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食物来源的矢车菊素-3-O-葡萄糖苷缓解氧化应激:来自胰岛细胞系和糖尿病 db/db 小鼠的证据。

Food-derived cyanidin-3--glucoside alleviates oxidative stress: evidence from the islet cell line and diabetic db/db mice.

机构信息

Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-food Processing, Fuli Institute of Food Science, College of Biosystems Engineering and Food Science, National Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Postharvest Handling of Ministry of Agriculture, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China.

Tea Research Institute, College of Agriculture & Biotechnology, Zhejiang University, Hangzhou, 310058, China.

出版信息

Food Funct. 2021 Nov 15;12(22):11599-11610. doi: 10.1039/d1fo02385c.

Abstract

Type 2 diabetes mellitus is a disease associated with an oxidative milieu that often leads to adverse health outcomes. Multiple anthocyanins have been reported to possess outstanding antioxidant activity, however, their effects on hyperglycemia-related oxidative stress remain elusive. In the present study, cyanidin-3--glucoside (C3G), a typical anthocyanin with various widely accepted health benefits, was applied to alleviate oxidative stress in pancreas islets under the conditions of hyperglycemia. Firstly, significantly decreased mitochondrial membrane potential (MMP) and antioxidant enzymes, as well as increased reactive oxygen species (ROS) and O levels, were detected after exposure to a series of concentrations of high glucose (HG) and palmitic acid (PA), which manifested oxidative stress triggered by mitochondrial damage. To evaluate the antioxidant effect of C3G , the islet cell line NIT-1 was used, and results proved that C3G could effectively relieve cellular oxidative stress induced by HG and PA. Furthermore, we found that the antioxidant effect of C3G was achieved by activating mitophagy the PINK1-PARKIN signaling pathway. More importantly, an autophagy inhibitor chloroquine (CQ) was added to verify our findings at the protein level, and we observed the co-localization of mitochondria and lysosomes, which may form autophagolysosomes to clean damaged mitochondria. Immediately afterwards, more studies were conducted on pancreatic islets of diabetic db/db mice to verify the antioxidant effect of C3G discovered in islet cells. Along with the decline in fasting blood glucose, the oxidative stress in pancreas islets was successfully alleviated in diabetic db/db mice after supplementation with C3G. This was demonstrated by increased levels of ROS, and the impaired activities of anti-oxidative enzymes superoxide dismutase (SOD) and catalase (CAT) were partly reversed by C3G intervention. Our study has provided evidence for the alleviation effect of C3G against oxidative stress in pancreas islets, which may provide enlightenment for improving the health situation of diabetic patients in the future.

摘要

2 型糖尿病是一种与氧化环境相关的疾病,常导致不良健康后果。多种花色苷已被报道具有出色的抗氧化活性,但它们对高血糖相关氧化应激的影响仍不清楚。在本研究中,应用典型花色苷矢车菊素-3-葡萄糖苷(C3G)缓解高糖(HG)和棕榈酸(PA)作用下胰岛中的氧化应激。首先,在暴露于一系列浓度的 HG 和 PA 后,检测到线粒体膜电位(MMP)和抗氧化酶显著降低,活性氧(ROS)和 O 水平增加,表明线粒体损伤引发氧化应激。为了评估 C3G 的抗氧化作用,使用胰岛细胞系 NIT-1,结果表明 C3G 可以有效缓解 HG 和 PA 诱导的细胞氧化应激。此外,我们发现 C3G 的抗氧化作用是通过激活自噬(mitophagy)即 PINK1-PARKIN 信号通路实现的。更重要的是,添加自噬抑制剂氯喹(CQ)在蛋白水平验证我们的发现,观察到线粒体和溶酶体的共定位,可能形成自噬溶酶体来清除受损的线粒体。随后,对糖尿病 db/db 小鼠的胰岛进行了更多研究,以验证在胰岛细胞中发现的 C3G 的抗氧化作用。随着空腹血糖的下降,C3G 补充成功缓解了糖尿病 db/db 小鼠胰岛中的氧化应激。这表现为 ROS 水平的增加,并且 C3G 干预部分逆转了抗氧化酶超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的损伤。我们的研究为 C3G 缓解胰岛氧化应激提供了证据,这可能为未来改善糖尿病患者的健康状况提供启示。

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