Two New Antibacterial Iridoids from Patrinia rupestris

Two new iridoids （1 and 2） were isolated from the roots of Patrinia rupestris （Pail.） Juss. Their structures were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited strong antibacterial activities against Eschecichia coli and Staphylococcus aureus, respectively.

Isoflavones’effects on pharmacokinetic profiles of main iridoids from Gardeniae Fructus in rats

Gardeniae Fructus(GF)and Semen Sojae Praeparatum(SSP)are both medicine food homologies and widely used in Chinese clinical prescriptions together.The research investigated the pharmacokinetics of four iridoids in normal rats and isolfavones-fed rats,which were administered with isolfavones from SSP for 7,14,21 and 28 consecutive days.A validated LC-MS/MS method was developed for determining shanzhiside,genipin-1-gentiobioside,geniposide and their metabolite genipin in rat plasma.Plasma samples were pretreated by solid-phase extraction using paeoniflorin as the internal standard.The chromatographic separation was performed on a Waters Atlantis T3(4.6 mm×150 mm,3 mm)column using a gradient mobile phase consisting of acetonitril and water(containing 0.06%acetic acid).The mass detection was under the multiple reaction monitoring(MRM)mode via polarity switching between negative and positive ionization modes.The calibration curves exhibited good linearity(r>0.997)for all components.The lower limit of quantitation was in the range of 1 e10 ng/m L.The intra-day and inter-day precisions(RSD)at three different levels were both less than 12.2%and the accuracies(RE)ranged fromà10.1%to 16.4%.The extraction recovery of them ranged from 53.8%to 99.7%.Pharmacokinetic results indicated the bioavailability of three iridoid glycosides and the metabolite,genipin in normal rats was higher than that in rats exposed to isoflavones.With the longer time of administration of isoflavones,plasma concentrations of iridoids decreased,while genipin sulfate,the phase II metabolite of genposide and genipin-1-gentiobioside,appeared the rising exposure.The pharmacokinetic profiles of main iridoids from GF were altered by isoflavones.

Iridoids modulate inflammation in diabetic kidney disease: A review

In recent years,preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention.DKD has become a pervasive complication of type 2 diabetes.Given the complexity of its etiology and pathological mechanisms,current interventions,including drugs,dietary modifications,exercise,hypoglycemic treatments and lipid-lowering methods,often fall short in achieving desired therapeutic outcomes.Iridoids,primarily derived from the potent components of traditional herbs,have been the subject of long-standing research.Preclinical data suggest that iridoids possess notable renal protective properties;however,there has been no summary of the research on their efficacy in the management and treatment of DKD.This article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this condition.Additionally,it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora,potentially bolstering their therapeutic effects.This review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD,offering valuable insights for future research endeavors.

Anti-inflammatory iridoids from the stems of Cistanche deserticola cultured in Tarim Desert

In order to determine the chemical constituents of Cistanche deserticola cultured in Tarim desert,a systematically phytochemical investigation was carried out.The constituents were isolated by silica gel,Sephadex LH-20,MCI gel,ODS column chromatography,and semi-preparative HPLC.Their structures were determined on the basis of MS and NMR spectroscopic analyses,by chemical methods,and/or comparison with literature data.The anti-inflammatory activities of the isolates were evaluated for their inhibitory effects on the lipopolysaccharide(LPS)-induced nitric oxide(NO)production in BV-2 mouse microglial cells.Nine iridoids were isolated and identified as cistadesertoside A(1),cistanin(2),cistachlorin(3),6-deoxycatalpol(4),gluroside(5),kankanoside A(6),ajugol(7),bartsioside(8),and 8-epi-loganic acid(9).Compound 9 exhibited potent inhibition on the NO production with an IC_(50) value being 5.2 μmol·L^(-1),comparable to the positive control quercetin(4.3 μmol·L^(-1)).Compound 1 was a new iridoid,and compounds 5,6,and 8 were isolated from this species for the first time.

Discovery of New Iridoids as Farnesoid X Receptor Agonists from Morinda officinalis: Agonistic Potentials and Molecular Stimulation

The investigation of Morinda officinalis led to the isolation of twelve compounds(1-12),including three new iridoid glycosides morindallns A-C(1-3)and nine known compounds(4-12).Their structural identifications were conducted using HRMS,1D and 2D NMR,and electronic circular dichroism(ECD)spectra as well as quantum chemical computations.Compound 6 displayed the most significantly agonistic activity against farnesoid X receptor(FXR)with an EC_(50) value of 7.18 μM,and its agonistic effect was verified through the investigation of FXR downstream target genes including small heterodimer partner 1(SHP1),bile salt export pump(BSEP),and organic solute transporter subunit alpha and beta(OSTα and OSTβ).The potential interaction of compound 6 with FXR was analyzed by molecular docking and molecular dynamics stimulation,revealing that amino acid residues Leu287;Thr288,and Ser332 played a crucial role in the activation of compound 6 towards FXR.These findings suggested that compound 6 could be regarded as a potential candidate for the development of FXR agonists.

