Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences, University of Karachi, Karachi, Sindh, Pakistan.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Sindh, Pakistan.
PLoS One. 2020 Dec 21;15(12):e0241349. doi: 10.1371/journal.pone.0241349. eCollection 2020.
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.
炎性细胞因子诱导的β细胞凋亡是糖尿病的特征之一。能够抑制细胞因子诱导的细胞凋亡的小分子可以导致新的候选药物，这些药物可以与现有的糖尿病治疗干预措施联合使用。本研究评估了几种小布枯叶素（一种异香豆素衍生物）在细胞因子存在下对β细胞的作用。这些作用包括：（i）增加β细胞活力（通过测量细胞内 ATP 水平）；（ii）抑制β细胞凋亡（通过测量半胱天冬酶活性）；（iii）改善β细胞功能（通过测量葡萄糖刺激的胰岛素分泌）；（iv）改善β细胞线粒体生理功能。这些实验是使用大鼠β INS-1E 细胞系在存在或不存在小布枯叶素和炎性细胞因子混合物（白细胞介素-1β、肿瘤坏死因子-α和干扰素-γ）的情况下进行的，共进行了 48 小时。小布枯叶素显著抑制β细胞凋亡，这可以从减少半胱天冬酶-3 活性（IC50=7.29±2.45μM）推断出来，同时还增加了细胞内 ATP 水平（EC50=1.97±0.47μM）。小布枯叶素还显著增强了 INS-1E 细胞中的胰岛素分泌（EC50=6.73±2.15μM），可能是由于降低了一氧化氮的产生（IC50=6.82±2.83μM）。小布枯叶素恢复了线粒体膜电位（EC50=2.27±0.83μM），减少了 ROS 的产生（IC50=14.63±3.18μM），并改善了线粒体脱氢酶活性（EC50=1.39±0.62μM）。本研究首次表明，小布枯叶素通过其抗炎、抗氧化和抗凋亡特性，保护β细胞免受细胞因子诱导的凋亡，并恢复胰岛素分泌功能。总之，上述数据突出了小布枯叶素在糖尿病中的潜在应用价值。
