iridoids and aucubin

Aucubin is an iridoid glycoside widely spread in the families

Topics: Antioxidants; Chromatography, Liquid; Humans; Iridoid Glucosides; Iridoids

Aucubin (AU), an iridoid glycoside that is one of the active constituents of. To compile the protective effects and mechanisms of AU in NDs and provide a basis for further research.. We used 'aucubin' as the 'All Fields' or 'MeSH' in PubMed, Web of Science and China National Knowledge Infrastructure without any limitation to search all relevant articles as comprehensively as possible; we selected the articles on AU treatment of NDs for summary.. Studies reviewed herein reported that AU improved the symptoms or prognosis of Parkinson's disease, Alzheimer's disease, intracerebral haemorrhage, diabetic encephalopathy, epilepsy, anxiety and depression, and traumatic brain injury. The pharmacological mechanisms involved in repairing neuronal loss were postulated to include increasing γ-aminobutyric acid (GABA) content in the synapse, promoting differentiation of neural precursor cells into GABAergic neurons, providing antioxidant and anti-neuroinflammation activities, as well as enhancing autophagy and anti-apoptotic actions.. The protective effects of AU on some NDs have been confirmed. According to the pharmacological effects, AU is also highly likely to have protective effects on other NDs, which can be realized by further

Topics: Eucommiaceae; Humans; Iridoid Glucosides; Iridoids; Neural Stem Cells

The advances in the research on pharmacological activities of aucubin have been summarized in the last ten years. Aucubin is one of active components of Chinese medicinal herbs such as Eucommia ulmoides and has been shown wide pharmacological activities including hepatoproective, antitoxicanti-inflammatory, antioxidant, antiaging, antiosteoporosis and neurotrophic and should be further researched and utilized.

Topics: Aging; Animals; Anti-Inflammatory Agents; Antioxidants; Eucommiaceae; Glucosides; Iridoid Glucosides; Iridoids; Molecular Structure; Plants, Medicinal; Pyrans

SA and H

Topics: Antioxidants; Hydrogen Peroxide; Iridoids; Orobanchaceae; Phenols; Salicylic Acid

Countless reports describe the isolation and structural characterization of natural products, yet this information remains disconnected and underutilized. Using a cheminformatics approach, we leverage the reported observations of iridoid glucosides with the known phylogeny of a large iridoid producing plant family (Lamiaceae) to generate a set of biosynthetic pathways that best explain the extant iridoid chemical diversity. We developed a pathway reconstruction algorithm that connects iridoid reports via reactions and prunes this solution space by considering phylogenetic relationships between genera. We formulate a model that emulates the evolution of iridoid glucosides to create a synthetic data set, used to select the parameters that would best reconstruct the pathways, and apply them to the iridoid data set to generate pathway hypotheses. These computationally generated pathways were then used as the basis by which to select and screen biosynthetic enzyme candidates. Our model was successfully applied to discover a cytochrome P450 enzyme from Callicarpa americana that catalyzes the oxidation of bartsioside to aucubin, predicted by our model despite neither molecule having been observed in the genus. We also demonstrate aucubin synthase activity in orthologues of Vitex agnus-castus, and the outgroup Paulownia tomentosa, further strengthening the hypothesis, enabled by our model, that the reaction was present in the ancestral biosynthetic pathway. This is the first systematic hypothesis on the epi-iridoid glucosides biosynthesis in 25 years and sets the stage for streamlined work on the iridoid pathway. This work highlights how curation and computational analysis of widely available structural data can facilitate hypothesis-based gene discovery.

Topics: Cheminformatics; Iridoid Glucosides; Iridoids; Lamiaceae; Phylogeny

Aucubin (AU) is one of the widespread compounds belonging to the group of iridoid glycosides, which possesses numerous beneficial properties. Nonylphenol (NP), is a synthetic environmental toxicant that has the potential to cause male infertility through excessive production of reactive oxygen species. In the current study, the remedial potential of Aucubin was assessed against NP-generated testicular damage in male rats. Animals were distributed into four groups and treated for 56 days in this study. Control-group (0.1% DMSO + food), NP group (100 µg/kg), NP + AU group (100 µg/kg + 5 mg/kg) and AU group (5 mg/kg). NP exposure significantly (p < 0.05) reduced the activity of antioxidant enzymes i.e., glutathione reductase, catalase (CAT), superoxide dismutase, glutathione peroxidase (GPx), and total protein content (TPC), whereas the level of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) was enhanced substantially (p < 0.05). Treatment with AU substantially (p < 0.05) recovered activities of antioxidant enzymes, TPC, ROS, and TBARS levels. Moreover, decrease in the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone, sperm count, motility, sperm membrane integrity, and the number of spermatocytes of different stages along with the level of steroidogenic enzymes i.e., 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), and B-cell lymphoma 2 (Bcl-2) by NP administration were recovered to control values by AU treatment. However, AU mitigated the sperm abnormalities (head/midpiece/tail), the number of dead sperms, and proapoptotic proteins i.e., Bcl-2 associated X protein (Bax), caspase-9, and caspase-3 that were increased by NP. Besides, AU treatment recovered the NP-induced potential histopathological alterations in the testicular tissues such as the height of epithelium, seminiferous tubules diameter as well as the height of tunica propria. Overall, NP-induced toxicity was effectively recuperated by the AU administration. These results indicate that AU might be considered as a potential protective agent against testicular damage. The observed protection may be due to its antioxidant, anti-apoptotic, anti-inflammatory and androgenic potential.

Topics: Animals; Antioxidants; Glycosides; Iridoid Glucosides; Iridoids; Male; Oxidative Stress; Phenols; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Semen; Testis; Testosterone; Thiobarbituric Acid Reactive Substances

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is difficult to manage with currently available therapeutic drugs. Therefore, there is a need for novel therapeutic agents for treating CIPN. Goshajinkigan (GJG) is a Kampo formula composed of ten crude drugs. While GJG has been used for the treatment of CIPN, the active constituents of GJG and their underlying mechanisms of pharmacological effects are still unknown. Our previous study revealed that repetitive oral administration of the water extract of Plantaginis Semen, a crude drug ingredient of GJG, inhibited the mechanical allodynia induced by an intraperitoneal injection of paclitaxel in mice. To elucidate the active compounds of Plantaginis Semen, activity-guided separation of the water extract of Plantaginis Semen was performed. From the active fraction, four iridoids (1-4) were identified. Repetitive oral administration of aucubin (1) at 100 or 30 mg/kg and 100 mg/kg of the fraction crude 3 [primarily comprised of pedicularis-lactone (3)], showed anti-allodynic activity, suggesting 1 and 3 could be some of the active compounds responsible for the anti-allodynic property of Plantaginis Semen and GJG. Our study establishes that oral administration of 1 has potent anti-allodynic effect in addition to the activity of intraperitoneally administered 1 reported previously. Identification of active anti-allodynic compounds found in Kampo formulations will support the development of novel therapies for the management of CIPN in cancer patients.

