Abstract
Rationale
Alcoholism and obesity impart a deleterious impact on human health and affects the quality of life. Chronic consumption of alcohol and western diet has been reported to cause memory deficits. 7,8-dihydroxyflavone (7,8-DHF), a TrkB agonist, comprises antioxidant and anti-inflammatory properties in treating various neurological disorders.
Objectives
The current study was aimed to determine the protective effect and molecular mechanism of 7,8-DHF against alcohol and high-fat diet (HFD)-induced memory deficits in rats.
Methods
The adult male Wistar rats were given alcohol (3–15%) and HFD ad libitum for 12 weeks in different experimental groups. 7,8-DHF (5 mg/kg) was intraperitoneally injected daily for the last 4 weeks (9th–12th week).
Results
The alcohol and HFD administration caused cognitive impairment as evaluated through the Morris water maze (MWM) test in alcohol, HFD, and alcohol + HFD-fed animals. The last 4-week treatment of 7,8-DHF (5 mg/kg; i.p.) attenuated alcohol and HFD-induced memory loss. 7,8-DHF treatment also restored the glutathione (GSH) level along with attenuation of nitrite, malondialdehyde content (markers of oxidative and nitrosative stress), and reduction of the acetylcholinesterase activity in the hippocampus of alcohol and HFD-fed animals. Furthermore, the administration of 7,8-DHF caused downregulation of NF-κB, iNOS, and caspase-3 and upregulation of Nrf2, HO-1, and BDNF mRNA level in rat hippocampus.
Conclusion
7,8-DHF administration conferred beneficial effects against alcohol and HFD-induced memory deficit via its unique antioxidant, anti-inflammatory, anti-apoptotic potential, along with the activation of TrkB/BDNF signaling pathway in the hippocampus.
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Acknowledgments
The authors are immensely thankful to Gauhati Medical College and Hospital, Guwahati, Institutional Level Biotech hub and State Biotech Hub, College of Veterinary Sciences, Guwahati for providing technical support.
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The National Institute of Pharmaceutical Education and Research (NIPER) Guwahati provided financial support.
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The present study was carried out in accordance with the guidelines of the Committee for the Purpose of Control and Supervision of Experimentation on Animals (CPCSEA), New Delhi, India. The study protocol was approved by the Institutional Animals Ethics Committee at Gauhati Medical College and Hospital, Guwahati, India.
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Pandey, S.N., Kwatra, M., Dwivedi, D.K. et al. 7,8-Dihydroxyflavone alleviated the high-fat diet and alcohol-induced memory impairment: behavioral, biochemical and molecular evidence. Psychopharmacology 237, 1827–1840 (2020). https://doi.org/10.1007/s00213-020-05502-2
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DOI: https://doi.org/10.1007/s00213-020-05502-2