Skimmetin/osthole mitigates pain-depression dyad via inhibiting inflammatory and oxidative stress-mediated neurotransmit
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ORIGINAL ARTICLE
Skimmetin/osthole mitigates pain-depression dyad via inhibiting inflammatory and oxidative stress-mediated neurotransmitter dysregulation Lovedeep Singh 1 & Anudeep Kaur 1 & Saweta Garg 1 & Rajbir Bhatti 1 Received: 28 March 2020 / Accepted: 20 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 antidiabetic 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. Keywords Pain-depression . Skimmetin . Osthole . Cytokines . 5-HT . Norepinepinephrine
Introduction Depression is a psychiatric illness that negatively affects the feelings, thinking, and personality of an individual. According to the report of WHO, above 300 million people are suffering from depression (WHO 2017). From 2005 to 2015, an 18% increase in the incidence of depression has been observed and about 8 lakh people have been reported to commit suicide per year (WHO 2017). Depression and pain are close-fisted with each other in terms of occurrence and progression. Depression is often accompanied by cryptic painful somatic symptoms, which are usually neglected during clinical * Rajbir Bhatti [email protected] 1
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India
therapy (Nekovarova et al. 2014). Both depression and pain generate a vicious cycle in which depressive symptoms can ante-cede pain or vice-versa, forming a
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