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OBJECTIVE Vascular dementia(VaD)is associated with cerebral hypoperfusion,which results in long-term cognitive impairment and memory loss.Neuroin-flammation is an important mechanism of vascular demen-tia.Cornel iridoid glycoside(CIG)is the major active con-stituent isolated from the ripe fruit of Cornus officinalis.Previous studies have shown that CIG enhances neuro-logical function in VaD rats.In the present research,we attempted to clarify the molecular processes underlying the role of CIG on neuroinflammation in VaD.METHODS In vivo,we created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries(2VO).The rats were divided into sham operation,2VO,2VO + CIG(60 and120 mg·kg-1·d-1),and 2VO+ butylphthalide(100 mg·kg-1·d-1)groups and then treated rats with differ-ent concentrations of CIG.In vitro,BV2 microglia cells were induced with bacterial lipopolysaccharide(LPS)and interferon-γ(IFN-γ)to construct the model of microglias with analog neuroinflammation.Histopathology and biel-schowsky silver staining were used to detect myelin integrity and neuronal loss.Immunofluorescence was used to observe changes in microglia.Magnetic Luminex Assay was used to detect changes in inflammatory fac-tors.Western blotting,ELISA or calpain activity assay was used to measure the expression and activity of cal-pain,as well as the expression of NLRP3 inflammasome protein.Furthermore,NLRP3 overexpressing cells were used to further elucidate the potential anti-inflammatory molecular mechanism of CIG.RESULTS ① CIG improved neuronal impairment in the brain of 2VO rats.②CIG increased white matter(WM)integrity in 2VO rats.③ CIG reduced microglia inflammatory response in the cortex and hippocampus of 2VO rats.④ CIG inhibited calpain activity in the cortex and hippocampus of 2VO rats.⑤ CIG exerted anti-inflammatory effects on BV2 cells stimulated by LPS and IFN-γ.⑥ CIG Inhibited the expression and activity of calpain in LPS/IFN-γ-activated BV2 cells.⑦ The main component of CIG had a weak binding force to calpain1.⑧ CIG inhibited the activation of the NLRP3 inflammasome.⑨CIG reduced the activity of calpain induced by NLRP3 overexpression.CONCLU-SION CIG inhibits microglial polarization into a proinflam-matory state by attenuating the assembly of the NLRP3 inflammasome and calpain activation,thus reducing brain inflammation,WM injury,and the loss of neurons.To sum up,the present study suggests that CIG inhibits neuroinflammation.The NLRP3/calpain pathway may be the main pathway by which CIG protects against neuroin-flammation.
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Iridoid glycosides are widely distributed in Chinese materia medica (CMM) with various biological activities such as anti-inflammation. They are also used as quality control constituents in some Chinese medicines. Iridoid glycosides are usually divided into nine-carbon skeleton iridoid glycoside type, ten-carbon skeleton iridoid glycoside type, and secoiridoid glycoside type. In this paper, 15 representative iridoid glycosides from three types which are received extensive attention (including geniposide, catalpol, gentiopicroside, etc) have been selected. Their anti-inflammatory effects and possible related mechanisms are summarized to find out the acting feature of different types. Through comparing the structures and function characteristics, it was concluded that the anti-inflammatory effects of iridoid glycosides were mostly related to NF-κB pathway and MAPK pathway. They have obvious inhibitory effects on TNF-α, IL-6, and IL-1β inflammatory factors, some of which could play a role by reducing the expression of iNOS and COX-2 in NLRP3, Nrf2/HO-1, PI3K, and other pathways. From the structure-activity relationship, the double bond on the cyclopentane, the C-11 substituent and the bond formation after ring opening in iridoid glycosides all have important effects on its anti-inflammatory activities.
