Abstract
A high dose of dexamethasone induces neurodegeneration by initiating the inflammatory processes that lead to neural apoptosis. A dexamethasone administration model induces overproduction of amyloid-β (Aβ) and tau protein hyperphosphorylation and shows abnormalities of cholinergic function similar to Alzheimer’s disease (AD). This study aimed to investigate the protective effect of hexahydrocurcumin on the brain of dexamethasone-induced mice. The results showed that hexahydrocurcumin and donepezil attenuated the levels of amyloid precursor protein and β-secretase mRNA by reverse transcription polymerase chain reaction, decreased the expression of hyperphosphorylated tau, and improved synaptic function. Moreover, we found that hexahydrocurcumin treatment could decrease interleukin-6 levels by attenuating p65 of nuclear factor kappa-light-chain-enhancer (NF-κB) of activated beta cells. In addition, hexahydrocurcumin also decreased oxidative stress, as demonstrated by the expression of 4-hydroxynonenal and thereby prevented apoptosis. Therefore, our finding suggests that hexahydrocurcumin prevents dexamethasone-induced AD-like pathology and improves memory impairment.
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Funding
The work was supported by the Faculty of Medicine Research Fund, grant no. 064-2562, the Functional Food Research Center for Well-Being, the Center for Research and Development of Natural Products for Health, Chiang Mai University, the Thailand Research Fund (DBG6180030), the Center of Excellence for Innovation in Chemistry, and the Ministry of Higher Education, Science, Research and Innovation.
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Designed the study: JT, PJ; Animals and methodology: PJ, KP, CT and JT; Analysis and investigation: PJ and JT; Hexahydrocurcumin preparation: WC and AS; Review and editing: PJ, CT, AS, and JT; All author read and approved for final manuscript.
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This study performed under the guideline and approval for animal use by the ethics committee (No: 16/2561), Faculty of Medicine, Chiangmai University.
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Jearjaroen, P., Pakdeepak, K., Tocharus, C. et al. Inhibitory Effect of Hexahydrocurcumin on Memory Impairment and Amyloidogenesis in Dexamethasone-Treated Mice. Neurotox Res 39, 266–276 (2021). https://doi.org/10.1007/s12640-020-00269-y
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DOI: https://doi.org/10.1007/s12640-020-00269-y