Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids

• Published in: Current research in pharmacology and drug discovery Vol. 6; p. 100184
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2024; Elsevier
• Subjects: Diabetes; Endoplasmic reticulum stress; Flavonoids; Molecular mechanisms; Unfolded protein response; β-cells; Flavonoids; Diabetes; β-cells; Molecular mechanisms; Endoplasmic reticulum stress; Unfolded protein response
• ISSN: 2590-2571; 2590-2571
• DOI: 10.1016/j.crphar.2024.100184

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. [Display omitted] •Pancreatic β-cell dysfunction is a common feature in all forms of diabetes mellitus.•Pancreatic β-cells are highly prone to disruption of ER homeostasis.•Dietary flavonoids have shown prospects of alleviating ER stress-induced pancreatic β-cells dysfunction.•Dietary flavonoids modulate ER stress signaling and UPR through their pleiotropic pharmacological effects.