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OBJECTIVE: To study the chemical constituents from the rhizome of Phlomis umbrosa. METHODS: Chemical constituents were isolated by repeated column chromatographies(Toyopearl HW-40C and preparative HPLC). The structures were elucidated on the basis of spectral data analysis. RESULTS: Seventeen compounds were isolated from the 95% ethanol aqueous extract of P. umbrosa and the structures were identified as lamalbid (1), phloyoside (2), phloyoside Ⅱ(3), 6-O-acetylshanzhiside methyl ester(4), shanzhiside methyl ester (5), 8-acetylshanzhiside methyl ester(6), sesamoside(7), 5,9-epi-7,8-didehydropenstemoside(8), verbascoside(9), isoverbascoside(10), forsythoside B(11), alyssonoside(12), echinacoside(13), (17S)-2α,3α,18β,23,24-pentahydroxy-19(18→17)-abeo-28-norolean-12-en-21-one(14),(17S)-19(18→17)-abeo-12-en-28-norolean-2α,3α,18β,19,23,24-hexaol (15), friedelin(16), and daidzein(17). CONCLUSION: All compounds are isolated from this plant for the first time, compounds 1, 8, 16-17 are isolated from genus Phlomis for the first time.
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As a large category of natural products widely present in traditional Chinese medicine, iridoid glycosides have multiple pharmacological activities. Recent researches suggest that iridoid glycosides mainly exist in the forms of original form, aglycone and a series of their Ⅰ and Ⅱ metabolites under the biotransformation effect, and their metabolites have been proved to have multiple pharmacological activities. The research progress on metabolism and metabolite activities of several iridoid glycosides would be reviewed in this article, to provide a theoretical basis for the further development and utilization of iridoid compounds and their metabolites.
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Humans , Drugs, Chinese Herbal , Metabolism , Pharmacology , Iridoid Glycosides , Metabolism , PharmacologyABSTRACT
Objective: To investigate the chemical constituents of n-butanol fraction of the ethanol extracts from spray of Gentianae szechenyii. Methods: The chemical constituents were isolated and purified by repeated preparative high-performance liquid chromatography. The structures of the isolated compounds were identified on the basis of extensive spectroscopic techniques. Results: Six compounds were obtained in n-butanol fraction of the ethanol extracts from G. szechenyii and identified as gentizechenlioside A (1), szechenyin A (2), isoscoparin-2″-O-glucopyranoside (3), isoscoparin (4), gentiournosides D (5), and depressine (6). Conclusion: Compound 1 is a new iridoid glycoside which named as gentizechenlioside A.
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Glucagon-like peptide-1 (GLP-1) receptors belong to the class B of G protein coupled-receptors and are expressed in pancreas,lungs,GI tract,kidneys,heart and the central nervous system.During episodes of hyperglycemia activation of GLP-1 receptors located on pancreas islet β-cells facilitates insulin release and increases insulin sensitivity to regulate blood sugar.In the central nervous system,activation of GLP-1 receptors produces neuroprotection and analgesia.In this mini-review,we have summarized our recent work:1) identification of microglial GLP-1 receptor/IL-10/ β-endorphin pathway in the spinal cord;2) discovery of the mechanisms of activation of GLP-1 receptors by which analgesic Lamiophlomis rotata and its effective ingredients iridoid glycosides produce antinociception.Our work highlight that spinal microglial GLP-1 receptor might be a human-demonstrated target for the treatment of chronic pain.
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OBJECTIVE: To develop a method for simultaneous determination of six iridoid glycosides from Cymbaria dahurica.METHODS: Cymbaria dahurica collected from different regions were determined by HPLC. The separation was performed on Inertsil ODS-SP column (4.6 mm×250 mm,5 μm) at 30 ℃ by gradient elution with CH3OH-H2O as the mobile phase, with the detection wavelength set at 210 nm.RESULTS: Under the chromatographic conditions adopted in this study, all the calibration curves exhibited good linearity (r>0.999 4) in a relatively wide concentration range. The recovery of the method was within the range of 95.0%-98.0%, and the RSD was less than 3%. The contents of all the compounds (S1-S6) in samples from different habitats varied significantly.CONCLUSION: The quantitative method for evaluating the quality of Cymbaria dahurica is established and can be used for the quality control of Cymbaria dahurica.
