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Skimmetin/osthole mitigates pain-depression dyad via inhibiting inflammatory and oxidative stress-mediated neurotransmitter dysregulation

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Abstract

Pain and depression are often co-existing pathological states that promote mutual severity resulting in limited efficacy of current treatment strategies. Thus, there is a need to develop an efficacious alternate treatment regimen for pain-depression dyad. Skimmetin and osthole are molecules of natural origin that have been explored for an anti-hyperglycemic, anti-bacterial, anti-fungal, and anti-diabetic activities in preclinical studies. in animal models. The current study has been designed to explore the beneficial effect of skimmetin/osthole in reserpine-induced pain-depression dyad in mice. Female Swiss albino mice (n = 6) were challenged with reserpine (0.5 mg/kg s.c.) for the first 3 days to induce a pain-depression dyad-like state. Skimmetin (10 mg/kg i.p.) and osthole (10 mg/kg i.p.) were administered for 5 days consecutively, starting from the first day of study. Reserpine treatment significantly reduced the pain threshold in the pressure application measurement (PAM) and electronic von frey (eVF) test. In forced swim test (FST) and Morris water maze (MWM) test mice displayed an increased immobility time and latency to reach platform respectively. Biochemical results showed an increased level of TNF-α, IL-1β, TBARS, glutamate, and reduced level of GSH, norepinephrine, and serotonin in the reserpine treated group. Reserpine treatment also increased brain MAO-A activity. Skimmetin/osthole treatment was found to attenuate the behavioral and biochemical alterations induced by reserpine. The results of the current investigation delineated that skimmetin/osthole may exert anti-nociceptive, anti-depressant, and improved cognition via inhibiting inflammatory and oxidative stress-mediated neurotransmitter dysregulation.

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Acknowledgments

The authors are grateful to the Department of Science and Technology, Government of India, for funding received under EMR (EMR/2016/005878) and DST-PURSE. The authors gratefully acknowledge the financial support received from the University Grants Commission under RUSA scheme.

Funding

Department of Science and Technology, Government of India (EMR/2016/005878), DST-PURSE and University Grants Commission, RUSA 2.0 scheme.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India

    Lovedeep Singh, Anudeep Kaur, Saweta Garg & Rajbir Bhatti

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  1. Lovedeep Singh
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Correspondence to Rajbir Bhatti.

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The entire study involving the use of mice was approved by the Institutional. Animal Ethics Committee (Approval No. 226/CPCSEA/2016/07) and the experiments were conducted according to ethical guidelines of the Ministry of Environment and Forests, Government of India.

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Singh, L., Kaur, A., Garg, S. et al. Skimmetin/osthole mitigates pain-depression dyad via inhibiting inflammatory and oxidative stress-mediated neurotransmitter dysregulation. Metab Brain Dis 36, 111–121 (2021). https://doi.org/10.1007/s11011-020-00604-4

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