Effect of andrographolide on neuroinflammation in young epileptic rats by regulating cAMP/PKA/CREB signaling pathway
10.3969/j.issn.1000-484X.2025.04.012
- VernacularTitle:穿心莲内酯调节cAMP/PKA/CREB信号通路对幼年癫痫大鼠神经炎症的影响
- Author:
Jingfang GUO
1
;
Lei WU
1
;
He YANG
1
;
Aimin LI
1
Author Information
1. 荆州市中心医院儿科,荆州 434020
- Publication Type:Journal Article
- Keywords:
Andrographolide;
Cyclic adenosine monophosphate/protein kinase A/cAMP response element binding protein signaling pathway;
Epilepsy;
Neuroinflammation
- From:
Chinese Journal of Immunology
2025;41(4):841-846
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate effect of andrographolide(AG)on neuroinflammation in young epileptic rats by regulating cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response element binding protein(CREB)signaling pathway.Methods:SPF grade young SD rats were randomly divided into Control group,Model group,low-dose AG group(AG-L,125 mg/kg),high-dose AG group(AG-H,250 mg/kg)and high-dose AG+PKA inhibitor H-89 group(AG-H+H-89,250 mg/kg AG+2 mg/kg H-89),with 12 rats in each group.Epilepsy model of young rats was established by intraperitoneal injection of kainic acid(KA).Morris water maze test was used to detect learning and memory functions of rats.ELISA was used to detect levels of TNF-α,IL-10,malondialdehyde(MDA),superoxide dismutase(SOD)and cAMP in hippocampus of rats in each group.Histomorphology of hippo-campus was detected by Nissl staining.TUNEL test was usd to determine apoptosis rate of neurons in rat hippocampus.PKA and CREB mRNA expressions in hippocampus of rats in each group were detected by RT-qPCR.Western blot was used to detect protein expressions of PKA,Bax,Caspase-3,CREB,p-CREB and brain derived neurotrophic factor(BDNF)in hippocampus of rats in each group.Results:Compared with control group,escape latency,TNF-α and MDA levels in hippocampus,apoptosis rate of nerve cells,Bax and Caspase-3 protein expressions in Model group were obviously increased(P<0.05),target quadrant residence time,SOD,IL-10,cAMP levels,PKA,CREB mRNA and protein expressions,BDNF protein expression in hippocampus were decreased obviously(P<0.05),hippocampal tissue showed pathological damage and a large number of Nissl bodies were lost.Compared with Model group,cor-responding indexes of rats in AG-H group were contrary to the above(P<0.05),loss of Nissl corpuscles was reduced.H-89 alleviated improvement of AG on neuroinflammation in young epileptic rats.Conclusion:AG may reduce neuroinflammation in young epileptic rats by activating cAMP/PKA/CREB signaling pathway.
