Improvement effects and mechanism of total flavonoids from Bidens pilosa on Alzheimer’s disease
- VernacularTitle:鬼针草总黄酮对阿尔茨海默病的改善作用及机制
- Author:
Xiaojun PANG
1
;
Fengman TANG
2
;
Qianqian LI
3
Author Information
1. Dept. of Pharmacy，Qinzhou Second People’s Hospital，Guangxi Qinzhou 535099，China;College of Pharmacy，Guangxi Medical University，Nanning 530021，China
2. Dept. of Pharmacy，Qinzhou Maternal and Child Health Hospital，Guangxi Qinzhou 535099，China
3. Dept. of Pharmacy，Qinzhou Second People’s Hospital，Guangxi Qinzhou 535099，China
- Publication Type:Journal Article
- Keywords:
total flavonoids of Bidens pilosa;
Alzheimer’s disease;
PI3K/Akt signaling pathway;
network pharmacology
- From:
China Pharmacy
2025;36(24):3066-3072
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the improvement effects of total flavonoids from Bidens pilosa （TFB）against Alzheimer’s disease （AD） and elucidate its potential mechanism. METHODS The network pharmacology was adopted to explore active constituents and core targets of TFB for AD， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Based on the results of network pharmacology， an AD model was induced in male BALB/c mice by D-galactose subcutaneous injection and aluminum chloride gavage. The effects of TFB on behavioral indicators （including escape latency， the number of platform crossings， and the proportion of dwell time spent in the original platform quadrant）， as well as on acetylcholinesterase （AChE）， acetylcholine （ACh）， choline acetyltransferase （ChAT）， amyloid β-protein （Aβ）， phosphorylated Tau protein （p-Tau）， and inflammatory factors [interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α）] were investigated. Additionally， its effects on the pathological changes in hippocampal neurons， as well as the expressions of related proteins and mRNAs were evaluated. RESULTS Network pharmacology revealed 6 active components in TFB （e.g. luteolin， quercetin， kaempferol） and 165 overlapping targets with AD， including 29 core targets （Akt1， TP53， etc.）. The common targets were primarily enriched in biological processes such as positive regulation of gene expression and negative regulation of apoptotic processes， molecular functions including enzyme binding and identical protein binding， cellular components like extracellular space， plasma membrane and receptor complex， as well as signaling pathways such as cancer pathways and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. The results of animal experiments showed that， compared with model group， the pathological changes such as disordered arrangement， degeneration， and necrosis of neurons in the hippocampal CA3 region of mice in administration groups were alleviated. The escape latency （except for the low-dose TFB group）， the contents of AChE （except for the low-dose TFB group）， Aβ40， Aβ42 （except for the low-dose TFB group）， p-Tau （except for the low- and medium-dose TFB groups）， IL-1β， IL-6 （except for the low-dose TFB group）， and TNF- α in brain tissue， as well as the expressions of Bax and caspase-3 mRNA， were all significantly shortened/reduced/down-regulated. Conversely， the number of platform crossings， the proportion of dwell time spent in the original platform quadrant， the contents of ChAT and ACh， the phosphorylation levels of PI3K and Akt， and the mRNA expressions of PI3K， Akt and Bcl-2 （except for PI3K mRNA and Akt mRNA in the low- and medium-dose TFB groups， and Bcl-2 mRNA in the low-dose TFB group） were all significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS TFB can exert anti-AD effect through multiple components， multiple targets， and multiple pathways. Its underlying mechanisms may be related to the activation of the PI3K/Akt signaling pathway， improvement of the cholinergic system， reduction of Aβ deposition and Tau protein hyperphosphorylation， as well as inhibition of neuroinflammatory responses and neuronal apoptosis.
