Promiscuous or Dirty drug with Multifunctional Druggability nature of Curcumin (Curcuma longa Linn.); Repurposing in propranolol withdrawal-induced OCD related Anxiety: A promising drug discovery besides One-Drug-One-Receptor approach via in silico in vivo studies

Abstract

Background: Curcumin (Curcuma longa) and propranolol display a plethora of pharmacological activity linked with multifunctional druggable nature designated as a promiscuous or dirty drug (magic shotguns) that hit 'on-target as well as 'off-target' (anti-target). Multifactorial origins, with complex neuronal networks and broad-spectrum symptomatology, operates most CNS disorders. Anxiety is one of the comorbidities in the psychogenic spectrum of obsessive-compulsive disorder (OCD). The present study of OCD has been based on its multifunctionality and diverse drug potential, tailoring together the morbidity and comorbidity patterns of OCD. Very few multimodal drugs did trial in this regard, which has multifunctional druggability, except selective serotonin reuptake inhibitors (SSRIs) that work via the one-drug-one-receptor-one-disease approach; however, with inter-individual variability, unwanted side effects and limited multifunctionality with the druggable targets. SSRI success rates in OCD and its related disorder are minimal, especially in the adversity of comorbidity pattern. Objective: The principal objective of the current research was to testify the multifunctional druggable plethora of curcumin via repurposing of its dirty drug nature to reverse the obsessed anxiety of propranolol withdrawal-induce mice, besides the "one drug one receptor" approach or magic bullet. Methods: The present study evaluated OCD related anxiety-like behavior after different periods of abstinence (24 h, 7 and 21 days) from repeated propranolol (10 mg/kg) administration in mice. In addition, we also examined the action of curcumin (EERCL-50 mg/kg) and fluoxetine (20 mg/kg) for the attenuation or reversal of OCD related anxiety-like behavior after seven days to 24 hours propranolol withdrawal. The initial stage of the hypothesis toward the target of curcumin was identified via in-silico using SwissADME drug-likeness study, followed by in-vivo studies using Swiss albino mice. Evaluation for the same did use elevated plus maze (EPM), marble-burying behaviour (MBB) and motor activity (MA) test as a model. Further, did also investigate the antioxidant activity. Result: The result revealed a decrease in all parameters 24 hours and 14 days after exposure to propranolol, indicating anxious behaviour. The administration of curcumin and fluoxetine after 24 hrs of abstinence reduced animal anxiety in EPM; after the abstinence periods, the drug reduced the MA in the MBB. Curcumin reversed the anxiogenic effect induced by propranolol in EPM. The value of p<0.05 was considered statistically significant. Conclusion: Results revealed that propranolol might, to a large extent, impart to withdrawal-induced obsessed anxiety, and curcumin could effectively treat propranolol dependent obsessed mice. Further, curcumin anti-compulsive competency substantially showed promising success besides one drug-one receptor-one disease approach or magic bullet.