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没食子酸的抗糖尿病潜力:通过 PPAR-γ 和 Akt 信号转导提高葡萄糖转运体和胰岛素敏感性。

Antidiabetic potential of gallic acid from Emblica officinalis: Improved glucose transporters and insulin sensitivity through PPAR-γ and Akt signaling.

机构信息

Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382481, India.

Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382481, India.

出版信息

Phytomedicine. 2020 Jul 15;73:152906. doi: 10.1016/j.phymed.2019.152906. Epub 2019 Apr 1.

DOI:10.1016/j.phymed.2019.152906
PMID:31064680
Abstract

BACKGROUND

Nature has gifted a variety of vital phytochemicals having potential therapeutic application against various ailments. Emblica officinalis (E. officinalis), an ancient plant, has long been used as a remedy for diabetes and cardiovascular complications, and presence of abundant amount of gallic acid could be accountable for its medicinal potential.

PURPOSE

The study was aimed to determine the in-vivo and in-vitro anti-diabetic potential of gallic acid and fruit juice of E. officinalis. Molecular mechanism of gallic acid as well as fruit juice of E. officinalis for anti-diabetic potential has also been revealed.

EXPERIMENTAL STUDY DESIGN

Anti-diabetic potential of E. officinalis and gallic acid was evaluated in 3T3-L1 preadipocytes and various animal models like db/db mice and fructose administered rats. PPAR-γ expression and glucose translocation were observed using western blot and PCR techniques.

RESULTS

Treatment of E. officinalis fruit juice and gallic acid facilitated their glucose homeostasis; improved insulin sensitivity; reduced obesity; abridged elevated blood pressure and declined cholesterol level, and also induced adipogenesis in 3T3-L1 adipocytes. Mechanistically, treatment increased expression of PPAR-γ through activation of C/EBPs and simultaneously increased Glut4 translocation in 3T3-L1 adipocytes. Moreover, gallic acid treatment increased insulin sensitivity through activation of Akt rather than AMPK signaling pathway while fruit juice of E. officinalis showed dual activation, Akt and AMPK as well.

CONCLUSION

These findings reveal the role of gallic acid in E. officinalis mediated antidiabetic potential, and delineate the upregulation of pAkt, PPAR-γ and Glut4 in gallic acid mediated antidiabetic activity, thus providing potential therapy for diabetes and related disorders.

摘要

背景

大自然赋予了各种具有潜在治疗应用的重要植物化学物质,可用于治疗各种疾病。余甘子(E. officinalis)是一种古老的植物,长期以来一直被用作治疗糖尿病和心血管并发症的药物,其丰富的没食子酸含量可能是其药用潜力的原因。

目的

本研究旨在确定没食子酸和余甘子果汁的体内和体外抗糖尿病潜力。还揭示了没食子酸和余甘子果汁的抗糖尿病潜力的分子机制。

实验研究设计

在 3T3-L1 前脂肪细胞和 db/db 小鼠和果糖给药大鼠等各种动物模型中评估了余甘子和没食子酸的抗糖尿病潜力。使用 Western blot 和 PCR 技术观察 PPAR-γ 表达和葡萄糖转运。

结果

余甘子果汁和没食子酸的治疗促进了它们的葡萄糖稳态;改善了胰岛素敏感性;减少了肥胖;减轻了高血压和降低了胆固醇水平,并在 3T3-L1 脂肪细胞中诱导了脂肪生成。从机制上讲,通过激活 C/EBPs,治疗增加了 PPAR-γ 的表达,同时增加了 3T3-L1 脂肪细胞中的 Glut4 易位。此外,没食子酸通过激活 Akt 而不是 AMPK 信号通路增加了胰岛素敏感性,而余甘子果汁则表现出双重激活,Akt 和 AMPK 也是如此。

结论

这些发现揭示了没食子酸在余甘子介导的抗糖尿病潜力中的作用,并描述了在没食子酸介导的抗糖尿病活性中 pAkt、PPAR-γ 和 Glut4 的上调,从而为糖尿病和相关疾病提供了潜在的治疗方法。

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