Synergistic action of synthetic peptides and amphotericin B causes disruption of the plasma membrane and cell wall in Candida albicans.

The objective of this work was to evaluate the combination of synthetic peptides based on the γ-core motif of defensin PvD1 with amphotericin B (AmB) at different concentrations against Candida albicans. We applied the checkerboard assay using different concentrations of the commercial drug AmB and the synthetic peptides γ31-45PvD1++ and γ33-41PvD1++ against C. albicans, aiming to find combinations with synergistic interactions. Between these two interactions involving γ31-45PvD1++ and AmB, an additive effect was observed. One such interaction occurred at concentrations of 0.009 µM of peptide γ31-45PvD1++ and 13.23 µM of AmB and another condition of 0.019 µM of peptide γ31-45PvD1++ and 6.61 µM of AmB. The other two concentrations of the interaction showed a synergistic effect in the combination of synthetic peptide γ31-45PvD1++ and AmB, where the concentrations were 1.40 µM peptide γ31-45PvD1++ and 0.004 µM AmB and 0.70 µM γ31-45PvD1++ peptide and 0.002 µM AmB. We proceeded with analysis of the mechanism of action involving synergistic effects. This examination unveiled a range of impactful outcomes, including the impairment of mitochondrial functionality, compromise of cell wall integrity, DNA degradation, and a consequential decline in cell viability. We also observed that both synergistic combinations were capable of causing damage to the plasma membrane and cell wall, causing leakage of intracellular components. This discovery demonstrates for the first time that the synergistic combinations found between the synthetic peptide γ31-45PvD1++ and AmB have an antifungal effect against C. albicans, acting on the integrity of the plasma membrane and cell wall.

Recent advances and synergistic effect of bioactive zeolite imidazolate frameworks (ZIFs) for biosensing applications.

The rapid developments in the field of zeolitic imidazolate frameworks (ZIFs) in recent years have created unparalleled opportunities for the development of unique bioactive ZIFs for a range of biosensor applications. Integrating bioactive molecules such as DNA, aptamers, and antibodies into ZIFs to create bioactive ZIF composites has attracted great interest. Bioactive ZIF composites have been developed that combine the multiple functions of bioactive molecules with the superior chemical and physical properties of ZIFs. This review thoroughly summarizes the ZIFs as well as the novel strategies for incorporating bioactive molecules into ZIFs. They are used in many different applications, especially in biosensors. Finally, biosensor applications of bioactive ZIFs were investigated in optical (fluorescence and colorimetric) and electrochemical (amperometric, conductometric, and impedance) fields. The surface of ZIFs makes it easier to immobilize bioactive molecules like DNA, enzymes, or antibodies, which in turn enables the construction of cutting-edge, futuristic biosensors.

Biocompatible 2D Materials via Liquid Phase Exfoliation.

2D materials (2DMs), such as graphene, transition metal dichalcogenides (TMDs), and black phosphorus (BP), have been proposed for different types of bioapplications, owing to their unique physicochemical, electrical, optical, and mechanical properties. Liquid phase exfoliation (LPE), as one of the most effective up-scalable and size-controllable methods, is becoming the standard process to produce high quantities of various 2DM types as it can benefit from the use of green and biocompatible conditions. The resulting exfoliated layered materials have garnered significant attention because of their biocompatibility and their potential use in biomedicine as new multimodal therapeutics, antimicrobials, and biosensors. This review focuses on the production of LPE-assisted 2DMs in aqueous solutions with or without the aid of surfactants, bioactive, or non-natural molecules, providing insights into the possibilities of applications of such materials in the biological and biomedical fields.

Biological properties of caffeine, (+)-catechin, and theobromine: an in silico study.

We analyzed here the in silico biological activities of caffeine, (+)-catechin, and theobromine. For this, the PubChem database of the NIH (National Institutes of Health) was used to obtain the SMILE canonical form of the bioactive molecules, and the free software PASS Online (Prediction of Activity Spectra for Substances) from the Way2Drug portal. Also, we conducted an in vitro experiment using a chronic myeloid leukemia (CML) cell line (K562) to confirm some results found in in silico investigation. These cells were exposed to different concentrations of caffeine, (+)-catechin, and theobromine for 72 h. The results found in this in silico study suggested that caffeine, (+)-catechin, and theobromine showed excellent biological properties, such as antioxidant, anti-inflammatory, and anticarcinogenic, as well as protection against cardiovascular, diabetes, neurological, allergic, respiratory, and other therapeutic activities. These findings can be elucidated through the modulation exerted by these bioactive molecules in many biochemical pathways involved in organism homeostasis, such as free radical scavenger action, oxidoreductase inhibitor, membrane permeability inhibitor, and lipid peroxidase inhibitor. In addition, we have found here that caffeine, (+)-catechin, and theobromine have a remarkable anti-inflammatory activity which plays an important role in the therapeutic approach of COVID-19. Moreover, our in vitro findings confirmed the in silico results regarding anticancer activity since these molecules reduce cell proliferation at all tested concentrations. Therefore, since these molecules exhibit important medicinal activities, further investigations should be conducted to reveal new therapies to improve the treatments and prevention of numerous disorders and, consequently, promote human health.

