Endophytic fungi from marine seaweeds are the less studied group of organisms with vast medical applications. The aim of the present study was to evaluate antioxidant, antiangiogenic as well as wound healing potential of the endophytic fungus isolated from the seaweed Sargassum wightii. The morphological characters and the rDNA internal transcribed spacer sequence analysis (BLAST search in Gen Bank database) was used for the identification of endophytic fungus. The antioxidant potential of the ethyl acetate extract of endophytic fungus was assessed by, 1,1-diphenyl-2-picryl-hydrazyl radical scavenging method. The fungal extract was also analysed for reducing power, total phenolic and flavonoid content. Antiangiogenic activity of the fungal extract was studied in vitro by inhibition of wound healing scratch assay and in vivo by Chick chorioallantoic membrane assay. The endophytic fungus was identified as Cladosporium cladosporioides (Gen Bank ID – KT384175). The ethyl acetate extract of C. cladosporioides showed a significant antioxidant and angiosuppressive activity. The ESI-LC-MS analysis of the extract revealed the presence of wide range of secondary metabolites. Results suggest that C. cladosporioides extract could be exploited as a potential source for angiogenic modulators.

Fungal endophytes are less studied group of microorganisms with vast therapeutic potential. A polyphenol producing endophyticfungus was isolated from Zingiber officinale rhizome. The ethyl acetate extract of Aspergillus austroafricanus (EAE) was tested against five human pathogenic bacteria by disc diffusion method. Antioxidant activity of EAE was determined by DPPH, H₂O₂ and nitric oxide radical-scavenging methods. DNA protection from the OH radicals was tested by agarose gel electrophoresis. High-performance liquid chromatography was used to determine the total yield of polyphenols. The identity of the endophytic fungus was established as A. austroafricanus CGJ-B3 (GenBank accession No. KT780617) based on rDNA and phylogenetic analysis. EAE showed significant antioxidant, antimicrobial activity and DNA damage protection capacity. The HPLC analysis showed the presence of polyphenols such as p-coumaric acid, ferulic acid and cinnamic acid and the content was about 0.392 ± 0.08 µg/mg, 4.35 ± 0.16 µg/mg and 1.976 ± 0.11 µg/mg, respectively. A. austroafricanus CGJ-B3 isolated from Z. officinale is a promising potential pharmaceutical agent and can be used as an alternative source of polyphenols like p-coumaric acid, ferulic acid and cinnamic acid.

Background and Objectives: Cyclooxygenase-2 (COX-2) is mostly linked to inflammation and has been validated as a molecular target for treating inflammatory diseases. The present study aimed to identify novel compounds that could inhibit COX-2, which is associated with various diseases including inflammation, and in such a scenario, plant-derived biomolecules have been considered as attractive candidates. Materials and Methods: In the present study, physiochemical properties and toxicity of natural compounds/drugs were determined by SWISSADME and ProTox-II. In the present study, the molecular docking binding features of saffron derivatives (crocetin, picrocrocin, quercetin, safranal, crocin, rutin, and dimethylcrocetin) against human COX-2 protein were assessed. Moreover, protein-protein interactions, topographic properties, gene enrichment analysis and molecular dynamics simulation were also determined. Results: The present study revealed that picrocrocin showed the highest binding affinity of −8.1 kcal/mol when docked against the COX-2 protein. PROCHECK analysis revealed that 90.3% of the protein residues were found in the most favored region. Compartmentalized Protein–Protein Interaction identified 90 interactions with an average interaction score of 0.62, and the highest localization score of 0.99 found in secretory pathways. The Computed Atlas of Surface Topography of Proteins was used to identify binding pockets and important residues that could serve as drug targets. Use of WEBnmα revealed protein dynamics by using normal mode analysis. Ligand and Receptor Dynamics used the Molecular Generalized Born Surface Area approach to determine the binding free energy of the protein. Gene enrichment analysis revealed that ovarian steroidogenesis, was the most significant enrichment pathway. Molecular dynamic simulations were executed for the best docked (COX-2-picrocrocin) complex, and the results displayed conformational alterations with more pronounced surface residue fluctuations in COX-2 with loss of the intra-protein hydrogen bonding network. The direct interaction of picrocrocin with various crucial amino-acid residues like GLN²⁰³, TYR³⁸⁵, HIS^{386 and 388}, ASN³⁸², and TRP³⁸⁷ causes modifications in these residues, which ultimately attenuates the activity of COX-2 protein. Conclusions: The present study revealed that picrocrocin was the most effective biomolecule and could be repurposed via computational approaches. However, various in vivo and in vitro observations are still needed.

Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide. According to the WHO, every year, there is an increase in the rate of death globally due to CVDs, stroke, and myocardial infarction. Several risk factors contribute to the development of CVDs, one of which is hypoxia, defined as a reduction in oxygen levels. This major stressor affects aerobic species and plays a crucial role in the development of cardiovascular disease. Research has uncovered the “hypoxia-inducible factors (HIFs) switch” and investigated the onset, progression, acute and chronic effects, and adaptations of hypoxia, particularly at high altitudes. The hypoxia signalling pathways are closely linked to natural rhythms such as the circadian rhythm and hibernation. In addition to genetic and evolutionary factors, epigenetics also plays an important role in postnatal cardiovascular responses to hypoxia. Oxidized LDL-C initiates atherosclerosis amidst oxidative stress, inflammation, endothelial dysfunction, and vascular remodelling in CVD pathogenesis. Anti-inflammatory and antioxidant biomarkers are needed to identify individuals at risk of cardiovascular events and enhance risk prediction. Among these, C-reactive protein (CRP) is a recognized marker of vascular inflammation in coronary arteries. Elevated pro-atherogenic oxidized LDL (oxLDL) expression serves as an antioxidant marker, predicting coronary heart disease in apparently healthy men. Natural antioxidants and anti-inflammatory molecules protect the heart by reducing oxidative stress, enhancing vasodilation, and improving endothelial function. For instance, the flavonoid quercetin exerts antioxidant and anti-inflammatory effects primarily by activating the Nrf2/HO-1 signaling pathway, thereby enhancing cellular antioxidant defense and reducing reactive oxygen species. Carotenoids, such as astaxanthin, exhibit potent antioxidant activity by scavenging free radicals and preserving mitochondrial integrity. The alkaloid berberine mediates cardiovascular benefits through activation of AMO-activated protein kinase (AMPK) and inhibition of nuclear factor kappa B [NF-kB] signalling, improving lipid metabolism and suppressing inflammatory cytokines. Emerging evidence highlights microRNAs (miRNAs) as potential regulators of oxidative stress via endothelial nitric oxide synthase (eNOS) and silent mating-type information regulation 2 homolog (SIRT1). While the exact mechanisms remain unclear, their benefits are likely to include antioxidant and anti-inflammatory effects, notably reducing the susceptibility of low-density lipoproteins to oxidation. Additionally, the interactions between organs under hypoxia signalling underscore the need for a comprehensive regulatory framework that can support the identification of therapeutic targets, advance clinical research, and enhance treatments, including FDA-approved drugs and those in clinical trials. Promising natural products, including polysaccharides, alkaloids, saponins, flavonoids, and peptides, as well as traditional Indian medicines, have demonstrated anti-hypoxic properties. Their mechanisms of action include increasing haemoglobin, glycogen, and ATP levels, reducing oxidative stress and lipid peroxidation, preserving mitochondrial function, and regulating genes related to apoptosis. These findings emphasise the importance of anti-hypoxia research for the development of effective therapies to combat this critical health problem. A recent approach to controlling CVDs involves the use of antioxidant and anti-inflammatory therapeutics through low-dose dietary supplementation. Despite their effectiveness at low doses, further research on ROS, antioxidants, and nutrition, supported by large multicentre trials, is needed to optimize this strategy.

Hypoxia-inducible factors (HIF) belong to the basic helix loop helix–PER ARNT SIM (bHLH-PAS) family of transcription factors that induce metabolic reprogramming under hypoxic condition. The phylogenetic studies of hypoxia-inducible factor-1α (HIF-1α) sequences across different organisms/species may leave a clue on the evolutionary relationships and its probable correlation to tumorigenesis and adaptation to low oxygen environments. In this study, we have aimed at the evolutionary investigation of the protein HIF-1α across different species to decipher their sequence variations/mutations and look into the probable causes and abnormal behaviour of this molecule under exotic conditions. In total, 16 homologous sequences for HIF-1α were retrieved from the National Center for Biotechnology Information. Sequence identity was performed using the Needle program. Multiple aligned sequences were used to construct the phylogeny using the neighbour-joining method. Most of the changes were observed in oxygen-dependent degradation domain and inhibitory domain. Sixteen sequences were clustered into 5 groups. The phylogenetic analysis clearly highlighted the variations that were observed at the sequence level. Comparisons of the HIF-1α sequence among cancer-prone and cancer-resistant animals enable us to find out the probable clues towards potential risk factors in the development of cancer.