Modulatory Effects of Alpha-Mangostin Mediated by SIRT1/3-FOXO3a Pathway in Oxidative Stress-Induced Neuronal Cells
Issued Date
2022-01-28
Resource Type
eISSN
2296861X
Scopus ID
2-s2.0-85124400571
Journal Title
Frontiers in Nutrition
Volume
8
Rights Holder(s)
SCOPUS
Bibliographic Citation
Frontiers in Nutrition Vol.8 (2022)
Suggested Citation
Ruankham W., Suwanjang W., Phopin K., Songtawee N., Prachayasittikul V., Prachayasittikul S. Modulatory Effects of Alpha-Mangostin Mediated by SIRT1/3-FOXO3a Pathway in Oxidative Stress-Induced Neuronal Cells. Frontiers in Nutrition Vol.8 (2022). doi:10.3389/fnut.2021.714463 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83340
Title
Modulatory Effects of Alpha-Mangostin Mediated by SIRT1/3-FOXO3a Pathway in Oxidative Stress-Induced Neuronal Cells
Author's Affiliation
Other Contributor(s)
Abstract
Background: alpha-Mangostin, a polyphenolic xanthone, is primarily found in the pericarp of mangosteen throughout Southeast Asia and is considered as the “Queen of Fruit” in Thailand. Nonetheless, it is not clarified how alpha-mangostin protects neuronal cells against oxidative stress. Objective: In this study, molecular mechanisms underlying the neuroprotective effect of alpha-mangostin in defending hydrogen peroxide (H2O2)-induced neurotoxicity was explored. Methods: cytotoxicity, reactive oxygen species (ROS) generation, apoptotic cascades, and protein expression profiles were performed incorporation of molecular docking. Results: Human SH-SY5Y cells were pretreated with 1 μM alpha-mangostin for 3 h prior to exposure to 400 μM H2O2. alpha-Mangostin significantly inhibited oxidative stress-induced cell death in neuronal cells by reducing BAX protein, decreasing caspase-3/7 activation, and increasing anti-apoptotic BCL-2 protein. Collectively, alpha-mangostin was demonstrated to be a prominent ROS suppressor which reversed the reduction of antioxidant enzymes (CAT and SOD2). Surprisingly, alpha-mangostin significantly promoted the expression of the sirtuin family and the FOXO3a transcription factor exerting beneficial effects on cell survival and longevity. A molecular docking study predicted that alpha-mangostin is directly bound to the active site of SIRT1. Conclusion: Findings from this study suggest that alpha-mangostin potentially serves as a promising therapeutic compound against oxidative stress by activation of the SIRT1/3-FOXO3a pathway comparable to the effect of memantine, an anti-AD drug used for the treatment of moderate to severe dementia.