Design, synthesis and drug resistance reversal potential of novel curcumin mimics Van D: Synergy potential of curcumin mimics.

Being crucial part of plant-based novel discovery of drug from natural resources, a study was done to explore the antibacterial potential of curcumin mimics in combination with antibiotics against multidrug resistant isolates of Pseudomonas aeruginosa. The best candidate Van D, a curcumin mimics reduced the MIC of tetracycline (TET) up to 16 folds against multidrug resistant clinical isolates. VanD further inhibited the efflux pumps as evident by ethidium bromide efflux and by in-silico docking studies. In another experiment, it was also found that Van D inhibits biofilm synthesis. This derivative kills the KG-P2, an isolate of P. aeruginosa in a time dependent manner, the post-antibiotic effect (PAE) of tetracycline was extended as well as mutant prevention concentration (MPC) of TET was also decreased. In Swiss albino mice, Van D reduced the proinflammatory cytokines concentration. In acute oral toxicity study, this derivative was well tolerated and found to be safe up to 1000 mg/kg dose. To the best of our knowledge, this is the first report on curcumin mimics as synergistic agent via inhibition of efflux pump.

Effect of ethanolic extract of Cyperus rotundus L. against isoprenaline induced cardiotoxicity.

Interruption of blood supply to the heart results in acute myocardial infarction (AMI), and further damages the heart muscles. Available drugs for the treatment MI have one or other side effects, and there is a need for development of better alternative drugs from herbal sources. Here, we evaluated cardioprotective effect of Cyperus rotundus on isoprenaline- induced myocardial infarction. Thirty five Wistar rats, aged 60-100 days with body wt. 150-200 g, pretreated with ethanolic extract of Cyperus rotundus L. (@ 250 and 500 mg/kg body wt.) orally before induction of myocardial necrosis by administrating isoprenaline (85 mg/kg, s.c.) on 19th and 20th day of the pretreatment period. The treated rats were examined for gross functioning of heart, heart weight/body wt. Ratio, and also observed histopathologically. Further, activities of various cardiac enzymes such as aspartate transaminase, alanine transaminase, creatinine kinase-myoglobulin, lactate dehydrogenase, and the gold marker troponin-I were also determined. The levels altered by isoproterenol were found to be restored significantly by the test extracts especially at higher dose. Biochemical observations viz., serum ALT (P <0.0001), AST (P <0.0001), creatine kinase-myoglobulin (CK-MB) (P <0.0001), LDH (P <0.0001) demonstrated significant cardioprotective activity of the ethanolic extract of C. rotundus (500 mg/kg body wt.), against isoprenaline induced myocardial infarction. These results were also substantiated by physical parameters and histopathological observations. All these results were comparable with that of two standard drugs metoprolol (10 mg/kg/day), ramipril (3 mg/kg/day) as well as polyherbal formulation Abana (50 mg/kg/day).