Anti-inflammatory effect of curcumin in an accelerated senescence model of Wistar rat: an in vivo and in-silico study.

Curcumin, a biphenolic substance derived from turmeric (Curcuma longa), offers a number of health-beneficial effects, including anti-inflammatory, cardiovascular protection, anti-cancerous, and anti-angiogenic. By interacting with the PPARγ (Peroxisome Proliferator-Activated Receptor-γ), curcumin inhibits NF-κB. These biological outcomes seem to be the outcome of NF-κB inhibition mediated by curcumin. The current study explores the in vivo impact of curcumin on several inflammatory parameters during aging in Wistar rats. An in-silico docking simulation study using Maestro and Desmond, Schrödinger, was carried out to further validate the experimental findings. According to our observation, rats given curcumin supplementation had a considerably (p ≤ 0.05) reduced level of inflammation. By generating numerous polar and hydrophobic interactions and exhibiting little conformational deviation throughout the simulation, in silico investigations showed that the proposed ligand curcumin had a high affinity for the enzyme COX-2. During simulation, protein-ligand complexes of curcumin with the other targets viz. 5-LOX, TNF-α and IL-6 also demonstrated improved binding and minimal fluctuation. The COX-2 and 5-LOX enzymes and the cytokines (TNF-α and IL-6) implicated in inflammation may have been inhibited by curcumin, highlighting its function as a multi-target inhibitor. Our study provides convincing support for the idea that eating a diet high in curcumin may help to reduce inflammation and help to explain some of its health-beneficial effects.Communicated by Ramaswamy H. Sarma.

Identification of candidate target genes of oral squamous cell carcinoma using high-throughput RNA-Seq data and in silico studies of their interaction with naturally occurring bioactive compounds.

Oral Squamous Cell Carcinoma (OSCC) accounts for more than 90% of all kinds of oral neoplasms that develop in the oral cavity. It is a type of malignancy that shows high morbidity and recurrence rate, but data on the disease's target genes and biomarkers is still insufficient. In this study, in silico studies have been performed to find out the novel target genes and their potential therapeutic inhibitors for the effective and efficient treatment of OSCC. The DESeq2 package of RStudio was used in the current investigation to screen and identify differentially expressed genes for OSCC. As a result of gene expression analysis, the top 10 novel genes were identified using the Cytohubba plugin of Cytoscape, and among them, the ubiquitin-conjugating enzyme (UBE2D1) was found to be upregulated and playing a significant role in the progression of human oral cancers. Following this, naturally occurring compounds were virtually evaluated and simulated against the discovered novel target as prospective drugs utilizing the Maestro, Schrodinger, and Gromacs software. In a simulated screening of naturally occurring potential inhibitors against the novel target UBE2D1, Epigallocatechin 3-gallate, Quercetin, Luteoline, Curcumin, and Baicalein were identified as potent inhibitors. Novel identified gene UBE2D1 has a significant role in the proliferation of human cancers through suppression of 'guardian of genome' p53 via ubiquitination dependent pathway. Therefore, the treatment of OSCC may benefit significantly from targeting this gene and its discovered naturally occurring inhibitors.Communicated by Ramaswamy H. Sarma.

Lichen planus drugs re-purposing as potential anti COVID-19 therapeutics through molecular docking and molecular dynamics simulation approach.

Background and Aim: The present study intends to investigate COVID-19 by targeting their main proteins with 17 selected drugs used for treating Oral Lichen Planus (OLP) which is a chronic muco-cutaneous disorder. Here, an attempt is made to gain better insight into the structure of various drugs targeting specific proteins which will be helpful in developing drugs useful for therapeutic and preventive measures. Method: In silico studies, molecular docking and molecular dynamic simulations were performed to repurpose the therapeutic drugs (n = 17) which were used to treat OLP against COVID-19. In addition, the maximum binding affinities of the key protein spike glycoprotein, main-protease (Mpro) of coronavirus, and Angiotensin-Converting Enzyme-2 (ACE-2) in the human body were evaluated with the selected drugs. Results: Epigallocatechin-3-gallate (EGCG) showed the highest docking values among the drugs selected for repurposing. Among the target proteins, EGCG has shown maximum binding affinity with ACE-2 receptor. Further, according to the molecular dynamic simulation studies, EGCG has shown the least conformational fluctuations with Mpro. Conclusion: EGCG can be a potential inhibitor drug which can bind with ACE-2 receptor thus inhibiting the interaction of mainly Mpro protein and spike glycoprotein of SARS-CoV-2. Relevance for Patients: EGCG, a natural compound shows antiviral potential having considerably high affinity and stability with SARS-CoV-2. It might be further employed as a lead drug against selective inhibitors of SARS-CoV-2 for the therapeutic management of COVID-19 patients after necessary clinical trials.

Lichen planus drugs re-purposing as potential anti COVID-19 therapeutics through molecular docking and molecular dynamics simulation approach.

Background and Aim: The present study intends to investigate COVID-19 by targeting their main proteins with 17 selected drugs used for treating Oral Lichen Planus (OLP) which is a chronic muco-cutaneous disorder. Here, an attempt is made to gain better insight into the structure of various drugs targeting specific proteins which will be helpful in developing drugs useful for therapeutic and preventive measures. Method: In silico studies, molecular docking and molecular dynamic simulations were performed to repurpose the therapeutic drugs (n = 17) which were used to treat OLP against COVID-19. In addition, the maximum binding affinities of the key protein spike glycoprotein, main-protease (Mpro) of coronavirus, and Angiotensin-Converting Enzyme-2 (ACE-2) in the human body were evaluated with the selected drugs. Results: Epigallocatechin-3-gallate (EGCG) showed the highest docking values among the drugs selected for repurposing. Among the target proteins, EGCG has shown maximum binding affinity with ACE-2 receptor. Further, according to the molecular dynamic simulation studies, EGCG has shown the least conformational fluctuations with Mpro. Conclusion: EGCG can be a potential inhibitor drug which can bind with ACE-2 receptor thus inhibiting the interaction of mainly Mpro protein and spike glycoprotein of SARS-CoV-2. Relevance for Patients: EGCG, a natural compound shows antiviral potential having considerably high affinity and stability with SARS-CoV-2. It might be further employed as a lead drug against selective inhibitors of SARS-CoV-2 for the therapeutic management of COVID-19 patients after necessary clinical trials.