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Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol (4), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC50 values of 0.98, 0.90, and 5 μg/mL against ABTS, DPPH, and H2O2, respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC50 values of 42.76, 10.70, and 7.40 μg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.Objective: This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.

Breast cancer begins in the breast cells, mainly impacting women. It starts in the cells that line the milk ducts or lobules responsible for producing milk and can spread to nearby tissues and other body parts. In 2020, around 2.3 million women across the globe received a diagnosis, with an estimated 685,000 deaths. Additionally, 7.8 million women were living with breast cancer, making it the fifth leading cause of cancer-related deaths among women. The mutational changes, overexpression of drug efflux pumps, activation of alternative signalling pathways, tumour microenvironment, and cancer stem cells are causing higher levels of drug resistance, and one of the major solutions is to identify multitargeted drugs. In our research, we conducted a comprehensive screening using HTVS, SP, and XP, followed by an MM/GBSA computation of human-approved drugs targeting HER2/neu, BRCA1, PIK3CA, and ESR1. Our analysis pinpointed IRESSA (Gefitinib-DB00317) as a multitargeted inhibitor for these proteins, revealing docking scores ranging from −4.527 to −8.809 Kcal/mol and MM/GBSA scores between −49.09 and −61.74 Kcal/mol. We selected interacting residues as fingerprints, pinpointing 8LEU, 6VAL, 6LYS, 6ASN, 5ILE, and 5GLU as the most prevalent in interactions. Subsequently, we analysed the ADMET properties and compared them with the standard values of QikProp. We extended our study for DFT computations with Jaguar and plotted the electrostatic potential, HOMO and LUMO regions, and electron density, followed by a molecular dynamics simulation for 100 ns in water, showing an utterly stable performance, making it a suitable drug candidate. IRESSA is FDA-approved for lung cancer, which shares some pathways with breast cancers, clearing the hurdles of multitargeted drugs against breast and lung cancer. This has the potential to be groundbreaking; however, more studies are needed to concreate IRESSA’s role.

Areca catechu seeds and their extract/s are currently used to treat various ailments and infections including snakebites. The purpose of this investigation was to assess the inhibiting/neutralizing effect of ethyl acetate and aqueous ethanolic seed extracts of A. catechu on Bungarus caeruleus (krait) venom. The enzyme activities and their inhibition were evaluated using standard procedures (in vitro). In vivo studies were conducted using chick embryos and murine models. The extracts inhibited hyaluronidase and phospholipase A2 activities. Protease activity was neutralized by the aqueous ethanolic extract only. The IC50 value of aqueous ethanolic extract for hyaluronidase was 0.001 g/mL, while that for the ethyl acetate extract for phospholipase A2 was 0.006 g/mL. In addition, both the extracts neutralized the indirect hemolysis and fibrinogenolytic activity induced by B. caeruleus venom. The LD50 for the chick embryos was 4.9 µg/egg. The 50 and 100 µg aqueous ethanolic extracts neutralized the LD50 and the challenging dose (3LD50) of venom effectively in the chick embryo model. The LD50 of B. caeruleus venom in mice was 0.1927 µg/kg; the extract extended the survival time of the mice from 25 min to 30 and 35 min in 1:10 and 1:20 ((w/w) venom:extract) ratios, respectively. The extract also neutralized myotoxic activity. The A. catechu seed extract showed promising inhibitory properties against B. caeruleus venom. In this regard, academia and industries should work collaboratively to develop and formulate a cost-effective first-aid drug.