Abstract
The Chinese medicinal formula, Qinggan (QG) Huoxue (HX) Recipe (R) exerts a range of pharmacological effects, including reversible steatosis, decreased levels of inflammatory cytokines and lipid peroxidation resistance. The aim of the present study was to determine the specific mechanisms of QGHXR hepatoprotection through the lipopolysaccharide-Kupffer cell (LPS-KC) signal conduction pathway in rats with alcoholic liver disease (ALD). ALD rats were exposed to the compound factors, QGR and HXR. Hematoxylin and eosin staining was conducted to evaluate the pathological changes in the liver following QGHXR treatment and an enzyme-linked immunosorbent assay was performed to measure the content of tumor necrosis factor (TNF)-α in the plasma. Immunohistochemical staining was conducted to examine the expression of cell differentiation antigen (CD) 68 and 14. In addition, western blot analysis and reverse transcription-polymerase chain reaction were used to measure the expression of Toll-like receptor 4 (TLR4), phosphorylated-extracellular regulated protein kinases (p-ERK), nuclear factor (NF)-κB, CD14 and TNF-α. Following stimulation with the compound factors, the rats exhibited increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as marked pathological changes. Furthermore, the related molecules in the LPS-KC pathway were upregulated and QGHXR was identified to be effective in the LPS-KC signal conduction pathway in the ALD rats. QGHXR was superior to QGR and HXR in reducing the serum ALT and AST levels, regulating CD14, TLR4, NF-κB, ERK and TNF-α as well as improving the pathological changes. The results indicated that QGHXR therapy may provide a novel strategy for treating ALD via regulation of the related molecules in the LPS-KC signaling pathway.
Highlights
Alcoholic liver disease (ALD) is a common clinical complication resulting from long-term alcohol abuse
The results indicated that QGHXR therapy may provide a novel strategy for treating ALD via regulation of the related molecules in the lipopolysaccharide‐Kupffer cell (LPS‐KC) signaling pathway
LPS recognition by Toll‐like receptor 4 (TLR4) and cell differentiation antigen (CD14) on liver macrophages and activation of downstream signaling pathways, which culminate in the activation of transcription factors, such as nuclear factor (NF)‐κB, lead to increased inflammatory cytokine production in ALD
Summary
Alcoholic liver disease (ALD) is a common clinical complication resulting from long-term alcohol abuse. Alcohol‐induced sensitization of liver macrophages by portal endotoxins/LPS is considered to be a hallmark of ALD. LPS recognition by Toll‐like receptor 4 (TLR4) and cell differentiation antigen (CD14) on liver macrophages and activation of downstream signaling pathways, which culminate in the activation of transcription factors, such as nuclear factor (NF)‐κB, lead to increased inflammatory cytokine production in ALD. The importance of alcohol‐induced reactive oxygen species and interactions with TLR pathways in macrophages that lead to inflammation are becoming increasingly evident. These signaling pathways induce pro‐ and anti‐inflammatory cytokines, which are significant in ALD [3,4,5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
