Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117330. doi: 10.1016/j.jep.2023.117330. Epub 2023 Oct 19.
Traditional Chinese medicine (TCM) holds that non-alcoholic fatty liver disease (NAFLD) belong to the category of "thoracic fullness". Polygonum perfoliatum L. (PPL), a Chinese medicinal herb with the effect of treating thoracic fullness, was recorded in the ancient Chinese medicine book "Supplements to Compendium of Materia Medica". It has been used since ancient times to treat NAFLD. However, the underlying mechanism and active components of PPL against NAFLD remains unclear.
To identify the main active components and the anti-NAFLD mechanism of PPL.
Network pharmacology, UPLC/QE-HFX analysis, and molecular docking were employed to determine the main bioactive compounds and key targets of PPL for the NAFLD treatment. This effect was further validated with administration of PPL (200 mg/kg and 400 mg/kg) to NAFLD model mice for 5 weeks. Systemic signs of obesity, biochemical parameters, and histological changes were characterized. Immunohistochemistry, western blot, and PCR analysis were conducted to elucidate the mechanistic pathways through which PPL exerts its effects.
Network pharmacology revealed 77 crossover genes between the PPL and NAFLD. The kyoto encyclopedia of genes and genomes (KEGG) analysis show that PPL treat NAFLD mainly regulating glucose-lipid metabolism mediated by PI3K/AKT signal pathway. The Gene Ontology (GO) enrichment analysis show that PPL treat NAFLD mainly regulating inflammation mediated by cytokine-mediated signaling pathway. In accordance with the anticipated outcomes, administration of PPL in a dose-dependent manner effectively mitigated insulin resistance induced by a high-fat diet (HFD) by activating the PI3K/AKT signaling pathway. Histopathological evaluation corroborated the hepatoprotective effects of PPL against HFD-induced hepatic steatosis, as evidenced by the inhibition of de novo fatty acid synthesis and promotion of fatty acid β-oxidation (FAO). Further research showed that PPL blocked cytokine production by inhibiting the NF-κB pathway, thereby reducing immune cell infiltration. Furthermore, five flavonoids from PPL, including quercetin, baicalein, galangin, apigenin, and genistein were identified as key compounds based on ingredient-target-pathway network analysis. Molecular docking show that these active compounds have favorable binding interactions with AKT1, PIK3R1, and MAPK1, further confirming the impact of PPL on the PI3K/AKT pathway.
Through the combination of network pharmacology prediction and experimental validation, this work determined that therapeutic effect of PPL on NAFLD, and such protective effect is mediated by activating PI3K/AKT-mediated glucolipid metabolism pathway and hepatic NF-κB-mediated cytokine signaling pathway.
传统中医认为非酒精性脂肪性肝病（NAFLD）属于“胸满”范畴。具有治疗胸满功效的中草药-虎杖（PPL），在古代医学书籍《本草纲目》中就有记载，自古以来就被用于治疗 NAFLD。然而，PPL 治疗 NAFLD 的潜在机制和活性成分仍不清楚。
鉴定 PPL 的主要活性成分和抗 NAFLD 机制。
采用网络药理学、UPLC/QE-HFX 分析和分子对接技术，确定 PPL 治疗 NAFLD 的主要生物活性化合物和关键靶点。通过给予 PPL（200mg/kg 和 400mg/kg）治疗 5 周的 NAFLD 模型小鼠，进一步验证其效果。研究了全身性肥胖体征、生化参数和组织学变化。通过免疫组织化学、Western blot 和 PCR 分析阐明了 PPL 发挥作用的机制途径。
网络药理学揭示了 PPL 和 NAFLD 之间存在 77 个交叉基因。京都基因与基因组百科全书（KEGG）分析表明，PPL 主要通过 PI3K/AKT 信号通路调节葡萄糖-脂质代谢来治疗 NAFLD。基因本体论（GO）富集分析表明，PPL 主要通过细胞因子介导的信号通路调节炎症来治疗 NAFLD。与预期结果一致，PPL 以剂量依赖的方式给药，通过激活 PI3K/AKT 信号通路，有效缓解高脂肪饮食（HFD）引起的胰岛素抵抗。组织病理学评估证实了 PPL 对 HFD 诱导的肝脂肪变性具有保护作用，这表现在抑制新脂肪酸合成和促进脂肪酸β氧化（FAO）。进一步的研究表明，PPL 通过抑制 NF-κB 通路抑制细胞因子的产生，从而减少免疫细胞浸润。此外，基于成分-靶标-通路网络分析，从 PPL 中鉴定出 5 种类黄酮，包括槲皮素、黄芩素、高良姜素、芹菜素和染料木黄酮，它们是关键化合物。分子对接表明，这些活性化合物与 AKT1、PIK3R1 和 MAPK1 具有良好的结合相互作用，进一步证实了 PPL 对 PI3K/AKT 通路的影响。
通过网络药理学预测和实验验证的结合，本研究确定了 PPL 治疗 NAFLD 的疗效，这种保护作用是通过激活 PI3K/AKT 介导的糖脂代谢途径和肝 NF-κB 介导的细胞因子信号通路来介导的。