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Alzheimer's disease (AD) is the most common neurodegenerative disease in the aging population. Abnormal hyperphosphorylation of tau is the main cause of AD. Protein phosphatases 2A (PP2A) can increase the hyperphosphorylation of tau. Cornel iridoid glycoside (CIG) is one of the main components extracted from Cornus of ficinalis. The aim of the present study was to investigate the effects and the underlying mechanisms of CIG on enhancing PP2A activity. SK-N-SH cells were exposed to 20 nmol·L-1 okadaic acid (OA, an inhibitor of PP2A) for 6 h to induce the hyper-phosphorylation of tau, in order to define the effect of CIG on the activity of PP2A and posttranslational modification of PP2A catalytic subunit C (PP2Ac). We found that OA significantly decreased PP2A activity, increased the phosphorylation of PP2Ac, and enhanced tau hyper-phosphorylation. Pre-incubation of CIG significantly attenuated the OA-induced tau hyper-phosphorylation at Ser 199/202 and Ser 396, and recovered the activity of PP2A. CIG inhibited PP2Ac phosphorylation at Tyr 307 and increased Src phosphorylation. In conclusion, the mechanism of CIG inhibition of tau hyper-phosphorylation was activation of PP2A to reduce the level of p-Src for a reduction of PP2Ac phosphorylation at Tyr307.
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This study is to develop an UPLC-PDA method for determination of 10 major components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity UPLCR BEH C₁₈（2.1 mm ×100 mm,1.7 μm）, and the column temperature was at 30 ℃. The mobile phase consists of water containing 0.2% phosphoric acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.4 mL•min⁻¹. The detection wave length was set at 237 and 325 nm, and the injection volume was 1 μL in the UPLC system. The linear range of 10 detected compounds were good (r≥0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of ten major components in P. hookeri.
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OBJECTIVE: To study the chemical constituents of Yao medicine, Zhongliuteng, the stems of Pileostegia tomentella. METHODS: The chemical constituents were isolated and purified by silica gel chromatography repeatedly, and their structures were identified by spectral analysis and chemical METHODS. RESULTS: Thirteen compounds were isolated from the stems of P. tomentella and the structures were identified as 1-O-(β-D-glucosyl)-2-[2-methoxy-4-(ω-hydroxypropyl) phenoxy]propan-3-ol(1), (+)-lyoniresinol-3a-O-β-D-glucopyranoside (2), syringin (3), coniferin (4), dihydroconiferin (5), but-3-enyl-β-D-glucoside (6), 4-(2, 3-dihydroxypropyl)-2, 6-dimethoxy phenyl β-D-glucopyranoside (7), nikoenoside (8), protocatechuic acid ethyl ester (9), 8-methoxy coumarin-7-O-β-D-glucopyranoside (10), 6-O-R-L-rhamnopyranosyl-β-D-glucopyranoside methyl salicylate (11), nicotinamide (12), and 3, 5-di-O-caffeoyl quinicacid methyl ester (13). CONCLUSION: All compounds were obtained from the genus for the first time.
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Objective To develop a method for determination of iridoid glycosides in Morinda officinalis How.and optimize the extraction methods for iridoid glycosides in Morinda officinalis How.Methods The iridoid glycosides, including monotropein, deacetyl asperulosidic acid,asperulosidic acid and asperuloside as standards, HPLC method was developed to determine the content of iridoid glycosides in Morinda officinalis How.The separation was performed on Venusil MP C18 (250 mm×4.6 mm, 5 μm) column.The mobile phase was acetonitrile (A)-0.2% phosphoric acid and 0.01 disodium hydrogen phosphate buffer salt (B) with gradient elution (0-12 min, 1%-2% A;12-30 min, 2%-25% A).The detection wavelength was 235 nm.The flow rate was set at 1.0 ml/min and the column temperature at 25 ℃.The injection volume was 20 μl.Single factor analysis and orthogonal test were used to optimize extraction method of iridoid glycosides in Morinda officinalis How.Results Monotropein, deacetyl asperulosidic acid, asperulosidic acid and asperuloside showed good linearity (r>0.999 5) in the ranges of 0.375-12 μg, 0.13-4.16 μg, 0.016-0.516 μg and 0.012-0.384 μg, respectively.This validated method has good repeatability, precision, recovery and stability.It was conformed to meet the requirements and regulation.The optimal extraction method included soaking the raw materials with 16 times of 10% ethanol for 9 h, and then extraction by percolation with the flow rate of 0.8 BV/h.Conclusion The HPLC method sensitively and precisely determined the content of iridoid glycosides in Morinda officinalis How.The optimized extraction method extracted these constituents effectively.
