The underlying mechanisms of Jie-Du-Hua-Yu granule for protecting rat liver failure

Abstract

Objectives

Jie-Du-Hua-Yu (JDHY) granule is a combination of six traditional Chinese medicines with known therapeutic effect in treating acute liver failure (ALF). The aim of this study was to investigate the amelioration efficacy of JDHY in lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF in rat and explore the possible molecular mechanism underlying the therapeutic efficacy.

Materials and methods

The efficacy of JDHY was determined by assessing hepatic pathology and function in LPS and D-GalN challenged Wistar rat. We also evaluated the effect of JDHY on LPS-induced Kupffer cells by measuring inflammatory cytokines and determining the phenotypic function. By means of bioinformatics analysis of liver tissue and validation in Kupffer cells, we identified possible pathways involved in the pharmacologic action of mechanism of JDHY.

Results

JDHY could attenuate LPS-induced liver injury in rat by inhibiting apoptosis and increasing hepatic activity. In vitro study showed that JDHY could decrease the production of proinflammatory cytokines (tumor necrosis factor-α, IL6, and interferon-γ), increase anti-inflammatory cytokines (IL10, IL13), and promote cell survival and proliferation, possibly due to inhibition of IκB/nuclear factor-κB (NF-κB) signaling pathway and expression of CD14 and CXCL2, which was consistent with the findings from bioinformatics analysis.

Conclusion

Our results revealed that JDHY protected against LPS-induced liver damage both in vitro and in vivo, by inhibiting the NF-κB-mediated inflammatory pathway, indicating its potential function to treat liver diseases.

Keywords:

• JDHY
• liver failure
• NF-κB

Acknowledgments

1. National Natural Science Foundation of China: The mechanism research of the white flower lotus detoxification prescription inhibits hepatitis B virus replication via mir-122 target gene regulatory network (No 81660827).

2. National Natural Science Foundation of China: The feature analysis of microRNA regulates anti-HBV in hepatocyte endogenous immune signaling network and the intervention mechanism study of white flower lotus detoxification (no 81303066).

3. National Natural Science Foundation of China: The mechanism research of Jie-Du-Hua-Yu granule regulates NLRP3 inflammatory body activation to antagonism hepatic failure via miRNAs/NF-κB/ROS (No 81774236).

4. National Natural Science Foundation of China: The disorder characteristic analysis of fulminant hepatic failure pDCs-CTL/CD4+CD25+Treg immune network and the intervention effect of Jie-Du-Hua-Yu granule (No 81460718).

5. Major projects of Guangxi scientific research and technology development plan: Investigation and analysis of the type of traditional Chinese medicine constitution of patients with chronic hepatitis b in Guangxi and the study on the standardized intervention program of TCM (No 1598011-7).

Disclosure

The authors report no conflicts of interest in this work.

Supplementary material

Table S1 The gene primers for qPCR