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Phosphoglycerate kinase-1 (PGK1) is an enzyme found in the cells and tissues of the human body. Deficiency of this enzyme leads to deadly neurodegenerative diseases, such as stroke, amyotrophic lateral sclerosis (ALS), Parkinson's disease and apoptosis. Since there is no ideal drug candidate to cure such diseases by activating this enzyme, this study aimed to discover a new potent candidate from cyanobacteria using in silico pharmacological applications. The preparation of both the protein and the ligands was performed in Maestro 13.2, followed by docking using a range of modules, including Prepwizard, Ligprep, Sitemap, Glidgrid and Glide Dock, with different modes, such as HTVS, SP, XP and Desmond v6.8. Among the 240 docked cyanobacterial metabolites, lyngbyastatin, hoiamide D, lyngbyastatin 4, lyngbyastatin I, lyngbyastatin 7, tigicamide A, hoiamide and symlocamid A, showed remarkable docking and energy values. These compounds exhibit better potency as promising drugs at the target residues than reference molecules, as evidenced by better docking scores, energies, lower root mean square deviation (RMSD) with stronger binding affinities in molecular docking and MD simulations. The study demonstrated that these compounds are the first to be identified as triggers of PGK1, and it was anticipated that these metabolites would show beneficial effects when tested in both in vitro and in vivo studies of such deadly neurodegenerative diseases. The results obtained in the study suggested that these metabolites may provide a beneficial drug effect to reduce the complications associated with PGK1. The current work is aimed to identify a potent candidate in treating neurodegenerative diseases caused by phosphoglycerate kinase 1 (PGK1) dysfunction. Hence, 240 secondary metabolites identified/isolated from the various cyanobacterial species were selected based on their prevailing pharmacological properties. Eventually, lyngbyastatin (a cyclic depsipeptide) was known to be an effective candidate for neurogenerative diseases, revealing better stability even than the standard drug terazosin. Based on the findings, the present study proposes that it could act as an effective neuroprotective agent and further clinical studies are suggested to validates its efficacy. [ABSTRACT FROM AUTHOR]

Viral outbreaks facilitated by global travel and modernity pose significant threats to global health. Influenza viruses, particularly α-influenza and β-influenza strains, have been plaguing human populations since time immemorial. Despite their long-standing impact, effective drugs are yet to be developed, and co-infection with these viruses can lead to severe health complications. In light of these challenges, this study aimed to investigate the potential antiviral molecules sourced from cyanobacteria and herbs. We conducted virtual screening using ligand-based docking to identify potential phytochemicals and cyanobacterial metabolites as candidates for further evaluation. Subsequently, pharmacophore modeling was employed to validate the binding modes of the selected compounds, followed by MM-GBSA calculations to assess their binding affinities and stabilities within the viral target. Among the molecules investigated, the cyanobacterial compound Symplocamide A (−8.042) demonstrated notable outcomes in docking than the herb molecules in the docked ligand. This finding suggests its potential as a therapeutic agent against influenza A virus proteins. Additionally, cyanobacterial molecules such as Lyngbyastatins 3 (−8.001), Lyngbyastatin G1 (−7.501), and Kempenopeptide (−6.128) exhibit stronger binding affinities and more potent docking scores, making them promising candidates for targeting viral proteins in potential therapeutic applications. The present study reveals the possibility of harnessing cyanobacterial molecules as novel antiviral agents against influenza viruses. Ultimately, we believe that this research will serve as a stepping stone in the quest for innovative drugs to combat respiratory diseases caused by viral infections. [ABSTRACT FROM AUTHOR]

Ficus auriculata Lour. (Moraceae) is an underutilized wild edible fruit widely consumed for its nutritional properties. The present study aimed to determine the phytochemical composition and in vitro antioxidant, enzyme inhibitory, anti-inflammatory and anti-cancerous properties of the F. auriculata fruit extracts through in vitro digestion (oral, gastric and intestinal phases). The extracts were obtained by hot extraction and cold maceration methods using aqueous and methanolic solvents. Major phytoconstituents identified through LC-MS was subjected to molecular docking against the target proteins. The elemental analysis shows the presence of major elements; high levels of total phenolics (124.61 ± 0.82 mg gallic acid equivalent/g), flavonoids (76.38 ± 0.82 mg quercetin equivalent/g), vitamin E (32.48 ± 0.09 mg alpha-tocopherol equivalent/g), and carbohydrate (34.59 ± 0.45 mg glucose equivalent/g) in hot extracted methanolic undigested extract (HEM UD) and high level of total protein (124.71 ± 0.34 mg bovine serum albumin equivalent/g) in cold extracted methanolic undigested fruit extract were found. HEM UD showed high antioxidant activity in 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), 2,2-diphenyl-1-picryl-hydrazyl, and superoxide radical scavenging assays with IC 50 of 53.30 ± 0.57, 80.69 ± 0.12, and 65.47 ± 1.13 μg/mL, respectively. The HEM UD extract also potentially inhibited the enzyme activity of α-amylase, α-glucosidase, tyrosinase, and protein denaturation (IC 50 of 67.76 ± 1.22, 83.18 ± 1.23, 87.24 ± 1.15, and 65.76 ± 0.60 μg/mL). The most potent extract (HEM UD) was studied for its anticancer effects by MTT assay against the MCF-7 and HeLa cell lines and showed the IC 50 of 89.80 ± 0.56 and 60.76 ± 0.04 μg/mL, respectively. The LC-MS analysis elucidated ten phytoconstituents. Based on the molecular docking study, querciturone could potentially be an effective constituent in treating diabetes and inflammation-related issues. The findings indicated the ability of F. auriculata fruits as a promising functional food. [Display omitted] • The present study identified substantially high content of macro and microminerals. • High level of phenolics, flavonoids, vitamin E, and carbohydrate was recorded. • Through in vitro digestion, bioaccessibility of Ficus auriculata fruits was confirmed. • The extract displayed low cytotoxicity with notable anticancer effects. • Maximum binding affinity and docking score was recorded with querciturone. [ABSTRACT FROM AUTHOR]

The study was aimed to investigate the phytochemical composition, antioxidant, antibacterial and enzyme inhibitory effects of Psydrax dicoccos leaf (PDL). Hydroalcoholic extract (HAE) was recorded with high concentration of total phenolics (59.68 ± 0.3 mg GAE/g), total flavonoids (57.85 ± 0.5 mgQRE/g) and proanthocyanidin (24.98 ± 0.17 mgAAE/g). Ethyl acetate (31.76 ± 1.52 mgQE/g), methanolic (34.99 ± 0.16 mgAAE/g) and aqueous (75.00 ± 0.30 mgGAE/g) extracts showed a high amount of total flavanols, vitamin E and total tannins, respectively. GC-MS analysis facilitated the identification of 56 metabolites with squalene and cinnamic acid as prominent compounds. HAE showed moderate α-amylase (IC50 of 48.94 ± 0.5 µg/mL) and α-glucosidase (IC50 of 46.98 ± 0.5 µg/mL) inhibitory activities. HAE is also perceived as a potent radical scavenger, reducing agent, metal chelating power, and total antioxidant capacity. For antibacterial activity, the aqueous extract was most effective with the MIC ranged from 87.5 to 175 µg/mL. Further characterization and in vivo studies are suggested to validate its traditional claim as a potential source of therapeutic agents. [ABSTRACT FROM AUTHOR]