Effects of Different Compounding of Formulae on Content of Gardenoside in Yin Chen Hao Decoction

In order to observe the effects of the ground and intact Zhi Zi (Fructus Gardeniae) and different combinations of the ingredients and refined single Chinese drug granules in Yin Chen Hao Decoction compound prescription on the contents of gardenoside (an effective component of the prescription), the contents of gardenoside were determined with reversed phase high performance liquid chromatography (HPLC), with acetonitrile-water (15:85) as mobile phase, at wave length 238nm. The results indicated that the gardenoside-decocted-out rates in the decoctions prepared by different combinations of the ingredients with the ground Zhi Zi (Fructus Gardeniae) all were higher significantly than those in the decoction with intact Zhi Zi (Fructus Gardeniae), and generally, different combinations of the ingredients in the decoction had only little effect on the gardenoside-decocted-out rate.

A new iridoid from Incarvillea delavayi

A new iridoid was isolated from the 80% ethanol extract of the whole plant of Incarvillea delavayi. Its structure was defined, and named incarvillic acid, on the basis of spectral evidences.

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.

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.

Cornel iridoid glycoside induces autophagy to protect against tau oligomer neurotoxicity induced by activation of glycogen synthase kinase-3β

Tau oligomers are the etiologic molecules of Alzheimer disease(AD), and correlate strongly with neuronal loss and exhibit neurotoxicity. Recent evidence indicates that small tau oligomers are the most relevant toxic aggregate species. The aim of the present study was to investigate the mechanisms of cornel iridoid glycoside(CIG) on tau oligomers and cognitive functions. We injected wortmannin and GF-109203 X(WM/GFX, 200 μmol·L-1 each) into the lateral ventricles to induce tau oligomer and memory impairment in rats. When oral y administered with CIG at 60 and 120 mg·kg-1 per day for 14 d, CIG decreased the escape latency in Morris water maze test. We also found that CIG restored the expression of presynaptic p-synapsin, synaptophysin, and postsynaptic density-95(PSD-95) decreased by WM/GFX in rat cortex. CIG reduced the accumulation of tau oligomers in the brain of WM/GFX rats and in cells transfected with wild type glycogen synthase kinase-3β(wt GSK-3β). In addition, CIG up-regulated the levels of ATG7, ATG12, Beclin-1, and LC3 II in vivo and in vitro, suggesting the restoration of autophagy function. These results suggest that CIG could ameliorate memory deficits and regulate memory-associated synaptic proteins through the clearance of tau oligomers accumulation. Moreover, CIG clears tau oligomers by restoring autophagy function.

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.

Two New Iridoid Glucosides from Clerodendrum serratum

Two new iridoid glucosides, named 7 beta -coumaroyloxyugandoside (1) and 7 beta - cinnamoyloxyugandoside (2) were isolated from the leaves of Clerodendrum serratum, and their structures were elucidated by spectral means.

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.

A New Iridoid Glucoside from Lagotis yunnanensis

Phytochemical investigation of Lagotis yunnanensis led to the isolation and identification of a new iridoid glucoside 1, named as 10-O-(3,4-dimethoxy-(E)-cinnamoyl)aucubin. Its structure was elucidated by spectroscopie methods.

A New Acylated Iridoid Glucoside from Avicennia marina

A new acylated iridoid glucoside, namely, 2＇-O-（5-phenyl-2E, 4E-pentadienoyl）- mussaenosidic acid, was isolated from the aerial parts of the mangrove plant Avicennia marina. The structure of the new compound was established on the basis of various NMR spectroscopic analyses, including 2D NMR techniques （^1H-^1H COSY, HMQC, and HMBC） and HR-FAB-MS. This compound displayed moderate antioxidant activity.

Isolation and Purification of Unstable Iridoid Glucosides from Traditional Chinese Medicine by Preparative High Performance Liquid Chromatography Coupled with Solid-phase Extraction

An efficient preparative method was successfully developed for isolation and purification of unstable components from medicinal plant extracts, using a combined method of preparative high performance liquid chro-matography(HPLC) and solid-phase extraction(SPE). The aim of this study was to obtain an effective method with high preparative efficiency and importantly to avoid the transformation of unstable compounds. The preparative HPLC system was based on an LC/MS controlled four-channel autopurification system. The SPE method was performed with a C18 packing material to trap the target compounds and to remove the acidic additive derived from the mobile phase. Using this method, the unstable iridoid glucosides(IGs) as model compounds were successfully isolated and purified from the extract of Hedyotis diffusa Willd. Six IGs(including one new minor IG) and one nucleotide compound were simultaneously obtained, each with a purity of 91% as determined by HPLC. The structures of the isolated compounds were identified by UPLC/Q-TOF MS, UV, 1D and/or 2D NMR. It was demonstrated that the combination of preparative HPLC with SPE is a versatile tool for preparative purification of unstable compounds from complex natural products.

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.

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.