Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
BMC Complement Med Ther. 2023 May 8;23(1):151. doi: 10.1186/s12906-023-03977-y.
Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in high glucose and high insulin-induced insulin-resistant HepG2 cells.
The effects of methanolic, chloroform and total extracts on cell proliferation were assessed by the MTT assay. The potential of non-toxic extracts on glucose utilization in insulin-resistant HepG2 cells was checked using a glucose oxidase assay. AKT and AMP-activated protein kinase (AMPK) pathway activation and mRNA expression levels of insulin receptor (INSR), glucose transporter 1 (GLUT1), and glucose transporters 4 (GLUT4) were determined by western blotting and real-time PCR, respectively.
We found that high concentrations of methanolic and both low and high concentrations of total extracts were able to enhance glucose uptake in an insulin-resistant cell line model. Moreover, AKT and AMPK phosphorylation were significantly increased by the high strength of methanolic extract, while total extract raised AMPK activation at low and high concentrations. Also, GLUT 1, GLUT 4, and INSR were elevated by both methanolic and total extracts.
Ultimately, our results shed new light on methanolic and total PSC-FEs as sources of potential anti-diabetic medications, restoring glucose consumption and uptake in insulin-resistant HepG2 cells. These could be at least in part due to re-activating AKT and AMPK signaling pathways and also increased expression of INSR, GLUT1, and GLUT4. Overall, active constituents present in methanolic and total extracts of PCS are appropriate anti-diabetic agents and explain the use of these PSC fruits in traditional medicine for the treatment of diabetes.
彭祖果（PSC）在治疗地中海地区糖尿病方面常被应用。在这里，我们研究了不同的彭祖果提取物（PSC-FE）对高糖和高胰岛素诱导的胰岛素抵抗 HepG2 细胞中葡萄糖消耗和胰岛素信号通路关键介质的影响。
通过 MTT 测定法评估甲醇、氯仿和总提取物对细胞增殖的影响。使用葡萄糖氧化酶测定法检查非毒性提取物对胰岛素抵抗 HepG2 细胞葡萄糖利用的潜力。通过 Western blot 和实时 PCR 分别测定 AKT 和 AMP 激活蛋白激酶（AMPK）途径的激活以及胰岛素受体（INSR）、葡萄糖转运蛋白 1（GLUT1）和葡萄糖转运蛋白 4（GLUT4）的 mRNA 表达水平。
我们发现高浓度甲醇和总提取物在胰岛素抵抗细胞模型中均能增强葡萄糖摄取。此外，高强度甲醇提取物显著增加 AKT 和 AMPK 的磷酸化，而总提取物在低浓度和高浓度时均能提高 AMPK 的激活。此外，GLUT1、GLUT4 和 INSR 也被甲醇和总提取物上调。
总之，我们的结果为甲醇和总 PSC-FE 作为潜在抗糖尿病药物提供了新的视角，可恢复胰岛素抵抗 HepG2 细胞中的葡萄糖消耗和摄取。这至少部分归因于重新激活 AKT 和 AMPK 信号通路以及增加 INSR、GLUT1 和 GLUT4 的表达。总体而言，PSC 甲醇和总提取物中的活性成分是合适的抗糖尿病药物，解释了这些 PSC 果实在传统医学中用于治疗糖尿病的用途。
