TY - JOUR
T1 - Endoplasmic reticulum stress in pancreatic β-cell dysfunction
T2 - The potential therapeutic role of dietary flavonoids
AU - Mbara, Kingsley C.
AU - Fotsing, Marthe C.D.
AU - Ndinteh, Derek T.
AU - Mbeb, Claudine N.
AU - Nwagwu, Chinekwu S.
AU - Khan, Rene
AU - Mokhetho, Kopang C.
AU - Baijnath, Himansu
AU - Nlooto, Manimbulu
AU - Mokhele, Shoeshoe
AU - Leonard, Carmen M.
AU - Tembu, Vuyelwa J.
AU - Tarirai, Clemence
N1 - Publisher Copyright:
© 2024
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - Diabetes
KW - Endoplasmic reticulum stress
KW - Flavonoids
KW - Molecular mechanisms
KW - Unfolded protein response
KW - β-cells
UR - http://www.scopus.com/inward/record.url?scp=85194042962&partnerID=8YFLogxK
U2 - 10.1016/j.crphar.2024.100184
DO - 10.1016/j.crphar.2024.100184
M3 - Review article
AN - SCOPUS:85194042962
SN - 2590-2571
VL - 6
JO - Current Research in Pharmacology and Drug Discovery
JF - Current Research in Pharmacology and Drug Discovery
M1 - 100184
ER -