A new iridoid glycoside from Gardenia jasminoides

A new iridoid glycoside, 6＇-O-sinapoylgeniposide, was isolated from Gardeniajasminoides Ellis and its structure was elucidated on the basis of 1D and 2D NMR, HR-ESI-MS techniques.

Iridoid Glycosides from Buddleja lindeyana

Aim To study the chemical constituents of Buddleja lindeyana. Methods The constituents were separated and purified by different methods of chromatography, and their structures were elucidated by IR, MS and NMR. Results Three iridoid glycosides and two other compounds were isolated from Buddleja lindeyana. Their structures were elucidated to be 6-O-feruloylajugol ( 1 ), erythro-6-oxo-4′-( 3-methoxyl-4-hydroxyphenylglycol-8')-feruloylaj-ugol ( 2 ), threo-6-oxo-4′-(3-methoxyl-4-hydroxyphenylglycol-8')-feruloylajugol ( 3 ), tetra-cosanoic acid 2,3-dihydroxypropyl ester (4), and galactitol (5). Conclusion All the compounds have been isolated from this plant for the first time. Compounds 1, 2 and 3 have protective effect agains MPP+ -induced apoptosis.

A New Iridoid Glycoside and a New Iridoid from Pedicularis kansuensis f. albiflora

A new iridoid glycoside 1 and a new iridoid 2 were isolated from the whole plant of Pedicularis kansuensis f. albiflora. Their structures were elucidated by spectroscopie methods.

Cornel Iridoid Glycoside Suppresses Hyperactivity Phenotype in rTg4510 Mice through Reducing Tau Pathology and Improving Synaptic Dysfunction

rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer’s disease(AD).Besides cognitive impairments,rTg4510 mice also show abnormal hyperactivity behavior.Cornel iridoid glycoside(CIG)is an active ingredient extracted from Cornus officinalis,a traditional Chinese herb.The purpose of the present study was to investigate the effects of CIG on the emotional disorders such as hyperactivity,and related mechanisms.The emotional hyperactivity was detected by locomotor activity test and Y maze test.Immunofluorescent and immunohistochemical analyses were conducted to measure neuron loss and phosphorylated tau.Western blotting was used to detect the expression of related proteins.The results showed that intragastric administration of CIG for 3 months decreased the hyperactivity phenotype,prevented neuronal loss,reduced tau hyperphosphorylation and aggregation in the amygdala of rTg4510 mice.Meanwhile,CIG alleviated the synaptic dysfunction by increasing the expression of N-methyl-D-aspartate receptors(NMDARs)subunits GluN1 and GluN2A andαamino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunits GluA1 and GluA2,and increased the level of phosphorylated Ca2+/calmodulin dependent protein kinase IIα(p-CaMK IIα)in the brain of rTg4510 mice.In conclusion,CIG may have potential to treat the emotional disorders in tauopathies such as AD through reducing tau pathology and improving synaptic dysfunction.

A new iridoid glycoside from Veronica sibirica

A new iridoid glycoside,versibirioside（1）,and a known iridoid glycoside,verbaspinoside（2）,were isolated from the whole plant of Veronica sibirica L.Their structures were elucidated by spectroscopic methods,including 2D-NMR spectra.

Cornel Iridoid Glycoside Regulates Modification of Tau and Alleviates Synaptic Abnormalities in Aged P301S Mice

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

TWO NEW IRIDOID GLYCOSIDES FROM PEDICULARIS PLICATA

Two new iridoid glycosides,plicatoside A and plicatoside B,were isolated from whole plants of Pedicularis plicata.Their structures were identified as 2'-O-β-D-glucosyl ixoroside and 4'-O-β-D-xylosyl mussaenoside by means of chemical evidence and spectral data.