Topics: Animals; Drugs, Chinese Herbal; Hyperalgesia; Iridoid Glucosides; Iridoids; Lactones; Male; Medicine, Kampo; Mice; Mice, Inbred C57BL; Paclitaxel; Peripheral Nervous System Diseases; Plant Extracts; Plantago

Topics: Anti-Bacterial Agents; Antioxidants; Bacteria; China; Chlorogenic Acid; Chromatography, High Pressure Liquid; Eucommiaceae; Flavonoids; Fungi; Gutta-Percha; Iridoid Glucosides; Iridoids; Kaempferols; Lignans; Metabolome; Phenols; Plant Bark; Plant Extracts; Plant Leaves; Plants, Medicinal; Quercetin; Rutin

In this study, we report the first phytochemical analysis of polar fraction of Pedicularis kerneri Dalla Torre growing in Dolomites, Italy. Several iridoid glucosides were isolated, namely aucubin (1), monomelittoside (2), plantarenaloside (3), euphroside (4), mussaenosidic acid (5) and 8-epiloganic acid (6), showing a composition in accordance with previous study on this genus. The studied samples, collected from Dolomites, presented a chemotype already recognised in species from North America, characterised by euphroside (4) and aucubin (1) as main components, but the main character was the presence of monomelittoside (2) never reported in this genus. The identification of verbascoside (7), leucosceptoside A (9) and echinacoside (10) complete the systematic framing of this species since is ascertained the co-occurrence of phenylethanoid glycosides with iridoids in Lamiales species.

Topics: Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Italy; Molecular Structure; Pedicularis; Phenols; Plant Extracts

We analysed the ethanolic extract from Ajuga genevensis L. (Lamiaceae) growing in Dolomites, part of Italian Alps. Three new compounds for this species were identified: rosmarinic acid (1), oleanolic acid (2) and maslinic acid (3), representative of two different classes of chemical compounds (phenylpropanoids and pentacyclic triterpenes). A. genevensis resulted to be a valuable source of these compounds endowed with interesting biological activities (i.e. antioxidant, neuroprotective, anti-inflammatory, antiproliferative). The recognition of compounds (1), (2) and (3) may also confirm the ethnomedicinal uses of this plant. From a chemotaxonomical point of view, it is worth noting that iridoids were not evidenced in this accession. Iridoids are considered chemotaxonomic marker in Lamiales, and, in contrast with a previous study on this species, the presence of aucubin was not confirmed. In addition, the presence of large amounts of rosmarinic acid (1) was unexpected for a species that does not belong to subfamily Nepetoideae.

Topics: Ajuga; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Antioxidants; Cinnamates; Depsides; Iridoid Glucosides; Iridoids; Italy; Medicine, Traditional; Neuroprotective Agents; Oleanolic Acid; Plant Extracts; Rosmarinic Acid; Triterpenes

A re-examination of Scrophularia canina L. confirmed the presence of iridoid glucosides considered as chemotaxonomic markers for the Scrophulariaceae family, like aucubin, harpagide and 8-O-acetylharpagide, besides the further presence of 8-epiloganic acid, which is, indeed, considered the biogenetic precursor of iridoids normally found in Scrophulariaceae, and was recognised here for the first time in the studied species. Also verbascoside and (E)-phytol were evidenced for the first time in S. canina. The former compound is an almost ubiquitous glycosidic phenyl-ethanoid, which attains systematic importance when in co-occurrence with iridoids, and its taxonomical implications were discussed. The latter compound, even though it is omnipresent, is interestingly endowed with several biological activities, which may give an additional reason for the traditional uses of this plant.

Topics: Classification; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Molecular Structure; Plant Extracts; Plant Stems; Scrophularia

1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

Topics: Animals; Chlorogenic Acid; Drugs, Chinese Herbal; Estrogens; Glucosides; Iridoid Glucosides; Iridoids; Lignans; Mice; Ovariectomy; Tissue Distribution

In this study we examined the inhibition of hepatic dyslipidemia by Eucommia ulmoides extract (EUE). Using a screening assay for BAX inhibition we determined that EUE regulates BAX-induced cell death. Among various cell death stimuli tested EUE regulated palmitate-induced cell death, which involves lysosomal BAX translocation. EUE rescued palmitate-induced inhibition of lysosomal V-ATPase, α-galactosidase, α-mannosidase, and acid phosphatase, and this effect was reversed by bafilomycin, a lysosomal V-ATPase inhibitor. The active components of EUE, aucubin and geniposide, showed similar inhibition of palmitate-induced cell death to that of EUE through enhancement of lysosome activity. Consistent with these in vitro findings, EUE inhibited the dyslipidemic condition in a high-fat diet animal model by regulating the lysosomal localization of BAX. This study demonstrates that EUE regulates lipotoxicity through a novel mechanism of enhanced lysosomal activity leading to the regulation of lysosomal BAX activation and cell death. Our findings further indicate that geniposide and aucubin, active components of EUE, may be therapeutic candidates for non-alcoholic fatty liver disease.

Topics: Animals; bcl-2-Associated X Protein; Cathepsin B; Cell Death; Diet, High-Fat; Enzyme Inhibitors; Eucommiaceae; Female; Humans; Iridoid Glucosides; Iridoids; Liver; Lysosomes; Non-alcoholic Fatty Liver Disease; Palmitates; Rats; Rats, Sprague-Dawley

Eucommia ulmoides Oliver is a natural product widely used as a dietary supplement and medicinal plant. Here, we examined the potential regulatory effects of Eucommia ulmoides Oliver extracts (EUE) on hepatic dyslipidemia and its related mechanisms by in vitro and in vivo studies. EUE and its two active constituents, aucubin and geniposide, inhibited palmitate-induced endoplasmic reticulum (ER) stress, reducing hepatic lipid accumulation through secretion of apolipoprotein B and associated triglycerides and cholesterol in human HepG2 hepatocytes. To determine how EUE diminishes the ER stress response, lysosomal and proteasomal protein degradation activities were analyzed. Although proteasomal activity was not affected, lysosomal enzyme activities including V-ATPase were significantly increased by EUE as well as aucubin and geniposide in HepG2 cells. Treatment with the V-ATPase inhibitor, bafilomycin, reversed the inhibition of ER stress, secretion of apolipoprotein B, and hepatic lipid accumulation induced by EUE or its component, aucubin or geniposide. In addition, EUE was determined to regulate hepatic dyslipidemia by enhancing lysosomal activity and to regulate ER stress in rats fed a high-fat diet. Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemia.

Topics: Cholesterol; Endoplasmic Reticulum Stress; Eucommiaceae; Hep G2 Cells; Humans; Iridoid Glucosides; Iridoids; Liver; Lysosomes; Plant Extracts; Triglycerides

In this study, we report the isolation and identification of several compounds from Plantago sempervirens Crantz, collected in the protected area of Majella National Park. We examined the polar fraction, in particular the iridoidic one. Aucubin, caryoptoside, plantarenaloside and gardoside were isolated and identified. For the first time, in this species, 8-epiloganic acid was recognised. Also, verbascoside, a phenylethanoid glycoside, was recognised in this plant.

