桃叶珊瑚苷减轻糖尿病性神经病理性疼痛中微胶质细胞有氧糖酵解的升高及炎症反应醛糖还原酶

Aucubin mitigates the elevation of microglial aerobic glycolysis and inflammation in diabetic neuropathic pain aldose reductase.

作者信息

Zheng Xue-Zhen, Yu Hong-Yan, Chen Ye-Ru, Fang Jian-Sheng

机构信息

Department of Anesthesiology, The First People's Hospital of Chun'an County, Hangzhou 311700, Zhejiang Province, China.

Department of Anaesthesiology, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou 310058, Zhejiang Province, China.

出版信息

World J Diabetes. 2025 May 15;16(5):103915. doi: 10.4239/wjd.v16.i5.103915.

DOI:10.4239/wjd.v16.i5.103915

PMID:40487600

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12142183/

Abstract

BACKGROUND

Treatment of diabetic neuropathy is often limited by side effects. Aucubin, an iridoid glycoside derived from natural plants, exhibits notable anti-inflammatory and antioxidant properties.

AIM

To investigate the effects of aucubin on diabetic neuropathic pain (DNP) and glycolysis and inflammation in microglia.

METHODS

Streptozotocin (STZ) was used to establish a DNP animal model. Blood glucose levels and body weight of mice were measured following STZ administration. Paw withdrawal threshold was calculated for mechanical allodynia. Paw withdrawal latency was recorded for thermal hyperalgesia. The open field test and elevated plus maze was used to assess locomotor activity and anxiety-like behavior. Western blotting was utilized for analysis of protein expression. Immunofluorescence staining was measured for morphometric analysis of microglia. Glycolysis and ATP synthesis in BV-2 cell lines were detected by metabolic extracellular flux analysis. The SwissTargetPrediction and STRING databases were used for comprehensive screening to identify potential target proteins for aucubin. The molecular docking between the possible target proteins and aucubin was investigated using Auto Dock Tool. The BV-2 cell line was transfected with lentiviral AKR1B1-shRNA to further ascertain the function of AKR1B1 in the impact of aucubin on aerobic glycolysis and inflammation during high glucose stimulation.

RESULTS

Aucubin significantly improved pain and anxiety-like behavior in STZ-induced diabetic mice and restored microglial aerobic glycolysis and inflammation. Several public databases and molecular docking studies suggested that AKR1B1, MMP2 and MMP9 are involved in the effect of aucubin on DNP. Aucubin failed to restore aerobic glycolysis and inflammation in the context of AKR1B1 deficiency.

CONCLUSION

Aucubin has potential as a therapeutic agent for alleviating DNP by inhibiting expression of AKR1B1.

摘要

背景

糖尿病神经病变的治疗常受副作用限制。桃叶珊瑚苷是一种源自天然植物的环烯醚萜苷，具有显著的抗炎和抗氧化特性。

目的

研究桃叶珊瑚苷对糖尿病性神经病理性疼痛（DNP）以及小胶质细胞糖酵解和炎症的影响。

方法

使用链脲佐菌素（STZ）建立DNP动物模型。在给予STZ后测量小鼠的血糖水平和体重。计算机械性异常性疼痛的爪部撤离阈值。记录热痛觉过敏的爪部撤离潜伏期。采用旷场试验和高架十字迷宫评估运动活动和焦虑样行为。利用蛋白质免疫印迹法分析蛋白质表达。通过免疫荧光染色对小胶质细胞进行形态计量分析。采用代谢细胞外通量分析检测BV-2细胞系中的糖酵解和ATP合成。使用SwissTargetPrediction和STRING数据库进行综合筛选，以鉴定桃叶珊瑚苷的潜在靶蛋白。使用Auto Dock Tool研究可能的靶蛋白与桃叶珊瑚苷之间的分子对接。用慢病毒AKR1B1-shRNA转染BV-2细胞系，以进一步确定AKR1B1在高糖刺激期间桃叶珊瑚苷对有氧糖酵解和炎症影响中的作用。