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隐绿原酸通过抑制铁死亡对糖尿病体内外β细胞功能的保护作用

The Protective Effects of Cryptochlorogenic Acid on β-Cells Function in Diabetes in vivo and vitro via Inhibition of Ferroptosis.

作者信息

Zhou Yi

机构信息

Department of Endocrinology, Xiamen Hospital, Beijing University of Traditional Chinese Medicine (Xiamen Hospital of Traditional Chinese Medicine), Xiamen, Fujian 361008, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2020 Jun 8;13:1921-1931. doi: 10.2147/DMSO.S249382. eCollection 2020.

DOI:10.2147/DMSO.S249382
PMID:32606852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7294720/
Abstract

PURPOSE

Mulberry leaf extract has exerted better antidiabetic activities, while the effects of major active components in mulberry leaf extract are still unclear. Cryptochlorogenic acid (CCA) as the major active component in mulberry leaf extracts was investigated herein.

MATERIALS AND METHODS

Rats were treated with 50mg/kg streptozotocin for the establishment of diabetic model in vivo, and cells were treated with 33.3 mM glucose for the establishment of cell model in vitro. HE staining assay was performed for observation of pancreatic pathology and aldehyde fuchsin staining assay for examining islet cell numbers. The iron content was detected via Perls staining assay with iron assay kit (ab83366). The malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG) were detected by corresponding kits. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed for assessment of gene level and Western blot for measurement of protein expression level. The cell survival was detected via CCK-8 assay.

RESULTS

The blood glucose level, iron content, accumulation of lipid peroxides and islet injury in diabetic model were all improved by CCA via a concentration-dependent manner. CCA functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes.

CONCLUSION

CCA exerted excellent antidiabetic effects via inhibition of ferroptosis, so it may be a promising agent for diabetes therapy, providing a new avenue for diabetes treatment.

摘要

目的

桑叶提取物已表现出较好的抗糖尿病活性，但其主要活性成分的作用仍不清楚。本文对桑叶提取物中的主要活性成分隐绿原酸（CCA）进行了研究。

材料与方法

用50mg/kg链脲佐菌素处理大鼠以建立体内糖尿病模型，用33.3mM葡萄糖处理细胞以建立体外细胞模型。进行苏木精-伊红（HE）染色检测胰腺病理，用醛复红染色检测胰岛细胞数量。通过铁检测试剂盒（ab83366）的普鲁士蓝染色法检测铁含量。用相应试剂盒检测丙二醛（MDA）、谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）。进行实时定量聚合酶链反应（RT-qPCR）评估基因水平，用蛋白质印迹法检测蛋白质表达水平。通过CCK-8法检测细胞存活率。

结果

CCA以浓度依赖性方式改善了糖尿病模型中的血糖水平、铁含量、脂质过氧化物积累和胰岛损伤。在糖尿病中，CCA通过激活胱氨酸/谷氨酸转运体系统（XC）/谷胱甘肽过氧化物酶4（GPX4）/核因子E2相关因子2（Nrf2）抑制铁死亡，并抑制核受体辅激活因子4（NCOA4）发挥作用。

结论

CCA通过抑制铁死亡发挥了优异的抗糖尿病作用，因此它可能是一种有前景的糖尿病治疗药物，为糖尿病治疗提供了新途径。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/562e/7294720/ede00ce4d2ce/DMSO-13-1921-g0006.jpg
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