Gypenoside IX Ameliorates Hypertension Induced by Obesity via Inactivation of the Mitogen-Activated Protein Kinase Pathway

Gynostemma pentaphyllum (Thunb.) Makino is a Chinese herb known to alleviate hyperlipidemia and obesity. In the present study, the effect and the mechanism of the effect of gypenoside IX, a bioactive constituent of G. pentaphyllum on the obesity-related hypertension in rats has been explored. The rats were fed a high fat diet to induce obesity leading to hypertension. Treatment of these hypertensive rats with gypenoside IX resulted in decreased systolic and diastolic blood pressure, body weight, and alleviation of pathological manifestations in myocardium and aorta. Furthermore, gypenoside IX antagonized the high fat diet-induced relative increase in the expressions of angiotensin-converting enzyme, angiotensin 11 receptor type 1 and 2 proteins, and the B-type natriuretic peptide and atrial natriuretic peptide messenger RNAs. However, the concentrations of angiotensin II, adrenaline, and norepinephrine increased, whereas that of cyclic guanosine monophosphate decreased. The levels of malondialdehyde increased and that of reduced glutathione, superoxide dismutase, and catalase decreased in high fat diet rats that were reversed by the gypenoside IX treatment. There was a significant increase in the relative protein levels for phospho-extracellular signal-regulated kinase/extracellular signal-regulated kinase, phospho-c-Jun N[H.sub.2]-terminal kinase/c-Jun N[H.sub.2]-terminal kinase, and p-p38/p-38 that was ameliorated by gypenoside IX. In conclusion, gypenoside IX inhibits the renin-angiotensin system activation and oxidative stress through the inactivation of the mitogen-activated protein kinase pathway in obesity-mediated hypertension in rats. Keywords: Gypenoside IX, Hypertension, MAPK, Obesity Abbreviations Used: Angiotensin-converting enzyme, ACE; Angiotensin II, Ang II; Analysis of variance, ANOVA; Atrial natriuretic peptide, ANP; Angiotensin II receptor type 1, AT1; Angiotensin II receptor type 2, AT2; Bicinchoninic acid, BCA; B-type natriuretic peptide, BNP; Blood pressure, BP; Cyclic GMP, cGMP; Chronic kidney disease, CKD; Enzyme-linked immunosorbent assay, ELISA; Adrenaline, EP; Extracellular signal-regulated kinase, ERK; Gynostemma pentaphyllum, GP; Gypenoside IX, GPIX; Reduced glutathione, GSH; Hematoxylin and Eosin, H High fat diet, HFD; High performance liquid chromatography, HPLC; Ischemia-reperfusion, l/R; c-Jun NH2-terminal kinase, JNK; Mitogen-activated protein kinase, MAPK; Malondialdehyde, MDA; Norepinephrine, NE; A stress stimulated kina