Lancemaside A from Codonopsis lanceolata prevents hypertension by inhibiting NADPH oxidase 2-mediated MAPK signalling and improving NO bioavailability in rats

초록

Objectives This study investigated whether lancemaside A (LMA) can prevent hypertension and assessed the mechanisms of action of LMA in rats. Methods Hypertension was induced by chronic immobilization stress and nicotine administration. Hypertensive vehicle rats were treated with LMA (1, 20, or 40 mg/kg) or nifedipine (10 mg/kg) as a positive control daily for 3 weeks. Key findings In hypertensive vehicle rats, LMA dose-dependently reduced systolic blood pressure. LMA doses of 20 and 40 mg/kg reduced the aortic expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)2 (both P < 0.01), and 40 mg/kg LMA reduced serum malondialdehyde (P < 0.01). Serum nitrite levels were significantly higher in LMA treated rats than in hypertensive vehicle rats, with LMA doses of 20 and 40 mg/kg reducing the expression of endothelial nitric oxide synthase in rat aortas (P P < 0.01, respectively). LMA also reduced the aortic levels of nuclear factor kappa B and the activation of the three isoforms of mitogen-activated protein kinase (MAPK). Conclusions Lancemaside A prevents hypertension in rats by inhibiting the activation of MAPK signalling and the impairment in nitric oxide bioavailability due to NOX2-mediated oxidative stress. Thus, LMA may act as a preventive agent for hypertension.

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