Topics: Glucosides; Iridoid Glucosides; Iridoids; Italy; Magnetic Resonance Spectroscopy; Phenols; Plantago; Spectrometry, Mass, Electrospray Ionization

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

Five new unsaturated iridolactones 3-7 related to natural cytotoxic oxylipins, Tei 9826, and iridolactone 2, were prepared by parallel synthesis from natural aucubin. It was found that perpivaloyl iridoid glucosides 2, 3, and 4 were markedly cytotoxic against both L1210 and KB-3-1 cell lines.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cyclopentanes; Drug Design; Glucosides; Humans; Inhibitory Concentration 50; Iridoid Glucosides; Iridoids; Mice; Structure-Activity Relationship

In this study, the neuroprotection of aucubin and its mechanism were evaluated in the rat model of diabetic encephalopathy. Diabetes mellitus (DM) rats were stratified by cognitive capability (CC), and assigned to four treatment groups for aucubin treatment (doses of 0, 1, 5 or 10 mg/kg aucubin), with a further two groups of non-DM rats ranked by CC as controls for aucubin (doses of 0 or 5 mg/kg aucubin). Neuroprotection was estimated by the indexes of behavior and histology. Behavioral testing was performed in a Y-maze. The surviving neurons in CA1-CA4 and subiculum (SC) of the hippocampus were counted under a microscope. In addition, the apoptotic neurons in the CA1 of the hippocampus were also examined by using TUNEL staining. In order to clarify the mechanism of aucubin's neuroprotection, the activities of endogenous antioxidants and nitric oxide synthase (NOS) together with the content of lipid peroxide in the hippocampus were assayed. The results proved that aucubin significantly reduced the content of lipid peroxide, regulated the activities of antioxidant enzymatic and decreased the activity of NOS. All these effects indicated that aucubin was a potential neuroprotective agent and its neuroprotective effects were achieved, at least in part, by promoting endogenous antioxidant enzymatic activities.

Topics: Animals; Antioxidants; Brain Diseases; Cognition Disorders; Diabetes Mellitus, Experimental; Glucosides; Hippocampus; Iridoid Glucosides; Iridoids; Lipid Peroxides; Male; Malondialdehyde; Neurons; Neuroprotective Agents; Nitric Oxide Synthase; Rats; Rats, Wistar

In a greenhouse experiment using Plantago lanceolata, plants grown with different arbuscular mycorrhizal (AM) fungal species differed in constitutive levels of chemical defense depending on the species of AM fungi with which they were associated. AM fungal inoculation also modified the induced chemical response following herbivory by the specialist lepidopoteran herbivore Junonia coenia, and fungal species varied in how they affected induced responses. On average, inoculation with AM fungi substantially reduced the induced chemical response as compared with sterile controls, and inoculation with a mixture of AM fungi suppressed the induced response of P. lanceolata to herbivory. These results suggest that AM fungi can exert controlling influence over plant defensive phenotypes, and a portion of the substantial variation among experimental tests of induced chemical responses may be attributable to AM fungi.

Topics: Analysis of Variance; Animals; Butterflies; Feeding Behavior; Glomeromycota; Glucosides; Iridoid Glucosides; Iridoids; Larva; Mycorrhizae; North Carolina; Plantago

Two saponins: scrokoelziside A (1), scrokoelziside B (2), one iridoid glycoside, eurostoside (3), and two flavonoids: nepitrin (4) and homoplantaginin (5), were isolated from the leaves of Scrophularia ningpoensis for the first time. Moreover, eight known compounds: cane sugar (6), harpagide (7), aucubin (8), 6-O-methylcatalpol (9), harpagoside (10), angoroside C (11), beta-sitosterol (12) and beta-sitosterol glucoside (13) were isolated from the roots of S. ningpoensis. Furthermore, the antimicrobial activity of the extracts of the leaves of S. ningpoensis and the 10 compounds (1, 2, 3, 4, 5, 7, 8, 9, 10, 11) was studied in vitro against eight reference strains of bacteria by using the disc-diffusion method and micro-well dilution assay. The extracts of leaves and scrokoelziside A are effective against beta-haemolytic streptococci but had no effect against other strains. The extract of roots and other compounds showed no activity against all bacterial strains at the test concentration.

Topics: Anti-Infective Agents; Bacteria; Flavonoids; Glucosides; Glycosides; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Luteolin; Microbial Sensitivity Tests; Molecular Structure; Plant Extracts; Plant Leaves; Plant Roots; Pyrans; Scrophularia; Sitosterols; Triterpenes

This study elucidated possible mechanisms for the different anti-inflammatory potencies exhibited by the water extracts of Eucommia ulmoides bark and Plantago asiatica seeds, which contain various iridoids. Water extracts of both herbal materials were tested in vitro with a battery of assay models: lipopolysaccharide-induced thromboxane B(2) for cyclooxygenase-1 (COX-1), prostaglandin E(2) for cyclooxygenase-2 (COX-2), the translocation of nuclear factor-kappaB (NF-kappaB), and tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) production in RAW 264.7 cells. The contents of the iridoid glycosides, aucubin (AU), catalpol (CA), and geniposide (GE), were quantified by high-performance liquid chromatography (HPLC). Neither E. ulmoides nor P. asiatica suppressed the COX-1 enzyme. P. asiatica significantly inhibited COX-2 (concentration required for 50% inhibition [IC(50)] = 8.61 (microg/mL), TNFalpha (IC(50) = 9.63 (microg/mL), and NO (IC(50) = 8.65 (microg/mL) production. P. asiatica blocked the translocation of NF-kappaB from the cytosol to the nucleus. E. ulmoides suppressed only the COX-2 enzyme (IC(50) = 9.92 (microg/mL). The results of the HPLC analysis revealed that P. asiatica contained three iridoid glycosides, AU, CA, and GE. E. ulmoides contained CA and GE, but no AU was detected. The difference in the anti-inflammatory potencies of E. ulmoides and P. asiatica appears to be dependent on the presence of AU. Considering the IC(50) values, both herbal extracts exhibit modest and less potent anti-inflammatory activities than common synthetic non-steroidal anti-inflammatory drugs.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Eucommiaceae; Glucosides; Glycosides; Inflammation Mediators; Iridoid Glucosides; Iridoids; Mice; Plant Extracts; Plantago; Seeds

X-ray diffraction analyses of iridoid glycoside aucubin (1) and its aglycone aucubigenin (2) are reported. It was found that crystals of 1 are orthorhombic, with P2(1)2(1)2(1) space group, both cyclopentane ring and pyran ring adopt envelope conformations, and the Glc moiety is in the (4)C(1) conformation. Crystals of 2 are monoclinic, with space group P2(1), the cyclopentane and pyran rings also adopt the envelope conformation. The absolute configurations of 1 and 2 were also determined. Intensive O-H . . . O hydrogen bonds in both crystal lattices were observed.

Topics: Crystallography, X-Ray; Glucosides; Hydrogen Bonding; Iridoid Glucosides; Iridoids; Pyrans

To introduce the hairy root of Eucommia ulmoides, and screen put the excellent roots.. Hairy roots were obtained by infecting the different explants of E. ulmoides. Aucubin content was detected by HPLC.. The best transformation condition was embryonic axis infected by twenty minutes bacillus water dip-dye and three-days co-culture. Liquid culture was better than solid culture, and advantageous to accumulating of biomass and medical contents of hairy root. The E1 was the excellent roots.. Hairy root of E. ulmoides will be useful for the production of active components in aucubin.

