Drug Design, Development and Therapy (Feb 2019)
The underlying mechanisms of Jie-Du-Hua-Yu granule for protecting rat liver failure
Abstract
Hua Qiu,1 Dewen Mao,1 Nong Tang,2 Fuli Long,1 Rongzhen Zhang,1 Minggang Wang,1 Qinglan Shi,1 Jiahuan Li,1 Qin Jiang,1 Yueqiao Chen,1 Xiufeng Wang1 1Department of Liver Disease, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi 530023, China; 2Graduate School, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China 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
