Network pharmacology combined with experimental validation show that apigenin as the active ingredient of Campsis grandiflora flower against Parkinson’s disease by inhibiting the PI3K/AKT/NF-κB pathway.

Network pharmacology combined with experimental validation show that apigenin as the active ingredient of Campsis grandiflora flower against Parkinson’s disease by inhibiting the PI3K/AKT/NF-κB pathway.

Publication date: Aug 18, 2024

The exploration of novel natural products for Parkinson’s disease (PD) is a focus of current research, as there are no definitive drugs to cure or stop the disease. Campsis grandiflora (Thunb. ) K. Schum (Lingxiaohua) is a traditional Chinese medicine (TCM), and the exact active constituents and putative mechanisms for treating PD are unknown. Through data mining and network pharmacology, apigenin (APi) was identified as the main active ingredient of Lingxiaohua, and key targets (TNF, AKT1, INS, TP53, CASP3, JUN, BCL2, MMP9, FOS, and HIF1A) of Lingxiaohua for the treatment of PD were discovered. The primary routes implicated were identified as PI3K/AKT, Apoptosis, TNF, and NF-_705B pathways. Subsequently, therapeutic potential of APi in PD and its underlying mechanism were experimentally evaluated. APi suppressed the release of mediators of inflammation and initiation of NF-_705B pathways in MES23. 5 cells induced by MPP+. APi suppressed caspase-3 activity and apoptosis and elevated p-AKT levels in MES23. 5 cells. Pretreatment with LY294002, a PI3K inhibitor, resulted in APi treatment blocking the activation of NF-_705B pathway and expression of inflammatory factors in MES23. 5 cells by activating the PI3K/AKT pathway. In conclusion, APi protects dopaminergic neurons by controlling the PI3K/AKT/NF-_705B pathway, giving novel insights into the pharmacological mechanism of Lingxiaohua in treating PD.

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Concepts Keywords
Chinese Animals
Exploration Apigenin
Parkinson Apigenin
Pharmacology Apoptosis
Tp53 Cell Line
Flowers
Humans
Mice
Network Pharmacology
NF-kappa B
NF-kappa B
Parkinson Disease
Phosphatidylinositol 3-Kinases
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-akt
Signal Transduction

Semantics

Type Source Name
drug DRUGBANK Apigenin
disease MESH Parkinson’s disease
drug DRUGBANK Alpha-1-proteinase inhibitor
pathway REACTOME Apoptosis
pathway REACTOME Release
drug DRUGBANK Coenzyme M
disease MESH inflammation
pathway REACTOME Reproduction
disease MESH neuroinflammation
disease MESH oxidative stress
disease MESH neurological disorders
drug DRUGBANK Ethanol
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH comorbidity
disease MESH depressive disorders
drug DRUGBANK Dopamine
disease MESH death
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Methionine
drug DRUGBANK beta-Sitosterol
drug DRUGBANK Aspartame
drug DRUGBANK Proline
disease MESH pathogenesis
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Rotenone
pathway REACTOME Autophagy
drug DRUGBANK Ranitidine
drug DRUGBANK Polydatin
drug DRUGBANK Hexocyclium
pathway KEGG Drug metabolism
disease MESH parkinsonism
disease MESH Fibrosis
disease MESH Liver Disease
drug DRUGBANK Dapagliflozin
drug DRUGBANK Myricetin
drug DRUGBANK Icariin
drug DRUGBANK Carboxyamidotriazole
drug DRUGBANK Curcumin
drug DRUGBANK Pramipexole
drug DRUGBANK Levodopa
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
pathway KEGG Parkinson disease
pathway REACTOME TNF signaling
drug DRUGBANK Vincamine
disease MESH Psychiatric Illnesses
disease MESH Multiple Sclerosis

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