Sun Wen, Xu Guangyuan, Guo Xuan, Luo Guangbin, Wu Lili, Hou Yi, Guo Xiangyu, Zhou Jingxin, Xu Tunhai, Qin Lingling, Fan Yixin, Han Li, Matsabisa Motlalepula, Ma Xuesheng, Liu Tonghua
Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.
Department of Endocrinology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1333-1339. doi: 10.3892/mmr.2017.6684. Epub 2017 Jun 2.
Asiatic acid (AA) has been demonstrated to exhibit anti-diabetic activity. However, the mechanisms and underlying signaling pathways remain to be elucidated. The present study was performed to confirm the protective effect of AA and demonstrate its ability to regulate the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase‑3β (GSK‑3β) signaling pathway in db/db mice. Db/db mice fed on a high‑fat diet were used to model diabetes mellitus. Modeled mice were divided randomly into the model control, pioglitazone hydrochloride tablet (PH) and AA groups. Age‑matched C57 BL/6J mice served as normal controls. Lipid and glucose levels, and glycogen synthesis rates were assessed following treatment. Pathological changes were detected using hematoxylin and eosin staining. Expression of the PI3K/AKT/GSK‑3β signaling pathway at the mRNA level was measured using quantitative polymerase chain reaction analysis. The model control group revealed typical characteristics of obesity and diabetes, including high glucose and lipid levels, and decreased glycogen synthesis. Four weeks of treatment with AA or PH ameliorated these abnormalities. AA and PH treatments mitigated the upregulation of PI3K, AKT, insulin receptor, and insulin receptor substrate‑1 mRNA expression in modeled mice. Furthermore, AA and PH treatments decreased GSK‑3β and glucose‑6‑phosphatase mRNA expression compared with the normal control group. The results of the present study confirmed that AA possesses anti‑diabetic activity in db/db mice. The PI3K/AKT/GSK‑3β signaling pathway may mediate this protective effect.
齐墩果酸（AA）已被证明具有抗糖尿病活性。然而，其作用机制和潜在的信号通路仍有待阐明。本研究旨在证实AA的保护作用，并证明其调节db/db小鼠中磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/糖原合酶激酶-3β（GSK-3β）信号通路的能力。以高脂饮食喂养的db/db小鼠作为糖尿病模型。将造模小鼠随机分为模型对照组、盐酸吡格列酮片（PH）组和AA组。年龄匹配的C57 BL/6J小鼠作为正常对照组。治疗后评估血脂和血糖水平以及糖原合成率。采用苏木精-伊红染色检测病理变化。使用定量聚合酶链反应分析测定PI3K/AKT/GSK-3β信号通路在mRNA水平的表达。模型对照组呈现出肥胖和糖尿病的典型特征，包括高血糖和高血脂水平以及糖原合成减少。用AA或PH治疗四周改善了这些异常情况。AA和PH治疗减轻了造模小鼠中PI3K、AKT、胰岛素受体和胰岛素受体底物-1 mRNA表达的上调。此外，与正常对照组相比，AA和PH治疗降低了GSK-3β和葡萄糖-6-磷酸酶mRNA的表达。本研究结果证实AA在db/db小鼠中具有抗糖尿病活性。PI3K/AKT/GSK-3β信号通路可能介导了这种保护作用。