Cornel iridoid glycoside inhibits PP2Ac demethylation by regulationg PME-1

OBJECTIVE PP2Ac demethyl⁃ation is regulated by LCMT(a specific leucine carboxyl methyltransferase catalyzing methyla⁃tion of PP2A)and PME(a specific methylester⁃ase catalyzing demethylation of PP2A.This study was to investigate the mechanism of Cor⁃nel iridoid glycoside(CIG)on PP2A catalytic sub⁃unit C(PP2Ac).METHODS Recombined lentivi⁃rus vector was used to deliver PME-1 genetic materials into N2a cells or transfected LCMT-1 siRNA into N2a cells to block the expression of LCMT-1.Twenty-four hours later,cells were rinsed twice with cold PBS(pH 7.4)and CIG at different concentrations(50,100 and 200 g·L^(-1),respectively)were added for 24 h.Western blotting was used to PP2Ac,demethylaion/methylation PP2Ac,LCMT-1 and PME-1.The ac⁃tivity of PP2A was detected by a biochemical as⁃say.RESULTS①Lentivirus transferred PME-1 was expressed at high level in the N2a cells after transduction.Correspondingly,the demethylation of PP2Ac was increasing and PP2A activity was decreasing after transduction.Treatment with CIG for 24 h reversed the increase of PME-1 and demethylation of PP2Ac without influencing LCMT-1 expression.PP2A activity was also sig⁃nificantly enhanced in CIG treatment group,compared with the cells after PME-1 transduc⁃tion.②LCMT-1 siRNA significantly decreased LCMT-1 expression.CIG did not affect LCMT-1expression.however,demethylation of PP2Ac is increased in siRNA-transfected cells and CIG could reversed the high demethylation of PP2Ac and PP2A activity.CONLUSION CIG increases methylation of PP2A subunit C by inhibiting PME-1.

Iridoid Glycosides from Pedicularis dolichocymba Hand.-Mazz.

During investigation of the chemical constituents of the whole plant ethanol extract of Pedlcularis dollchocymba Hand.-Mazz. （Scrophularlaceae）, four new irldold glycosides, dolichocymbosides A （compound 1）, B （compound 2）, C （compound 3） and D （compound 4）, were Isolated. Their structures were determined based on spectral data Including 1D and 2D-nuclear magnetic resonance spectroscopy （^1H-^1H COSY, HSQC, HMBC, ROESY） and FAB-MS.

UPLC/Q-TOF-MS analysis of iridoid glycosides and metabolites in rat plasma after oral administration of Paederia scandens extracts

A rapid and validated UPLC-MS method was developed for investigating the absorbed components of Paederia scandens(Lour.) Merrill(P.scandens) in rat plasma.The bioactive constituents in plasma samples from rats administrated orally with P.scandens extract were analyzed by Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Four prototype compounds were identified in rat serum as potential bioactive components of P.scandens by comparing their retention times and mass spectrometry data or by mass spectrometry analysis and retrieving the reference literatures.Glucuronidation after deglycosylation was the major metabolic pathway for the iridoid glycosides in P.scandens.These results showed that the methods had high sensitivity and resolution and were suitable for identifying the bioactive constituents in plasma after oral administration of P.scandens.providing helpful chemical information for further pharmacological and mechanistic researched on the P.scandens.

Anti-TMV and Insecticidal Potential of Four Iridoid Glycosides from Gardenia Jasminoides Fruit

In agriculture, pests are largely controlled by agricultural chemicals. The vast majority of these pesticides are synthetic compounds, some of which are based on natural products, and a few of which are synthetic versions of natural products. Pests have evolved resistance to many of the current pesticides, often by alterations in the molecular target site. Thus, pesticides with new molecular target sites and modes of action are needed.

One New Iridoid Glycoside from Hedyotis tenelliflora

Objective To study the chemical constituents of Hedyotis tenelliflora.Methods The compounds were isolated by chromatographic separation technology.The structures were identified on the basis of chemical and spectral data.Results Four iridoid glycosides were isolated from the whole plant of H.tenelliflora.On the basis of the chemical and spectral methods,their structures were elucidated as teneoside C(1),harpagoside(2),harpagide(3),and asperulosidic acid(4).Conclusion Compound 1 is a new compound,and compounds 2 and 3 are isolated from H.tenelliflora for the first time.

