Capturing the antimicrobial profile of Paeonia officinalis, Jasminum officinale and Rosa damascene against methicillin resistant Staphylococcus aureus with metabolomics analysis and network pharmacology.

In the current study, we evaluated the in vitro antibacterial efficacy of the roots' extracts of Jasminum officinale, Rosa damascene and Paeonia officinalis against MRSA (methicillin-resistant Staphylococcus aureus) by well diffusion technique. The root extract of P. officinalis exerted a potent anti-MRSA with MIC 0.4673 µg/ml, while both J. officinale and R. damascene exhibited very weak activity. Therefore, chemical profiling of the crude extract P. officinalis roots assisted by LC-HR-ESI-MS was performed and led to the dereplication of twenty metabolites of different classes, in which terpenes are the most abundant compounds. On a molecular level, network pharmacology was used to determine the targets of active metabolites to bacterial infections, particularly MRSA. Online databases PubChem, UniProt, STRING, and Swiss Target Prediction were used. In addition to using CYTOSCAPE software to display and analyze the findings, ShinyGO and FunRich tools were used to identify the gene enrichment analysis to the set of recognized genes. The results detected the identified metabolites were annotated by 254 targets. ALB, ACHE, TYMS, PRKCD, PLG, MMP9, MMP2, ERN1, EDNRA, BRD4 were found to be associated with MRSA infection. The top KEGG pathway was the vascular smooth muscle contraction pathway according to enrichment FDR. The present study suggested a possible implication of P. officinalis roots as a potent candidate having a powerful antibacterial activity against MRSA.

Ursolic acid inhibits NF-κB signaling and attenuates MMP-9/TIMP-1 in progressive osteoarthritis: a network pharmacology-based analysis.

Osteoarthritis (OA) is a degenerative joint disease, characterized by infiltration of monocytes into the synovial joint which promotes inflammation, stiffness, joint swelling, cartilage degradation and further bone destruction. The leaves of Ocimum forskolei have been used for inflammation-related disease management in traditional medicine. Additionally, the downregulation of NF-κB and the MMP/TIMP-1 ratio has been shown to protect against OA. The LC-HR-MS metabolic analysis of Ocimum yielded 19 putative compounds, among which ursolic acid (UA) was detected. Ursolic acid possesses significant anti-inflammatory effects and has been reported to downregulate oxidative stress and inflammatory biomarkers. It was tested on rats in a model of intra-articular carrageenan injection to investigate its efficacy on osteoarthritis progression. The UA emulgel exerted chondroprotective, analgesic and local anaesthetic efficacies confirmed via histopathological investigation and radiographical imaging. A network pharmacology followed by molecular docking highlighted TNF-α, TGF-ß and NF-κB as the top filtered genes. Quantitative real-time PCR analysis showed that UA significantly attenuated serum levels of TNF-α, IL-1ß, NF-κB, MMP-9/TIMP-1 and elevated levels of TGF-ß. Taken together, these results suggest that UA could serve as a functional food-derived phytochemical with a multi-targeted efficacy on progression of OA, regulating the immune and inflammatory responses, particularly, attenuating chondrocytes degeneration via suppression of NF-κB and MMP-9/TIMP-1. Accordingly, UA might be a promising alternative to conventional therapy for safe, easily applicable and effective management of OA.

Metabolomic profiling of Medicago sativa-derived fungal endophytes and evaluation of their biological activities.

This study aimed to discover the potential of Medicago sativa-derived fungal endophytes as a prospective source of bioactive metabolites. In the present study, three different strains of fungal endophyte Aspergillus terreus were isolated from leaves L, roots T and stems St of Medicago sativa to explore their biological and chemical diversity. These isolated fungi were exposed to different fermentation conditions by adding various chemical elicitors to their solid fermentation media. According to LC-HRESIMS-based metabolomics and multivariate analysis, each chemical treatment had a different effect on the chemical profiles of the fungi. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) proposed several compounds with anticancer action against MCF-7 (a human breast cancer cell line) and MDA-MB-231 (a human epithelial breast cancer cell line).

Natural products reverse cancer multidrug resistance.

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

Investigation of bioactive components responsible for the antibacterial and anti-biofilm activities of Caroxylon volkensii by LC-QTOF-MS/MS analysis and molecular docking.

Caroxylon volkensii is a wild desert plant of the family Amaranthaceae. This study represents the first report of the metabolomic profiling of C. volkensii by liquid chromatography quadrupole-time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The dereplication study of its secondary metabolites led to the characterization of 66 known compounds. These compounds include catecholamines, tyramine derivatives, phenolic acids, triterpenoids, flavonoids, and others. A new tyramine derivative, alongside other known compounds, was reported for the first time in the Amaranthaceae family. The new derivative and the first-reported compounds were putatively identified through MS/MS fragmentation data. Given the notorious taxonomical challenges within the genus Salsola, to which C. volkensii previously belonged, our study could offer a valuable insight into its chemical fingerprint and phylogenetic relationship to different Salsola species. The antibacterial potential of C. volkensii methanolic extract (CVM) against Pseudomonas aeruginosa was screened. The minimum inhibitory concentration (MIC) of CVM ranged from 32 to 256 µg mL-1. The anti-quorum sensing potential of CVM resulted in a decrease in the percentage of strong and moderate biofilm-forming isolates from 47.83% to 17.39%. It revealed a concentration-dependent inhibitory activity on violacein formation by Chromobacterium violaceum. Moreover, CVM exhibited an in vivo protective potential against the killing capacity of P. aeruginosa isolates. A molecular docking study revealed that the quorum-sensing inhibitory effect of CVM can be attributed to the binding of tyramine conjugates, ethyl-p-digallate, and isorhamnetin to the transcriptional global activator LasR.

Antimicrobial secondary metabolites and antioxidant activities of fungal endophytes associated with Ziziphus spina-christi (L.) Desf. (Nabq) leaves.

A total of 20 endophytic fungi were isolated (ZSEFL1-ZSEFL20) from Ziziphus spina-christi (L.) Desf. (Nabq) leaves. Four isolates A2/ZSEFL2, Alternaria alternata, D/ZSEFL14, Aspergillus niger, E/ZSEFL15, Epicoccum nigrum, and S/ZSEFL19, Penicillium crustosum were found to show the most promising antimicrobial activities either in plug or disc diffusion screening assays against Gram-positive, Gram-negative bacteria and pathogenic fungi. Antimicrobial activity was tested against Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, