Magnesium lithospermate B improves pulmonary artery banding induced right ventricular dysfunction by alleviating inflammation via p38MAPK pathway

Chen Qu; Ying Xu; Xilan Yang; Xiang Lu

doi:10.1016/j.pupt.2020.101935

Magnesium lithospermate B improves pulmonary artery banding induced right ventricular dysfunction by alleviating inflammation via p38MAPK pathway

Pulm Pharmacol Ther. 2020 Aug:63:101935. doi: 10.1016/j.pupt.2020.101935. Epub 2020 Aug 9.

Authors

Chen Qu¹, Ying Xu², Xilan Yang³, Xiang Lu⁴

Affiliations

¹ Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Nanjing Medical University, Nanjing, Jiangsu, China.
² Intensive Care Unit, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University, Nanjing, Jiangsu, China.
³ Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: luxiang66@njmu.edu.cn.

PMID: 32783991
DOI: 10.1016/j.pupt.2020.101935

Abstract

Backgroud: Magnesium lithospermate B (MLB) is a major bioactive component of Slavia miltiorrhiza, which has been widely used in heart diseases on account of its anti-inflammatory, anti-oxidative, anti-proliferative and anti-fibrotic properties. Substance P(SP) is a small molecule neuropeptide, which was secreted much more during heart failure, and has an obvious function of immune enhancement and inflammation induction. This study aimed to investigate the protective effects of MLB on pulmonary artery banding (PAB) induced right ventricular (RV) dysfunction.

Methods: The mouse model of PAB was established. The mice were intraperitoneal (IP) injection treated with MLB (10 mg kg^-1·d^-1) for 4 weeks and p38 mitogen-activated protein kinase (MAPK) activator was given at the same time. Echocardiography were performed on day 28. Then the hearts were harvested, and substance P (SP), inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and cardiac fibrosis were detected. The macrophages and fibroblasts were stimulated by SP separately, and then treated with MLB as well as p38MAPK activator. The inflammatory cytokines from macrophage, the proliferation and fibrosis of cardiac fibroblasts were measured. The expression of p38MAPK proteins were confirmed by immunoblotting.

Findings: MLB preserved RV ejection fraction (EF), FS, RV/(LV + septum), HW/BW index and blunted RV inflammation as well as fibrosis. Phosphorylated-p38 (p-p38) MAPK was up-regulated, which was partially reversed by MLB treatment. However, p38MAPK activator abolished the effects of MLB on RV dysfunction, suggesting a key role of p38MPAK pathway in the effects of MLB reversing RV dysfunction. In external experiment, MLB reversed the increase of inflammatory cytokines from macrophage, the proliferation and fibrosis of cardiac fibroblasts which was simulated by SP. In accordance with in vivo study, p38MAPK activator abolished the effects of MLB on macrophage as well as fibroblasts.

Interpretation: MLB improves PAB induced right ventricular remodeling by alleviating inflammation via p38MAPK pathway. Thus, MLB may offer the therapeutic potential for the patients of RV dysfunction.

Keywords: Inflammation; Magnesium lithospermate B; Pulmonary artery banding; Right ventricular dysfunction; p38MAPK pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Drugs, Chinese Herbal
Humans
Inflammation
MAP Kinase Signaling System*
Mice
Pulmonary Artery
Rats
Rats, Sprague-Dawley
Ventricular Dysfunction, Right*
p38 Mitogen-Activated Protein Kinases

Substances

Drugs, Chinese Herbal
lithospermate B
p38 Mitogen-Activated Protein Kinases