Qingkailing Oral Liquid modulates AMPK/PI3K/AKT signaling to attenuate NAFLD pathogenesis

LIAN Lifang; ZHANG Yuefeng; ZHOU Xiaoqin; WANG Qiuyun; XIE Zhiyong

doi:10.13471/j.cnki.acta.snus.ZR20250084

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Qingkailing Oral Liquid modulates AMPK/PI3K/AKT signaling to attenuate NAFLD pathogenesis

更新时间：2025-09-19

- Qingkailing Oral Liquid modulates AMPK/PI3K/AKT signaling to attenuate NAFLD pathogenesis
- Acta Scientiarum Naturalium Universitatis Sunyatseni Pages: 1-9(2025)
- 作者机构：
  
  1.中山大学药学院（深圳），广东深圳 518107
  2.广州白云山明兴制药有限公司，广东广州 510250
- 作者简介：
- 基金信息：
- DOI：10.13471/j.cnki.acta.snus.ZR20250084
  CLC： R285
- Received：17 May 2025，
  
  Revised：2025-06-16，
  
  Accepted：14 July 2025，
  
  Published Online：2025-09，
- 稿件说明：
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LIAN Lifang, ZHANG Yuefeng, ZHOU Xiaoqin, et al. Qingkailing Oral Liquid modulates AMPK/PI3K/AKT signaling to attenuate NAFLD pathogenesis[J/OL]. Acta scientiarum naturalium universitatis sunyatseni, 2025, 1-9.
DOI：

LIAN Lifang, ZHANG Yuefeng, ZHOU Xiaoqin, et al. Qingkailing Oral Liquid modulates AMPK/PI3K/AKT signaling to attenuate NAFLD pathogenesis[J/OL]. Acta scientiarum naturalium universitatis sunyatseni, 2025, 1-9. DOI： 10.13471/j.cnki.acta.snus.ZR20250084.

摘要

非酒精性脂肪肝（NAFLD， nonalcoholic fatty liver disease）作为全球第一大慢性肝病，其发病机制复杂，临床尚无特效治疗药物，故深入探索其干预策略具有重要意义。本研究构建了脂质累积模型，评估清开灵口服液（QKL，qingkailing oral liquid）减轻NAFLD的脂质累积的疗效，结合网络药理学筛选作用靶标，并通过qPCR和Western Blot分析关键信号通路基因及蛋白表达。结果显示：①

=0.5%、1%和2%的QKL干预48 h后，HepG2和AML-12细胞脂质累积模型内脂滴体积和数量均显著减少，TG含量呈剂量依赖性地降低，

=2% QKL干预效果与2 mmol/L二甲双胍相当；② 网络药理学预测磷脂酰肌醇3-激酶（PI3K，phosphatidylinositol 3-kinase）-蛋白激酶B（Akt

，protein kinase B）、腺苷酸激活蛋白激酶（AMPK，adenosine monophosphate-activated protein kinase）等信号通路在QKL干预中发挥重要作用，且QKL与AMPK、PI3K等靶点具有潜在的结合活性；③ QKL可能通过双重调控AMPK-SREBP1与PI3K-AKT-mTOR信号通路，进而有效缓解肝细胞脂质蓄积。本研究基于“体外模型-网络药理学-实验验证”策略，系统探讨QKL干预NAFLD脂质代谢的分子机制，为中药现代化和NAFLD治疗提供新的策略。

Abstract

Nonalcoholic fatty liver disease （NAFLD）is the most prevalent and worlwide chronic liver disease. Due to the complex pathogenesis and lacking targeted therapies， it is critically significant to explore intervention strategies. In this study， we first established a lipid accumulation model to evaluate the efficacy of Qingkailing oral liquid （QKL） in alleviating NAFLD-associated lipid accumulation. Network pharmacology was employed to screen potential therapeutic targets， followed by validation of key signaling pathway genes and protein expression via qPCR and Western blot. The results showed that： ① After 48 h of treatment with

=0.5%， 1%， and 2% QKL， both HepG2 and AML-12 lipid accumulation models exhibited a significant reduction in lipid droplet size and number. The triglyceride （TG） content decreased in a dose-dependent manner， with

=2% QKL showing comparable efficacy to 2 mmol/L metformin. Network pharmacology predicted that key pathways， including phosphatidylinositol 3-kinase （PI3K）-protein kinase B （Akt） and adenosine monophosphate-activated protein kinase （AMPK）， play crucial roles in QKL-mediated intervention. Molecular docking suggested potential binding activity between QKL and targets such as AMPK and PI3K. ② QKL likely exerts its anti-lipid accumulation effects through dual regulation of the AMPK-SREBP1 and PI3K-AKT-mTOR signaling pathways， thereby effectively mitigating hepatic lipid deposition. ③This study employed an integrated “

in vitro

modeling-network pharmacology-experimental validation” strategy to systematically investigate the molecular mechanisms by which QKL modulates lipid metabolism in NAFLD， providing novel in

sights for both modernization of traditional Chinese medicine and the development of therapeutic strategies against NAFLD.

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