In silico screening of the phytochemicals present in Clitoria ternatea L. as the inhibitors of snake venom phospholipase A2 (PLA2).

Millions of people suffer from snake bite envenomation, and its management is a challenge, even today. Medicinal plants have attracted the researcher's attention for their outstanding advantages in treating many diseases, including snake venom poisoning. Clitoria ternatea L, is a plant popularly known for its various pharmacological effects especially, anti-snake venom property. However, the molecular mechanism behind this is poorly understood. It is reported that snake venom PLA2 is an extensively studied toxic factor. This study is meant to screen the compound's capability to act as inhibitors of the Daboia russelli snake venom PLA2 through molecular docking and dynamics studies. Our results show that among the 27 compounds taken for the study, only Kaempferol showed good interaction profile with the conserved catalytic active site residues, His48 and Asp49. The pharmacophore features of the compound also demonstrate its exact fitting at the binding pocket. Further RMSD, RMSF, Rg, and hydrogen bond analysis confirmed the stable binding of Kaempferol with PLA2 through molecular dynamic simulations for 100 ns. In addition, the MM/PBSA binding free energy calculation of the complex was also affirming the docking results. The binding free energy (BFE) of Kaempferolis better than the reference compound. ADME and Lipinski's rule of five reveals its drug like properties.Communicated by Ramaswamy H. Sarma.

Surface refined AuQuercetin nanoconjugate stimulates dermal cell migration: possible implication in wound healing.

Refining nutraceutical conjugated metal nanoparticles (NPs) and understanding their interactions with the cellular micro-environment is necessary for their application in nanomedicine. In the present experiment, we studied the effect of quercetin functionalized gold nanoparticles (AuQurNP) on skin fibroblast and keratinocyte cell migration. Spherical shaped AuQurNPs of 47 nm in size were formed due to the interaction of hydroxyl and carbonyl groups of quercetin with Au atoms as revealed by incremental algorithm-based analysis. AuQurNP containing up to 5 µg l-1 of Au with quercetin (5.2 ± 1.6 ng ml-1) was least toxic to fibroblasts. AuQurNP effectively reduced the generation of intracellular ROS (up to 63%) through free-radical scavenging activity. AuQurNP also enhanced the rate of migration of fibroblasts (24 h) and keratinocytes (20 h) in artificially created wounds. The rate of migration of the cells towards the wound edge was in the order of AuQurNP > control > quercetin > AuNP. AuQurNP also significantly increased the expression of TGFß1 protein, thereby inducing the downstream SMAD complex (SMAD 2-4). Downregulation of the inhibitory protein SMAD 7 by AuQurNP helped in the nuclear translocation of SMADs 3 and 4. Collectively, the present in vitro study demonstrates the action of AuQurNP on the SMAD family and the interconnected molecular mechanism leading to the cell migration process.

Molecular docking and dynamic studies of crepiside E beta glucopyranoside as an inhibitor of snake venom PLA2.

Alternative treatments from plant-derived small molecules for neutralizing the venom lethality in snake envenomation are prevalent now. Elephantopus scaber, a tropical plant species has been recognized for its various pharmacological activities and especially anti-snake venom property; however, the molecular basis for this property is not understood. It is reported that snake venom PLA2 is a toxic factor with pharmacological effects independent of their catalytic activity. Here we report the inhibition of catalytic property of Cobra and Viper (group I and group II) snake venom PLA2 by the phytocompounds from E. scaber through molecular docking and dynamics studies. Initially, Lipinski's rule, ADMET, and molecular docking studies were carried out. Our results show that among 124 phytocompounds, crepiside E (deacylcynaropicrin-3' beta-glucopyranoside) has shown interactions with the conserved catalytic active site residues, His 48 and Asp 49, in both the PLA2s. Further, molecular dynamic simulations for 60 ns confirmed the stability of crepiside E in the active site of PLA2s and were found to be stable throughout the simulation. In order to understand the drug-likeness of crepiside E, pIC50 and MMGBSA scores were correlated by performing a linear regression analysis. Crepiside E was found to have similar chemical features to that of doxycycline, a known PLA2 inhibitor as indicated by a similarity score of 64.15%. Hence, it is concluded that crepiside E beta glucopyranoside present in Elephantopus scaber contributes to neutralizing the snake venom.

Frequent seizures and polytherapy can impair quality of life in persons with epilepsy.

CONTEXT: Careful evaluation of pharmacotherapy, seizure control and quality of life (QOL) are helpful in improving epilepsy care but such data are relatively meager from developing countries. AIMS: To audit pharmacotherapy, seizure control and QOL in persons with epilepsy and to identify factors associated with impaired QOL. SETTINGS AND DESIGN & MATERIALS AND METHODS: The study was carried out using a cross-sectional design in the setting of a tertiary care epilepsy center in India. Persons with epilepsy with > 12 months follow-up at this Center and aged > 16 years were eligible for enrollment. Persons with other disabilities or pregnancy were excluded. Subjects were interviewed with a standard questionnaire and an adapted version of Quality of Life in Epilepsy - 31 (QOLIE-31). Data pertaining to treatment at the time of referral to this center was extracted from medical records. STATISTICAL ANALYSIS USED: Chi-square test, analysis of variance and multiple regression analysis were carried out for statistical significance. RESULTS: One hundred and twelve patients with epilepsy (59 males, mean age 31.2+/-10.7 years) were included. Forty-seven (42%) persons had Generalized Epilepsy (GE) and 65 persons (58%) had Localization-Related Epilepsy (LRE). At entry 24 persons (21.4%) were not on treatment and 59 persons (64.8%) had frequent seizures. At last follow-up 64 persons (57.1%) were seizure-free, 83 persons (74.1%) were on monotherapy and 29 were (25.9%) on polytherapy. Cost of drug at entry was INR 2276 (monotherapy) and INR 3629 (polytherapy) (45 INR = 1 USD). At the time of last follow-up, it was 1898 and 4929 respectively. QOLIE-31 Total Score (TQOL) ranged from 22.6 to 94.4 (mean 68.0 +/- 15.8). Multiple regression analysis showed significant correlation between low TQOL score and polytherapy (P=0.002) and occurrence of one or more seizures per month (P=0.001). CONCLUSIONS: Frequent seizures and polytherapy are associated with lower QOL in persons with epilepsy.