Topics: Culture Media; Eucommiaceae; Glucosides; Iridoid Glucosides; Iridoids; Plant Roots; Tissue Culture Techniques

The cytotoxic activity of Stachys plants and of aucubin and harpagide against MCF7-breast adenocarcinoma, HeLa-cervix adenocarcinoma, A431-skin carcinoma of epithelial origin is reported in this study. Cisplatin and doxorubicin were use as reference compound.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Cytotoxins; Female; Glucosides; Humans; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Neoplasms; Phytotherapy; Plant Components, Aerial; Plant Extracts; Pyrans; Stachys

Topics: Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Evaluation, Preclinical; Glucosides; Humans; Iridoid Glucosides; Iridoids; Lung Neoplasms; Phytotherapy; Plant Extracts; Rats; Treatment Outcome; Tumor Cells, Cultured

Meridian tropism (MT) theory is a core principle of traditional Chinese medicine (TCM) theories and plays an essential role in instructing clinical pharmacy. The scientific explanation of MT theory will certainly further promote the reasonable, effective application of TCM. In view of the MT of Cortex Eucommiae (CE), aucubin (AU), the effective component of CE, was appointed and observed its distribution in rat tissues following a single intravenous (i.v.) dose. A simple, inexpensive and accurate high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of AU in rat tissues. Acceptable intra-day and inter-day precision and accuracy at high, medium and low concentration ranged from 0.56% to 4.18% and 0.73% to 4.53%, respectively. Good assay and extraction recoveries were obtained with a single and relatively fast precipitation protein step. The mean assay recovery and extraction recovery of AU were 94.7% and 90.9%, respectively. All tissues reached maximum AU level at 5 min post-dose. Considerable AU was present in kidney and liver. AU concentration was highest in kidney and remained much higher than that in other tissues over the experiment course. Lung, heart, spleen and testis were also detected to contain AU. The results closely conformed to the MT of CE and clearly demonstrated that AU was one of the material bases of the MT of CE.

Topics: Animals; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucosides; Iridoid Glucosides; Iridoids; Male; Rats; Rats, Sprague-Dawley; Reference Standards; Reproducibility of Results; Tissue Distribution

Oxidative stress has been suggested as a contributory factor in development and complication of diabetes. The aim of the present study was to determine the protective effect of aucubin on lipid peroxidation and activities of antioxidant defense systems and to conduct immunohistochemical evaluation of pancreas in streptozotocin-induced diabetic rats. Lipid peroxidation was determined by assessing the concentration of malondialdehyde and activities of antioxidant enzymes - catalase, glutathione peroxidase and superoxide dismutase in liver and kidneys of rats were determined. Changes of blood glucose and immunohistochemical evaluation on pancreas were also investigated as part of the pathology of diabetes. In our study, aucubin treatment lowered blood glucose. Diabetic rats exhibited an increase in the level of lipid peroxidation and decrease in activities of antioxidant enzymes in liver and kidneys as compared to control rats. Administration of aucubin to diabetic rats for 15 days significantly reversed damage associated with diabetes. In addition, diabetic rats showed an obvious decrease in insulin immunoreactivity and the number of beta cells in pancreas, but the pancreas of aucubin-treated rats were improved and the number of immunoreactive beta cells were significantly increased. These results indicated that aucubin may have value as a safe preventive or therapeutic agent against diabetes mellitus.

Topics: Animals; Antioxidants; Blood Glucose; Catalase; Diabetes Mellitus, Experimental; Glucosides; Glutathione Peroxidase; Immunohistochemistry; Insulin-Secreting Cells; Iridoid Glucosides; Iridoids; Lipid Peroxidation; Male; Malondialdehyde; Pancreas; Protective Agents; Rats; Rats, Wistar; Streptozocin; Superoxide Dismutase

Aucubin, an iridoid glycoside isolated from the leaves of Aucuba japonica, inhibits human non-small cell lung cancer A549 cells by blocking cell cycle progression in the G(0)/G(1) phase and inducing apoptosis. An ELISA showed that the G(0)/G(1) phase arrest is due to p53-mediated induction of p21. Enhancement of Fas and its two ligands, membrane-bound and soluble Fas ligand, may be responsible for the apoptotic effect induced by aucubin. The present study shows, for the first time, that the induction of p53 and activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of aucubin in A549 cells.

Topics: Antibodies; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Drug Evaluation, Preclinical; Fas Ligand Protein; fas Receptor; Gene Expression Regulation, Neoplastic; Genes, p53; Glucosides; Humans; Iridoid Glucosides; Iridoids; Lung Neoplasms

Hippocampal neuronal apoptosis accompanied by impairment of cognitive function occurs in primary diabetic encephalopathy. In this study, we investigated the neuroprotective mechanism of the iridoid glycoside, aucubin, using rats (n=8). Diabetes mellitus was induced in the rats by intraperitoneal (i.p.) injection of streptozotocin (60 mg/kg body weight). After 65 d, half of the DM rats were administered aucubin (5 mg/kg; i.p.) for 15 d, yielding treatment DM+A. A third group of rats received no streptozotocin or aucibin, and served as controls (CON). Encephalopathy was assessed using Y-maze behavioral testing. Rats were euthanized on Day 87, and hippocampi were excised for visual (light and transmission electron microscopic) and immunochemical (Western blot; immunohistochemical) assessments of the CA1 subfield for apoptosis and expression of regulatory proteins Bcl-2 and Bax. Treatment responses to all the parameters examined (body weight, plasma glucose, Y-maze error rates, pyramidal cell ultrastructure, proportions of apoptotic cells, levels of expression of Bcl-2 and Bax, and survivability of neuronal cells) were identical: there were highly significant differences between DM and CON groups (P<0.001), but the effects were significantly moderated (P<0.01) in DM+A compared with DM. These findings confirm the association of apoptosis with the encephalopathic effects of diabetes mellitus, and suggest a major role of the expression levels of Bcl-2 and Bax in the regulation of apoptotic cell death. All of the results suggest that aucubin could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.

Topics: Animals; Blotting, Western; Brain Damage, Chronic; Diabetes Complications; Diabetes Mellitus, Experimental; Glucosides; Immunohistochemistry; Iridoid Glucosides; Iridoids; Male; Microscopy, Electron, Transmission; Neuroprotective Agents; Rats; Rats, Wistar

Treatment of aucubin (1) with tert-butyldimethylsilyl chloride under alkaline conditions permitted regioselective silylation of either the primary hydroxyl groups at C-9 and C-6' or both primary hydroxyl groups and the secondary allylic hydroxyl group at C-6. Acetylation with acetic anhydride, followed by selective removal of the silyl groups and Mitsunobu reaction involving phthalimide as nitrogen donor, gave a stereospecific entry to aminoside antibiotic analogues: 10,6'-diamino-10,6'-dideoxyaucubin (16) and (6R)-6,10,6'-triamino-6,10,6'-trideoxyaucubin (17).

