Icariside E4 通过磷酸化 AMPK 和抑制 HepG2 细胞中的 MID1IP1 的降血脂作用,Phytotherapy Research

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Icariside E4 通过磷酸化 AMPK 和抑制 HepG2 细胞中的 MID1IP1 的降血脂作用
Phytotherapy Research ( IF 6.1 ) Pub Date : 2022-08-02 , DOI: 10.1002/ptr.7584
Jin Young Suh ₁ , Hyo-Jung Lee ₁ , Deok Yong Sim ₁ , Ji Eon Park ₁ , Chi-Hoon Ahn ₁ , Su-Yeon Park ₁ , Nari Shin ₁ , Bonglee Kim ₁ , Bum Sang Shim ₁ , Sung-Hoon Kim ₁

Affiliation

尽管已知淫羊藿苷 E4 (IE4) 具有抗痛、抗氧化、抗阿尔茨海默病和抗炎作用，但目前尚无证据表明 IE4 对脂质代谢有影响。因此，在与 MID1 相互作用蛋白 1 (MID1IP1) 和 AMPK 信号相关的 HepG2 肝细胞癌细胞 (HCC) 中研究了 IE4 的降脂机制。在这里，IE4 没有显示出对 HepG2 细胞的任何毒性，但通过油红 O 染色减少了 HepG2 细胞中的脂质积累。MID1IP1 耗竭降低了 HepG2 细胞中 SREBP-1c 和脂肪酸合酶 (FASN) 的表达并诱导了 ACC 的磷酸化。实际上，IE4 激活了 AMPK 和 ACC 的磷酸化并抑制了 HepG2 细胞中 MID1IP1 的表达。此外，IE4 抑制 SREBP-1c、肝 X 受体-α (LXR)、和 FASN 用于 HepG2 细胞中的从头脂肪生成。有趣的是，AMPK 抑制剂化合物 C 逆转了 IE4 降低 MID1IP1、SREBP-1c 和 FASN 并激活 HepG2 细胞中 AMPK/ACC 磷酸化的能力，表明 AMPK/ACC 信号通路在 IE4 诱导的降脂作用中的重要作用。综上所述，这些发现表明 IE4 通过激活 AMPK 和抑制 MID1IP1 在 HepG2 细胞中具有降脂潜力，可作为治疗脂肪肝疾病的有效候选药物。

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Hypolipogenic effects of Icariside E4 via phosphorylation of AMPK and inhibition of MID1IP1 in HepG2 cells

Though icariside E4 (IE4) is known to have anti-noceptive, anti-oxidant, anti-Alzheimer and anti-inflammatory effects, there was no evidence on the effect of IE4 on lipid metabolism so far. Hence, the hypolipogenic mechanism of IE4 was investigated in HepG2 hepatocellular carcinoma cells (HCCs) in association with MID1 Interacting Protein 1(MID1IP1) and AMPK signaling. Here, IE4 did not show any toxicity in HepG2 cells, but reduced lipid accumulation in HepG2 cells by Oil Red O staining. MID1IP1 depletion decreased the expression of SREBP-1c and fatty acid synthase (FASN) and induced phosphorylation of ACC in HepG2 cells. Indeed, IE4 activated phosphorylation of AMPK and ACC and inhibited the expression of MID1IP1 in HepG2 cells. Furthermore, IE4 suppressed the expression of SREBP-1c, liver X receptor-α (LXR), and FASN for de novo lipogenesis in HepG2 cells. Interestingly, AMPK inhibitor compound C reversed the ability of IE4 to reduce MID1IP1, SREBP-1c, and FASN and activate phosphorylation of AMPK/ACC in HepG2 cells, indicating the important role of AMPK/ACC signaling in IE4-induced hypolipogenic effect. Taken together, these findings suggest that IE4 has hypolipogenic potential in HepG2 cells via activation of AMPK and inhibition of MID1IP1 as a potent candidate for treatment of fatty liver disease.

更新日期：2022-08-02

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