Aspirin Curcumin Ester Inhibits High Glucose/Aβ1-42-induced Microglial Inflammatory Response by Regulating Glucose Metabolism Reprogramming
10.13422/j.cnki.syfjx.20261006
- VernacularTitle:阿司匹林姜黄素酯通过调控糖代谢重编程抑制高糖/Aβ1-42诱导的小胶质细胞炎症反应
- Author:
Wenjing YU
1
;
Miao YANG
2
;
Chunxiang HE
2
;
Ze LI
2
;
Jiawei HE
2
;
Ping LI
2
;
Zhenyan SONG
2
;
Shaowu CHENG
1
Author Information
1. Medical School， Hunan University of Chinese Medicine， Changsha 410208， China
2. Hunan Province Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine， Hunan University of Chinese Medicine， Changsha 410208， China
- Publication Type:Journal Article
- Keywords:
microglia;
glycolysis;
aspirin curcumin ester;
Alzheimer's disease;
neuroinflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(22):124-137
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of aspirin curcumin ester （CA） on the activation and glucose metabolism reprogramming of the mouse microglia （BV2） model of inflammation induced by high glucose/β-amyloid （Aβ）1-42， and to explore the potential mechanism of CA in reducing neuroinflammatory response in the brain. MethodsThe BV2 activation model was constructed by high glucose combined with Aβ1-42 oligomers. BV2 cells were treated with Aβ1-42 oligomers （10 μmol·L-1） in a high glucose （50 mmol·L-1） environment and allocated into normal， high glucose， Aβ， and high glucose + Aβ groups. The cell morphology of each group was observed under a bright field. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to assess the mRNA levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） as well as glycolysis-related glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phospofructokinase-2/fructose-2，6-bisphosphatase 3 （PFKFB3）， and pyruvate kinase M2 （PKM2）. To reveal the effects of CA on inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ1-42， this study established the BV2 cell model of inflammatory activation by high glucose and Aβ1-42 oligomer intervention. The cells were allocated into normal， model （50 mmol·L-1 glucose + 10 μmol·L-1 Aβ1-42）， CA （10 μmol·L-1）， 2DG （0.2 mmol·L-1）， and DADA （1 mmol·L-1） groups. Cell counting kit-8 （CCK-8） was used to detect cell survival rate. The cell morphology of each group was observed under a bright field. The expression of inflammatory factors TNF-α， IL-6， and IL-1β and glycolysis-related key enzymes GLUT1， HK2， PFKFB3， and PKM2 at the mRNA level in each group was measured by real-time PCR. The protein levels of GLUT1， HK2， PFKFB3， and PKM2 were determined by Western blot. The glycolysis rate in each group was measured by seahorse. LC-MS was employed to identify the glucose metabolism intermediates. The morphology of mitochondria in cells was observed by electron microscopy. ResultsConstruction of the BV2 cell model： Compared with the normal group， the Aβ group and the high glucose + Aβ group showed more amoeboid-shaped cells and cell aggregation. The high glucose + Aβ group exhibited increased the mRNA levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， as well as those of key glycolytic enzymes GLUT1， HK2， PFKFB3， and PKM2 （P<0.01）. The Aβ group also showed significantly increased mRNA levels of PKM2 and PFKFB3 （P<0.01）. Effects of CA on the inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ1-42： Compared with the normal group， the model group exhibited amoeboid-shaped cells and cell aggregation， upregulated mRNA levels of TNF-α， IL-1β， IL-6， iNOS， GLUT1， HK2， PFKFB3， and PKM2 （P<0.01） and protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， an increased basal glycolysis rate （P<0.01）， a decreased compensatory glycolysis rate （P<0.01）， increased glycolytic intermediates and reduced TCA cycle intermediates. In addition， the mitochondria in the model group exhibited a decreased number （P<0.05）， impaired crista integrity （P<0.01）， an increased proportion of vacuolization （P<0.01）， and abnormal mitochondrial morphology. Compared with those in the model group， the number of amoeboid-shaped BV2 cells reduced in the CA and 2DG groups， while most BV2 cells in the DADA group became elongated spindle-shaped. All the three treatment groups showed downregulated mRNA levels of TNF-α， IL-1β， IL-6， GLUT1， HK2， PFKFB3， and PKM2 （P<0.05， P<0.01）， downregulated protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， and slow compensatory glycolysis and basal glycolysis （P<0.05， P<0.01）. Glycolytic intermediates were decreased and TCA cycle intermediates were increased in the CA and 2DG groups. Mitochondrial morphology largely returned to the normal level in all the three treatment groups， with an increase in mitochondrial number （P<0.05）， improved crista integrity （P<0.05， P<0.01）， and a decreased proportion of vacuolization （P<0.05）. ConclusionAβ1-42 oligomers can activate BV2 cells and enhance glycolytic activity in the high glucose environment. CA can reduce the expression of inflammatory factors and inhibit the activation of BV2 cells by regulating the glucose metabolism reprogramming in BV2 cells.
