Aqueous Extract of Guava (Psidium guajava L.) Leaf Ameliorates Hyperglycemia by Promoting Hepatic Glycogen Synthesis and Modulating Gut Microbiota.

Aqueous Extract of Guava (Psidium guajava L.) Leaf Ameliorates Hyperglycemia by Promoting Hepatic Glycogen Synthesis and Modulating Gut Microbiota.
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番石榴 (Psidium guajava L.) 叶水提取物通过促进肝糖原合成和调节肠道微生物群改善高血糖。

DOI:
10.3389/fphar.2022.907702
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发表时间:
2022
影响因子:
5.6
通讯作者:
Hu, Fang
Hu, Fang
中科院分区:
医学2区
文献类型:
--
作者:
Chu, Shuzhou;Zhang, Feng;Wang, Huiying;Xie, Lijun;Chen, Zhinan;Zeng, Weimin;Zhou, Zhiguang;Hu, Fang

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2型糖尿病(T2 DM)是一个主要的全球性健康问题。番石榴番石榴被广泛用作食物和民间药物。以前的研究已经显示了它的抗糖尿病和抗炎特性。然而,其根本机制仍然是难以捉摸的。在这项研究中,我们评估了番石榴叶水提取物(GvAEx)对2型糖尿病的潜在治疗作用,并探讨了其潜在的机制,在体内和体外。在糖尿病db/db小鼠中管饲施用GvAEx 12周。我们的结果表明,GvAEx显著降低空腹血糖水平(p < 0.01),改善葡萄糖耐量和胰岛素敏感性(分别为p < 0.01,p < 0.05)。此外,GvAEx增加肝糖原积累,葡萄糖摄取,并降低致凋亡基因的mRNA表达水平。此外,GvAEx处理引起肝细胞膜中葡萄糖转运蛋白2(GLUT 2)表达升高。值得注意的是,我们首次从肠道微生物群的角度阐述了GvAEx降血糖作用的可能机制。GvAEx显著改变了肠道微生物群的组成,并增加了肠道中产生短链脂肪酸(SCFA)的毛螺菌科和阿克曼菌属。GvAEx可通过调节肝脏糖代谢和恢复肠道菌群来缓解2型糖尿病的高血糖和胰岛素抵抗。因此,GvAEx具有开发抗T2 DM药物的潜力。
Type 2 diabetes mellitus (T2DM) is a major global health concern. Psidium guajava L. (guava) is widely used for food as well as a folk medicine. Previous studies have shown its anti-diabetic and anti-inflammatory properties. However, the underlying mechanisms remains to be elusive. In this study, we assessed the potential therapeutic effects of aqueous extract of guava leaves (GvAEx) on T2DM and explored their potential mechanisms in vivo and in vitro. GvAEx was gavage administered for 12 weeks in diabetic db/db mice. Our results have demonstrated that GvAEx significantly lowered fasting plasma glucose levels (p < 0.01) and improved glucose tolerance and insulin sensitivity (p < 0.01, p < 0.05, respectively). Additionally, GvAEx increased hepatic glycogen accumulation, glucose uptake and decreased the mRNA expression levels of gluconeogenic genes. Furthermore, GvAEx-treatment caused higher glucose transporter 2 (GLUT2) expression in the membrane in hepatocytes. Notably, for the first time, we have elaborated the possible mechanism of the hypoglycemic effect of GvAEx from the perspective of intestinal microbiota. GvAEx has significantly changed the composition of microbiota and increased short chain fatty acid (SCFA) -producing Lachnospiraceae family and Akkermansia genus in the gut. Taken together, GvAEx could alleviate hyperglycemia and insulin resistance of T2DM by regulating glucose metabolism in the liver and restoring the gut microbiota. Thus, GvAEx has the potential for drug development against T2DM.
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