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Abstract A new iridoid glycoside, barlupulin C methyl ester (1), together with two known phenylethanoid glycosides (2 and 3) and three known simple phenolic glycosides (4-6) were isolated from the aerial parts of Barleria lupulina Lindl., Acanthaceae. The structure of the new compound (1) was elucidated through 1D and 2D NMR spectroscopic data, and HR-ESIMS. Interestingly, compound (1) has a formate group attached to the C-6 hydroxy group of the glucose unit. Compounds 2-6 were identified as poliumoside (2), decaffeoylacteoside (3), protocatechuic acid 4-O-β-glucoside (4), vanillic acid 4-O-β-glucoside (5), and leonuriside A (6) on the basis of NMR spectroscopic data analyses and comparison with those reported in the literature. Compounds 3-6 were isolated from B. lupulina for the first time.
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The present study was designed to investigate the non-alkaloid compounds from the leaves and stems of Vinca major cultivated in Yunnan Province, China. The compounds were isolated using chromatographic techniques. The structures were elucidated by 1D- and 2D-NMR spectroscopic methods in combination with UV, IR, and MS analyses. The 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging activity of Compounds 1-7 were evaluated. One new iridoid glycoside (compound 1), together with 11 known compounds, were isolated from Vinca major. Compounds 1, 5, and 6 showed moderate DPPH-scavenging activity, with IC50 values being 70.6, 32.8, and 62.2 μmol·L(-1), respectively. In conclusion, compound 1 is a newly identified iridoid glycoside with moderate antioxidant activity.
Subject(s)
Antioxidants , Pharmacology , Iridoid Glycosides , Chemistry , Pharmacology , Plant Leaves , Chemistry , Plant Stems , Chemistry , Vinca , ChemistryABSTRACT
Objective: To study the chemical constituents of Yao medicine Zhongliuteng, the canes of Pileostegia tomentella. Methods: The chemical constituents were isolated and purified by silica gel chromatography repeatedly from the canes of P. tomentella and their structures were identified by spectral analysis and chemical methods. Results: Sixteen compounds were isolated from the canes of P. tomentella and their structures were identified as loganic acid (1), 4-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (4S)-4-hydroxyl-β-ionone (2), resorcinol (3), daphnin (4), skimmin (5), umbelliferone (6), vogeloside (7), diethyl phthalate (8), secologanin (9), secologanin dimethyl acetal (10), sweroside (11), foliasalacioside B (12), benzyl-O-β-D-apiofuranosyl-(1″→6')-β-D-glucopyranoside (13), maltose (14), glucose (15), and daucosterol (16). Conclusion: All compounds are obtained from the plant for the first time, and all compounds are also obtained from the plants of Pileostegia Hook. f. et Thoms. for the first time except compounds 5, 6 and 16.
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OBJECTIVE: To study the chemical constituents of Swertia binchuanensis. METHODS: The constituents were isolated and purified by column chromatography of silica gel. Their structures were identified on the basis of spectral analysis and chemical properties. RESULTS: Five compounds are isolated and identified as 7-O-[α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl]-1, 8-dihydroxy-3-methoxyxanthone(1), 3-O-β-D-glucopyranosyl-1,8-dihydroxyl-5-methoxyxanthone(2), 7-O-β-D-glucopyranosyl-1,8-di-hydroxyl-3-methoxyxanthone(3), amarogentin(4), and amaroswerin(5). CONCLUSION: All of the compounds were isolated from S. binchuanensis for the first time.
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OBJECTIVE: To investigate the chemical constituents from the whole plants of Lagopsis supina. METHODS: The compounds were isolated and purified by various column chromatography, and their structures were identified based on their physiochemical properties and spectroscopic data. RESULTS: Thirteen compounds were isolated from the n-hexane, dichloromethane, and water extracts of the whole plants of Lagopsis supina by using various chromatographic methods. Their structures were identified as phytol(1), daucosterol(2), 8-O-acetylharpagide(3), antirrinoside(4), ajugoside(5), ajugol(6), harpagide(7), 1-O-caffeoyl-β-D-glucopyranose(8), 1-O-coumaroyl-β-D-glucopyranose(9), 2-hydroxy-5-(2-hydroxyethyl)phenyl-1-O-β-D-glucopyranoside(10), methyl 2-O-β-D-glucopyranosylbenzoate(11), adenosine(12), and sucrose(13), respectively. CONCLUSION: Compounds 1 and 3-13 are isolated from the plants of Lagopsis genus for the first time.
