Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.

Beta cell apoptosis induced by proinflammatory cytokines is one of the hallmarks of diabetes. Small molecules which can inhibit the cytokine-induced apoptosis could lead to new drug candidates that can be used in combination with existing therapeutic interventions against diabetes. The current study...

Full description

Bibliographic Details
Main Authors: Sajid Ali Rajput, Munazza Raza Mirza, M Iqbal Choudhary
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0241349
id doaj-3bc93dac449f4b01b392f51a3a8727a0
record_format Article
spelling doaj-3bc93dac449f4b01b392f51a3a8727a02021-03-04T12:45:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011512e024134910.1371/journal.pone.0241349Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.Sajid Ali RajputMunazza Raza MirzaM Iqbal ChoudharyBeta cell apoptosis induced by proinflammatory cytokines is one of the hallmarks of diabetes. Small molecules which can inhibit the cytokine-induced apoptosis could lead to new drug candidates that can be used in combination with existing therapeutic interventions against diabetes. The current study evaluated several effects of bergenin, an isocoumarin derivative, in beta cells in the presence of cytokines. These included (i) increase in beta cell viability (by measuring cellular ATP levels) (ii) suppression of beta cell apoptosis (by measuring caspase activity), (iii) improvement in beta cell function (by measuring glucose-stimulated insulin secretion), and (iv) improvement of beta cells mitochondrial physiological functions. The experiments were carried out using rat beta INS-1E cell line in the presence or absence of bergenin and a cocktail of proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon- gamma) for 48 hr. Bergenin significantly inhibited beta cell apoptosis, as inferred from the reduction in the caspase-3 activity (IC50 = 7.29 ± 2.45 μM), and concurrently increased cellular ATP Levels (EC50 = 1.97 ± 0.47 μM). Bergenin also significantly enhanced insulin secretion (EC50 = 6.73 ± 2.15 μM) in INS-1E cells, presumably because of the decreased nitric oxide production (IC50 = 6.82 ± 2.83 μM). Bergenin restored mitochondrial membrane potential (EC50 = 2.27 ± 0.83 μM), decreased ROS production (IC50 = 14.63 ± 3.18 μM), and improved mitochondrial dehydrogenase activity (EC50 = 1.39 ± 0.62 μM). This study shows for the first time that bergenin protected beta cells from cytokine-induced apoptosis and restored insulin secretory function by virtue of its anti-inflammatory, antioxidant and anti-apoptotic properties. To sum up, the above mentioned data highlight bergenin as a promising anti-apoptotic agent in the context of diabetes.https://doi.org/10.1371/journal.pone.0241349
collection DOAJ
language English
format Article
sources DOAJ
author Sajid Ali Rajput
Munazza Raza Mirza
M Iqbal Choudhary
spellingShingle Sajid Ali Rajput
Munazza Raza Mirza
M Iqbal Choudhary
Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.
PLoS ONE
author_facet Sajid Ali Rajput
Munazza Raza Mirza
M Iqbal Choudhary
author_sort Sajid Ali Rajput
title Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.
title_short Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.
title_full Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.
title_fullStr Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.
title_full_unstemmed Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells.
title_sort bergenin protects pancreatic beta cells against cytokine-induced apoptosis in ins-1e cells.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2020-01-01
description Beta cell apoptosis induced by proinflammatory cytokines is one of the hallmarks of diabetes. Small molecules which can inhibit the cytokine-induced apoptosis could lead to new drug candidates that can be used in combination with existing therapeutic interventions against diabetes. The current study evaluated several effects of bergenin, an isocoumarin derivative, in beta cells in the presence of cytokines. These included (i) increase in beta cell viability (by measuring cellular ATP levels) (ii) suppression of beta cell apoptosis (by measuring caspase activity), (iii) improvement in beta cell function (by measuring glucose-stimulated insulin secretion), and (iv) improvement of beta cells mitochondrial physiological functions. The experiments were carried out using rat beta INS-1E cell line in the presence or absence of bergenin and a cocktail of proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon- gamma) for 48 hr. Bergenin significantly inhibited beta cell apoptosis, as inferred from the reduction in the caspase-3 activity (IC50 = 7.29 ± 2.45 μM), and concurrently increased cellular ATP Levels (EC50 = 1.97 ± 0.47 μM). Bergenin also significantly enhanced insulin secretion (EC50 = 6.73 ± 2.15 μM) in INS-1E cells, presumably because of the decreased nitric oxide production (IC50 = 6.82 ± 2.83 μM). Bergenin restored mitochondrial membrane potential (EC50 = 2.27 ± 0.83 μM), decreased ROS production (IC50 = 14.63 ± 3.18 μM), and improved mitochondrial dehydrogenase activity (EC50 = 1.39 ± 0.62 μM). This study shows for the first time that bergenin protected beta cells from cytokine-induced apoptosis and restored insulin secretory function by virtue of its anti-inflammatory, antioxidant and anti-apoptotic properties. To sum up, the above mentioned data highlight bergenin as a promising anti-apoptotic agent in the context of diabetes.
url https://doi.org/10.1371/journal.pone.0241349
work_keys_str_mv AT sajidalirajput bergeninprotectspancreaticbetacellsagainstcytokineinducedapoptosisinins1ecells
AT munazzarazamirza bergeninprotectspancreaticbetacellsagainstcytokineinducedapoptosisinins1ecells
AT miqbalchoudhary bergeninprotectspancreaticbetacellsagainstcytokineinducedapoptosisinins1ecells
_version_ 1714801656187584512