lignans and Hypertension--Renal

Renal fibrosis participates in the progression of hypertension-induced kidney injury. The effect of SIRT3, a member of the NAD+-dependent deacetylase family, in hypertensive nephropathy remains unclear. In this study, we found that SIRT3 was reduced after angiotensin II (AngII) treatment both in vivo and in vitro. Furthermore, SIRT3-knockout mice aggravated hypertension-induced renal dysfunction and renal fibrosis via chronic AngII infusion (2000 ng/kg per minute for 42 days). On the contrary, SIRT3-overexpression mice attenuated AngII-induced kidney injury compared with wild-type mice. Remarkably, a co-localization of SIRT3 and KLF15, a kidney-enriched nuclear transcription factor, led to SIRT3 directly deacetylating KLF15, followed by decreased expression of fibronectin and collagen type IV in cultured MPC-5 podocytes. In addition, honokiol (HKL), a major bioactive compound isolated from Magnolia officinalis (Houpo), suppressed AngII-induced renal fibrosis through activating SIRT3-KLF15 signaling. Taken together, our findings implicate that a novel SIRT3-KLF15 signaling may prevent kidney injury from hypertension and HKL can act as a SIRT3-KLF15 signaling activator to protect against hypertensive nephropathy.

Topics: Acetylation; Angiotensin II; Animals; Biphenyl Compounds; Disease Models, Animal; Fibrosis; Gene Expression; Gene Expression Regulation; Hypertension, Renal; Kidney; Kruppel-Like Transcription Factors; Lignans; Mice; Mice, Knockout; Models, Biological; Nephritis; Nuclear Proteins; Podocytes; Protein Binding; Signal Transduction; Sirtuin 3

Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from the seeds of Linum usitatissimum L. (Linaceae).. To investigate the effect of FLC in deoxycorticosterone acetate (DOCA)-salt induced experimental renal hypertension in rats.. Hypertension was induced in uninephrectomized (UNTZD) male Wistar rats (230-280 g) by injecting DOCA (25 mg/kg, subcutaneously, twice weekly) and supplementing 1% NaCl in drinking water for 5 weeks. The rats were divided in six groups. Captopril (30 mg/kg, p.o.) and FLC (200, 400 and 800 mg/kg, p.o.) were administered daily to the rats of groups III-VI, respectively, for 5 weeks. Various hemodynamic and biochemical parameters were investigated as well as histology of kidney and heart were carried out.. In this study, the FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) decreased the systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. It also significantly (p < 0.01, p < 0.001) decreased elevated end diastolic pressure (EDP), dP/dt max and dP/dt min, organs weights (kidney and heart) and activities of hepatic, renal and cardiac marker enzymes in the serum. Furthermore, FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) restored altered antioxidant status, serum electrolyte level, lipid profile values, and histological abnormalities. Captopril (30 mg/kg) showed maximum antihypertensive effect but low dose of FLC (200 mg/kg) was not enough to show the antihypertensive activity.. FLC possessed antihypertensive effect via modulation of endogenous enzymes in DOCA-salt induced renal hypertension in rats.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Captopril; Desoxycorticosterone Acetate; Flax; Heart; Hypertension, Renal; Kidney; Lignans; Lipids; Male; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Ventricular Function, Left