Department of Integrated Traditional Chinese & Western Medicine, Southwest Medical University, Luzhou, China.
Hepatobiliary Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.
Pharm Biol. 2023 Dec;61(1):520-530. doi: 10.1080/13880209.2023.2182892.
Qutan Huoxue decoction (QTHX) is used to treat non-alcoholic steatohepatitis (NASH) with good efficacy in the clinic. However, the mechanism is not clear yet.
This study investigates the mechanism of QTHX in the treatment of NASH.
Potential 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.
Network 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) ( < 0.01). Meanwhile, QTHX increased expression of SOCS1 and decreased expression of TLR4, Myd88, NF-κB.
The 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.
祛瘫活血汤（QTHX）在临床上治疗非酒精性脂肪性肝炎（NASH）疗效确切，但作用机制尚不清楚。
本研究旨在探讨 QTHX 治疗 NASH 的作用机制。
采用网络药理学预测 QTHX 的潜在作用途径。40 只 Sprague Dawley（SD）大鼠（半正常饮食，半高脂肪饮食）喂养 6-8 周后，提取原代肝细胞和枯否细胞，采用 0.4 微米 Transwell 培养系统共培养。然后，用正常血清处理正常共培养细胞，用不同浓度（0、5、7.5 或 10μg/ml）的含 QTHX 血清处理 NASH 共培养细胞 24h。采用活性荧光法、Western blot 和 PCR 法检测靶基因的表达。
网络药理学表明，QTHX 的保肝作用与其抗炎反应、氧化应激和脂质受体信号有关。10μg/ml 的 QTHX 可显著降低原代肝细胞的炎症反应和脂质水平（ALT：46.43±2.76U/L，AST：13.96±1.08U/L，TG：0.25±0.01mmol/L，TC：0.14±0.05mmol/L），与 0μg/ml 的 NASH 组相比（ALT：148±9.22U/L，AST：53.02±2.30U/L，TG：0.74±0.07mmol/L，TC：0.91±0.07mmol/L）（P<0.01）。同时，QTHX 增加了 SOCS1 的表达，降低了 TLR4、Myd88 和 NF-κB 的表达。
本研究提示 QTHX 通过激活 SOCS1/NF-κB/TLR4 通路治疗 NASH 大鼠，提示 QTHX 可进一步开发为潜在的保肝药物。
