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Protective Effect of Esculetin, Natural Coumarin in Mice Model of Fibromyalgia: Targeting Pro-Inflammatory Cytokines and MAO-A

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Abstract

Fibromyalgia is a refractory syndrome characterized by chronic wayward pain and complex co-morbid psychological trepidation. The current treatments have a limited role and proper clinical benefits are far from satisfactory. Naturally occurring coumarins such as osthole are known to have analgesic and anti-inflammatory activities. Therefore, the current investigation was designed to explore the potential of natural coumarin esculetin (2.5, 5, and 10 mg/kg) in mitigating reserpine-induced fibromyalgia in Swiss albino mice. Esculetin is a 6,7 dihydroxy-coumarin obtained from various plant sources such as Aesculus hippocastanum L, Ceratostigma willmottianum, Citrus limonia, etc. Reserpine (0.5 mg/kg/day s.c.) treatment for first 3 days, significantly altered the behavior of mice as evidenced by reduced paw withdrawal threshold in pressure application measurement (PAM) test and electronic von-Frey (eVF) test, increased immobility time in forced swim test (FST), increased latency to reach the platform in Morris water maze (MWM) test and reduced number of square crossed in the open field test (OFT). These behavioral deficits with reserpine treatment were integrated with a reduced level of serotonin (5-HT), reduced glutathione (GSH), along with an increase in monoamine oxidase-A (MAO-A) activity, pro-inflammatory cytokines (IL-1β, TNF-α), thiobarbituric acid reactive substances (TBARS) and glutamate level. Esculetin (10 mg/kg/day i.p) treatment for 5 days, significantly abrogated reserpine induced behavioral and biochemical alterations. Whereas, no significant improvement was observed with lower doses of esculetin i.e. 2.5 and 5 mg/kg.

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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 scheme.

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Authors and Affiliations

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

    Lovedeep Singh, Anudeep Kaur, Saweta Garg, Amrit Pal Singh & Rajbir Bhatti

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  1. Lovedeep Singh
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  2. Anudeep Kaur
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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/2018/23) 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. Protective Effect of Esculetin, Natural Coumarin in Mice Model of Fibromyalgia: Targeting Pro-Inflammatory Cytokines and MAO-A. Neurochem Res 45, 2364–2374 (2020). https://doi.org/10.1007/s11064-020-03095-y

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