Topics: Amination; Anti-Bacterial Agents; Bacteria; Glucosides; Iridoid Glucosides; Iridoids; Microbial Sensitivity Tests; Molecular Structure; Stereoisomerism

Optimize the technic condition of Duzhong Jiangya prescription with Semi-bionic Extraction.. Using homogeneous design, under the same materials granularity, decoction temperature, consumption of water, filtration, concentration, and taking aucubin, hydrochloric acid stachydrine, maloicacid, baicalin, ethanol extract, dry extract as the indexes, the results were comprehensive considered to optimize the semi-bionic extraction condtions.. The optimized SBE extraction conditions are the following: pH values of the water for the thrice extraction is 5.845 3, 7.496 1, 8.011 7, and the total extraction time is 3.418 0 h.. Considering the fact of manufacture, the SBE extraction conditions are the following: pH values of the water for the thrice extraction is 6.0, 7.5, 8.0, and the thrice extraction time is 1.5, 1.0, 1.0 h.

Topics: Antihypertensive Agents; Drug Combinations; Drugs, Chinese Herbal; Eucommiaceae; Flavonoids; Glucosides; Hydrogen-Ion Concentration; Iridoid Glucosides; Iridoids; Leonurus; Plants, Medicinal; Proline; Prunella; Scutellaria baicalensis; Technology, Pharmaceutical; Time Factors; Triterpenes; Uncaria; Ursolic Acid

The monoterpenoid composition of Verbascum conocarpum and Scrophularia trifoliata, both endemic plants of Sardinia, was examined. The main chemotaxonomic markers of Scrophulariaceae, the iridoids aucubin, verbascoside and catalpol, were isolated.

Topics: Antineoplastic Agents, Phytogenic; Biomarkers; Classification; Glucosides; Humans; Iridoid Glucosides; Iridoids; Italy; Phenols; Phytotherapy; Plant Extracts; Quaternary Ammonium Compounds; Scrophularia; Verbascum

Ultraviolet-B (UVB) irradiation has been demonstrated to produce reactive oxygen species (ROS) in the cells and skin, which induces the synthesis of matrix metalloproteinases (MMPs), causing skin photoaging. Using the human skin fibroblast HS68 cell line in the present study, we investigated the photoprotective effects of aucubin from Eucommia ulmoides. Pretreatment with aucubin significantly inhibited the production of MMP-1 by 57% when compared to the UVB-irradiated cells. Additionally, the senescence-associated beta-galactosidase (SA beta-gal) activity was markedly decreased in the presence of aucubin, which indicates it as an antiphoto-induced aging compound. As the effect of aucubin was determined against ROS, the inhibited ROS formation and malondialdehyde (MDA) levels, and the increased cell viability and glutathione (GSH) level were observed with aucubin under UVB irradiation. Based upon these results, it was suggested that aucubin might play an important role in the cellular defense mechanism against UV radiation-induced photoaging. An understanding of the antioxidant properties of aucubin could, in part, act to elucidate its protective mechanism on the human skin photoaging.

Topics: beta-Glucosidase; Eucommiaceae; Fibroblasts; Free Radicals; Glucosides; Glutathione; Humans; Hydrogen Peroxide; Iridoid Glucosides; Iridoids; Matrix Metalloproteinase 1; Oxidative Stress; Penicillamine; Skin; Ultraviolet Rays

The discovery of new topoisomerase I inhibitors is necessary since most of the antitumor drugs are targeted against type II and only a very few can specifically affect type I. Topoisomerase poisons generate toxic DNA damage by stabilization of the covalent DNA-topoisomerase cleavage complex and some have therapeutic efficacy in human cancer. Two iridoids, aucubin and geniposide, have shown antitumoral activities, but their activity against topoisomerase enzymes has not been tested. Here it was found that both compounds are able to stabilize covalent attachments of the topoisomerase I subunits to DNA at sites of DNA strand breaks, generating cleavage complexes intermediates so being active as poisons of topoisomerase I, but not topoisomerase II. This result points to DNA damage induced by topoisomerase I poisoning as one of the possible mechanisms by which these two iridoids have shown antitumoral activity, increasing interest in their possible use in cancer chemoprevention and therapy.

Topics: Camptothecin; DNA Damage; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Enzyme Inhibitors; Glucosides; Humans; Iridoid Glucosides; Iridoids; Neoplasms; Pyrans; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Tumor Cells, Cultured

Of 30 herbal plants tested, the methanol extracts of Eucommia ulmoides (52%), Evodia officinalis (45%), and Pleuropterus multiflorus (41%) each showed a potent inhibitory effect on the matrix metalloproteinase-1 (MMP-1) production in ultraviolet B (UVB)-irradiated human fibroblasts. Aucubin was isolated as the MMP-1 inhibitor from E. ulmoides, and significantly suppressed the production of MMP-1 by nearly 57% compared to the control. It also reduced MMP-1 mRNA expression. These results suggest that aucubin is a photoprotective phytochemical, and could be used as a potential agent in preventing photoaging.

Topics: Eucommiaceae; Fibroblasts; Gene Expression Regulation, Enzymologic; Glucosides; Humans; Iridoid Glucosides; Iridoids; Matrix Metalloproteinase 1; Plant Extracts; Radiation-Protective Agents; RNA, Messenger; Skin; Ultraviolet Rays

The aim of this study was to evaluate the in vitro antioxidant activity of the methanol extract of Plantago bellardii All. aerial parts. This was assessed by two different tests, scavenging of 1,1-diphenyl-2-picrylhydrazil (DPPH) radical, and inhibition of lipid peroxidation on liposomes prepared from bovine brain extract. In both tests the extract showed a potent antioxidant effect. The characterization of the major compounds in the extract as rutin, geniposide and verbascoside was performed by isolation and HPLC comparison with authentic samples. They were quantified by HPLC for the flavonoids and colorimetry for iridoids. The compounds that contribute most to the antioxidant activity were shown to be verbascoside and rutin.

Topics: Antioxidants; Glucosides; Iridoid Glucosides; Iridoids; Molecular Structure; Phenols; Plant Extracts; Plantago; Pyrans; Rutin

To study the chemical constituents of Buddleja purdomii W. W Smith.. The constituents were isolated and purified by various chromatographic methods and structurally identified by spectral analysis.. 4 compounds were obtained as cryptomeridiol (I), aucubin (II), galactilol (III), daucosterol (IV).. All these compounds are obtained from this plant for the first time.

Topics: Buddleja; Galactitol; Glucosides; Iridoid Glucosides; Iridoids; Molecular Structure; Naphthalenes; Plants, Medicinal; Sitosterols

The novel iridoid glycoside 2 was prepared in six steps (15% overall yield) from natural aucubin (1) and fully characterized. Compound 2, which comprises the same conjugated cyclopentenone pharmacophore as known antitumor oxylipins and prostaglandins, displayed significant antiproliferative in vitro activity towards leukemia L1210 cells. The Michael addition of nucleophilic thiols to compound 2 occurred on a different position compared to classical delta7-prostaglandin A1 methyl ester. The resulting adducts 7a and 7b were fully characterized, and their MS fragmentation patterns were elucidated.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Dose-Response Relationship, Drug; Glucosides; Iridoid Glucosides; Iridoids; Mice; Molecular Structure

Plants are often attacked by multiple enemies, including pathogens and herbivores. While many plant secondary metabolites show specific effects toward either pathogens or herbivores, some can affect the performance of both these groups of natural enemies and are considered to be "generalized defense compounds". We tested whether aucubin and catalpol, two iridoid glycosides present in ribwort plantain (Plantago lanceolata), confer in vivo resistance to both the generalist insect herbivore Spodoptera exigua and the biotrophic fungal pathogen Diaporthe adunca using plants from P. lanceolata lines that had been selected for high- and low-leaf iridoid glycoside concentrations for four generations. The lines differed approximately three-fold in the levels of these compounds. Plants from the high-selection line showed enhanced resistance to both S. exigua and D. adunca, as evidenced by a smaller lesion size and a lower fungal growth rate and spore production, and a lower larval growth rate and herbivory under both choice and no-choice conditions. Gravimetric analysis revealed that the iridoid glycosides acted as feeding deterrents to S. exigua, thereby reducing its food intake rate, rather than having post-ingestive toxic effects as predicted from in vitro effects of hydrolysis products. We suggest that the bitter taste of iridoid glycosides deters feeding by S. exigua, whereas the hydrolysis products formed after tissue damage following fungal infection mediate pathogen resistance. We conclude that iridoid glycosides in P. lanceolata can serve as broad-spectrum defenses and that selection for pathogen resistance could potentially result in increased resistance to generalist insect herbivores and vice versa, resulting in diffuse rather than pairwise coevolution.

