Anggreini Putri, Kuncoro Hadi, Sumiwi Sri Adi, Levita Jutti
Doctoral Program in Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, Indonesia.
Department of Pharmacognosy and Medicinal Chemistry, Faculty of Pharmacy, Mulawarman University, Samarinda, East Kalimantan, Indonesia.
J Exp Pharmacol. 2024 Oct 9;16:351-364. doi: 10.2147/JEP.S473763. eCollection 2024.
The prevalence of non-alcoholic fatty liver disease (NAFLD) is currently of great concern due to its risk of developing T2DM and cardiovascular disease. The development of NAFLD may be initiated by de novo lipogenesis in the hepatocytes. Sirtuin1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK), are responsible for the lipogenesis mechanism. Interestingly, plant sterols, such as beta-sitosterol and stigmasterol, have the potential to lower the LDL-cholesterol in dyslipidemic patients. Beta-sitosterol was present in the ethanol extract of herbs at a concentration of 283.55 µg/g extract. This sterol interacted with the active allosteric-binding site of SIRT1 and AMPK similarly to the proteins' activators.
To investigate the anti-lipogenesis activity of the ethanol extract of (ELM) in the liver tissue of rats through the SIRT1 and AMPK levels.
Forty male Wistar rats were used in this study: (1) normal control group; (2) high-fat high-fructose diet (HFHFD) rats; (3) HFHFD rats treated with metformin; (4) HFHFD rats treated with resveratrol; (5) HFHFD rats treated with beta-sitosterol; (6-8) HFHFD rats treated with ELM doses of 200, 400, and 600 mg/kg BW. Rats in the normal control group were fed regular chow, while other groups of rats were given HFHFD for 35 days. All drugs were given orally on D15 till D35. On D35, the rats were sacrificed, and the liver organs were examined for the liver index, morphology, NAFLD activity score (NAS), and levels of SIRT1 and AMPK.
ELM improves the morphology, the liver index, the steatosis condition, and the NAS of HFHFD-induced NAFLD rats. ELM increases the levels of SIRT1 and AMPK in the liver tissue of HFHFD-induced NAFLD rats.
ELM may have the potential to inhibit de novo lipogenesis by increasing the levels of SIRT1 and AMPK.
非酒精性脂肪性肝病（NAFLD）的患病率因其发展为2型糖尿病和心血管疾病的风险而备受关注。NAFLD的发展可能由肝细胞中的从头脂肪生成引发。沉默调节蛋白1（SIRT1）和腺苷单磷酸激活蛋白激酶（AMPK）负责脂肪生成机制。有趣的是，植物甾醇，如β-谷甾醇和豆甾醇，有降低血脂异常患者低密度脂蛋白胆固醇的潜力。β-谷甾醇以283.55μg/g提取物的浓度存在于草药的乙醇提取物中。这种甾醇与SIRT1和AMPK的活性变构结合位点相互作用，类似于蛋白质的激活剂。
通过SIRT1和AMPK水平研究[草药名称]乙醇提取物（ELM）在大鼠肝脏组织中的抗脂肪生成活性。
本研究使用40只雄性Wistar大鼠：（1）正常对照组；（2）高脂高果糖饮食（HFHFD）大鼠；（3）用二甲双胍治疗的HFHFD大鼠；（4）用白藜芦醇治疗的HFHFD大鼠；（5）用β-谷甾醇治疗的HFHFD大鼠；（6 - 8）用200、400和600mg/kg体重剂量的ELM治疗的HFHFD大鼠。正常对照组的大鼠喂食常规饲料，而其他组的大鼠给予HFHFD 35天。所有药物在第15天至第35天口服给药。在第35天，处死大鼠，检查肝脏器官的肝脏指数、形态、NAFLD活动评分（NAS）以及SIRT1和AMPK水平。
ELM改善了HFHFD诱导的NAFLD大鼠的形态、肝脏指数、脂肪变性状况和NAS。ELM增加了HFHFD诱导的NAFLD大鼠肝脏组织中SIRT1和AMPK的水平。
ELM可能有通过增加SIRT1和AMPK水平来抑制从头脂肪生成的潜力。
