| In vitro: |
| WORLD JOURNAL OF GASTROENTEROLOGY,2008, 14(23). | | Negundoside,an irridiod glycoside from leaves of Vitex negundo,protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride.[Reference: WebLink] | To evaluate the protective effect of 2'-p-hydroxy benzoylmussaenosidic acid [Negundoside(NG) ,against carbon tetrachloride(CCl4) -induced toxicity in HuH-7 cells.
METHODS AND RESULTS:
CCl4 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 CCl4 toxicity. Liver cells(HuH-7) were treated with CCl4,and the mechanism of the cytoprotective effect of NG was assessed. Silymarin,a known hepatoprotective drug,was used as control. NG protected HuH-7 cells against CCl4 toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl4 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 Ca2+ levels and maintenance of intracellular glutathione homeostasis. Decreased mitochondrial membranepotential(MMP) ,induction of caspases mediated DNA fragmentation and cell cycle arrest,as a result of CCl4 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) .
CONCLUSIONS:
NG exerts a protective effect on CYP2E1-dependent CCl4 toxicity via inhibition of lipid peroxidation,followed by an improved intracellular calcium homeostasis and inhibition of Ca2+-dependent proteases. | | Phytotherapy research, 2010, 24(3):454-458. | | Modulation of P-glycoprotein ATPase activity by some phytoconstituents.[Reference: WebLink] |
METHODS AND RESULTS:
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).
CONCLUSIONS:
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. |
|
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)