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人参提取物可改善2型糖尿病小鼠的胰岛损伤并促进β细胞再生。

Ginseng extract improves pancreatic islet injury and promotes β-cell regeneration in T2DM mice.

作者信息

Yin Jianying, Huang Yuanfeng, Wang Ke, Zhong Qin, Liu Yuan, Ji Zirui, Liao Yiwen, Ma Zhiyuan, Bei Weijian, Wang Weixuan

机构信息

Traditional Chinese Medicine Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.

Guangdong Provincial Research Center of Integration of Traditional Chinese Medicine and Western Medicine in Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.

出版信息

Front Pharmacol. 2024 Jun 25;15:1407200. doi: 10.3389/fphar.2024.1407200. eCollection 2024.

Abstract

INTRODUCTION

. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting β-cell regeneration.

METHODS

The T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet β-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind β-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses.

RESULTS AND DISCUSSION

The present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1β decreased. Ginseng extract preserved normal islet morphology, increased nascent β-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing β-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to β-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance β-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

摘要

引言

人参(五加科;人参根及根茎)是东亚地区常用的传统植物,已显示出在治疗神经损伤疾病和糖尿病方面的功效。然而,其在缓解2型糖尿病(T2DM)中的具体作用和机制尚需进一步研究。本研究的目的是探讨人参提取物的药理作用,并阐明其在保护胰岛和促进β细胞再生方面的潜在机制。

方法

通过链脲佐菌素联合高脂饮食诱导建立T2DM小鼠模型。在给予人参提取物后的第7天和第28天处死两批小鼠。检测体重、空腹血糖水平和葡萄糖耐量。通过苏木精-伊红(H&E)染色检查胰岛的形态变化。采用酶联免疫吸附测定(ELISA)法检测血清胰岛素、胰高血糖素、胰高血糖素样肽-1(GLP-1)和炎症因子水平。通过胰岛素与增殖细胞核抗原(PCNA)双免疫荧光染色评估人参提取物促进胰岛β细胞再生的能力。此外,通过胰岛素与胰高血糖素双免疫荧光染色,结合免疫组织化学染色和蛋白质免疫印迹分析,探讨β细胞再生的机制。

结果与讨论

本研究表明,人参提取物可缓解小鼠T2DM症状,包括降低血糖水平和改善葡萄糖耐量。给予人参提取物后,血清胰岛素、GLP-1和白细胞介素-10(IL-10)水平升高,而胰高血糖素、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平降低。人参提取物保持了正常的胰岛形态,增加了新生β细胞数量,抑制了胰岛内的炎症浸润,此外,它降低了α细胞比例,同时增加了β细胞比例。机制上,人参提取物可能抑制无翅型MMTV整合位点家族成员A(ARX)和肌肉萎缩相关因子B(MAFB)的表达,提高胰腺十二指肠同源盒基因1(MAFA)水平以促进α细胞向β细胞转化,并激活蛋白激酶B(AKT)-叉头框蛋白M1(FOXM1)/细胞周期蛋白D2以增强β细胞增殖。我们的研究表明,人参提取物可能是治疗T2DM的一种有前景的疗法,尤其是对胰岛损伤患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9a/11234855/6b9634c06a8d/fphar-15-1407200-g001.jpg

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