Negundoside

Quality Assessment of Medicinal Product and Dietary Supplements Containing Vitex agnus-castus by HPLC Fingerprint and Quantitative Analyses.[Pubmed:31155557]

Chem Pharm Bull (Tokyo). 2019;67(6):527-533.

In this study, we aimed to evaluate the quality of 11 products sold in Japan (one medicinal product and 10 dietary supplements) containing/claiming to contain chasteberry extract (fruit of Vitex agnus-castus L.) using HPLC fingerprint (15 characteristic peaks), quantitative determination of chemical marker compounds, and a disintegration test. The HPLC profile of the medicinal product was similar to that of the reference standard of V. agnus-castus fruit dry extract obtained from European Directive for the Quality of Medicines (EDQM), whereas the profiles of some dietary supplements showed great variability, such as different proportions of peaks or lack of peaks. Results of the principal component analysis of the fingerprint data were consistent with those of the HPLC profile analysis. The contents of two markers, agnuside and casticin, in dietary supplements showed wide variability; this result was similar to that achieved with the HPLC fingerprint. In particular, agnuside and/or casticin was not detected in two dietary supplements. Furthermore, one dietary supplement was suspected to be contaminated with V. negundo, as evidenced from the results of agnuside to casticin ratio and assay of Negundoside, a characteristic marker of V. negundo. Results of the disintegration test showed poor formulation quality of two dietary supplements. These results call attention to the quality problems of many dietary supplements, such as incorrect or poor-quality origin, different contents of the active ingredient, and/or unauthorized manufacturing procedures.

New Iridoid Glycosides with Antidepressant Activity Isolated from Cyperus rotundus.[Pubmed:26726748]

Chem Pharm Bull (Tokyo). 2016;64(1):73-7.

Based on bioactive screening results, two new iridoid glycosides, named rotunduside G (1) and rotunduside H (2), were isolated from the rhizomes of Cyperus rotundus, together with four known ones, Negundoside (3), nishindaside (4), isooleuropein (5) and neonuezhenide (6). Their structures were elucidated on the basis of spectroscopic methods and from literature values. In mice models of despair, 1 and 2 showed significant antidepressant activity.

Synthesis of novel lipidated iridoid glycosides as vaccine adjuvants: 6-O-palmitoyl Agnuside elicit strong Th1 and Th2 response to ovalbumin in mice.[Pubmed:23954198]

Int Immunopharmacol. 2013 Nov;17(3):593-600.

Novel lipidated analogs of iridoids viz., Agnuside and Negundoside with different chain length were synthesized and tested for immune adjuvant activity in the presence of weak antigen ovalbumin. Based on in vitro assay, 6-O-palmitoyl Agnuside (AG-3) was further taken up for detailed in vivo activity and found to significantly enhance the production of anti OVA IgG titer, neutralizing antibody (IgG1 and IgG2a) titer as well as soluble mediators of a Th1 (IL-2, IFN-gamma)/Th2 response (IL-4) and proliferation of T lymphocyte subsets (CD4/CD8) and co stimulatory molecules CD80/CD86. Furthermore, the SAR studies revealed that presence of acyl group at aglycon moiety of these iridoid glycosides is crucial for immune adjuvant activity.

Validated high performance thin layer chromatographic method for simultaneous quantification of major iridoids in Vitex trifolia and their antioxidant studies.[Pubmed:22226914]

J Pharm Biomed Anal. 2012 Mar 5;61:207-14.

Negundoside (1), agnuside (2) and 6'-p-hydroxy benzoyl mussaenosidic acid (3) are known bioactive metabolites in Vitex trifolia. In the present study a simple precise and reproducible method was developed for simultaneous quantitation of NS (1), AS (2) and HMA (3) and the antioxidant capacity of above markers has also been determined. Marker compounds have been resolved using silica gel 60 F(254) plates, petroleum ether (60-80)/toluene/acetone/water (10:10:80:2 v/v/v/v) as the mobile phases. The method does not employ any derivatisation procedure and can be used as a quality control tool for routine analysis of drugs V. trifolia and V. negundo together with their commercial extracts. NS (1), AS (2) and HMA (3) showed significant activity in DPPH and NO radical scavenging assays.

A new iridoid glycoside from Vitex negundo Linn (Verbenacea).[Pubmed:19731139]

Nat Prod Res. 2009;23(13):1201-9.

