J Agric Food Chem. 2019 Dec 18;67(50):13929-13938. doi: 10.1021/acs.jafc.9b05632. Epub 2019 Dec 5.
Lipid accumulation is a typical characteristic of nonalcoholic fatty liver disease (NAFLD). The inhibition of lipid accumulation is regarded as a potential treatment for NAFLD. In this study, we investigated the effects of γ-mangostin or α-mangostin on lipid accumulation in a cell model. Analysis of the inhibitory effects of γ-mangostin on lipid accumulation revealed that it downregulated NAFLD-related biochemical parameters and stimulated the SIRT1/LKB1/AMPK pathway. Consequently, it suppressed lipid synthesis and enhanced fatty acid oxidation. Moreover, we demonstrated that the blockage of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C abrogated the promoting effect of AMPK. Similar results were also observed for α-mangostin. The effects of α-mangostin on lipid accumulation were inferior to those of γ-mangostin. The differences in CPT1A activity might be originated from their different chemical structures. Our results suggested that γ-mangostin and α-mangostin can be exploited as potential candidates for NAFLD treatment.
脂类积累是非酒精性脂肪肝（NAFLD）的一个典型特征。抑制脂类积累被认为是治疗 NAFLD 的一种潜在方法。在本研究中，我们研究了 γ-倒捻子素或 α-倒捻子素对细胞模型中脂类积累的影响。分析 γ-倒捻子素对脂类积累的抑制作用表明，它下调了与 NAFLD 相关的生化参数，并刺激了 SIRT1/LKB1/AMPK 通路。因此，它抑制了脂质合成并增强了脂肪酸氧化。此外，我们证明了 AMP 激活蛋白激酶（AMPK）的药理学抑制剂 Compound C 阻断了 AMPK 的促进作用。α-倒捻子素也观察到了类似的结果。α-倒捻子素对脂类积累的影响不如 γ-倒捻子素显著。CPT1A 活性的差异可能源于它们不同的化学结构。我们的研究结果表明，γ-倒捻子素和 α-倒捻子素可被开发为治疗 NAFLD 的潜在候选药物。
