PDF(Pubmed)
Abstract：
Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research. Aim: To discuss the role of BBR in the whole body\'s systemic metabolic regulation and further explore its therapeutic potential and targets. Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets. Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5\'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipid-regulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases. Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets.
摘要：
背景：代谢失衡是许多疾病的共同基础。作为天然异喹啉生物碱，小檗碱（BBR）在调节糖脂代谢和治疗代谢紊乱方面显示出巨大的前景。然而,相关机制尚缺乏系统研究。目的:探讨BBR在全身代谢调控中的作用,进一步探讨其治疗潜力和作用靶点。方法:以动物和细胞实验为基础,综述了BBR调节全身代谢过程的机制。使用治疗靶点数据库（TTD）总结潜在的代谢相关靶点，DrugBank,GeneCards,和尖端文学。分子建模用于探索BBR与潜在靶标的结合。结果：BBR调节全身代谢反应，包括消化，循环,免疫，内分泌，和运动系统通过腺苷5'-单磷酸（AMP）激活的蛋白激酶（AMPK）/哺乳动物雷帕霉素靶（mTOR），sirtuin(SIRT)1/叉头盒O(FOXO)1/固醇调节元件结合蛋白(SREBP)2、核因子红系2相关因子(Nrf)2/血红素加氧酶(HO)-1等信号通路。通过这些反应,BBR发挥低血糖作用，调脂,抗炎,抗氧化，和免疫调节。分子对接结果表明,BBR能够调控靶向FOXO3、Nrf2、NAD(P)H醌氧化还原酶1(NQO1)的代谢,谷胱甘肽过氧化物酶（Gpx）4和磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）。评估目标临床效果，我们发现BBR具有抗衰老的治疗潜力，抗癌，缓解肾脏疾病,调节神经系统，缓解其他慢性病。结论:本综述通过探讨BBR调节代谢的机制,阐明潜在靶标与小分子代谢产物之间的相互作用。这将有助于药理学家识别与这些靶标相互作用的新的有希望的代谢物。