Topics: Adaptation, Physiological; Animals; Biological Evolution; Feeding Behavior; Fungi; Glucosides; Iridoid Glucosides; Iridoids; Plantago; Plants, Edible; Spodoptera

Studies on plant-defensive chemistry have mainly focused on plants in direct interaction with aboveground and occasionally belowground herbivores and pathogens. Here we investigate whether decomposers and the spatial distribution of organic residues in soil affect plant-defensive chemistry. Litter concentrated in a patch (vs. homogeneously mixed into the soil) led to an increase in the aucubin content in shoots of Plantago lanceolata. Earthworms increased total phytosterol content of shoots, but only when the litter was mixed homogeneously into the soil. The phytosterol content increased and aphid reproduction decreased with increasing N concentration of the shoots. This study documents for the first time that earthworms and the spatial distribution of litter may change plant-defensive chemistry against herbivores.

Topics: Animals; Aphids; Glucosides; Iridoid Glucosides; Iridoids; Nitrogen; Nitrogen Radioisotopes; Oligochaeta; Phytosterols; Plant Leaves; Plant Shoots; Plantago; Soil

To elucidate a possible mechanism for the anti-inflammatory action of iridoid glycosides, the effects of both aucubin (AU) and its hydrolyzed product (H-AU) by beta-glucosidase treatment were studied on the production of TNF-alpha in RAW 264.7 cells. H-AU suppressed the production of both mRNA for TNF-alpha and subsequent TNF-alpha protein in the culture, but AU did not. The production of TNF-alpha protein was inhibited in a dose-dependent manner with an IC (50) of 9.2 microM. In addition, treatment with H-AU blocked both the I-kappa B alpha degradation and the translocation of NF-kappa B from the cytosol fraction to the nuclear fraction (55 % inhibition) in the culture. However, treatment with H-AU did not affect the intracellular level of cAMP formed by forskolin treatment in human monocytes U937 culture, implying that there is no influence on the cAMP level in other cell systems. The present study indicates a possible justification for those medicinal plants containing iridoid glycoside that have been used for the treatment of inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Glucosides; Inhibitory Concentration 50; Iridoid Glucosides; Iridoids; Macrophages; Mice; NF-kappa B; Phytotherapy; Plant Extracts; Plant Leaves; Plantago; RNA, Messenger; Seeds; Tumor Necrosis Factor-alpha

Induction of allelochemicals is one way that plants efficiently deploy defenses against herbivory. In two separate experiments we investigated the time course of this inductive response and the importance of the timing of herbivory for Plantago lanceolata (Plantaginaceae). We found a localized induced response of catalpol and the ratio of catalpol to total iridoid glycosides in damaged leaves that was evident at d 6 after caterpillars of the specialist Junonia coenia were put onto the plants. On the whole plant level, we detected small, but significant changes in the iridoid glycoside metabolism of P. lanceolata on several different days following herbivory. We also found considerable change in the amounts of allelochemicals produced during P. lanceolata's ontogeny. This ontogenetic effect might help to explain some of the reasons why induction may be difficult to detect in P. lanceolata. We also investigated the importance of the timing of herbivory on P. lanceolata's inductive response, but neither herbivory after 5 wk of growth nor after 6 or 7 wk of growth induced an increase in aucubin or catalpol.

Topics: Glucosides; Iridoid Glucosides; Iridoids; Plant Leaves; Plantago; Time Factors

The absorption spectroscopic determination of aucubin by condensation with p-dimethylaminobenzaldehyde was optimized in this paper. A high sensitive method was established and the linearity range of the method was from 4.5 to 45 microg x mL(-1). The influences of the factors, such as the dosage of coloring agent, reaction time, heating temperature and the dose of acid etc., on the system were studied. And the result indicated that all of the factors had obvious effects on the system. The method has been applied to determining the content of aucubin in the extract of Eucommia olive with satisfactory results.

Topics: Catalysis; Dosage Forms; Eucommiaceae; Glucosides; Hydrogen Peroxide; Iridoid Glucosides; Iridoids; Pharmaceutical Preparations; Surface-Active Agents; Temperature; Time Factors

Antigen (Ag)-stimulated mast cells induce synthesis and production of cytokines including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 with proinflammatory and immune regulatory properties. Expression of TNF-alpha and IL-6 was regulated by a transcription factor, nuclear factor (NF)-kappaB. The iridoid glycoside, aucubin, has been found as a natural constituent of many traditional oriental medicinal plants. We studied the effect of aucubin on the TNF-alpha and IL-6 expression in Ag-stimulated rat basophilic leukemia (RBL)-2H3 mast cells. We show that aucubin inhibited Ag-induced TNF-alpha and IL-6 production and expression in a dose-dependent manner with IC(50) of 0.101 and 0.19 microg/ml, respectively. Maximal inhibition of TNF-alpha and IL-6 production was 73 +/- 4.3% and 88.8 +/- 5%, respectively. Aucubin also inhibited Ag-induced nuclear translocation of p65 subunit of NF-kappaB and degradation of IkappaBalpha. Inhibition of NF-kappaB activation by aucubin might be specific since activator protein-1 binding activity was not affected. In conclusion, these results suggest that aucubin is a specific inhibitor of NF-kappaB activation in mast cells, which might explain its beneficial effect in the treatment of chronic allergic inflammatory diseases.

Topics: Animals; beta-N-Acetylhexosaminidases; Blotting, Western; Cell Nucleus; Dose-Response Relationship, Drug; Glucosides; Histamine; I-kappa B Proteins; Immunohistochemistry; Inhibitory Concentration 50; Interleukin-6; Iridoid Glucosides; Iridoids; Microscopy, Fluorescence; NF-kappa B; NF-KappaB Inhibitor alpha; Rats; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Transcription Factor RelA; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

The plantain is used in herbal medicines and for pasturage. Two cultivars of plantain (Plantago lanceolata L.), Grasslands Lancelot and Ceres Tonic, were sown in spring. Changes in catalpol, aucubin, and acteoside concentrations in the leaves during the growing season and by drying after harvesting were quantitatively determined by high-performance liquid chromatography. The concentration of catalpol was relatively low, fluctuating between 1 and 2% of dry matter during the growing season, and there was no clear-cut seasonal change. From spring to midfall, the aucubin concentration increased from 2.1 to 4.8% in Grasslands Lancelot and from 1.0 to 2.7% in Ceres Tonic. These increases were gradual over the season, except for during midsummer, when aucubin concentrations were relatively constant. The acteoside concentration increased from 3.4 to 7.1% in Grasslands Lancelot and from 1.5 to 4.1% in Ceres Tonic over the course of the growing season, although in the summer it declined steadily to lows of 2.5% in Grasslands Lancelot and 1.9% in Ceres Tonic. Our data suggested that midfall was the appropriate time for harvesting plantain for medicinal use. The concentrations of the bioactive compounds steadily decreased in the initial stages of drying both under natural climatic conditions and at 60 degrees C. The development of processing methods to minimize the loss of bioactive compounds is imperative.

