DataSheet1_Ginseng extract improves pancreatic islet injury and promotes β-cell regeneration in T2DM mice.pdf

IntroductionPanax ginseng C. A. Mey. (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.
MethodsThe 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 DiscussionThe 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.

引言：人参（Panax ginseng C. A. Mey.，五加科，人参根及根茎）是东亚地区广泛应用的传统药用植物，已被证实对神经损伤类疾病与糖尿病具有治疗功效。但其缓解2型糖尿病（type 2 diabetes mellitus, T2DM）的具体作用与机制仍需进一步研究。本研究旨在探究人参提取物的药理作用，阐明其保护胰岛并促进β细胞再生的潜在机制。
方法：通过链脲佐菌素（streptozotocin）联合高脂饮食诱导构建2型糖尿病小鼠模型。分别在给予人参提取物后的第7天和第28天处死两批次小鼠，检测其体重、空腹血糖水平与葡萄糖耐量。采用苏木精-伊红（H & E）染色观察胰岛的形态学变化。通过酶联免疫吸附测定（ELISA）检测血清胰岛素、胰高血糖素、胰高血糖素样肽-1（GLP-1）及炎症因子水平。采用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及蛋白质印迹（western blot）分析，探究β细胞再生的潜在机制。
结果与讨论：本研究发现，人参提取物可缓解小鼠的2型糖尿病症状，包括降低血糖水平并改善葡萄糖耐量。给予人参提取物后，小鼠血清胰岛素、GLP-1及白细胞介素-10（IL-10）水平升高，而胰高血糖素、肿瘤坏死因子-α（TNF-α）及白细胞介素-1β（IL-1β）水平降低。人参提取物可维持胰岛正常形态，增加新生β细胞群体数量，抑制胰岛内炎症浸润；同时降低α细胞比例，升高β细胞比例。机制层面，人参提取物可能通过抑制ARX与MAFB的表达、升高MAFA水平以促进α细胞向β细胞转化，并激活AKT-FOXM1/细胞周期蛋白D2（cyclin D2）通路以增强β细胞增殖。本研究表明，人参提取物有望成为治疗2型糖尿病的潜在疗法，尤其适用于存在胰岛损伤的患者。