Nanocomposites and their application in antimicrobial packaging.

The advances in nanocomposites incorporating bioactive substances have the potential to transform the food packaging sector. Different nanofillers have been incorporated into polymeric matrixes to develop nanocomposite materials with improved mechanical, thermal, optical and barrier properties. Nanoclays, nanosilica, carbon nanotubes, nanocellulose, and chitosan/chitin nanoparticles have been successfully included into polymeric films, resulting in packaging materials with advanced characteristics. Nanostructured antimicrobial films have promising applications as active packaging in the food industry. Nanocomposite films containing antimicrobial substances such as essential oils, bacteriocins, antimicrobial enzymes, or metallic nanoparticles have been developed. These active nanocomposites are useful packaging materials to enhance food safety. Nanocomposites are promising materials for use in food packaging applications as practical and safe substitutes to the traditional packaging plastics.

Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools.

Compounds derived from natural sources continue to serve as chemical scaffolds for designing prophylactic/therapeutic options for human healthcare. In this study, we aimed to systematically unravel the chemical profile and antioxidant and anti-inflammatory activities of myrtle methanolic extract (MMEx) using in vitro, in vivo, and in silico approaches. High levels of TPC (415.85 ± 15.52 mg GAE/g) and TFC (285.80 ± 1.64 mg QE/g) were observed. Mass spectrophotometry (GC-MS) analysis revealed the presence of 1,8-cineole (33.80%), α-pinene (10.06%), linalool (4.83%), p-dimethylaminobenzophenone (4.21%), thunbergol (4%), terpineol (3.60%), cis-geranyl acetate (3.25%), and totarol (3.30%) as major compounds. MMEx induced pronounced dose-dependent inhibition in all assays, and the best antioxidant activity was found with H2O2, with an IC50 of 17.81 ± 3.67 µg.mL-1. MMEx showed a good anti-inflammatory effect in vivo by limiting the development of carrageenan-induced paw edema. The pharmacokinetic profiles of the active molecules were determined using the SwissADME website, followed by virtual screening against anti-inflammatory targets including phospholipase A2 (PLA-2), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and NF-κB. A pharmacokinetic study revealed that the molecules have good absorption, distribution, and metabolism profiles, with negative organ toxicity. Among the compounds identified by GC-MS analysis, pinostrobin chalcone, cinnamyl cinnamate, hedycaryol, totarol, and p-dimethylaminobenzophenone were observed to have good binding scores, thus appreciable anti-inflammatory potential. Our study reveals that MMEx from Algerian Myrtus communis L. can be considered to be a promising candidate for alleviating many health complaints associated with oxidative stress and inflammation.

Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration.

Recently, nanotechnologies have become increasingly prominent in the field of bone tissue engineering (BTE), offering substantial potential to advance the field forward. These advancements manifest in two primary ways: the localized application of nanoengineered materials to enhance bone regeneration and their use as nanovehicles for delivering bioactive compounds. Despite significant progress in the development of bone substitutes over the past few decades, it is worth noting that the quest to identify the optimal biomaterial for bone regeneration remains a subject of intense debate. Ever since its initial discovery, poly(lactic-co-glycolic acid) (PLGA) has found widespread use in BTE due to its favorable biocompatibility and customizable biodegradability. This review provides an overview of contemporary advancements in the development of bone regeneration materials using PLGA polymers. The review covers some of the properties of PLGA, with a special focus on modifications of these properties towards bone regeneration. Furthermore, we delve into the techniques for synthesizing PLGA nanoparticles (NPs), the diverse forms in which these NPs can be fabricated, and the bioactive molecules that exhibit therapeutic potential for promoting bone regeneration. Additionally, we addressed some of the current concerns regarding the safety of PLGA NPs and PLGA-based products available on the market. Finally, we briefly discussed some of the current challenges and proposed some strategies to functionally enhance the fabrication of PLGA NPs towards BTE. We envisage that the utilization of PLGA NP holds significant potential as a potent tool in advancing therapies for intractable bone diseases.