Topics: Chromatography, High Pressure Liquid; Climate; Desiccation; Glucosides; Iridoid Glucosides; Iridoids; Phenols; Plant Leaves; Plantago; Pyrans; Seasons

Aucubin, an iridoid glucoside, was investigated to determine whether it has a stimulating effect on alpha-amanitin excretion in alpha-amanitin intoxicated rats, and whether there is binding activity to calf thymus DNA. High-performance liquid chromatography (HPLC) analysis of alpha-amanitin in rat urine allowed quantitative measurement of the alpha-amanitin concentration with a detection limit of 50 ng/ml. In this system, a group treated with both alpha-amanitin and aucubin showed that alpha-amanitin was excreted about 1.4 times faster than in the alpha-amanitin only treated group. Our previous results showed that the toxicity of alpha-amanitin is due to specific inhibition of RNA polymerase activity and the resultant blockage of the synthesis of certain RNA species in the nucleus. However, no significant activity change on RNA polymerase from Hep G2 cells was observed when aucubin was treated with alpha-amanitin at any concentration tested. Nevertheless, aucubigenin inhibited both DNA polymerase (IC50, 80.5 microg/ml) and RNA polymerase (IC50, 135.0 microg/ml) from the Hep G2 cells. The potential of both alpha-amanitin and aucubin to interact with DNA were examined by spectrophotometric analysis. Alpha-Amanitin showed no significant binding capacity to calf thymus DNA, but aucubin was found to interact with DNA, and the apparent binding constant (Kapp) and apparent number of binding sites per DNA phosphate (Bapp) were 0.45 x 10(4) M(-1) and 1.25, respectively.

Topics: Amanitins; Animals; Brain; Cattle; DNA-Directed DNA Polymerase; DNA-Directed RNA Polymerases; Drug Interactions; Enzyme Inhibitors; Glucosides; Humans; Iridoid Glucosides; Iridoids; Mice; Rats; Rats, Sprague-Dawley; Thymus Gland; Tumor Cells, Cultured

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

Several methods for the extraction of two iridoid glycosides, catalpol and aucubin, from the plant matrix (Veronica longifolia leaves) were compared. Pressurized hot water extraction and hot water extraction were the most efficient isolation techniques for both. Pressurized liquid extraction and maceration with various organic solvents were also tested. Relative to the amounts extracted with hot water, ethanol extracted only 22% of catalpol and 25% of aucubin and pressurized hot water extracted 83% of catalpol and 92% of aucubin. The lowest relative standard deviations, 22% for catalpol and 8% for aucubin, were achieved with hot water extraction (13 repetitions), and the highest relative standard deviations, 76% for catalpol and 73% for aucubin, with pressurized liquid extraction (five repetitions). A fast capillary electrophoretic method was developed for the quantitative determination of catalpol and aucubin.

Topics: Chromatography, Micellar Electrokinetic Capillary; Glucosides; Hot Temperature; Iridoid Glucosides; Iridoids; Plant Leaves; Pressure; Pyrans; Solvents

The iridoid glucoside aucubin can irreversibly bind to proteins through the formation of its aglycone. In view of a possible involvement of these protein adducts in the toxicity of aucubin, we investigated the mechanism of binding of aucubin to proteins. [3H]aucubin in itself did not result in binding to protein whereas it covalently bound to rat serum albumin as a function of exposure time and dose in the presence of beta-glucosidase. The rate and extent of protein binding were significantly increased in the presence of the imine-trapping agent sodium cyanide. Oral administration of [3H]aucubin to rats showed that the total radioactivity in plasma remained at a similar level for up to 6 h once peak level was reached, suggesting that a considerable amount of radioactivity might be covalently associated with plasma proteins. The levels of radioactivity in the liver and kidney after oral dosing were higher than those after i.v. dosing. These results indicate that the open-chain aglycone of aucubin can form an imine bond with a nucleophilic site of the protein and these irreversible bindings may partially contribute to its biological and toxic effects.

Topics: Administration, Oral; Animals; beta-Glucosidase; Blood Proteins; Dose-Response Relationship, Drug; Glucosides; Imines; Injections, Intravenous; Iridoid Glucosides; Iridoids; Kidney; Liver; Male; Protein Binding; Pyrans; Rats; Rats, Sprague-Dawley; Serum Albumin; Sodium Cyanide; Tissue Distribution; Tritium

We have reported that collagen synthesis was stimulated by the administration of a hot water extract from the leaves of Eucommia ulmoides OLIVER, Eucommiaceae (Du-Zhong leaves) in false aged model rats. In this paper, we set out to examine the compounds in Du-Zhong leaves that stimulated collagen synthesis in false aged model rats. In experiment 1, a methanol extract of Du-Zhong leaves also stimulated collagen synthesis in aged model rats. An acetone fraction was derived from the methanol extract by silica gel chromatography in experiment 2. The acetone fraction mainly contained iridoides mono-glycosides such as geniposidic acid and aucubin. The administration of geniposidic acid or aucubin stimulated collagen synthesis in aged model rats in experiments 3 and 4 (significance (p<0.05)). The reported pharmacological effects of Du-Zhong leaves, including healing organs and strengthening bone and muscle, are closely related to collagen metabolism. It appears that geniposidic acid and aucubin are the actual compounds in Du-Zhong which caused the effect in our experiments.

Topics: Aging; Animals; Body Weight; Collagen; Drugs, Chinese Herbal; Glucosides; Granuloma; Iridoid Glucosides; Iridoids; Magnoliopsida; Male; Organ Size; Plant Leaves; Pyrans; Rats; Rats, Wistar

The iridoid glycosides including aucubin (AU), catalpol (CA), swertimarin (SW), and gardenoside (GA) are frequently found as natural constituents of many traditional oriental medicinal plants including Chinese herbs. Among these iridoid glycosides, AU was systematically studied for its potent liver-protective activities using experimental systems of hepatic damage. AU showed high liver-protective activity against carbon tetrachloride-induced hepatic damage in mice. Also AU showed significant protective activity against alpha-amanitin-induced hepatic damage in mice, and it prevented a depression of liver RNA biosynthesis caused by alpha-amanitin administration. Potent antidotal effects on mushroom poisoning in beagle dogs ingested with aqueous extract of Amanita virosa was observed; beagle dogs completely survived, even when AU administration was withheld for half an hour after mushroom poisoning. In addition, AU was found to suppress hepatitis B viral DNA replication in vitro. Conversion of AU to its aglycone form appeared to be a prerequisite step for an exhibition of such antiviral activity.