Iridoid glycosides extracted from Zhizi(Fructus Gardeniae)decrease collagen-induced platelet aggregation and reduce carotid artery thrombosis in an invivo rat model

OBJECTIVE: To investigate the anti-platelet aggregation and antithrombotic effects in rats of iridoid glycosides extracted from Zhizi (FructusGardeniae). METHODS: The present study evaluated the antithrombotic activity of iridoid glycosides (IGs) in a rat model of carotid artery thrombosis. The effects on coagulation, such as thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT), and the effect on collagen-induced platelet aggregation in vivo were investigated. Rats were intragastrically administered IGs (50, 100 or 200 mg/ kg) twice daily for 3 days. RESULTS: IGs were shown for the first time to have an antithrombotic action through the inhibition of platelet aggregation, with little effect on the coagulation time of peripheral blood. Our results also showed that IGs may significantly and dose-dependently reduce arterial thrombus load in a model of carotid artery thrombosis and inhibit collagen-induced platelet aggregation in rats. IGs (100or 200 mg/kg) had no significant effect on APTT and PT, but did lengthenTT at a higher dose. CONCLUSION: These data, together with the previously reported neuroprotective effects of IGs in rats with cerebral ischemia, suggest that the antithrombotic action of IGs may potentially contribute to the treatment of cerebral ischemic diseases, including cerebral apoplexy.

The chemical constituents from the roots of Gentiana crassicaulis and their inhibitory effects on inflammatory mediators NO and TNF-α

Chemical study on the roots of Gentiana crassicaulis Duthie ex Burk(Gentianaceae)afforded 15 compounds,including two new iridoid glycosides,qinjiaosides B(1)and C(2).Their structures were elucidated by spectroscopic methods and chemical evidence.The isolated iridoid glycosides 1,4-6 and 8-11 were tested for their anti-inflammatory activity by the inhibitory effects on LPS-induced NO and TNF-αproduction in macrophage RAW264.7 cells.All of them showed inhibitory effects on inflammatory mediators NO at a concentration of 15μM,while 5 and 9 displayed the most potential inhibitory effects on TNF-awith IC50 of 0.06 and 0.05μM,respectively.The structure-activity relationships(SARs)of these iridoid derivatives were discussed.

Comparative Study on“Long-Dan”,“Qin-Jiao”and Their Adulterants by HPLC Analysis

“Long-Dan”and“Qin-Jiao”are two important TCM herbs since ancient times in China.In the Chinese Pharmacopoeia,the dried roots and rhizomes of four species from the genus Gentiana,e.g.Gentiana manshurica,G.scabra,G.triflora and G.rigescens,are recorded under the name of Gentianae Radix et Rhizoma(“Long-Dan”in Chinese),while the other four species from the same genus including G.macrophylla,G.crassicaulis,G.straminea and G.duhurica are recorded and used as the raw materials of Gentianae Macrophyllae Radix(“Qin-Jiao”in Chinese).On the basis of the establishment of a validated HPLC–UV method for quantifying simultaneously,five iridoid glycosides,e.g.loganic acid(1),swertiamarinin(2),gentiopicroside(3),sweroside(4)and 20-(o,m-dihydroxybenzyl)sweroside(5)have been used successfully as chemical markers for the comparison of the species used as“Long-Dan”,“Qin-Jiao”and their adulterants in the present study.The results suggested that four iridoid glycosides 1–4 commonly existed in both“Long-Dan”and“Qin-Jiao”,while 20-(o,m-dihydroxybenzyl)sweroside(5)also existed as one of the major components in“Dian-Long-Dan”species.Moreover,the contents of compounds 1–5 were various in different“LongDan”and“Qin-Jiao”species.Herein,we profiled and compared three“Long-Dan”species,four“Qin-Jiao”species and five adulterants by applying multivariate statistical techniques to their HPLC data sets to establish the differences and/or similarities.

Non-alkaloid constituents of Vinca major

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 62.2μmaol·L 1, respectively. In conclusion, compound 1 is a newly identified iridoid glycoside with moderate antioxidant activity.