Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province, 133002, China.
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province, 133002, China; Clinical Research Center, Affiliated Hospital of Yanbian University, Yanji, Jilin Province, 133002, China.
Chem Biol Interact. 2019 Sep 25;311:108794. doi: 10.1016/j.cbi.2019.108794. Epub 2019 Aug 14.
Acanthoic acid (AA) is a pimaradiene diterpene isolated from Acanthopanax koreanum Nakai (Araliaceae), with anti-inflammatory and hepatic-protective effects. The present study intended to reveal the effect and mechanism of AA on nonalcoholic fatty liver disease (NAFLD) associated with lipid accumulation by activating Farnesoid X receptor (FXR) and liver X receptors (LXRs) signaling. C57BL/6 mice were received a modified Lieber-DeCarli diet with 71% high-fat (L-D) and treated with AA (20 and 40 mg/kg) or equal volume of saline for 12 weeks. The regulation of AA on lipid accumulation was also detected in pro-steatotic stimulated AML12 cells with palmitic acid (PA). When L-D diet-fed mice were treated with AA, loss in body weight, liver index, and liver lipid droplet were observed along with reduced triglyceride (TG) and serum transaminase. Furthermore, AA decreased sterol regulatory element binding protein 1 (SREBP-1) and target genes expression, regulated PPARα and PPARγ expressions, ameliorated hepatic fibrosis markers, enhanced hepatic FXR and LXR, and regulated AMPK-LKB1 and SIRT1 signaling pathway. Moreover, AA attenuated lipid accumulation via FXR and LXR activation in steatotic AML-12 cells, which was confirmed by guggulsterones (FXR antagonist) or GW3965 (LXR agonist). Activation of FXR and LXR signaling caused by AA might increase AMPK-SIRT1 signaling and then contribute to modulating lipid accumulation and fatty acid synthesis, which suggested that activated FXR-LXR axis by AA represented an effective strategy for relieving NAFLD.
刺囊酸（AA）是从刺五加（五加科）中分离得到的一种松香二萜，具有抗炎和保肝作用。本研究旨在通过激活法尼醇 X 受体（FXR）和肝 X 受体（LXRs）信号通路，揭示 AA 对脂肪堆积相关的非酒精性脂肪性肝病（NAFLD）的作用及机制。C57BL/6 小鼠给予 71%高脂肪（L-D）改良 Lieber-DeCarli 饮食，并给予 AA（20 和 40mg/kg）或等体积生理盐水治疗 12 周。还在棕榈酸（PA）刺激的前脂肪细胞 AML12 中检测 AA 对脂肪堆积的调节作用。当 L-D 饮食喂养的小鼠用 AA 治疗时，观察到体重、肝指数和肝脂肪滴丢失，同时甘油三酯（TG）和血清转氨酶降低。此外，AA 降低固醇调节元件结合蛋白 1（SREBP-1）和靶基因表达，调节过氧化物酶体增殖物激活受体α和γ（PPARα 和 PPARγ）表达，改善肝纤维化标志物，增强肝 FXR 和 LXR，并调节 AMPK-LKB1 和 SIRT1 信号通路。此外，AA 通过激活 FXR 和 LXR 减少脂肪细胞内的脂肪堆积，在脂肪变性的 AML-12 细胞中证实了这一点，这可以通过 guggulsterones（FXR 拮抗剂）或 GW3965（LXR 激动剂）证实。AA 激活 FXR 和 LXR 信号可能会增加 AMPK-SIRT1 信号，从而有助于调节脂质积累和脂肪酸合成，这表明 AA 激活的 FXR-LXR 轴代表了缓解 NAFLD 的有效策略。
