and genetic basis of iridoid production in blueberry.

Topics: Blueberry Plants; Chromatography, Liquid; Fruit; Iridoids; Mass Spectrometry; Molecular Structure; Phylogeny; Plant Breeding; Plant Leaves; Species Specificity

Monotropein is a natural iridoid glycoside enriched in Morinda officinalis and has been used for medicinal purposes in China. In the present study, we systematically examined its effects on ovariectomy (OVX)-induced osteoporosis in mice and osteoblastic MC3T3-E1 cells for the first time. Eight-week-old female C57/BL6 mice were used to evaluate the osteoprotective effect of monotropein. Results showed that administration of monotropein (40 or 80 mg/kg/day) for four weeks exerted good bone protective effects as evidenced by the increase of bone mineral content (BMC), bone mineral density (BMD), bone volume fraction (BVF) and improvement of bone microstructure. Monotropein also enhanced the parameters of biomechanical properties, including maximum load, maximum stress and elastic modulus of femur in OVX mice. In addition, monotropein treatment decreased the serum levels of interleukin 1 (IL-1), interleukin 6 (IL-6) and soluble receptor activator of NF-κB ligand (sRANKL) in OVX mice. In this study, we also assessed the effects of monotropein on the proliferation and differentiation of osteoblastic MC3T3-E1 cells in vitro. After incubation for 48h, the cell proliferation was increased at the concentration of 10 μM, 25 μM, 50 μM and 100 μM. ALP activities were significantly increased after treatment with monotropein for 72h. Quantitative analyses with alizarin red staining showed significantly increased mineralization of MC3T3-E1 cells after treatment with monotropein for 28 days. Based on these results, monotropein may serve as a new candidate or a leading compound for antiosteoporosis.

Topics: 3T3 Cells; Animals; Biomarkers; Biomechanical Phenomena; Bone Density; Female; Femur; Interleukin-1; Interleukin-6; Iridoids; Mice; Mice, Inbred C57BL; Morinda; Osteoblasts; Osteogenesis; Osteoporosis; Ovariectomy; Plant Roots; RANK Ligand

Monotropein, the primary iridoid glycoside isolated from Morindacitrifolia, has been previously reported to possess potent antioxidant and antiosteoporotic properties. However, there is no direct evidence correlating the antiosteoporotic effect of monotropein with its observed antioxidant capacity, and the molecular mechanisms involved in mediating these processes remain unclear. Therefore, the aim of the present study was to investigate the protective effects of monotropein against oxidative stress in osteoblasts and the mechanisms involved in mediating this process. Osteoblast viability was evaluated using the MTT assay. The mitochondrial membrane potential and reactive oxygen species were detected by flow cytometry analyses. Western blotting and enzyme‑linked immunosorbent assays were performed to detect protein expression levels. A significant reduction in osteoblast viability was observed at 24 h following exposure to various concentrations (100‑1,000 µM) of H2O2 compared with untreated osteoblasts. The cytotoxic effect of H2O2 was notably reversed when osteoblasts were pretreated with 1‑10 µg/ml monotropein. Pretreatment with 1-10 µg/ml monotropein increased the mitochondrial membrane potential and reduced the generation of reactive oxygen species in osteoblasts following exposure to H2O2. In addition, the H2O2‑induced increase in apoptotic markers (caspase-3 and caspase-9) and H2O2-induced reduction in sirtuin 1 levels were significantly reversed following pretreatment of cells with monotropein. Furthermore, monotropein significantly reduced H2O2‑induced stimulation of NF‑κB expression, in addition to the expression of a number of proinflammatory mediators. These results indicate that monotropein suppresses apoptosis and the inflammatory response in H2O2‑induced osteoblasts through the activation of the mitochondrial apoptotic signaling pathway and inhibition of the NF‑κB signaling pathway.

Topics: Alkaline Phosphatase; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cell Differentiation; Cell Survival; Cells, Cultured; Cyclooxygenase 2; Hydrogen Peroxide; Iridoids; Male; Matrix Metalloproteinases; Membrane Potential, Mitochondrial; NF-kappa B; Nitric Oxide Synthase Type II; Osteoblasts; Oxidative Stress; Rats; Reactive Oxygen Species

