<br>姜黄素和白藜芦醇通过 PI3K/AKT/mTOR 和 HIF-1/VEGF 级联减轻代谢相关性脂肪肝疾病中的肝脏脂肪变性的先进作用,Biomedicine & Pharmacotherapy

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姜黄素和白藜芦醇通过 PI3K/AKT/mTOR 和 HIF-1/VEGF 级联减轻代谢相关性脂肪肝疾病中的肝脏脂肪变性的先进作用
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2023-08-04 , DOI: 10.1016/j.biopha.2023.115279
Yuhui He, Huan Wang, Shiling Lin, Tao Chen, Dennis Chang, Yibin Sun, Chenxiang Wang, Yang Liu, Yusheng Lu, Jianyuan Song, Shaohua Li, Wen Xu, Yanxiang Lin, Yanfang Zheng, Xian Zhou, Qiumei Huang, Mingqing Huang

代谢相关脂肪肝病（MAFLD）是最常见的慢性肝病，目前尚无可行的治疗方法。姜黄素 (Cur) 和白藜芦醇 (Res) 是两种天然产物，已对其改善 MAFLD 的潜力进行了研究。然而，虽然这些化合物已被单独研究，但它们的组合使用以及协同或增强效应的潜力仍未被探索。本研究旨在探讨姜黄素 (Cur) 和白藜芦醇 (Res) 作为潜在联合疗法治疗 MAFLD 的效果。 Cur、Res 和 Cur+Res 在棕榈酸 (PA) 诱导的 HepG2 细胞中进行了测试。采用Goto-Kakizaki大鼠建立MAFLD模型。动物用载体对照（模型组）、Cur（150 mg/kg）、Res（150 mg/kg）、Cur+Res（150 mg/kg，8:2）或二甲双胍（Met，阳性对照）治疗，400 mg/kg/天）口服灌胃，持续 4 周。 Wistar大鼠作为对照组。通过网络药理学阐明 Cur 和 Res 的分子作用，然后进行 q-PCR 和免疫印迹。 Cur+Res 在降低 PA 诱导的 HepG2 细胞中甘油三酯、总胆固醇和脂质积累方面表现出协同作用。该组合还显着减轻了 MAFLD 大鼠的肝脏脂肪变性。网络药理学表明，Cur 和 Res 的相互作用与 PI3K/AKT/mTOR 和 HIF-1 信号通路相关的多个分子靶点的调节有关。实验结果证实，Cur+Res 标准化了 PI3K/AKT/mTOR 和 HIF-1 信号通路中的基因靶标和蛋白表达，包括 PI3K、mTOR、STAT-3、HIF-1α 和 VEGF。本研究证明了 Cur 和 Res 联合使用可以减轻 MAFLD，其机制至少部分与 PI3K/AKT/mTOR 和 HIF-1 信号通路的调节有关。

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Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade

Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated individually, their combined use and the potential for a synergistic or augmented effect remain unexplored. This study aims to investigate the effect of curcumin (Cur) and resveratrol (Res) as a potential combination therapy on MAFLD. Cur, Res and Cur+Res were tested in palmitic acid (PA)-induced-HepG2 cells. MAFLD model was established using Goto-Kakizaki rats. The animals were treated with vehicle control (model group), Cur (150 mg/kg), Res (150 mg/kg), Cur+Res (150 mg/kg, 8:2, ), or metformin (Met, positive control, 400 mg/kg/day) oral gavage for 4 weeks. Wistar rats were used as the control group. Network pharmacology was conducted to elucidate the molecular actions of Cur and Res, followed by q-PCR and immunoblotting . Cur+Res exhibited synergistic effects in reducing triglyceride, total cholesterol and lipid accumulation in PA-induced HepG2 cells. The combination also markedly attenuated hepatic steatosis in the MAFLD rats. Network pharmacology illustrated that the interaction of Cur and Res was associated with the modulation of multiple molecular targets associated with the PI3K/AKT/mTOR and HIF-1 signaling pathways. Experimental results confirmed that Cur+Res nomalised the gene targets and protein expressions in the PI3K/AKT/mTOR and HIF-1 signaling pathways, including PI3K, mTOR, STAT-3, HIF-1α, and VEGF. The present study demonstrated an advanced effect of Cur and Res in combination to attenuate MAFLD, and the mechanism is at least partly associated with the modulation of the PI3K/AKT/mTOR and HIF-1 signaling pathways.

更新日期：2023-08-04

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