Qinggan Huoxue Recipe Protects against Experimental Alcoholic Liver Fibrosis through CXCL16 Inhibition

Abstract

Background. Qinggan Huoxue recipe (QGHXR), a traditional Chinese medicinal formula, has a protective effect against liver fibrosis. However, the underlying mechanisms remain unclear. Objective. This study investigated the antifibrotic role of QGHXR and its underlying mechanisms. Methods. The composition of QGHXR was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Female C57BL/6J mice were fed either a Lieber–DeCarli liquid diet or pair-fed control diet and intraperitoneally injected with CCl4 for 8 weeks (n = 8). In week 5, the mice were administered 100, 200, and 400 mg/kg QGHXR via oral gavage daily for 4 weeks. Results. UPLC-MS result showed that QGHXR contained 45 compounds including salvianolic acid A, scutellarin, baicalin, rutin, and chai saponin D. QGHXR alleviated pathological alterations in the liver. The alanine aminotransferase (ALT) level was reduced to 44.88 ± 4.39 U/L, aspartate aminotransferase (AST) to 76.25 ± 4.17 U/L, alkaline phosphatase (ALP) to 60.75 ± 5.41 U/L, and acetaldehyde to 38.54 ± 1.01 U/L compared with that of the control group (ALT 72.38 ± 5.19 U/L, AST 119.63 ± 9.82 U/L, and ALP 98.63 ± 6.71 U/L and acetaldehyde 64.86 ± 4.70 U/L). QGHXR inhibited lipid overproduction and fibrotic gene expression. The serum concentration of chemokine C-X-C ligand 16 (CXCL16) was reduced to 62.83 ± 6.80 pg/ml compared with that of the control group (130.91 ± 13.72 pg/mL). QGHXR downregulated CXCL16 mRNA and protein expressions. Pharmacological CXCL16 treatment reversed the QGHXR-induced protective effects in ethanol plus CCl4 fed mice. QGHXR reduced CXCL16 levels (91.97 ± 5.86 pg/ml) in LPS-stimulated RAW264.7 cells compared with that of the control group (148.68 ± 8.62 pg/ml) and inhibited toll-like receptor 4 and nuclear factor-kappa B phosphorylation. Conclusions. This study demonstrated that QGHXR mitigates experimental alcoholic liver fibrosis by CXCL16 inhibition, and may be considered a potential therapeutic agent for treating liver fibrosis.