Protective Effect of Esculetin, Natural Coumarin in Mice Model of Fibromyalgia: Targeting Pro-Inflammatory Cytokines and
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ORIGINAL PAPER
Protective Effect of Esculetin, Natural Coumarin in Mice Model of Fibromyalgia: Targeting Pro‑Inflammatory Cytokines and MAO‑A Lovedeep Singh1 · Anudeep Kaur1 · Saweta Garg1 · Amrit Pal Singh1 · Rajbir Bhatti1 Received: 30 March 2020 / Revised: 4 July 2020 / Accepted: 9 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Fibromyalgia · Esculetin · IL-1 β · TNF-α · MAO-A · 5-HT
Introduction Fibromyalgia is a chronic neurologic syndrome of complex etiology characterized by increased pain sensitivity, escalated number of tender points, extreme tiredness, muscle stiffness, and poor sleep. Some patients may present these symptoms alone or may be associated with various co-morbidities such as depression, anxiety, migraine, cognitive impairment, irritable bowel syndrome, etc. [1, 2]. According to the American College of Rheumatology (ACR), the prevalence of fibromyalgia is more in women, though it can also affect men. It often begins in middle adulthood but can occur in teenagers and in old people [3]. It Includes reduced levels of biogenic amines, increased level of excitatory amino-acid, inflammatory cytokines, and oxidative stress markers [4]. * Rajbir Bhatti [email protected] 1
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India
Widespread chronic and persistent pain is a primary sympto
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