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Glycitein prevents reserpine-induced depression and associated comorbidities in mice: modulation of lipid peroxidation and TNF-α levels

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Abstract

Depression is a debilitating mood disorder affecting millions worldwide and continues to pose a significant global health burden. Due to the multifaceted nature of depression, the current treatment regimens are not up to mark in terms of their multitargeting potential and least side effect profile. Molecules within the isoflavone class demonstrate promising potential in alleviating depression and associated conditions, offering a multifaceted approach to manage mental health concerns. Therefore, the current study was designed to explore the potential of glycitein, an isoflavone in managing reserpine-induced depression and associated comorbidities in mice. Reserpine (0.5 mg/kg; i.p.) administration for the first 3 days induced depression and associated comorbidities as evidenced by increased immobility time in forced swim test (FST) and tail suspension test (TST), along with reduced locomotor activity in the open field test (OFT) and increased latency to reach the platform in the Morris water maze (MWM) test. Reserpine treatment also upregulated and downregulated the brain thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) levels, respectively. Furthermore, reserpine administration also uplifted the level of TNF-α in the serum samples. Glycitein (3 mg/kg and 6 mg/kg; p.o.) treatment for 5 days prevented the depressive effect of reserpine. It also improved the spatial memory at both dose levels. Moreover, in biochemical analysis, glycitein also reduced the brain TBARS and serum tumor necrosis factor-alpha (TNF-α) levels. Whereas, no significant effect was seen on the brain GSH level. Glycitein (6 mg/kg) was found to be more effective than the 3 mg/kg dose of glycitein. Overall results delineate that glycitein has the potential to manage depression and impaired memory by inhibiting lipid peroxidation and inflammatory stress.

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Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

The authors gratefully acknowledge the financial assistance provided by the University Institute of Pharma Sciences, Chandigarh University.

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Diksha performed all the experiments and wrote the manuscript. Lovedeep Singh conceptualized the study and also helped in writing the manuscript. Lovedeep Singh and Diksha revised the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Lovedeep Singh.

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The entire animal study was approved by the Institutional Animal Ethics Committee on 4 Jan 2023 (approval no. CU/2022/IAEC/7/10). All the experiments were carried out by the Ministry of Environment and Forests’ ethical guidelines.

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Diksha, Singh, L. Glycitein prevents reserpine-induced depression and associated comorbidities in mice: modulation of lipid peroxidation and TNF-α levels. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03007-9

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