The Efficacy and Mechanism of Kaempferol in Preventing perioperative neurocognitive disorders in t he Elderly: Based on Network Pharmacology and Experimental Verification

Abstract

AbstractObjective This research, founded on network pharmacology, molecular docking, and experimental validation, seeks to elucidate the probable therapeutic effects of Kaempferol (Kae) on perioperative neurocognitive disorders (PND), along with its operational mechanism. Methods Key target points for the potential preventive effects of Kae on PND were discerned through the Geo database and network pharmacology techniques. An animal model was established for PND through laparotomy. The model and therapeutic outcomes were verified using the Morris water maze (MWM) and open field tests, subsequently, mechanisms of hub target regulation were confirmed through methods such as WB, q-PCR, immunofluorescence, flow cytometry, JC-1 staining for mitochondrial membrane potential (ΔΨm) assessment, and Calcein-AM staining. In vivo and in vitro experimental models were utilized to study the impact of Kae on microglial cell activation and inflammation, as well as Kae’s rescuing effect on neuronal apoptosis, thereby exploring its neuroprotective action mechanism. Results Network pharmacology analysis revealed that Kae could potentially exert its therapeutic effect by regulating key targets such as p-AKT1, p-JUN, PPARG, and CASPASE − 3. These targets primarily function within inflammation and immune modulation related pathways such as the AGE-RAGE signaling pathway, TNF-α signaling pathway, and apoptosis. In vivo and in vitro model experiments demonstrated that Kae significantly influenced the activation and inflammatory response of microglial cells, indicating possible neuroprotective effects. Additionally, Kae was able to mitigate the apoptosis of primary neurons induced by LPS, a phenomenon that Kae rescues in a concentration-dependent manner. Conclusion By regulating key targets such as p-AKT1, p-JUN, PPARG, and CASPASE-3, Kae might play a role in the prevention and treatment of PND, demonstrating neuroprotective and cognitive function improvement effects.