Electrospun Nanofibers Encapsulated with Natural Products: A Novel Strategy to Counteract Skin Aging.

The skin is the primary tissue affected by wounds and aging, significantly impacting its protective function. Natural products are widely used in cosmetics, representing a new approach to preventing age-related damage. Nanomedicine combines nanotechnology and traditional treatments to create innovative drugs. The main targets of nanotechnological approaches are wound healing, regeneration, and rejuvenation of skin tissue. The skin barrier is not easily permeable, and the creation of modern nanodevices is a way to improve the passive penetration of substances. In this study, Helichrysum italicum oil (HO) was combined with different types of electrospun nanofibers to study their protective activity on the skin and to evaluate their future application for topical treatments. In the present research, we used biodegradable polymers, including polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), which were characterized by a scanning electron microscope (SEM). All results show a positive trend in cell proliferation and viability of human skin stem cells (SSCs) and BJ fibroblasts pre-treated with combined nanofibers and then exposed to UV stress. Gene expression analysis revealed the activation of a molecular rejuvenation program in SSCs treated with functionalized nanofibers before UV exposure. Understanding the mechanisms involved in skin changes during aging allows for the future application of nanomaterials combined with HO directly to the patients.

Enhanced osteogenicity of the demineralized bone-dermal matrix composite by the optimal partial demineralization for sustained release of bioactive molecules.

Allogenic demineralized bone matrix (DBM), processed to expose bioactive proteins imbedded by calcium salts, is widely used for bone repair and regeneration as an alternative to the autologous bone graft. However, demineralized bone matrices from tissue banks vary significantly in residual calcium content and osteogenicity for clinical bone regeneration. The present study produced DBM with various residual calcium contents by partial demineralization using ethylenediaminetetraacetic acid disodium (EDTA) and hydrochloric acid. Compositional analysis reveals that, as the percent weight loss of bone materials increases from 0% to 74.9% during demineralization, the residual calcium content of DBM decreases from 24.8% to 0.2% and collagen content increases from 29.7% to 92.6%. Calorimetrical analysis and Fourier transform infrared (FTIR) analysis demonstrated that demineralization to the residual calcium content of <4% enables the complete exposure and/or release of bone collagen fibers and other bioactive molecules. In order to evaluate the relationship between the extent of demineralization and the osteogenicity of DBM, DBM particles were fabricated with the aid of acellular dermal matrix (ADM) microfibers to form flexible foam-like DBM/ADM composites. Proteomic analysis identified various type collagens and bone formation-related bioactive molecules in both ADM and DBM. Using the rat bilateral Φ = 5 mm calvarium defect repair model, the study had shown that the DBM/ADM composite with ~20% DBM residual calcium (e.g., ~40% calcium being removed) maximized the osteogenicity for bone defect repair after 4 and 8 weeks. DBM with ~40% calcium removal had the maximal osteogenicity presumably through the sustained release of bioactive molecules during the process of bone regeneration.

Traditional uses, hepatoprotective potential, and phytopharmacology of Tinospora cordifolia: a narrative review.

OBJECTIVES: Despite significant advancements in modern medicine, effective hepatoprotective medication with minimal side effects is still lacking. In this context. Tinospora cordifolia, an Indian Ayurvedic liana, has attracted much attention. KEY FINDINGS: Traditionally, T. cordifolia has been found to be effective in the treatment of jaundice; according to the literature, T. cordifolia is a hepatoprotective agent, and the CCl4 model is the most frequently used to evaluate its potential. Its hepatoprotective effects might be attributed to alkaloids (berberine, palmatine, and jatrorrhizine) and sinapic acid. Berberine decreases inflammation by inhibiting the proinflammatory cascade triggered by TNF-α and reduces nitrosative stress by inhibiting iNOS. T. cordifolia also exhibits anticancer, anti-inflammatory, antimicrobial, antioxidant, and other activities; it is safe at concentrations up to 2000 mg/kg. Its biological action can be attributed to polyphenols, alkaloids, steroids, terpenoids, and glycosides. T. cordifolia has also been found to be an active ingredient in several polyherbal formulations used to treat chemical-mediated hepatotoxicity. CONCLUSION: T. cordifolia's hepatoprotective effects are mediated by the inhibition of lipid peroxidation, the management of oxidative stress, and other factors. T. cordifolia can be used to manage liver disorders and as a hepatoprotective supplement in the food industry. The bioprospecting of its alkaloids can lead to the development of novel formulations against hepatic ailments.

