Network pharmacology and molecular docking integrated strategy to investigate the pharmacological mechanism of palmatine in Alzheimer's disease

The key molecular mechanism of palmatine in the treatment of Alzheimer's disease (AD) was investigated in this article.Network pharmacology techniques constructed drug-target-disease relationship networks and predictive pathways of action. At the cellular level, lipopolysaccharide (LPS) was used to induce Raw 264.7 cells to establish an inflammation model, and interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α indicators were examined. Apoptosis was detected using Hoechst 33258. At the animal level, LPS was used to induce AD animal model, and behavioral performance were examined by water maze, and serum biochemical indexes were measured by ELISA. And the expression of PI3K and P-AKT was observed by immunohistochemistry. Finally, molecular level validation was performed using the molecular docking technique.The result of Network pharmacological was predicted that palmatine may treat AD mainly through the PI3K pathway. Palmatine has no significant effect on Raw264.7 cells viability within 0.05 mg/ml, Palmatine can significantly induce Raw264.7 cells to secret IL-6 and IL1-β in a concentration-dependent manner, but it has not obvious impact on NO and TNF-α. Palmatine has a significant restorative effect on the cell viability of Raw264.7 in a concentration of 0.1 mg/ml. Palmatine can be concentration-dependent to downregulate the secretion of LPS-induced IL-6. At the same time, Palmatine also has a significant effect on the level of TNF-α induced by LPS, it also can slightly downregulate the secretion of IL-1β. The results of Hoechst33258 showed that cells in the 0.025 mg/ml and 0.5 mg/ml delivery groups increased with different degrees of bright blue fluorescence, and apoptosis rate decreased. Animal experiments showed that palmatine effectively improved the learning and memory ability of AD mice. The immunohistochemical results exhibited that the expression of PI3K and P-AKT in the model group decreased, but they were obvious reversed by palmatine The molecular docking results showed that palmatine and key targets had good docking, among which the binding to ERBB2, CDC42, MDM2, and mTOR was the most likely.Palmatine has neuroprotective effects. Palmatine could effectively ameliorate memory impairment in AD mice by promoting the PI3K-AKT pathway. Molecular docking results showed that palmatine has a better binding ability with mTOR.