枸杞子通过提高 SIRT1 和 AMPK 的水平抑制高脂高果糖诱导大鼠肝细胞的新脂肪生成活性

Q2 Medicine Journal of Experimental Pharmacology Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.2147/JEP.S473763
Putri Anggreini, Hadi Kuncoro, Sri Adi Sumiwi, Jutti Levita
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引用次数: 0

摘要

背景:目前,非酒精性脂肪肝(NAFLD)的发病率因其诱发 T2DM 和心血管疾病的风险而备受关注。非酒精性脂肪肝的发生可能是由肝细胞中的新生脂肪生成开始的。Sirtuin1(SIRT1)和单磷酸腺苷激活蛋白激酶(AMPK)负责脂肪生成机制。有趣的是,β-谷甾醇和豆固醇等植物固醇有可能降低血脂异常患者的低密度脂蛋白胆固醇。β-谷甾醇存在于微叶枸杞草的乙醇提取物中,浓度为 283.55 µg/g 提取物。目的:通过 SIRT1 和 AMPK 水平,研究微叶枸杞子乙醇提取物(ELM)在大鼠肝组织中的抗血脂生成活性:本研究使用了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)二甲双胍治疗的HFHFD大鼠;(4)白藜芦醇治疗的HFHFD大鼠;(5)β-谷甾醇治疗的HFHFD大鼠;(6-8)ELM剂量为200、400和600 mg/kg体重的HFHFD大鼠。正常对照组大鼠喂食普通饲料,其他组大鼠喂食 HFHFD 35 天。所有药物均从第 15 天开始口服,直至第 35 天。D35日,大鼠被处死,并检查肝脏指数、形态、非酒精性脂肪肝活动评分(NAS)以及SIRT1和AMPK的水平:结果:ELM改善了HFHFD诱导的非酒精性脂肪肝大鼠的肝脏形态、肝脏指数、脂肪变性状况和NAS。结果:ELM能改善HFHFD诱导的非酒精性脂肪肝大鼠的肝脏形态、肝脏指数、脂肪变性状况和NAS,提高HFHFD诱导的非酒精性脂肪肝大鼠肝组织中SIRT1和AMPK的水平:结论:ELM可通过提高SIRT1和AMPK的水平来抑制新生脂肪生成。
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Lygodium microphyllum Inhibits de Novo Lipogenesis Activity in the Hepatocytes of High-Fat High-Fructose-Induced Rats by Increasing the Levels of SIRT1 and AMPK.

Background: 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 Lygodium microphyllum 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.

Purpose: To investigate the anti-lipogenesis activity of the ethanol extract of L. microphyllum (ELM) in the liver tissue of rats through the SIRT1 and AMPK levels.

Methods: 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.

Results: 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.

Conclusion: ELM may have the potential to inhibit de novo lipogenesis by increasing the levels of SIRT1 and AMPK.

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来源期刊
Journal of Experimental Pharmacology
Journal of Experimental Pharmacology Medicine-Pharmacology (medical)
CiteScore
7.40
自引率
0.00%
发文量
43
审稿时长
16 weeks
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