Exploring the potential of Brazilian Amazonian scorpion venoms: A comprehensive review of research from 2001 to 2021.

The Amazon biome is home to many scorpion species, with around two hundred identified in the region. Of these, forty-eight species have been reported in Brazil so far and six of them are of medical importance: Tityus apiacas, T. metuendus, T. obscurus, T. raquelae, T. silvestris, and T. strandi. Three non-medically important species have also been studied: Opisthanthuscayaporum, Brotheas amazonicus and Rhopalurus laticauda. The venom of the scorpion T. obscurus is the most studied, followed by O. cayaporum. We aim to update the study of these Amazonian scorpion species. We will explore the harmful and beneficial properties of scorpion venom toxins and how they could be applied in drug development. This systematic review will focus on collecting and analyzing venoms from scorpions in Brazil. Only papers on Amazonian scorpion venom studies published between 2001 and 2021 (scientific articles, theses, and dissertations) were selected, based on the lists of scorpions available in the literature. Species found in the Amazon but not confirmed to be Brazilian were omitted from the review. Theses and dissertations were chosen over their derived articles. We found 42 eligible studies (13 theses, 27 articles and 2 patents) out of 17,950 studies and a basic statistical analysis was performed. The literature showed that T. obscurus was the most studied venom with 28 publications, followed by O. cayaporum with seven articles, B. amazonicus with four articles, T. metuendus with two article and R. laticauda with one article. No publication on the characterization of T. silvestris and T. apiacas venoms were found during the reviewed period, only the clinical aspects were covered. There is still much to be explored despite the increasing number of studies conducted in recent years. Amazonian scorpions have promising potential for pharmaceutical and clinical applications.

A Novel Bifidobacterium longum ssp. longum Strain with Pleiotropic Effects.

Postbiotics are gaining increasing interest among the scientific community as well as at the level of food processing enterprises. The aim of this preliminary study was to characterise the metabolic diversity of a novel Bifidobacterium longum strain, BIOCC 1719, of human origin. The change after 24 h cultivation in three media was assessed using a metabolomic approach. Milk-based substrates favoured the activity of the strain, promoting the production of B vitamins, essential amino acids, bile acids, and fatty acids. Vitamins B1, B2, B6, B7, and B12 (with an average increase of 20-30%) were produced in both whole milk and whey; the increased production in the latter was as high as 100% for B7 and 744% for B12. The essential amino acids methionine and threonine were produced (>38%) in both milk and whey, and there was an increased production of leucine (>50%) in milk and lysine (126%) in whey. Increases in the content of docosahexaenoic acid (DHA) by 20%, deoxycholic acid in milk and whey (141% and 122%, respectively), and cholic acid (52%) in milk were recorded. During the preliminary characterisation of the metabolic diversity of the novel B. longum strain, BIOCC 1719, we identified the bioactive compounds produced by the strain during fermentation. This suggests its potential use as a postbiotic ingredient to enrich the human diet.

Recent Progress in the Application of Exosome Analysis in Ovarian Cancer Management.

Exosomes are very small (nano-sized) vesicles participating in tumor development by involvement in intercellular communication mediated by transferring biocomponents. Exosomes appear to play vital roles in various cancer development, such as ovarian cancer, a common malignancy in women. Several hallmarks of ovarian cancer are reported to be affected by the exosome-- mediated cellular cross-talk, including modulating peritoneal dissemination and chemoresistance. Since the expression of some biomolecules, such as miRNAs and mRNA, is changed in ovarian cancer, these exo-biomolecules can be applied as prognostic, diagnostic, and therapeutic biomarkers. Also, the selective loading of specific chemotherapeutic agents into exosomes highlights these biocarries as potential delivery devices. Exosomes could be artificially provided and engineered to better target the site of interest in ovarian cancer. In the present review, we summarize the notable achievement of exosome application in ovarian cancer management to gain applicable transitional insight against this cancer.

Platelet hyperactivity: a comparison of water-soluble, bioactive compound levels in commercial tomato products and water-soluble tomato concentrate, a supplement with an approved EFSA antiplatelet health effect.

