Exploring the synergistic potential of pomegranate fermented juice compounds against oxidative stress-induced neurotoxicity through computational docking and experimental analysis in human neuroblastoma cells.

Autor: Akter R; Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, Gyeonggido, Republic of Korea., Morshed MN; Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, Gyeonggido, Republic of Korea., Awais M; Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, Gyeonggido, Republic of Korea., Kong BM; Department of Oriental Medicine and Biotechnology, College of Life Sciences Kyung Hee University, Yongin, Gyeonggido, Republic of Korea., Oh SW; SMART FRUIT CO., LTD., Guri, Gyeonggi-do, Republic of Korea., Oh JH; Fruitycompany Co., Ltd., Guri, Gyeonggi-do, Republic of Korea., Alrefaei AF; Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia., Yang DC; Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, Gyeonggido, Republic of Korea.; AIBIOME, 6, Jeonmin-ro 30beon-gil, Yuseong-gu, Daejeon, 34214, Republic of Korea., Yang DU; AIBIOME, 6, Jeonmin-ro 30beon-gil, Yuseong-gu, Daejeon, 34214, Republic of Korea., Ali S; Department of Horticulture and Life Science, Yeungnam University, Republic of Korea.
Jazyk: angličtina
Zdroj: Heliyon [Heliyon] 2024 Jul 20; Vol. 10 (15), pp. e34993. Date of Electronic Publication: 2024 Jul 20 (Print Publication: 2024).
DOI: 10.1016/j.heliyon.2024.e34993
Abstrakt: This study explored the neuroprotective potential of fermented pomegranate (PG-F) against hydrogen peroxide (H 2 O 2 )-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanisms. The fermentation process, involving probiotics, transforms the hydrolyzable tannins in pomegranate juice into ellagic acid (EA) and gallic acid (GA), which are believed to contribute to its health benefits. Molecular docking simulations confirmed the stable interactions between EA, GA, and proteins associated with the antioxidant and anti-apoptotic pathways. PG-F significantly enhanced the viability of H 2 O 2 -treated cells, as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, cell morphology observations, and Hoechst 33342 staining. PG-F mitigated the H 2 O 2 -induced intracellular reactive oxygen species (ROS) levels, restored mitochondrial membrane potential, and upregulated antioxidant gene expression. The PG-F treatment also attenuated the H 2 O 2 -induced imbalance in the Bax/Bcl-2 ratio and reduced the cleaved caspase-3, caspase-7, and caspase-9 levels, suppressing the apoptotic pathways. Further insights showed that PG-F inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and facilitated the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2), highlighting its role in modulating the key signaling pathways. A combined treatment with equivalent concentrations of EA and GA, as found in PG-F, induced remarkable cellular protection. Drug combination analysis using the Chou-Talalay method revealed a synergistic effect between EA and GA, emphasizing their combined efficacy. In conclusion, PG-F has significant neuroprotective effects against H 2 O 2 -induced neurotoxicity by modulating the antioxidant and anti-apoptotic pathways. The synergistic action of EA and GA suggests the therapeutic potential of PG-F in alleviating oxidative stress-associated neurodegenerative diseases.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024 The Authors.)
Databáze: MEDLINE
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