Dichamanetin attenuates hydrogen peroxide-induced cytotoxicity in retinoic acid (RA) -differentiated human neuroblastoma (SH-SY5Y) cells
- 1Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia
- 2School of Science, Monash University Malaysia
Abstract
Background Alzheimer’s disease (AD) is a leading neurodegenerative disorder that imposes a significant global socioeconomic burden. It is characterised as progressive cognitive decline and a complex multifactorial pathology. Despite extensive research, current therapeutic options are limited. Emerging evidence suggests that oxidative stress is critical in the early pathological event preceding the classical hallmarks of AD. Targeting oxidative stress is a promising strategy for treating AD. Flavonoids are attractive due to their antioxidant, anti-inflammatory, and neuroprotective effects in AD. Dichamanetin (C29H24O6) is a rare C-benzylated flavanone that seldom occur in nature with reported antibacterial, and anti-malarial. Importantly, it has been suggested to possess anti-Alzheimer’s disease in-silico. However, neither its antioxidative nor neuroprotective potential has been explored in-vitro. Thus, this study aimed to address this gap by establishing an efficient method for the synthesis of dichamanetin and investigating its antioxidant properties and neuroprotective potential against hydrogen peroxide (H₂O₂)-induced cytotoxicity in-vitro. Methods In this study, we described the synthesis of dichamanetin using microwave irradiation and investigated its antioxidative activity using DPPPH and FRAP assay. Furthermore, we studied dichamanetin’s neuroprotective potential against hydrogen peroxide (H2O2)-insult as an in-vitro AD model using three treatment conditions include pre-treatment, co-treatment, and staggered co-treatment using CCK-8 cell viability assay. Results Dichamanetin was synthesised via microwave irradiation method, overcoming the limitations of isolation and purification from natural sources which often resulted in low yield. The improved synthesis method produced a good yield of 50% and purity of 95–97% determined via LC-MS and 1H NMR analyses. It shows that dichamanetin has low antioxidative activity as shown by FRAP ability. Importantly, it was non-cytotoxic to cholinergic neurons at concentrations below 3.125 µg/mL. It is shown to be a potent neuroprotectant in protecting the cholinergic neurons against H2O2-insult at 0.781 µg/mL, eliciting the highest neuroprotective effect in 6-hour staggered co-treatment comparable to quercetin and donepezil. Conclusions Dichamanetin attenuated H₂O₂-induced cytotoxicity in RA-differentiated SH-SY5Y cells, supporting its potential as a neuroprotective candidate against oxidative stress. Further studies are warranted to elucidate the underlying mechanisms and validate its efficacy, pharmacokinetics, safety, and therapeutic potential in relevant in vivo models of Alzheimer’s disease. Graphical Abstract
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BibTeX
@article{zainuddin2026dichamanetin,
title = {{Dichamanetin attenuates hydrogen peroxide-induced cytotoxicity in retinoic acid (RA) -differentiated human neuroblastoma (SH-SY5Y) cells}},
author = {Muhammad-Safuan Zainuddin and Chee-Wei Ang and Saatheeyavaane Bhuvanendran and Adzzie-Shazleen Azman},
journal = {Beni-Suef University Journal of Basic and Applied Sciences},
year = {2026},
month = oct,
doi = {10.1186/s43088-026-00842-y},
url = {https://doi.org/10.1186/s43088-026-00842-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dichamanetin attenuates hydrogen peroxide-induced cytotoxicity in retinoic acid (RA) -differentiated human neuroblastoma (SH-SY5Y) cells
AU - Muhammad-Safuan Zainuddin
AU - Chee-Wei Ang
AU - Saatheeyavaane Bhuvanendran
AU - Adzzie-Shazleen Azman
PY - 2026
DA - 2026/10/25
JO - Beni-Suef University Journal of Basic and Applied Sciences
DO - 10.1186/s43088-026-00842-y
UR - https://doi.org/10.1186/s43088-026-00842-y
AB - Background Alzheimer’s disease (AD) is a leading neurodegenerative disorder that imposes a significant global socioeconomic burden. It is characterised as progressive cognitive decline and a complex multifactorial pathology. Despite extensive research, current therapeutic options are limited. Emerging evidence suggests that oxidative stress is critical in the early pathological event preceding the classical hallmarks of AD. Targeting oxidative stress is a promising strategy for treating AD. Flavonoids are attractive due to their antioxidant, anti-inflammatory, and neuroprotective effects in AD. Dichamanetin (C29H24O6) is a rare C-benzylated flavanone that seldom occur in nature with reported antibacterial, and anti-malarial. Importantly, it has been suggested to possess anti-Alzheimer’s disease in-silico. However, neither its antioxidative nor neuroprotective potential has been explored in-vitro. Thus, this study aimed to address this gap by establishing an efficient method for the synthesis of dichamanetin and investigating its antioxidant properties and neuroprotective potential against hydrogen peroxide (H₂O₂)-induced cytotoxicity in-vitro. Methods In this study, we described the synthesis of dichamanetin using microwave irradiation and investigated its antioxidative activity using DPPPH and FRAP assay. Furthermore, we studied dichamanetin’s neuroprotective potential against hydrogen peroxide (H2O2)-insult as an in-vitro AD model using three treatment conditions include pre-treatment, co-treatment, and staggered co-treatment using CCK-8 cell viability assay. Results Dichamanetin was synthesised via microwave irradiation method, overcoming the limitations of isolation and purification from natural sources which often resulted in low yield. The improved synthesis method produced a good yield of 50% and purity of 95–97% determined via LC-MS and 1H NMR analyses. It shows that dichamanetin has low antioxidative activity as shown by FRAP ability. Importantly, it was non-cytotoxic to cholinergic neurons at concentrations below 3.125 µg/mL. It is shown to be a potent neuroprotectant in protecting the cholinergic neurons against H2O2-insult at 0.781 µg/mL, eliciting the highest neuroprotective effect in 6-hour staggered co-treatment comparable to quercetin and donepezil. Conclusions Dichamanetin attenuated H₂O₂-induced cytotoxicity in RA-differentiated SH-SY5Y cells, supporting its potential as a neuroprotective candidate against oxidative stress. Further studies are warranted to elucidate the underlying mechanisms and validate its efficacy, pharmacokinetics, safety, and therapeutic potential in relevant in vivo models of Alzheimer’s disease. Graphical Abstract
SN - 2314-8543
SN - 2314-8535
ER -