The aim of this study was to evaluate and compare the concentration of water-soluble bioactive compounds in tomato products (polyphenols profile, water-soluble vitamins and nucleophilic substances) with the concentration of the same bioactive molecules existing in a water-soluble patented tomato extract, water-soluble tomato extract (WSTC), commercially available as FruitFlow®. This patented tomato extract has been recognised by EFSA (European Food Safety Authority) in a specific Health Claim declaration as having an "Antiplatelet health effect". More than 100 commercial tomato samples, coming from 18 different processing tomato companies worldwide, were analysed and compared with the FruitFlow® supplement. According to the multivariate statistical analyses applied to the data matrix, it is possible to conclude that the commercial tomato products measured (pastes, purees, others) show a significantly higher concentration of water-soluble bioactive molecules (nucleosides/nucleotides and polyphenols) responsible for an anti-platelet aggregation effect than the FruitFlow® dietary supplement.

Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug-resistant epilepsy (DRE).

Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug-resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator-activated receptor α (PPARα) and sirtuin1 (SIRT1) genes-key regulators in energy and lipid metabolism-and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency. Blood samples collected before VNS device implantation, after acute VNS stimulus, and following gradual intensity increments up to therapeutic levels revealed that VNS increases SIRT1 and PPARα expression and erythrocyte concentrations of PPARα ligands. Additionally, we observe reduced de novo lipogenesis biomarkers in erythrocytes, indicating that VNS may influence systemic lipid and energy metabolism. Our findings suggest that VNS could enhance neuronal function by modulating energy metabolism, thus potentially reducing seizure frequency in subjects with DRE. Future research targeting SIRT1 and PPARα may provide innovative therapeutic strategies for managing DRE. Plain Language Summary: The exact mechanism of VNS is still unknown. This study investigated the effects of VNS Therapy on energetic metabolism, suggesting possible novel biomarkers for DRE subjects and neuromodulation therapies.

Argentine squid (Illex argentinus): A source of mycosporine-like amino acids with antioxidant properties.

Here we report on the occurrence of mycosporine-like amino acids (MAAs) in the Argentine shortfin squid, Illex argentinus, the second fishery resource mostly exploited in the Argentinean continental shelf. The total content of four MAAs was evaluated by reverse-phase-HPLC in different tissues (eyes, skin, liver, and gonads). Also, the antioxidant activity of crude extracts was assessed by in-vitro determinations: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Folin-Ciocalteu, and ferrous ion-chelating capacity assays. The content of MAAs was found to be almost ten times higher in female gonads than in other tissues (11,89 ± 0,56 mg/g dry weight). Extracts from skin, female gonads and eyes, exhibit higher antioxidant activity than the reference compounds ascorbic acid and TROLOX. Overall, Argentine squid waste is a promising potential source of MAAs with antioxidant and UV photoprotective properties, which could bear interest in food, cosmetic and pharmaceutical industries, thus encouraging maximal and sustainable use of fishing resources.

Self-Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Paclitaxel (PTX) is a well-established and highly effective anti-cancer drug for peripheral solid tumors. However, the application of PTX in GBM is hindered by several limitations, including poor water solubility, restricted entry across the blood-brain barrier (BBB), and enhanced excretion by efflux transporters. P-glycoprotein (P-gp) is a crucial efflux transporter that is abundantly present in cerebral vascular endothelial cells and GBM cells. It plays a significant role in the exocytosis of PTX within tumor tissues. METHODS: Recently, we have developed a novel technique for creating self-assembled nanoparticles utilizing a range of natural bioactive molecules. These nanoparticles can encapsulate insoluble drugs and effectively cross the BBB. In additional, we revealed that certain nanoparticles have the potential to act as P-gp inhibitors, thereby reducing the excretion of PTX. In this study, we conducted a screening of bioactive molecular nanoparticles to identify those that effectively inhibit the function of P-gp transporters. RESULTS: Among the candidates, we identified ursolic acid nanoparticles (UA NPs) as the P-gp inhibitors. Furthermore, we prepared co-assembled UA NPs embedded with paclitaxel, referred to as UA-PTX NPs. Our results demonstrate that UA-PTX NPs can enhance the blood concentration of PTX, facilitate its entry into the BBB, and inhibit the function of P-gp, resulting in a decrease in the excretion of PTX. This discovery effectively addressed the above three issues associated with the use of PTX in glioma treatment. CONCLUSIONS: UA-PTX NPs demonstrate strong anti-tumor effects and show great potential for treating GBM.

Stability of Flavan-3-ols, Theaflavins, and Methylxanthines in 30 Industrial Green, Black, and White Tea (Camellia sinensis L.) Extracts Characterized via Liquid Chromatography Techniques.

