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

Tao Li; Jing-Jie Peng; E-Li Wang; Nian-Sheng Li; Feng-Lin Song; Jin-Fu Yang; Xiu-Ju Luo; Bin Liu; Jun Peng

doi:10.1055/a-0863-4741

Planta Medica, Table of Contents

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

Authors

Tao Li

¹Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
Jing-Jie Peng

²Department of Laboratory Medicine, the third Xiangya Hospital of Central South University, Changsha, China
E-Li Wang

¹Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
Nian-Sheng Li

¹Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
Feng-Lin Song

³Department of cardiovascular surgery, the second Xiangya Hospital, Central South University, Changsha, China
Jin-Fu Yang

³Department of cardiovascular surgery, the second Xiangya Hospital, Central South University, Changsha, China
Xiu-Ju Luo

²Department of Laboratory Medicine, the third Xiangya Hospital of Central South University, Changsha, China
Bin Liu

¹Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China

⁴Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
Jun Peng

¹Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China

⁵Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China

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

Full Text

References

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