Objectives: Inflammation is our body’s normal defense mechanism, but in some cases, it may be responsible for causing different kinds of disorders. Several anti-inflammatory drugs are present for the ailment of these disorders; however, the conventional anti-inflammatory drugs give side effects when used in long term and therefore it is better to use them in a low dose for a shorter duration of time. This study was designed to find out whether there is an augmentation of the therapeutic effectiveness of the anti-inflammatory drugs like diclofenac sodium (NSAID), prednisolone (steroid) and atorvastatin (statin) when in combination with ascorbic acid (antioxidant). Methods: Wistar Rats (n=144) were selected and divided into 24 groups of 6 rats in each. Carrageenan and formalin were used to induce local inflammation and neuropsychiatric effects respectively. The inhibitions of such responses were measured after administering a drug alone and in combination with ascorbic acid. Results: In case of carrageenan mediated inflammation, the combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave the highest inhibition of 74.19% compared to other groups of drugs. The combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave 97.25% inhibition for formalin mediated inflammation group. In both cases, combination therapy showed statistically significant anti-inflammatory activities compared to mono therapy (p values <0.05). Conclusion: All the data clearly indicate new combinations of drug therapy comprising of diclofenac sodium, prednisolone, atorvastatin with ascorbic acid, which may be more effective against both local edema and neuropsychiatric effect caused due to inflammation.

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Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Curaçao on three different occasions and the characterization of barbamide’s biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.