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Planta Med 2019; 85(09/10): 708-718
DOI: 10.1055/a-0863-4741
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Magnesium Lithospermate B Derived from Salvia miltiorrhiza Ameliorates Right Ventricle Remodeling in Pulmonary Hypertensive Rats via Inhibition of NOX/VPO1 Pathway

Tao Li
1   Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Jing-Jie Peng
2   Department of Laboratory Medicine, the third Xiangya Hospital of Central South University, Changsha, China
,
E-Li Wang
1   Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Nian-Sheng Li
1   Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Feng-Lin Song
3   Department of cardiovascular surgery, the second Xiangya Hospital, Central South University, Changsha, China
,
Jin-Fu Yang
3   Department of cardiovascular surgery, the second Xiangya Hospital, Central South University, Changsha, China
,
Xiu-Ju Luo
2   Department of Laboratory Medicine, the third Xiangya Hospital of Central South University, Changsha, China
,
Bin Liu
1   Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
4   Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
,
Jun Peng
1   Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
5   Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
› Author Affiliations
Further Information

Publication History

received 16 October 2018
revised 14 February 2019

accepted 21 February 2019

Publication Date:
01 March 2019 (online)

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Abstract

Right ventricle (RV) remodeling is a major pathological feature in pulmonary arterial hypertension (PAH). Magnesium lithospermate B (MLB) is a compound isolated from the roots of Salvia miltiorrhiza and it possesses multiple pharmacological activities such as anti-inflammation and antioxidation. This study aims to investigate whether MLB is able to prevent RV remodeling in PAH and the underlying mechanisms. In vivo, SD rats were exposed to 10% O2 for 21 d to induce RV remodeling, which showed hypertrophic features (increases in the ratio of RV weight to tibia length, cellular size, and hypertrophic marker expression), accompanied by upregulation in expression of NADPH oxidases (NOX2 and NOX4) and vascular peroxidase 1 (VPO1), increases in hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) production and elevation in phosphorylation levels of ERK; these changes were attenuated by treating rats with MLB. In vitro, the cultured H9c2 cells were exposed to 3% O2 for 24 h to induce hypertrophy, which showed hypertrophic features (increases in cellular size and hypertrophic marker expression). Administration of MLB or VAS2870 (a positive control for NOX inhibitor) could prevent cardiomyocyte hypertrophy concomitant with decreases in NOX (NOX2 and NOX4) and VPO1 expression, H2O2 and HOCl production, and ERK phosphorylation. Based on these observations, we conclude that MLB is able to prevent RV remodeling in hypoxic PAH rats through a mechanism involving a suppression of NOX/VPO1 pathway as well as ERK signaling pathway. MLB may possess the potential clinical value for PAH therapy.

Key words

Salvia miltiorrhiza - Lamiaceae - pulmonary arterial hypertension - magnesium lithospermate B - right ventricle remodeling - NADPH oxidase - vascular peroxidase1
 

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