Mechanism prediction and validation of Kaixinsan in ameliorating neuroinflammation in Alzheimer’s disease
- VernacularTitle:开心散改善阿尔茨海默病神经炎症的机制预测与验证
- Author:
Dandan XU
1
;
Yongchang ZENG
2
;
Shaoyu LIANG
3
;
Qi LIU
3
;
Junhong WU
3
;
Kang HE
1
Author Information
1. School of Pharmacy，Guizhou University of Traditional Chinese Medicine，Guiyang 550025，China
2. Preparation Department，the Affiliated Hospital of Traditional Chinese Medicine，Guangzhou Medical University，Guangzhou 510140，China
3. Geriatric Medicine Institute，Shenzhen Second People’s Hospital，Guangdong Shenzhen 518035，China
- Publication Type:Journal Article
- Keywords:
Kaixinsan;
Alzheimer’s disease;
neuroinflammation;
network pharmacology;
molecular docking;
NF-κB signaling
- From:
China Pharmacy
2025;36(12):1476-1482
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To predict and validate the potential mechanisms of Kaixinsan （KXS） in ameliorating neuroinflammation in Alzheimer’s disease （AD）. METHODS Network pharmacology was employed to identify core anti- inflammatory components and key inflammatory targets of KXS for AD. Gene ontology （GO） functional annotation， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， and molecular docking were performed. Based on these findings， male SD rats were used to establish an AD model via chronic D-galactose induction. The effects of KXS on AD rats were evaluated， including quantitative behavioral score， learning and memory parameters （escape latency， platform crossings， platform quadrant distance and time）， organ indexes （heart， liver， spleen， thymus）， histopathological alterations in the hippocampus， and expressions of inflammation-related pathway proteins and their upstream/downstream regulators. RESULTS Core anti-inflammatory components of KXS for AD included gomisin B， panaxytriol， gomisin A， enhydrin， vulgarin and panaxydol， while key inflammatory targets involved nuclear factor-kappa B subunit 1（ NFKB1）， nuclear factor-κB p65（ NF-κB p65）， interleukin-1β（ IL- 1β）， IL-6， Toll-like receptor 4 （TLR4）， tumor necrosis factor， nucleotide-binding domain leucine-rich repeat and pyrin domain- containing receptor 3 （NLRP3） and caspase-1 （CASP1）. GO and KEGG pathway enrichment involved inflammatory response， phosphorylation and the NF-κB signaling pathway. Molecular docking confirmed strong binding affinities between core components and key targets. Animal experiments demonstrated that， compared to the model group， KXS significantly alleviated histopathological damage （e.g.， neuronal shrinkage， reduced Nissl bodies in hippocampal CA1， CA3， and DG regions）， increased organ indexes （except for liver index） and Nissl-stained positive cells， improved learning and memory performance， and reduced behavioral scores （at the 8 and 12 weeks of the experiment） and protein expression of NF- κB p65， phosphorylated NF- κB p65， TLR4， NLRP3， CASP1 and IL-1β. CONCLUSIONS KXS effectively mitigates neuroinflammation， reduces hippocampal neuronal injury， and enhances learning and memory ability in AD rats， potentially through suppressing the NF-κB signaling pathway and its upstream/ downstream regulators.