Five compounds have been isolated from the leaves of Vitex negundo Linn (Verbenacea) and their structures established by spectral analysis. Compound 1 has been identified and characterised as a new iridoid with a novel structure which has never before been reported in literature from Vitex or any other source. Its structure has been established as 1,4a,5,7a-tetrahydro-1-beta-D-glucosyl-7-(3',4'-dihydroxybenzoyloxymethyl)-5-keto cyclopenta[c]pyran-4-carboxylic acid. Other compounds, 2, 3, 4 and 5, have been identified as luteolin-7-O-beta-D glucoside, nishindaside, Negundoside, and agnuside, respectively. Compound 2, a flavone-O-glycoside, is being reported from this plant for the first time, and compounds 3, 4 and 5 are structurally known iridoids.

Modulation of P-glycoprotein ATPase activity by some phytoconstituents.[Pubmed:19653312]

Phytother Res. 2010 Mar;24(3):454-8.

In the present investigation 16 phytoconstituents, which are active moieties found in several medicinal herbs, have been evaluated for their P-glycoprotein (P-gp) stimulation/inhibition profiles using a P-gp-dependent ATPase assay in rat jejunal membrane (in vitro). Acteoside, agnuside, catechin, chlorogenic acid, picroside -II and santonin showed an inhibitory effect. Negundoside, picroside -I and oleanolic acid caused a stimulatory effect. Andrographolide, apocyanin, berberine, glycyrrhizin, magniferin and piperine produced a biphasic response (stimulation at low concentration and inhibition at high concentration). The results suggested that a possible interaction of these phytoconstituents at the level of P-gp, could be an important parameter in determining their role in several key pharmacodynamic events.

Negundoside, an irridiod glycoside from leaves of Vitex negundo, protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride.[Pubmed:18595136]

World J Gastroenterol. 2008 Jun 21;14(23):3693-709.

AIM: To evaluate the protective effect of 2'-p-hydroxybenzoylmussaenosidic acid [Negundoside (NG), against carbon tetrachloride (CCl(4))-induced toxicity in HuH-7 cells. METHODS: CCl(4) is a well characterized hepatotoxin, and inducer of cytochrome P450 2E1 (CYP2E1)-mediated oxidative stress. In addition, lipid peroxidation and accumulation of intracellular calcium are important steps in the pathway involved in CCl(4) toxicity. Liver cells (HuH-7) were treated with CCl(4), and the mechanism of the cytoprotective effect of NG was assessed. Silymarin, a known hepatoprotective drug, was used as control. RESULTS: NG protected HuH-7 cells against CCl(4) toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl(4) toxicity was associated with a reduction in oxidative damage as reflected by decreased generation of reactive oxygen species (ROS), a decrease in lipid peroxidation and accumulation of intracellular Ca(2+) levels and maintenance of intracellular glutathione homeostasis. Decreased mitochondrial membrane potential (MMP), induction of caspases mediated DNA fragmentation and cell cycle arrest, as a result of CCl(4) treatment, were also blocked by NG. The protection afforded by NG seemed to be mediated by activation of cyclic adenosine monophosphate (cAMP) synthesis and inhibition of phospholipases (cPLA2). CONCLUSION: NG exerts a protective effect on CYP2E1-dependent CCl(4) toxicity via inhibition of lipid peroxidation, followed by an improved intracellular calcium homeostasis and inhibition of Ca(2+)-dependent proteases.

New acylated iridoid glucosides from Vitex altissima.[Pubmed:15620243]

J Nat Prod. 2004 Dec;67(12):2012-6.

Six new iridoid glucosides, 6'-O-trans-feruloylNegundoside (1), 6'-O-trans-caffeoylNegundoside (2), 2'-O-p-hydroxybenzoyl-6'-O-trans-caffeoylgardoside (3), 2'-O-p-hydroxybenzoyl-6'-O-trans-caffeoyl-8-epiloganic acid (4), 2'-O-p-hydroxybenzoyl gardoside (5), and 2'-O-p-hydroxybenzoyl-8-epiloganic acid (6), along with two known iridoids, agnuside and Negundoside, have been isolated from the ethyl acetate extractive of the leaves of Vitex altissima. The structures of these compounds were elucidated on the basis of spectral data interpretation. These isolates did not exhibit significant 5-lipoxygenase enzyme inhibitory activity, but compounds 2-4 showed potent antioxidant activity by both the superoxide (NBT riboflavin photoreduction) free-radical-scavenging and DPPH-radical-scavenging methods. Compounds 1, 2, and Negundoside were evaluated in a rat paw edema assay.