Ursolic acid and acteoside regulates multiple targets, bioprocesses and signal pathways against Alzheimer's disease pathogenesis. - GreenMedInfo Summary
Acteoside and ursolic acid synergistically protects HO-induced neurotrosis by regulation of AKT/mTOR signalling: from network pharmacology to experimental validation.
Pharm Biol. 2022 Dec ;60(1):1751-1761. PMID: 36102631
Yan-Jie Qu
CONTEXT: Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer's disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear.
OBJECTIVE: Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism.
MATERIALS AND METHODS: UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in HO-treated PC12 cells. The subsequent experiments were divided into Normal, Model (HOpre-treatment for 4 h), Control (HO+ solvent pre-treatment), UA (5 μM), ATS (40 μM), UA (5 μM) + ATS (40 μM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected.
RESULTS: The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED: 5 μM) + ATS (ED: 40 μM) could protect HO-induced (IC: 250 μM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1.
CONCLUSIONS: ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects HO-induced neurotrosis by regulation of AKT/mTOR signalling.
