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[牡丹皮成分抑制毒性晚期糖基化终末产物(AGEs)生成的作用及机制]

[Role and mechanism of Cortex Moutan components in inhibiting production of toxic advanced glycation end products (AGEs)].

作者信息

Li Jie, Chen Ting-Ting, Sun Nan-Nan, Yang Bing, Zhang Meng-Tao, Yin Shi-Yu, Zhang Zhu-Bin, Zhang Shao-Chan, Jia Xiao-Bin, Feng Liang

机构信息

the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) Hefei 230001, China.

School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing 211198, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2022 Jun;47(12):3215-3223. doi: 10.19540/j.cnki.cjcmm.20211208.301.

Abstract

Advanced glycation end products(AGEs) can lead to many diseases such as diabetes and its complications. In this study, an in vitro non-enzymatic glycosylation reaction model-bovine serum albumin/methylglyoxal(BSA/MGO) reaction system was constructed and incubated with Cortex Moutan extract. High performance liquid chromatography(HPLC) and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) were used to detect and identify the active components that inhibited the formation of AGEs in the co-incubation solution of Cortex Moutan extract and MGO, and differential components such as salvianan, paeoniside, benzoylpaeoniflorin, mudanpioside J, galloyloxypaeoniflorin, benzoyloxy-paeoniflorin, 5-hydroxy-3 s-hydroxymethyl-6-methyl-2,3-dihydro benzofuran, and galloylpaeoniflorin were screened out, which were inferred to be the potential active components of Cortex Moutan extract to capture MGO. In addition, BSA-glucose reaction system was performed to investigate the influence of different concentrations of Cortex Moutan extract(decoction concentrations: 40, 80, 120, 160, and 200 mg·mL~(-1)) on inhibiting the production of AGEs in vitro. The inhibitory effects of Cortex Moutan extract and the differential components galloylpaeoniflorin and benzoyl paeoniflorin on the production of AGEs in human umbilical vein endothelial cells(HUVECs) induced by high glucose was further evaluated. Cell apoptosis was observed by acridine orange and ethidium bromide(AO/EB) double fluorescence staining. The results showed that Cortex Moutan Cortex extract and its differential components had certain inhibitory effects on the formation of AGEs, and could reduce cell apoptosis. This study provided reference for the treatment of diabetic vascular complications by Cortex Moutan inhibiting the toxic AGEs.

摘要

晚期糖基化终产物(AGEs)可引发多种疾病,如糖尿病及其并发症。本研究构建了一种体外非酶糖基化反应模型——牛血清白蛋白/甲基乙二醛(BSA/MGO)反应体系,并与牡丹皮提取物共同孵育。采用高效液相色谱(HPLC)和超高效液相色谱-四极杆飞行时间质谱联用(UPLC-Q-TOF-MS/MS)技术,检测并鉴定牡丹皮提取物与MGO共同孵育溶液中抑制AGEs形成的活性成分,筛选出了丹酚酸、芍药苷、苯甲酰芍药苷、牡丹皮苷J、没食子酰芍药苷、苯甲酰氧基芍药苷、5-羟基-3s-羟甲基-6-甲基-2,3-二氢苯并呋喃和没食子酰芍药苷等差异成分,推测这些成分可能是牡丹皮提取物捕获MGO的潜在活性成分。此外,进行了BSA-葡萄糖反应体系实验,以研究不同浓度的牡丹皮提取物(水煎剂浓度:40、80、120、160和200mg·mL~(-1))对体外抑制AGEs生成的影响。进一步评估了牡丹皮提取物及其差异成分没食子酰芍药苷和苯甲酰芍药苷对高糖诱导的人脐静脉内皮细胞(HUVECs)中AGEs生成的抑制作用。通过吖啶橙和溴化乙锭(AO/EB)双荧光染色观察细胞凋亡情况。结果表明,牡丹皮提取物及其差异成分对AGEs的形成具有一定的抑制作用,且能减少细胞凋亡。本研究为牡丹皮抑制毒性AGEs治疗糖尿病血管并发症提供了参考。

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