Commercially available tea extracts for dietary supplements and nutraceuticals are standardized to characteristic components of Camellia sinensis L., such as epigallocatechin gallate (EGCG) and total catechins or polyphenols. However, since most commercial tea extracts are highly concentrated into only one molecule such as EGCG, the comparatively less stable catechin, the oxidative stability of the extract during the 24-month shelf life was questioned. It was hypothesized that the overall oxidative stability is reduced for highly purified/concentrated tea extracts due to the absence of other natural antioxidants stabilizing the complex mixture. Via liquid chromatographic analysis, the individual chromatographic profiles of 30 commercial white, green, and black tea extracts were evaluated and compared regarding oxidative stability and functional properties. The contents of bioactive flavan-3-ols, theaflavins, and methylxanthines differed much from what was claimed by the suppliers. At the end of the product shelf life, most of the commercial green and black tea extracts showed a decrease in the flavan-3-ol content, the main bioactive components of tea. A high EGCG content to the detriment of other possibly stabilizing flavan-3-ols or antioxidants in tea was found to explain the lower oxidative stability of such tea extract products. A natural overall composition of molecular structures was found to be superior to a strong enrichment in just one molecule.

Marine-Derived Compounds as Potential Inhibitors of Hsp90 for Anticancer and Antimicrobial Drug Development: A Comprehensive In Silico Study.

Marine compounds constitute a diverse and invaluable resource for the discovery of bioactive substances with promising applications in the pharmaceutical development of anti-inflammatory and antibacterial agents. In this study, a comprehensive methodology was employed, encompassing pharmacophore modeling, virtual screening, in silico ADMET assessment (encompassing aspects of absorption, distribution, metabolism, excretion, and toxicity), and molecular dynamics simulations. These methods were applied to identify new inhibitors targeting the Hsp90 protein (heat shock protein 90), commencing with a diverse assembly of compounds sourced from marine origins. During the virtual screening phase, an extensive exploration was conducted on a dataset comprising 31,488 compounds sourced from the CMNPD database, characterized by a wide array of molecular structures. The principal objective was the development of structure-based pharmacophore models, a valuable approach when the pool of known ligands is limited. The pharmacophore model DDRRR was successfully constructed within the active sites of the Hsp90 crystal structure. Subsequent docking studies led to the identification of six compounds (CMNPD 22591, 9335, 10015, 360799, 15115, and 20988) demonstrating substantial binding affinities, each with values below -8.3 kcal/mol. In the realm of in silico ADMET predictions, five of these compounds exhibited favorable pharmacokinetic properties. Furthermore, molecular dynamics simulations and total binding energy calculations using MM-PBSA indicated that these marine-derived compounds formed exceptionally stable complexes with the Hsp90 receptor over a 100-nanosecond simulation period. These findings underscore the considerable potential of these novel marine compounds as promising candidates for anticancer and antimicrobial drug development.

Potential Pharmacological Applications of Nigella Seeds with a Focus on Nigella sativa and Its Constituents against Chronic Inflammatory Diseases: Progress and Future Opportunities.

The leading cause of death worldwide has been identified as chronic illnesses, according to the World Health Organization (WHO). Chronic inflammatory conditions such as asthma, cancer, diabetes, heart disease, and obesity account for three out of every five deaths. Although many people benefit from using nonsteroidal anti-inflammatory medicines (NSAIDs) for pain and inflammation relief, there are significant adverse effects to using these medications. Medicinal plants possess anti-inflammatory properties with minimal or no side effects. Nigella sativa (NS), also known as black cumin, is one of the plants used in traditional medicine the most. Many studies on the NS have shown that their therapeutic properties are attributed to the seed, oil, and secondary metabolites. This plant has been studied extensively and has many medical uses, such as anti-inflammatory. NS or its phytochemical compounds, such as thymoquinone, can cause cell apoptosis via oxidative stress, block efflux pumps, enhance membrane permeability, and exert potent biocidal effects. Notwithstanding the extensively documented anti-inflammatory effectiveness observed in the experimental model, the precise mechanisms underlying its anti-inflammatory effects in diverse chronic inflammatory diseases and its multi-targeting characteristics remain largely unexplored. This review examines NS or its secondary metabolites, a valuable source for the therapeutic development of chronic inflammatory diseases. Most clinical studies were done for diabetes and cardiovascular disease; therefore, more studies are required to examine the NS extracts and phytoconstituents to treat cancer, obesity, diabetes, asthma, neurological disorders, and COVID-19. This study will be a significant resource for clinicians and biologists seeking a pharmaceutical solution for inflammatory diseases.