Mbara Kingsley C, Fotsing Marthe C D, Ndinteh Derek T, Mbeb Claudine N, Nwagwu Chinekwu S, Khan Rene, Mokhetho Kopang C, Baijnath Himansu, Nlooto Manimbulu, Mokhele Shoeshoe, Leonard Carmen M, Tembu Vuyelwa J, Tarirai Clemence
Nanomedicines Manufacturing, Biopharmaceutics and Diagnostics Research Laboratory, Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa.
Drug Discovery and Smart Molecules Research Laboratory, Centre for Natural Products Research (CNPR), Department of Chemical Sciences, University of Johannesburg, Doornfontein, Johannesburg, 2028, South Africa.
Curr Res Pharmacol Drug Discov. 2024 May 24;6:100184. doi: 10.1016/j.crphar.2024.100184. eCollection 2024.
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.
糖尿病（DM）是一种全球性的健康负担，其特征是胰腺β细胞丧失或功能障碍。在胰腺β细胞中，内质网（ER）应激是导致β细胞丧失或功能障碍的一个现实因素。尽管最近研究取得了进展，但现有的治疗方法，如生活方式改变和使用传统疗法，无法预防胰腺β细胞的丧失或功能障碍以消除疾病进展。因此，针对胰腺β细胞中的内质网应激及其随之而来的未折叠蛋白反应（UPR）可能是糖尿病治疗的一种潜在治疗策略。膳食植物化学物质因其广泛的生化和药理活性而在人类健康中具有治疗应用。黄酮类化合物通常从世界各地的水果和蔬菜中获得，在减轻内质网应激方面已显示出有前景的前景。包括槲皮素、山奈酚、杨梅素、异鼠李素、非瑟酮、淫羊藿苷、芹菜素、芹菜素苷、牡荆素、黄芩素、黄芩苷、橙皮苷、柚皮苷、柚皮素、表没食子儿茶素-3-没食子酸酯（EGCG）、鸢尾黄素、甘草素和刺槐素在内的膳食黄酮类化合物已显示出对胰腺β细胞内质网应激的抑制作用。膳食黄酮类化合物调节内质网应激信号成分、伴侣蛋白、转录因子、氧化应激、自噬、凋亡和炎症反应，以对胰腺β细胞内质网应激发挥其药理作用。本综述重点关注膳食黄酮类化合物作为潜在治疗佐剂在保护胰腺β细胞免受内质网应激方面的作用。还介绍了潜在作用机制的要点以及糖尿病管理中临床转化的可能策略。
