绿原酸可能改善糖尿病大鼠额叶的记忆功能和降低炎症水平。

Chlorogenic acid may improve memory function and decrease inflamation of frontal lobe in diabetic rat.

机构信息

Universitas Gadjah Mada, Faculty of Medicine, Public Health and Nursing, Yogyakarta, Indonesia.

Universitas Gadjah Mada, Faculty of Medicine, Public Health and Nursing, Department of Anatomy, Yogyakarta, Indonesia.

出版信息

Med J Malaysia. 2023 Jul;78(4):476-483.

PMID:37518915

Abstract

INTRODUCTION

Diabetes Mellitus (DM) is a chronic disease with many complications, one of which is diabetic encephalopathy which is characterised by memory dysfunction. Hyperglycaemia that occurs in DM will activate inflammatory pathways in neurons, including NF-κB pathway. Activation of this pathway produce proinflammatory agents such as MCP-1 and IL-6, which activate glial cells. Activation of glial cells is characterised by Glial Fibrillary Acid Protein (GFAP). Chlorogenic acid (CGA) has been reported to have anti-inflammatory effects and can improve memory function. This research aimed to determine the effect of CGA as anti-inflammation, its effect on memory function, mRNA expression of NF-κB, MCP-1, IL- 6, and GFAP of frontal lobe.

MATERIALS AND METHODS

A total of 24 male rats were randomly divided into six groups: control, DM 1.5 month (DM1.5), DM 2 months (DM2) and the group with three different doses of CGA 12.5 (CGA1), 25 (CGA2), and 50 (CGA3) mg/KgBW. Frontal lobe tissue is taken for analysis of mRNA expression for NF-κB, MCP-1, IL-6, and GFAP using Reverse Transcriptase PCR (RT-PCR). Samples were also taken for histopathology preparation and stained by immunohistochemistry method using anti-GFAP antibodies to observe glial cell activation in frontal lobe tissue.

RESULTS

The group that was given CGA at all doses have statistically significant better memory function, i.e. DM2 versus CGA1 (p = 0.036), CGA2 (p = 0.040), and CGA3 (p = 0.021). The result of mRNA expression in NF-κB was lower in the group given CGA, i.e. DM2 compared to CGA2 (p = 0.007). mRNA expression of MCP-1 was significantly lower in all CGA treatment groups compared to the non-CGA group (p = 0.000). IL-6 mRNA expression was lower than the group not given CGA, DM compared to CGA2 (p = 0.028). GFAP mRNA expression was lower than the group given CGA in DM, DM2 group compared to CGA1 (p = 0.04) and CGA3 (p = 0.004).

CONCLUSION

Administration of CGA can improve memory function at all doses given, and can reduce brain inflammatory activity, especially in the CGA2 group.

摘要

简介

糖尿病（DM）是一种慢性疾病，有许多并发症，其中之一是糖尿病性脑病，其特征是记忆功能障碍。DM 中发生的高血糖会激活神经元中的炎症途径，包括 NF-κB 途径。该途径的激活会产生促炎剂，如 MCP-1 和 IL-6，从而激活神经胶质细胞。神经胶质细胞的激活特征是胶质纤维酸性蛋白（GFAP）。已报道绿原酸（CGA）具有抗炎作用，并能改善记忆功能。本研究旨在确定 CGA 的抗炎作用，对记忆功能的影响，NF-κB、MCP-1、IL-6 和额叶的 GFAP 的 mRNA 表达。

材料和方法

总共 24 只雄性大鼠被随机分为六组：对照组、DM 1.5 个月（DM1.5）、DM 2 个月（DM2）和三个不同剂量的 CGA 12.5（CGA1）、25（CGA2）和 50（CGA3）mg/KgBW 的组。取额叶组织，使用逆转录酶 PCR（RT-PCR）分析 NF-κB、MCP-1、IL-6 和 GFAP 的 mRNA 表达。还取样本进行组织病理学准备，并通过免疫组织化学方法用抗 GFAP 抗体染色，观察额叶组织中神经胶质细胞的激活。

结果

所有剂量的 CGA 组的记忆功能均有统计学意义上的改善，即 DM2 与 CGA1（p = 0.036）、CGA2（p = 0.040）和 CGA3（p = 0.021）相比。NF-κB 表达的 mRNA 结果在给予 CGA 的组中较低，即 DM2 与 CGA2（p = 0.007）相比。所有 CGA 治疗组的 MCP-1 mRNA 表达均明显低于非 CGA 组（p = 0.000）。与未给予 CGA 的 DM 组相比，IL-6 mRNA 表达较低，DM 与 CGA2（p = 0.028）相比。与给予 CGA 的 DM 组相比，GFAP mRNA 表达较低，DM2 与 CGA1（p = 0.04）和 CGA3（p = 0.004）相比。