Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Anti-inflammatory effects of bitongling granules are mediated through the suppression of miR-21/p38 MAPK/TLR4/NF-κB signaling in H9C2 rat cardiac cells exposed to lipopolysaccharides

Yun-Xiang Cao¹, Dan Huang¹, Rui Lin², Rui-Kai Zong¹, Chuan-Bing Huang¹, Yue Wang², Jian Liu¹

¹Department of Rheumatology, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Rd, Hefei 230031; ²The Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210046, China; ³The Affiliated Hospital of Nanjing University of Chinese Medicine, 155 hanzhong road, Nanjing 210000..

For correspondence:-

Accepted: 11 February 2022 Published: 31 March 2022

Citation: Cao Y, Huang D, Lin R, Zong R, Huang C, Wang Y, et al. Anti-inflammatory effects of bitongling granules are mediated through the suppression of miR-21/p38 MAPK/TLR4/NF-κB signaling in H9C2 rat cardiac cells exposed to lipopolysaccharides. Trop J Pharm Res 2022; 21(3):507-514 doi: 10.4314/tjpr.v21i3.8

© 2022 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To assess the protective effects of bitongling granules on H9C2 cells exposed to lipopolysaccharides (LPS) in the management of rheumatoid arthritis (RA)-induced myocardial inflammation.

Methods: The effects of bitongling granule (BTLG) drug-containing serum were assessed in myocarditis models established in rat cardiac cells. MicroRNA-21 (miR-21) levels were evaluated by qRT-PCR while MTT assays were performed to assess cell viability. ELISA assay was used to evaluate tumor necrosis factor α (TNF-α), interleukin 17 (IL-17) and interleukin 6 (IL-6) levels in cell culture supernatants. Apoptosis was determined by flow cytometry (FCM). Quantitative mitogen-activated protein kinase (MAPK)/p38, toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB)/p65 levels were evaluated by western blot and immunofluorescence

Results: BTLG increased cardiac cell activity and exhibited anti-inflammatory effect. It also inhibited LPS-induced H9C2 apoptosis and suppressed p65 NF-κB phosphorylation (p-p65 NF-κB), TLR4, and p38 MAPK phosphorylation (p-p38 MAPK). BTLG also reduced miR-21 expression, and the overexpression of the miR-21 inhibitor in H9C2 suppressed apoptosis. Moreover, p-p38 MAPK, TLR4 and p-p65 NF-κB expression were down-regulated in miR-21 inhibitor transfected H9C2s. The inhibition of p38/TLR4/ NF-κB signaling might have occurred via the suppression of miR-21 by BTLG.

Conclusion: The results show that BTLG inhibits the inflammatory reaction involved in p38 MAPK/TLR4/ NF-κB signaling pathway and can prevent RA-induced cardiac disease, suggesting that BTLP treatment may be beneficial for the management of arthritic cardiomyopathy.

Keywords: Bitongling granules, Arthritic cardiomyopathy, miR-21, NF-κB, Inflammation