Osteoarthritis, characterized by a loss of articular cartilage accompanied with inflammation, is the most common age-associated degenerative disease. Monotropein, an iridoids glycoside isolated from the roots of Morinda officinalis How, has been demonstrated to exhibit anti-inflammatory activity. In the present study, monotropein was firstly to exhibit cartilage protective activity by down regulating the pro-inflammatory cytokines in the knee synovial fluid in vivo. The anti-apoptotic and anti-catabolic effects of monotropein on rat OA chondrocytes treated by IL-1β were investigated in vitro. In cultured chondrocytes, monotropein attenuated apoptosis in a dose-dependent manner in response to IL-1β stimulation. Moreover, treatment with monotropein, the expressions of MMP-3 and MMP-13 were significantly decreased, the expression of COL2A1 was increased. Taken together, these findings suggested that monotropein exerted anti-apoptosis and anti-catabolic activity in chondrocytes, which might support its possible therapeutic role in OA.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Blotting, Western; Cell Survival; Cells, Cultured; Chondrocytes; Disease Models, Animal; Interleukin-1beta; Iridoids; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Morinda; Osteoarthritis; Plant Roots; Primary Cell Culture; Rats, Inbred Strains

We previously demonstrated that monotropein isolated from the roots of Morinda officinalis (Rubiaceae) has anti-inflammatory effects in vivo. In the present study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of monotropein in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced colitis mouse model. Monotropein was found to inhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) mRNA in LPS-induced RAW 264.7 macrophages. Treatment with monotropein decreased the DNA binding activity of nuclear factor-κB (NF-κB). Consistent with these findings, monotropein also suppressed phosphorylation and degradation of inhibitory κB-α (IκB-α), and consequently the translocations of NF-κB. In the DSS-induced colitis model, monotropein reduced disease activity index (DAI), myeloperoxidase (MPO) activity, and inflammation-related protein expressions by suppressing NF-κB activation in colon mucosa. Taken together, these findings suggest that the anti-inflammatory effects of monotropein are mainly related to the inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Colitis; Cyclooxygenase 2; Dextran Sulfate; I-kappa B Proteins; Inflammation Mediators; Interleukin-1beta; Iridoids; Lipopolysaccharides; Macrophages; Mice; Morinda; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II; Peroxidase; Phosphorylation; Plant Roots; RNA, Messenger; Tumor Necrosis Factor-alpha

To determine the contents of monotropein in the different processed Products of Radix Morindae.. Kromasil C18 (150 mm x 4. 6 mm,5 micorm) column; The mobile phase was methol-0.4% phosphate solution (5:95-->28.8: 71.2, 15 min); The velocity of flow was 1 ml/min; The detection wavelength was at 210 nm; And column temperature was 25 degrees C RESULTS: There were obvious differences between the crude and kinds of different processed products of monotropein in the Radix Morindae, The contents of monotropein from the different processed products (crude drugs, removed from wood, processed with salt, prepared) were 13.92 mg/g,9.10 mg/g, 9.21 mg/g, 12.86 mg/g, respectively.. The different processing methods can make the contents of monotropein in the Radix Morindae.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Hot Temperature; Iridoids; Morinda; Plant Roots; Plants, Medicinal; Reproducibility of Results; Technology, Pharmaceutical

To investigate the chemical constituents of Pyrola calliatha.. The chemical constituents were isolated by various column chromatographic methods. The structures were identified by spectral data.. Ten compounds were isolated and identified as chimaphilin (1), uvaol(2), ursolic acid (3), 2beta,3beta,23-trihydroxy-12-ene-28-ursolic acid (4), daucosterol (5), 2alpha,3beta,23,24-tetrahydroxy-12-ene-28-ursolic acid (6), emodin (7), gallic acid (8), monotropein (9), adenosine (10).. Compounds 2,4,6,7,10 were obtained from this genus for the first time, compounds 5, 9 were obtained from this species for the first time. Antifungal activity of compounds 1-4, 6-9 were evaluated. Compound 1 showed the strong activity.

Topics: Antifungal Agents; Cryptococcus neoformans; Iridoids; Naphthoquinones; Plants, Medicinal; Pyrola; Triterpenes

The root of Morinda officinalis (Rubiaceae) is used to treat rheumatoid arthritis and impotence in the traditional Oriental medicine. To identify the antinociceptive anti-inflammatory components of this crude drug, we adopted an activity-directed fractionation approach. The active fraction of the BuOH extract of M. officinalis root was subjected to silica gel and ODS column chromatography to yield two diterpenes, compounds 1 and 2 and these were identified as monotropein and deacetylasperulosidic acid, respectively. The iridoid glycoside, monotropein, was tested for its anti-inflammatory antinociceptive effects using hot plate- and writhing antinociceptive assays and by using carrageenan-induced anti-inflammatory assays in mice and rats. Pretreatment with monotropein (at 20, 30 mg/kg/d, p.o.) significantly reduced stretching episodes and prolonged action time in mice. It also significantly reduced acute paw edema by carrageenan in rats. These results indicate that monotropein contributes to the antinociceptive and anti-inflammatory action of Morinda officinalis root.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Chromatography, Gel; Iridoids; Male; Mice; Mice, Inbred ICR; Morinda; Plant Roots; Rats; Rats, Sprague-Dawley; Spectrum Analysis