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OBJECTIVE: To compare the contents of three iridoid glycosides between Gardenia jasminoides and charred Gardenia jasminoides. METHODS: The contents of three iridoid glycosides (G1, G2, G3) were determined simultaneously by HPLC on Agilent C18(2) column at 35°C with acetonitrile-0.5% formic acid (18:82) as the mobile phase. The detection wavelength was set at 238, and 312 nm, and the flow rate was 1.0 mL · min1. RESULTS: The linear regression coefficients of the three components were greater than 0.9992, and the average recoveries were 101.93%, 102.44% and 100.23%, respectively. The contents and the total content of the three iridoid glycosides in Gardenia jasminoides all significantly decreased after being charred. CONCLUSION: The charring process has inconsistent effect on the three components, This study preliminarily reveals the change rule of Gardenia jasminoides during the charring process.
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OBJECTIVE: To study the chemical constituents in the fruits of Gardenia jasminoides var. radicans Makino. METHODS: Percolation with alcohol and liquid-liquid extraction methods were used to extract the constituents. And silica gel, reverse-phase octadecylsilyl(ODS), and sephadex LH-20 chromatographic methods were applied to isolate and purify compounds. MS, NMR spectroscopic methods were used to elucidate their structures. RESULTS: Ten compounds were isolated from the ethyl acetate fraction of the ethanolic extract of fruits from Gardenia jasminoides var. radicans Makino, and their structures were identified as seven iridoids: geniposide (1), 6α-hydrogeniposide (2), 6β-hydrogeniposide (3), 6α-methoxygeniposide (4), 6β-methoxygeniposide (5), 2'-O-(4″-Hydrooxycinnamoyl) mussaenosidic acid(6), 6″-O-trans-p-coumaroylgenipin genitiobioside(7); two quinic acid derivatives: 3, 5-di-O-caffeoyl-4-O-(3-hydroxyl-3-methyl) glutaroylquinic acid(8), methyl 3, 5-di-caffeoyl-4-O-(3-hydroxy-3-methyl)-glutaroylquinate(9); and one flavonoid: quercetin-3-O-β-D-glucopyranoside(10). CONCLUSION: Compounds 3-10 are isolated from Gardenia jasminoides var. radicans Makino for the first time.
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Objective: To study the chemical constituents from 60% ethanol extract of Lonicerae Flos. Methods: Chromatographic methods were used for the isolation and purification. The structures were identified on the basis of spectroscopic analysis. Results: Six compounds were isolated from Lonicerae Flos. They were identified as demethylsecologanol-7-O-arabinoside (1), 8-epiloganic acid (2), vogeloside (3), sweroside (4), secologanoside (5), and secoxyloganin (6). Conclusion: Compound 1 is a new iridoid glycoside named secologanoside A.
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OBJECTIVE: To establish a high performance capillary electrophoresis (HPCE) method for simultaneous determination of catalpol, aucubin, harpagide, harpagoside, acteoside and cinnamic acid in Scrophularia ningpoensis of different batches. METHODS: 60 mmol · L-1 sodium borate was used as buffer solution (pH 9.3), uncoated fused silica capillary (64.5 cm × 75 μm id, 56 cm of effective length) was used, separation voltage was 20 kV, detection wavelength was 210 nm, column temperature was maintained at 25°C, and the sample was injected at 50 kPa, 6s. RESULTS: Six index components showed good linearity (r > 0.9971) in the range of the tested concentration, and the average recoveries of the method were between 97.05%-103.43%. CONCLUSION: The method is simple, accurate and reproducible, and can be used for quality control of Scrophularia ningpoensis. Copyright 2012 by the Chinese Pharmaceutical Association.