Therapeutic Effect of Biejiaxiaozheng Pills on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through the NF-κB/Nrf2 Pathway.

Weibin Wu,Jian Yang,Liqiang Li,Guifeng Zhang,Yuying Hu,Xiaozhong Zhu,Pinyu Li

doi:10.1155/2021/3954244

Abstract

Aims To explore the effects of Biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway and to explore the possible antifibrotic mechanisms of the drug. Material and Method. A rat model of hepatic fibrosis was established via CCl4 induction. Liver function and antioxidant indices were detected using commercial kits. Hematoxylin-eosin and Masson staining were used to detect pathological changes in hepatic tissues. ELISA was used to measure plasma TNF-α, IL-β, and IL-6 levels. RT-PCR was used to measure changes in TNF-α, IL-β, and IL-6 levels in hepatic tissues. Changes in p65, P-p65, Nrf2, and HO-1 protein expression were detected using western blotting. Results In rats with hepatic fibrosis, Biejiaxiaozheng pills effectively improved liver function, alleviated fibrosis in hepatic tissues, and significantly reduced collagen accumulation. The pills significantly downregulated inflammatory cytokine expression in hepatic tissues by suppressing p65 phosphorylation and reduced plasma inflammatory cytokine levels to some extent. The pills upregulated Nrf2 and HO-1 expression in hepatic tissues, enhanced antioxidant potential, and upregulated plasma antioxidant levels. Conclusion Biejiaxiaozheng pills improved hepatic fibrosis symptoms and lesions in rats, likely by inhibiting the NF-κB pathway and promoting the Nrf2 pathway.

Highlights

Hepatic fibrosis is a type of hepatic pathological change induced by a long-term chronic injury of hepatocytes due to diseases such as nonalcoholic fatty liver disease and hepatitis B, and its main manifestation is the excessive deposition of extracellular matrix in hepatocytes [1, 2]
Hepatic fibrosis mainly occurs due to the activation and proliferation of hepatic stellate cells under the regulation of cytokines secreted by Kupffer cells, which enhances the synthesis of extracellular matrix and reduces its degradation, gradually leading to fibrosis formation [3, 4]
If drugs can improve the functions of the NF-κB and Nrf2 pathways, they can produce some therapeutic effects against hepatic fibrosis [10, 11]

Summary

Introduction

Hepatic fibrosis is a type of hepatic pathological change induced by a long-term chronic injury of hepatocytes due to diseases such as nonalcoholic fatty liver disease and hepatitis B, and its main manifestation is the excessive deposition of extracellular matrix in hepatocytes [1, 2]. Fibrosis can be effectively reversed if drug intervention is administered on time during the occurrence/progression of hepatic fibrosis [5, 6]. During this process, Kupffer cells are activated by external stimuli to secrete cytokines, and they further activate hepatic stellate cells via paracrine effect. The activated hepatic stellate cells can recruit a large number of Kupffer cells through similar paracrine effects. This cycle is maintained for a long period and continuously promotes hepatic fibrosis [7–9]. If drugs can improve the functions of the NF-κB and Nrf pathways, they can produce some therapeutic effects against hepatic fibrosis [10, 11]

Methods

Results

Conclusion