Nankar Rakesh, Prabhakar P K, Doble Mukesh
Bioengineering and Drug Design Lab, Department of Biotechnology, IIT Madras, Chennai 600036, India.
Lovely Faculty of Applied Medical Sciences, LPU, Phagwara, Punjab, India.
Phytomedicine. 2017 Dec 15;37:10-13. doi: 10.1016/j.phymed.2017.10.015. Epub 2017 Oct 24.
Ferulic acid, an anti-oxidant phytochemical present in several dietary components, is known to produce wide range of pharmacological effects. It is approved for use in food industry as a preservative and in sports food. Previous reports from our lab have shown synergistic interaction of ferulic acid with metformin in cell lines and diabetic rats. The purpose of this review is to compile information about anti-diabetic activity of ferulic acid in in vitro and in vivo models with special emphasis on activity of ferulic acid when combined with metformin. The mechanism of synergistic interaction between ferulic acid and metformin is also proposed after carefully studying effects of these compounds on molecules involved in glucose metabolism.
Scientific literature for the purpose of this review was collected using online search engines and databases such as ScienceDirect, Scopus, PubMed and Google scholar.
Ferulic acid forms resonance stabilized phenoxyl radical which scavenges free radicals and reduce oxidative stress. It improves glucose and lipid profile in diabetic rats by enhancing activities of antioxidant enzymes, superoxide dismutase and catalase in the pancreatic tissue. Combining ferulic acid with metformin improves both, in vitro glucose uptake activity and in vivo hypoglycemic activity of the latter. It is possible to reduce the dose of metformin by four folds (from 50 to 12.5 mg/kg body weight) by combining it with 10 mg of ferulic acid/kg body weight in diabetic rats. Ferulic acid improves glucose uptake through PI3-K pathway whereas metformin activates AMPK pathway to improve glucose uptake.
The synergistic interaction of ferulic acid and metformin is due their action on parallel pathways which are involved in glucose uptake. Due to synergistic nature of their interaction, it is possible to reduce the dose of metformin (by combining with ferulic acid) required to achieve normoglycemia. Since the dose of metformin is reduced, the dose associated side effects of metformin therapy can be reduced.
阿魏酸是一种存在于多种膳食成分中的抗氧化植物化学物质，已知具有广泛的药理作用。它被批准在食品工业中用作防腐剂和运动食品中使用。我们实验室之前的报告显示，阿魏酸与二甲双胍在细胞系和糖尿病大鼠中存在协同相互作用。本综述的目的是汇编有关阿魏酸在体外和体内模型中的抗糖尿病活性的信息，特别强调阿魏酸与二甲双胍联合使用时的活性。在仔细研究这些化合物对参与葡萄糖代谢的分子的影响后，还提出了阿魏酸与二甲双胍之间协同相互作用的机制。
本综述使用在线搜索引擎和数据库（如ScienceDirect、Scopus、PubMed和谷歌学术）收集科学文献。
阿魏酸形成共振稳定的苯氧自由基，可清除自由基并降低氧化应激。它通过增强胰腺组织中抗氧化酶超氧化物歧化酶和过氧化氢酶的活性，改善糖尿病大鼠的血糖和血脂水平。将阿魏酸与二甲双胍联合使用可提高后者的体外葡萄糖摄取活性和体内降血糖活性。在糖尿病大鼠中，将阿魏酸与10mg/kg体重的二甲双胍联合使用，可将二甲双胍的剂量降低四倍（从50mg/kg体重降至12.5mg/kg体重）。阿魏酸通过PI3-K途径改善葡萄糖摄取，而二甲双胍激活AMPK途径以改善葡萄糖摄取。
阿魏酸与二甲双胍的协同相互作用是由于它们对参与葡萄糖摄取的平行途径的作用。由于它们相互作用的协同性质，可以减少实现正常血糖所需的二甲双胍剂量（通过与阿魏酸联合使用）。由于二甲双胍的剂量降低，二甲双胍治疗相关的剂量副作用可以减少。
