SALUBRIOUS EFFECT OF ROTTLERIN ON HYPEROXALURIA INDUCED OXIDATIVE DAMAGE IN RATS

Objective: To investigate the in vitro oxidant scavenging properties of rottlerin and to study the potential role of rottlerin on ethylene glycol induced nephrocalcinosis in rats.Methods: In vitro oxidant scavenging properties of rottlerin were studied along with its effect on in vitro calcium phosphate mineralization. For the in vivo studies, hyperoxaluria was induced by administering 0.4 % ethylene glycol and 1 % ammonium chloride in drinking water to male wistar rats for 9 d. Rottlerin was administered intraperitoneally at 1mg/kg/d along with the hyperoxaluric agent. Total thiols content, activities of glutathione-S-transferase (GST), glutathione reductase (GR), Citrate synthase (CS), isocitrate dehydrogenase (ICDH), ATPase and urinary parameters were studied.Results: Rottlerin showed in vitro DPPH, superoxide, and ABTS radical scavenging activity along with inhibition of calcium phosphate mineralization in an in vitro homogeneous system. The diminished activities of GST, GR, ICDH, CS, ATPase and level of total thiols were considerably stabilized by rottlerin, suggesting that rottlerin provides protection against oxalate induced oxidative damage.Conclusion: We suggest that rottlerin protects the integrity of the renal cell by stabilizing the free-radical mediated damage. Thus, the present study reveals that the antioxidant nature of rottlerin protects the renal cells against oxalate-induced injury and thus, rottlerin may prevent against hyperoxaluria induced oxidative damage.Keywords: Rottlerin, Hyperoxaluria, Oxidative stress, Antioxidan

3D-QSAR, molecular docking and ADME studies on indole analogues reveal antidepressant activity through monoamine oxidase-A inhibition

1012-1029Monoamine oxidase (MAO) enzymes over see the concentration of neurotransmitters and intracellular amines in the brain and peripheral tissues by catalysing their oxidative deamination and represents a crucial target in drug designing for the management of neurological and psychiatric disorders. Present study is an effort to present an economical fast high throughput screening easy method to identify indole analogues as potent MAO inhibitors, using different computational techniques. CoMSIA field-based 3D-QSAR models have been developed by applying the partial least squares regression algorithm that exhibit satisfactory predictive and descriptive capability with statistical parameters R² (0.9557) and Q² (0.8529). Generated model (s) helped in explaining the key descriptors firmly related with MAO inhibitory activity and are used to generate library of 1853 indole derivatives. Library is evaluated and has resulted in the identification of 30 indole derivatives with high docking scores (−9.978 to −7.136) in comparison to the antidepressant standard drug Isocarboxazid (−7.125). Further, these compounds have been scrutinized through drug-likeliness profiles and Desmond's molecular dynamics simulations studies for 100 ns. Further in vitro and in vivo studies on these molecules might provide us with new drug candidate for the treatment of depression with high therapeutic index