Prediction of the mechanisms of action of Qutan Huoxue decoction in non-alcoholic steatohepatitis (NASH): a network pharmacology study and experimental validation.

contextQutan Huoxue decoction (QTHX) is used to treat non-alcoholic steatohepatitis (NASH) with good efficacy in the clinic. However, the mechanism is not clear yet.

objectiveThis study investigates the mechanism of QTHX in the treatment of NASH. MATERIALS AND

methodsPotential pathways of QTHX were predicted by network pharmacology. Fourty Sprague Dawley (SD) rats (half normal diet, half high-fat diet) were fed six to eight weeks, primary hepatocytes and Kupffer cells were extracted and co-cultured by the 0.4-micron trans well culture system. Then, the normal co-cultured cells were treated by normal serum, the NASH co-cultured cells were treated with various concentrations of QTHX-containing serum (0, 5, 7.5 or 10 μg/mL) for 24 h. The expression of targets were measured with Activity Fluorometric Assay, Western blot and PCR assay.

resultsNetwork pharmacology indicated that liver-protective effect of QTHX was associated with its anti-inflammation response, oxidative stress, and lipid receptor signalling. 10 μg/mL QTHX significantly reduced the inflammation response and lipid levels in primary hepatocytes (ALT: 46.43 ± 2.76 U/L, AST: 13.96 ± 1.08 U/L, TG: 0.25 ± 0.01 mmol/L, TC: 0.14 ± 0.05 mmol/L), comparing with 0 μg/mL NASH group (ALT: 148 ± 9.22 U/L, AST: 53.02 ± 2.30 U/L, TG: 0.74 ± 0.07 mmol/L, TC: 0.91 ± 0.07 mmol/L) (

conclusionsThe study suggested that QTHX treats NASH in rats by activating the SCOS1/NF-κB/TLR4 pathway, suggesting QTHX could be further developed as a potential liver-protecting agent.