Connexios Life Sciences Pvt Ltd.

The present study was aimed to evaluate the anticonvulsant activity of acteoside and explore its mechanism of action. Initially, the acteoside was evaluated in maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions, and later it was evaluated against N-methyl-D-aspartic acid (NMDA)-induced mortality in Swiss albino mice. Based on the response in these models, further evaluations were performed to explore the mechanism of action. In the results, the acteoside (10, 25, and 50 mg/kg) has shown significant anticonvulsant activity in the PTZ model (p < 0.01 for all doses); however, there was no protection observed in MES and NMDA models. Therefore, further mechanism-based studies were performed on the PTZ model, and the outcomes have revealed that there was a significant reduction in GABA (p < 0.01 for both regions) and elevation of glutamate (p < 0.01 for both regions) in the cortex and hippocampus regions of PTZ-treated animals. Further, the antioxidant levels (SOD, catalase, GPx, GR, GSH, LPO) were altered significantly (p < 0.01 for all parameters), with reduced GABA_A mRNA levels (p < 0.01) in the PTZ control compared with the normal control. Interestingly, co-administration of acteoside (25 mg/kg) (p < 0.01 for all parameters) has restored all the PTZ-induced alterations compared to PTZ-control. Moreover, the anti-PTZ action of acteoside was completely blocked in the presence of flumazenil, and thus confirmed the GABAergic mechanism behind the anticonvulsant activity of acteoside. Besides, actophotometer and rotarod tests have confirmed that the acteoside is free from central side effects like motor incoordination and locomotor deficits.

This study was designed to investigate possible interference of Xenobiotics with SUMOylation in eukaryotic cells. To begin with, we docked 71 chemical structures from PubChem with human SUMO1 and UBC9 protein structures using Auto Dock 4.2 and Hex 6.3 and selected five compounds for binding studies in Surface Plasmon Resonance (SPR) with human SUMO1. In SPR studies, only endosulfan showed binding to SUMO1 (K_d1.313 × 10-4 M). Further, we treated HePG2 and differentiated 3T3-L1 cells with endosulfan/bisphenol A/perfluorooctanoic acid (PFOA) to test induction of oxidative stress and SUMO isoform/UBC9 expression. Treatment with these compounds resulted in higher levels of nitric oxide (NO), NOS2A mRNA, and reactive oxygen species (ROS) associated with decreased NADPH levels. Additionally, treatment with these chemicals resulted in elevated mRNA levels of IL-6 and IL-1β in 3T3-L1 cells. In HePG2 cells, endosulfan treatment resulted in elevated mRNA levels of SUMO1, 3 and UBC9, whereas, treatment with bisphenol A resulted in increased mRNA of SUMO2, 3 and UBC9. Treatment with PFOA resulted in elevated mRNA levels of SUMO2. Apart from influencing the gene expression, endosulfan caused decrease in SUMO1-Sumoylation of few proteins. We propose that one reason for the severe health consequences of exposure to endosulfan/bisphenol could be due to induction of oxidative stress and modulation in SUMO and UBC9 gene expression.

This study was aimed to evaluate the beneficial role of inhalation budesonide(BUD) in improving the pulmonary functions, and reducing the hospital admission rate, worsening of asthma and commonly encountered adverse events in pediatric asthma.

The electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases to identify the randomized control trials(RCTs).

21 RCTs involving 12,787 subjects were included. The meta-analysis revealed that the BUD has reduced the hospitalization rate (Mantel-Haenszel (M-H), random effects odd ratio (RE-OR) of 0.34, p = 0.003, I² = 75%), and worsening of asthma (M-H, RE-OR 0.38, p = 0.001, I² = 73%); significantly improved the pulmonary functions such as FEV1 (Inverse variance (IV): 1.05, p < 0.0001, I² = 94%), PEFR (IV: 1.40, p < 0.0001, I² = 87%), morning PEF (IV: 1.04, p < 0.0001, I² = 91%), and evening PEF (IV: 1.29, p < 0.0001, I² = 92%) compared to control. Further, the incidences of adverse events like Pharyngitis (M-H, RE-OR 0.88, at 95% CI, p = 0.69, I² = 0%), Sinusitis (M-H, RE-OR 0.78, p = 0.79, I² = 0%), Respiratory infections (M-H, RE-OR 0.96, p = 0.46, I² = 0%), Otitis media (M-H, RE-OR 0.82, p = 0.32, I² = 12%) and Fever (M-H, RE-OR 0.78, p = 0.64, I² = 0%) were almost same between BUD and control.

The outcomes of the meta-analysis suggest that high-dose inhalation BUD could benefit the pediatric patients in minimizing the worsening of asthma and hospitalization rate, along with improving the pulmonary functions, with negligible adverse drug reactions.