Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600 036, India.
Phytomedicine. 2009 Dec;16(12):1119-26. doi: 10.1016/j.phymed.2009.05.021. Epub 2009 Aug 6.
The present study analyses the effect of two plant phenolic compounds, namely chlorogenic acid and ferulic acid, and a plant alkaloid, berberine, alone and also in combination with two commercial oral hypoglycemic drugs (OHD), namely metformin and 2,4-thiazolodinedione (THZ), on the uptake of 2-deoxyglucose (2DG) by L6 myotubes. 2-DG uptake is determined using an enzymatic assay. All the three natural products enhance the uptake of 2DG in time- and dose-dependent manner. A combination of different concentrations of chlorogenic acid and metformin or THZ, has a synergistic effect in the uptake of 2DG with a maximum of 5.0- and 5.3-times respectively, with reference to the base value (without the drugs or the natural products). Ferulic acid in combination with metformin or THZ has also shown a synergistic effect and the 2DG uptake increases by 4.98- and 5.11-fold when compared to the control respectively. Whereas, berberine, in combination with either metformin or THZ, has shown an additive effect with maximum 2DG uptake of 4.1- and 4.7-times from the base value, respectively. The synergistic interaction has been explained with the use of combination index and isobologram. Expression of GLUT4 and PPAR-gamma gene were elevated in chlorogenic acid and berberine treated cells, whereas expression of GLUT4 and PI3K transcripts were significantly enhanced in ferulic acid treated cells. The studies indicate that chlorogenic acid enhances glucose uptake by increasing GLUT4 expression via PI3K independent pathway whereas ferulic acid increases glucose uptake by PI3K dependent pathway. The current findings suggest that the phytochemicals can replace the commercial drugs in part, which could lead to a reduction in toxicity and side effects of the later.
本研究分析了两种植物酚类化合物，即绿原酸和阿魏酸，以及一种植物生物碱，小檗碱，单独使用以及与两种商业口服降糖药（OHD），即二甲双胍和 2,4-噻唑烷二酮（THZ）联合使用，对 L6 肌管摄取 2-脱氧葡萄糖（2DG）的影响。2-DG 的摄取通过酶测定法确定。所有三种天然产物均以时间和剂量依赖的方式增强 2DG 的摄取。不同浓度的绿原酸和二甲双胍或 THZ 的组合在 2DG 的摄取中具有协同作用，最大值分别为 5.0-和 5.3-倍，与基础值（无药物或天然产物）相比。阿魏酸与二甲双胍或 THZ 联合使用也显示出协同作用，与对照相比，2DG 的摄取分别增加了 4.98-和 5.11-倍。而小檗碱与二甲双胍或 THZ 联合使用则表现出相加作用，最大摄取量分别为基础值的 4.1-和 4.7-倍。协同作用已使用组合指数和等对图进行了说明。绿原酸和小檗碱处理的细胞中 GLUT4 和 PPAR-γ基因的表达增加，而阿魏酸处理的细胞中 GLUT4 和 PI3K 转录物的表达显著增强。研究表明，绿原酸通过独立于 PI3K 的途径增加 GLUT4 的表达来增强葡萄糖摄取，而阿魏酸通过 PI3K 依赖的途径增加葡萄糖摄取。目前的研究结果表明，植物化学物质可以部分替代商业药物，从而降低后者的毒性和副作用。
