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Normalization of HPA Axis, Cholinergic Neurotransmission, and Inhibiting Brain Oxidative and Inflammatory Dynamics Are Associated with The Adaptogenic-like Effect of Rutin Against Psychosocial Defeat Stress

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Abstract

Social defeat stress (SDS) due to changes in biochemical functions has been implicated in the pathogenesis of affective and cognitive disorders. Employing pharmacological approach with adaptogens in the management and treatment of psychosocial stress is increasingly receiving scientific attention. In this study, we investigated the neuroprotective effect of rutin, a bioflavonoid with neuroprotective and anti-inflammatory functions on neurobehavioral and neuro-biochemical changes in mice exposed to SDS. Groups of mice named the intruder mice received normal saline (10 mL/kg), rutin (5, 10, and 20 mg/kg, i.p.), and ginseng (50 mg/kg, i.p.) daily for 14 days, and then followed by 10 min daily SDS (physical/psychological) exposures to aggressor mice from days 7-14. Investigations consisting of neurobehavioral (locomotion, memory, anxiety, and depression) phenotypes, neuro-biochemical (oxidative, nitrergic, cholinergic, and pro-inflammatory cytokines) levels in discrete brain regions, and hypothalamic–pituitary–adrenal (HPA) axis consisting adrenal weight, corticosterone, and glucose concentrations were assessed. Rutin restored the neurobehavioral deficits and reduced the activity of acetylcholinesterase in the brains. Adrenal hypertrophy, increased serum glucose and corticosterone levels were significantly attenuated by rutin. SDS-induced release of tumor necrosis factor-alpha and interleukin-6 in the striatum, prefrontal cortex, and hippocampus were also suppressed by rutin in a brain-region-dependent manner. Moreover, SDS-induced oxidative stress characterized by low antioxidants (glutathione, superoxide-dismutase, catalase) and lipid peroxidation and nitrergic stress were reversed by rutin in discrete brain regions. Collectively, our data suggest that rutin possesses an adoptogenic potential in mice exposed to SDS via normalization of HPA, oxidative/nitrergic, and neuroinflammatory inhibitions. Thus, may be adopted in the management of neuropsychiatric syndrome due to psychosocial stress.

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Acknowledgements

The Authors are grateful to the technical staff of the Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Edo State, Nigeria.

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Pharmacology and Toxicology, University of Benin, Benin City, Edo State, Nigeria

    Joseph O.T. Emudainohwo, Emma Elohor Okpakpor & Ray I. Ozolua

  2. Department of Pharmacology, Faculty of Basic Medical Science, Delta State University, Delta State, Abraka, Nigeria

    Benneth Ben-Azu

  3. Department of Human Physiology, Faculty of Basic Medical Science, PAMO University of Medical Sciences, Rivers State, Port Harcourt, Nigeria

    Olusegun G. Adebayo

  4. Department of Human Physiology, Faculty of Basic Medical Sciences, Bayelsa Medical University, Bayelsa State, Yenagoa, Nigeria

    Wadioni Aduema

  5. Department of Pharmacology and Therapeutics, Faculty of Basic Medical Science, Rivers State University, Rivers State, Port Harcourt, Nigeria

    Christian Uruaka

  6. Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Science, University of Ibadan, Oyo State, Ibadan, Nigeria

    Abayomi M. Ajayi

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All authors contributed to this research work and the development of the final manuscript. EOTJ, BAB, OGA, and OIR designed the study and wrote the protocols; EOTJ, BAB, EEO, and AMA performed the experiments; EOTJ, AMA, and BAB did the ELISA study; EOTJ, BAB, AMA, UC, EEO, and OGA analyzed the data and literature searches; EOTJ, BAB, OGA, UC, and OIR contributed reagents/materials/analysis tools; EOTJ, BAB, OGA, and OGA. wrote the first draft of the manuscript; EOTJ, BAB, OGA, and OIR completed the final draft of the paper.

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Correspondence to Benneth Ben-Azu or Ray I. Ozolua.

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Emudainohwo, J.O., Ben-Azu, B., Adebayo, O.G. et al. Normalization of HPA Axis, Cholinergic Neurotransmission, and Inhibiting Brain Oxidative and Inflammatory Dynamics Are Associated with The Adaptogenic-like Effect of Rutin Against Psychosocial Defeat Stress. J Mol Neurosci 73, 60–75 (2023). https://doi.org/10.1007/s12031-022-02084-w

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