从糖尿病的发病机制看中药桑枝总生物碱的多重药理作用

The multiple pharmacological effects of Sangzhi alkaloids based on different pathogenesis of diabetes mellitus

尽管T2DM发病机制和防治研究不断深入,但全球T2DM患病率、发病率仍在攀升。随着T2DM病理生理机制研究更新,提高了对通过多种生物学途径有效控制血糖、保护胰岛β细胞、同时兼具减少心血管和肾脏等并发症风险药物的需求。源于自然界的天然药物常有多重药理作用且副作用小,与单纯化学合成药物相比,对糖尿病多病因治疗、保证治疗的安全性上,更具发展潜力。从中国传统中药材桑枝中提取分离的“有效组分”天然药物桑植总生物碱(SZ-A),具有独特的多重药理药效特点和更少的副作用。在胃肠道中,SZ-A可精准作用于双糖酶靶点,通过抑制糖苷酶的活性减缓葡萄糖的消化和吸收而快速控制餐后血糖,胃肠副作用比其他糖苷酶抑制剂类药物更小。本文基于充分的循证医学证据,深入阐释不同生物碱成分的协同机制,挖掘SZ-A用于糖尿病治疗的临床综合获益,探讨SZ-A用于MS治疗的发展潜力。

Despite researches on the pathogenesis,prevention and treatment of type 2 diabetes mellitus(T2DM)are progressing,the prevalence and incidence of T2DM are still rising worldwide.Updatedly,with the improved understanding of the pathophysiological mechanisms of T2DM,drugs with multiple biological pathways to effectively control blood glucose,protect isletβcells,and reduce the risk of cardiovascular and renal complications are highly needed.Nature medicines derived from nature often have multiple pharmacological effects and lttle side effects.Compared with those chemical synthesis drugs,they have more potential to develop with multiple mechanisms in the treatment of diabetes and to ensure the safety of treatment.However,the"effective component"natural drug Sangzhi alkaloids(SZ-A),isolated from the traditional Chinese medicine,has unique characteristics of multiple pharmacological effects and few side effects.In fact,SZ-A can accurately act on double saccharase targets,by inhibiting the activity of glycosidase,to slow down the digestion and absorption of glucose,and to control the postprandial blood glucose level.Moreover,risks of gastrointestinal side effects with SZ-A treatment are lower than other glycosidase inhibitor drugs.Based on several evidence,the aim of this study is to explain the synergistic mechanisms of different alkaloid components,to find the clinical benefit of SZ-A treatment,to explore the potential effects of SZ-A for the treatment of metabolic syndrome.