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...
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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 |
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