title: Mitigation of H(2)O(2)-Induced Mitochondrial-Mediated Apoptosis in NG108-15 Cells by Novel Mesuagenin C from Mesua kunstleri (King) Kosterm.
abstract: This study was aimed to isolate and evaluate neuroprotective compounds from the hexane extract of the bark of Mesua kunstleri (Clusiaceae) on H(2)O(2)-induced apoptosis in NG108-15 cells. Five 4-phenylcoumarins were isolated by using various chromatographic techniques via neuroprotective activity-guided fractionation and isolation from the active hexane extract. The chemical structures of the isolated compounds were confirmed by NMR spectroscopic data interpretation and comparison with literature values. Cell viability data demonstrated that mesuagenin C 3 significantly increased cell viability. Hoechst 33342/PI staining illustrated mesuagenin C 3 was able to abate the nuclear shrinkage, chromatin condensation and formation of apoptotic bodies. Pretreatment with mesuagenin C 3 reduced total annexin V positive cells and increased the level of intracellular glutathione (GSH). Mesuagenin C 3 attenuated membrane potential (Δψm), reduced Bax/Bcl-2 ratio and inactivated of caspase-3/7 and -9. These results indicated that mesuagenin C 3 could protect NG108-15 cells against H(2)O(2)-induced apoptosis by increasing intracellular GSH level, aggrandizing Δψm, and modulating apoptotic signalling pathway through Bcl-2 family and caspase-3/7 and -9. These findings confirmed the involvement of intrinsic apoptotic pathway in H(2)O(2)-induced apoptosis and suggested that mesuagenin C 3 may have potential therapeutic properties for neurodegenerative diseases.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Gomathi
authors.initials: G
authors.lastname: Chan
authors.forename: Muhamad Noor Alfarizal
authors.initials: MN
authors.lastname: Kamarudin
authors.forename: Daniel Zin Hua
authors.initials: DZ
authors.lastname: Wong
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.forename: Faizuri
authors.initials: F
authors.lastname: Abdul Latif
authors.forename: Aurengzeb
authors.initials: A
authors.lastname: Hasan
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.forename: Habsah
authors.initials: H
authors.lastname: Abdul Kadir