Huangjia Ruangan Granule Inhibits Inflammation in a Rat Model with Liver Fibrosis by Regulating TNF/MAPK and NF- κ B Signaling Pathways

Qiang Cai; Zongquan Wang; Rong Zhang; Lili Zhang; Sainan Cui; Huiyuan Lin; Xinran Tang; Dongying Yang; Xianrong Lin; Shasha Bai; Jin Gao; Lei Yang

doi:10.1155/2022/8105306

Huangjia Ruangan Granule Inhibits Inflammation in a Rat Model with Liver Fibrosis by Regulating TNF/MAPK and NF- κ B Signaling Pathways

Evid Based Complement Alternat Med. 2022 Jul 30:2022:8105306. doi: 10.1155/2022/8105306. eCollection 2022.

Authors

Qiang Cai¹, Zongquan Wang², Rong Zhang¹, Lili Zhang², Sainan Cui¹, Huiyuan Lin¹, Xinran Tang¹, Dongying Yang¹, Xianrong Lin¹, Shasha Bai¹, Jin Gao², Lei Yang¹

Affiliations

¹ School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
² Yingkerui (Hengqin) Pharmaceutical Research Institute Co., Ltd, Zhuhai 519000, China.

Abstract

The Huangjia Ruangan granule (HJRG) is a clinically effective Kampo formula, which has a significant effect on liver fibrosis and early liver cirrhosis. However, the mechanism underlying HJRG in treating liver fibrosis remains unclear. In this study, carbon tetrachloride (CCl₄) was used to induce liver fibrosis in rats to clarify the effect of HJRG on liver fibrosis and its mechanism. Using network pharmacology, the potential mechanism of HJRG was initially explored, and a variety of analyses were performed to verify this mechanism. In the liver fibrosis model, treatment with HJRG can maintain the liver morphology, lower the levels of AST and ALT in the serum, and ameliorate pathological damage. Histopathological examinations revealed that the liver structure was significantly improved and fibrotic changes were alleviated. It can effectively inhibit collagen deposition and the expression of α-SMA, reduce the levels of the rat serum (HA, LN, PC III, and Col IV), and inhibit the expression of desmin, vimentin, and HYP content in the liver. Analyzing the results of network pharmacology, the oxidative stress, inflammation, and the related pathways (primarily the TNF signaling pathway) were identified as the potential mechanism of HJRG against liver fibrosis. Experiments confirmed that HJRG can significantly increase the content of superoxide dismutase and glutathione and reduce the levels of malondialdehyde and myeloperoxidase in the rat liver; in addition, HJRG significantly inhibited the content of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and reduced the expression of inflammatory regulators (Cox2 and iNOS). Meanwhile, treatment with HJRG inhibited the phosphorylation of NF-κB P65, IκBα, ERK, JNK, and MAPK P38. Moreover, HJRG treatment reversed the increased expression of TNFR1. The Huangjia Ruangan granule can effectively inhibit liver fibrosis through antioxidation, suppressing liver inflammation by regulating the TNF/MAPK and NF-κB signaling pathways, thereby preventing the effect of liver fibrosis.