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Background: Cyclooxygenase (COX)-lipooxygenase (LOX) pathway plays a key role in the pathogenesis of renal ischemia/reperfusion (IR). Objective: This study was aimed to evaluate the role of dietary phenol caffeic acid (CA), alone and in combination with selective COX-2 inhibitor celecoxib (CEL) in IR-induced acute renal failure (ARF) in rats. Materials and Methods: Renal IR was induced by bilateral occlusion of renal pedicels for 90 min followed by reperfusion for 24 h. Rats were randomized into 4 groups: Sham, IR, CA + IR, and CA + CEL + IR, with 7 day treatment before IR. Serum creatinine (SCr), blood urea nitrogen (BUN), antioxidant enzymes, tumor necrosis factor alpha (TNF-α), and histopathological changes were evaluated in the kidney after IR. Results: Renal IR caused significant derangement in renal function and histology. In the IR group, an increase in lipid peroxidation and decreased antioxidant defense enzyme activity were observed. Pretreatment with CA and CA + CEL showed a significant decrease in the BUN, SCr, TNF-α, oxidative stress markers and corrected the histological changes in the kidney. Conclusion: This study demonstrated the renoprotective potential of CA and combination of CA + CEL in IR-induced ARF in rats. The plausible mechanisms for the efficacy of CA could be attributed to its ability to modulate the ­COX-LOX system in renal IR.

The stem bark of Ceiba pentandra (L.) Gaertner is claimed to be useful in the treatment of tumors in the southern part of India. This plant possesses a number of sesquiterpenoids and isoflavones which are known for their anticancer properties. The present study was designed to scientifically evaluate the cytotoxic potential of bark extracts in in vitro on Ehrlich ascites carcinoma (EAC), MCF-7 and B16F10 cells and in vivo in EAC (Liquid tumor) model and Dalton's lymphoma ascites (DLA or solid tumor) model. The bark was powdered and extracted successively with solvents viz., petroleum ether (PE), benzene, chloroform, acetone (AC), and ethyl alcohol in the sequential order of polarity. Cytotoxicity of dried extracts was screened on EAC cells by trypan blue assay. Three potent extracts namely petroleum ether, acetone, and ethanol were screened for their cytotoxicity on MCF-7 and B16F10 cells by MTT assay and nucleomorphological alteration by propidium iodide staining. Safe doses of these extracts were evaluated by acute toxicity study in mice. Extracts were found to be safe up to 300 mg/kg in acute toxicity study. Dosage of 1/10th and 1/20th of safe dose i.e., 15 and 30 mg/kg were selected for in vivo study. In the EAC model, both doses of the extracts showed a significant (P < 0.05) improvement in mean survival time and a maximum decline in tumor induced increase in body weight (an indirect measure of tumor weight) by the PE and AC treatment at 15 mg/kg compared to control. In the DLA-model, all extracts at both tested dose levels showed >50 % reduction in tumor weight and a significant reduction (P < 0.05) in tumor volume on the 30th day compared to control. It can be concluded that these extracts possess cytotoxic and antitumor activity.

Background Dehydrozingerone (DHZ) is an active ingredient of Zingiber officinale and structural half analogue of curcumin. In the present study, DHZ was evaluated for monoamine oxidase (MAO) inhibitory activity in silico and antidepressant activity in vivo. Method The binding affinity of DHZ with MAO-A (PDB ID: 2Z5Y) was assessed using Schrodinger's Maestro followed by free energy calculation, pharmacokinetic property prediction using Qikprop and Molecular dynamics simulation using Desmond. In vivo antidepressant activity of DHZ was evaluated on C57 BL/6 male mice using Escilatopram as the standard antidepressant. Open field test (OFT), forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant effect of the drugs on days 1 and 7. Following the behavioural study, neurotransmitters (noradrenaline, dopamine and serotonin) were estimated using liquid chromatography–mass spectrometry. Results DHZ demonstrated a greater binding affinity for the MAO-A enzyme compared to moclobemide in silico. Immobility in TST and FST were significantly (p < 0.05) reduced in vivo with 100mg/kg DHZ as compared to respective controls. DHZ treatment was more effective 1 h post treatment compared to vehicle control. A significant increase in levels of neurotransmitters was observed in mice brain homogenate in response to DHZ treatment, reassuring its antidepressant-like potential. Conclusion DHZ demonstrated MAO-A inhibition in silico, and the increased neurotransmitter levels in the brain in vivo were associated with an antidepressant-like effect.