Cho Suk Ju, Kang Kyoung Ah, Piao Mei Jing, Ryu Yea Seong, Fernando Pincha Devage Sameera Madushan, Zhen Ao Xuan, Hyun Yu Jae, Ahn Mee Jung, Kang Hee Kyoung, Hyun Jin Won
Jeju National University School of Medicine and Jeju Research Center for Natural Medicine, Jeju 63243, Republic of Korea.
Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 63243, Republic of Korea.
Biomol Ther (Seoul). 2019 Jan 1;27(1):85-91. doi: 10.4062/biomolther.2018.202.
Oxidative stress is considered a major contributor in the pathogenesis of diabetic neuropathy and in diabetes complications, such as nephropathy and cardiovascular diseases. Diabetic neuropathy, which is the most frequent complications of diabetes, affect sensory, motor, and autonomic nerves. This study aimed to investigate whether 7,8-dihydroxyflavone (7,8-DHF) protects SH-SY5Y neuronal cells against high glucose-induced toxicity. In the current study, we found that diabetic patients exhibited higher lipid peroxidation caused by oxidative stress than healthy subjects. 7,8-DHF exhibits superoxide anion and hydroxyl radical scavenging activities. High glucose-induced toxicity severely damaged SH-SY5Y neuronal cells, causing mitochondrial depolarization; however, 7,8-DHF recovered mitochondrial polarization. Furthermore, 7,8-DHF effectively modulated the expression of pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) under high glucose, thus inhibiting the activation of caspase signaling pathways. These results indicate that 7,8-DHF has antioxidant effects and protects cells from apoptotic cell death induced by high glucose. Thus, 7,8-DHF may be developed into a promising candidate for the treatment of diabetic neuropathy.
氧化应激被认为是糖尿病神经病变以及糖尿病并发症(如肾病和心血管疾病)发病机制的主要促成因素。糖尿病神经病变是糖尿病最常见的并发症,会影响感觉神经、运动神经和自主神经。本研究旨在调查7,8 - 二羟基黄酮(7,8 - DHF)是否能保护SH - SY5Y神经细胞免受高糖诱导的毒性。在当前研究中,我们发现糖尿病患者因氧化应激导致的脂质过氧化水平高于健康受试者。7,8 - DHF具有超氧阴离子和羟基自由基清除活性。高糖诱导的毒性严重损害SH - SY5Y神经细胞,导致线粒体去极化;然而,7,8 - DHF恢复了线粒体极化。此外,7,8 - DHF在高糖条件下有效调节促凋亡蛋白(Bax)和抗凋亡蛋白(Bcl - 2)的表达,从而抑制半胱天冬酶信号通路的激活。这些结果表明,7,8 - DHF具有抗氧化作用,并能保护细胞免受高糖诱导的凋亡性细胞死亡。因此,7,8 - DHF可能会被开发成为治疗糖尿病神经病变的有前景的候选药物。