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旧药新用：间苯三酚的抗糖尿病特性。

New Application of an Old Drug: Anti-Diabetic Properties of Phloroglucinol.

机构信息

Department of Hypertension and Diabetology, Medical University of Gdansk, 80-214 Gdansk, Poland.

Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, 15-089 Bialystok, Poland.

出版信息

Int J Mol Sci. 2024 Sep 24;25(19):10291. doi: 10.3390/ijms251910291.

DOI:10.3390/ijms251910291
PMID:39408621
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11477119/
Abstract

Phloroglucinol (PHG), an analgesic and spasmolytic drug, shows promise in preventing high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. In Wistar rats, 10 weeks of PHG treatment did not prevent HFD-induced weight gain but significantly mitigated fasting hyperglycemia, impaired insulin responses, and liver steatosis. This protective effect was not linked to hepatic lipogenesis or AMP-activated protein kinase (AMPK) activation. Instead, PHG improved mitochondrial function by reducing oxidative stress, enhancing ATP production, and increasing anti-oxidant enzyme activity. PHG also relaxed gastric smooth muscles via potassium channel activation and nitric oxide (NO) signaling, potentially delaying gastric emptying. A pilot intervention in pre-diabetic men confirmed PHG's efficacy in improving postprandial glycemic control and altering lipid metabolism. These findings suggest PHG as a potential therapeutic for NAFLD and insulin resistance, acting through mechanisms involving mitochondrial protection, anti-oxidant activity, and gastric motility modulation. Further clinical evaluation is warranted to explore PHG's full therapeutic potential.

摘要

间苯三酚（PHG）是一种止痛和解痉药物，在预防高脂肪饮食（HFD）诱导的非酒精性脂肪肝（NAFLD）和胰岛素抵抗方面显示出潜力。在 Wistar 大鼠中，10 周的 PHG 治疗并未预防 HFD 诱导的体重增加，但显著减轻了空腹高血糖、受损的胰岛素反应和肝脂肪变性。这种保护作用与肝脂肪生成或 AMP 激活蛋白激酶（AMPK）激活无关。相反，PHG 通过减少氧化应激、增加 ATP 产生和增加抗氧化酶活性来改善线粒体功能。PHG 还通过钾通道激活和一氧化氮（NO）信号传导使胃平滑肌松弛，可能会延迟胃排空。一项针对糖尿病前期男性的初步干预研究证实了 PHG 改善餐后血糖控制和改变脂质代谢的功效。这些发现表明 PHG 可能是治疗 NAFLD 和胰岛素抵抗的一种潜在药物，其作用机制涉及线粒体保护、抗氧化活性和胃动力调节。需要进一步的临床评估来探索 PHG 的全部治疗潜力。

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Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade.姜黄素和白藜芦醇通过 PI3K/AKT/mTOR 和 HIF-1/VEGF 级联减轻代谢相关脂肪性肝病肝脂肪变性的高级效应。
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