Topics: Amanita; Animals; Antiviral Agents; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Dogs; Drugs, Chinese Herbal; Female; Glucosides; Hepatitis B virus; Iridoid Glucosides; Iridoids; Liver; Mice; Microbial Sensitivity Tests; Mushroom Poisoning

The inhibition of ethoxy coumarin O-deethylase (ECOD) activity by aucubin and its aglycone was examined in a microsomal system and in freshly isolated hepatocytes. Aucubin was found to be inactive but the aglycone was found to be a potent time-dependent inhibitor of ECOD activity in both systems. The close structural similarity between the aglycone of aucubin and glutaraldehyde suggests a similar mechanism of enzyme inhibition through protein cross-linking by Schiff reactions. The similarity between the 2 compounds was demonstrated through their closely similar binding spectra to bovine serum albumin. The biological activities reported for the aglycone are suggested to be due to this similarity to glutaraldehyde.

Topics: 7-Alkoxycoumarin O-Dealkylase; Animals; Cattle; Cross-Linking Reagents; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Glucosides; Glutaral; In Vitro Techniques; Iridoid Glucosides; Iridoids; L-Lactate Dehydrogenase; Male; Microsomes, Liver; Molecular Structure; Protein Binding; Pyrans; Rats; Rats, Wistar; Schiff Bases; Serum Albumin, Bovine; Spectrophotometry, Ultraviolet

In vitro, the peracetates of penstemonoside, aucubin and catalpol, iridoids isolated from Parentucellia latifolia, antagonize the uterine muscular contractions induced by acetylcholine and calcium, in a similar way to papaverine. The antagonism is non-competitive against acetylcholine (pD2' values: 5.60 for the peracetates of penstemonoside, 5.74 for aucubin, 5.59 for catalpol, and 5.32 for papaverine) and competitive against calcium (pA2 values: 6.60 for the peracetates of penstemonoside, 6.34 for aucubin, 6.48 for catalpol, and 6.23 for papaverine). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the three iridoids. The reduction is similar for both phases. The antispasmodic activity of the three iridoids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, intracellular or both.

Topics: Acetylation; Animals; Female; Glucosides; In Vitro Techniques; Iridoid Glucosides; Iridoids; Male; Parasympatholytics; Plants; Pyrans; Rats; Uterus; Vas Deferens

A HPLC method for the determination of aucubin in P. asiatica, P. major and P. depressa was established. The mobile phase is MeOH-H2O (17:83). Good in producibility and high in rate of recovery, this method provides an effective way for the study of Plantago.

Topics: Chromatography, High Pressure Liquid; Glucosides; Iridoid Glucosides; Iridoids; Plantago; Plants, Medicinal

Aucubin, a promising hepatoprotecting iridoid glucoside, was given intravenously (iv), orally (po), intraperitoneally (ip), and hepatoportally (pv) to rats. A linear pharmacokinetic behavior was obtained after iv administation of 400-400 mg/kg of aucubin. The half-life of aucubin in the postdistributive phase (t1/2, beta), total-body plasma clearance (CLt), and volume of distribution (Vdss) were 42.5 min, 7.2 ml/min/kg, and 346.9 ml/kg, respectively, for a 40 mg/kg dose. There was no significant difference in the parameters as a reult of increasing dose. The partition coefficients of aucubin between n-octanol and buffers of pH 3.0-10.0 were low, while 18.5 +/- 1.3% of aucubin in whole blood partitioned into the blood cells. Plasma protein binding of aucubin was only 9%. The bioavailabilites of aucubin after administration at a dose of 100 mg/kg through pv, ip, and po routes were 83.5, 76.8, and 19.3%, respectively. The pH-stability profile indicated rapid degradation of aucubin at pH 1.2, 1.6, and 2.0, with degradation half-lives of 5.1, 5.8, and 14.8 hr, respectively, at 37 degrees C. Therefore, the low oral bioavailability of aucubin may be attributed to pH-instability in the gastric fluid, poor GI absorption due to low lipophilicity, and the possible metabolism in the GI mucosa and liver (so called first-pass effect).

Topics: Animals; Biological Availability; Blood Proteins; Drug Stability; Glucosides; Iridoid Glucosides; Iridoids; Male; Protein Binding; Rats; Rats, Inbred Strains; Solubility

Aucubin, an iridoid glucoside isolated from Aucuba japonica (Cornaceae), exhibited significant protective activity against alpha-amanitin intoxication in mice. When a single dose of aucubin was administered intraperitoneally, a 50% survival rate was obtained even when the treatment was withheld for 12 hr after alpha-amanitin administration. A possible mechanism of protective activity is partly due to a competitive effect of aucubin on alpha-amanitin inhibition of liver RNA biosynthesis.

Topics: Administration, Oral; Amanitins; Animals; Antidotes; Glucosides; Glycosides; Injections, Intraperitoneal; Iridoid Glucosides; Iridoids; Liver; Male; Mice; Mice, Inbred ICR; RNA

An iridoid glucoside, aucubin was isolated from Aucuba japonica leaves and its protective activities against CCl4-induced hepatotoxicity were evaluated by measuring the duration of hypnosis induced by hexobarbital after CCl4 challenge (0.2 ml/kg/day, po) and the levels of serum glutamic-oxalacetic (GOT) and serum glutamic-pyruvic transaminase (GPT). The duration of hypnosis for the saline control group, the CCl4 alone treated group and the aucubin plus CCl4 treated group was 24.8 +/- 8.5, 60.5 +/- 9.5 and 28.0 +/- 3.2 min, respectively. Treatment of mice with aucubin also effectively protected against CCl4-induced increased serum GOT and GPT activities. It was found that aucubin inhibited hepatic RNA and protein syntheses in vivo. Such inhibitory effects of aucubin might be responsible for protective activities against CCl4-induced liver damage.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Glucosides; Glycosides; Hexobarbital; Iridoid Glucosides; Iridoids; Liver; Mice; Protein Biosynthesis; RNA

1. A glycoside of the aucubin type has been isolated in crystalline form from Plantago and Buddleia species, and has been shown to be identical with catalpol (Lunn, Edward & Edward, 1962). Catalpol has not been found in the free state before, but occurs as its p-hydroxybenzoyl ester, catalposide, in the genus Catalpa. 2. A second glycoside of this type has been obtained in crystalline form from Buddleia, and has been shown to be a mono-O-methyl derivative of catalpol, for which the name ;methylcatalpol' is proposed. 3. Both Plantago and Buddleia species are known to contain aucubin. The concentrations of this glycoside and catalpol are comparable in Plantago. In Buddleia methylcatalpol predominates somewhat over catalpol. Yields of the individual glycosides were about 0.1% of the fresh weight of the leaves. 4. Bobbitt, Spiggle, Mahboob, Philipsborn & Schmid (1962) have suggested structures for catalposide and catalpol based on chemical and physical evidence, in particular on n.m.r. spectra. Reappraisal of this evidence and additional measurements have now confirmed these structures and show that the Buddleia glycoside is the 6-O-methyl derivative of catalpol.

Topics: Buddleja; Chemistry, Pharmaceutical; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Plant Leaves; Plantago; Plants, Medicinal; Research; Spectrum Analysis