糖尿病(DM)是一种全球性的健康负担,其特征是胰腺β细胞的损失或功能障碍。在胰腺β细胞中,内质网(ER)应激是导致β细胞丢失或功能障碍的生命事实。尽管最近的研究取得了进展,现有的治疗方法,如改变生活方式和使用常规治疗方法,无法预防胰腺β细胞的丢失或功能障碍,从而阻止疾病进展.因此,靶向ER应激和随后的胰腺β细胞未折叠蛋白反应(UPR)可能是糖尿病治疗的潜在治疗策略.膳食植物化学物质由于其广泛的生化和药理活性而在人类健康中具有治疗性应用。黄酮类化合物,它们通常从世界各地的水果和蔬菜中获得,在缓解ER压力方面显示出了有希望的前景。膳食类黄酮,包括槲皮素,山奈酚,杨梅素,异鼠李素,Fisetin,淫羊藿苷,芹菜素,apigetrin,vitexin,黄芩素,黄芩苷,金黄素橙皮苷,柚皮苷,表没食子儿茶素3-O-没食子酸橙皮苷(EGCG),tectoriginin,甘草素,和刺槐素对胰腺β细胞内质网应激有抑制作用。膳食类黄酮调节内质网应激信号成分,伴侣蛋白质,转录因子,氧化应激,自噬,凋亡,和炎症反应,以发挥其对胰腺β细胞内质网应激的药理作用。本文综述了膳食类黄酮作为潜在的治疗佐剂在保护胰腺β细胞免受内质网应激中的作用。还介绍了潜在作用机制的重点以及DM管理中临床翻译的可能策略。
Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic β-cells. In pancreatic β-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to β-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic β-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic β-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic β-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic β-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic β-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM.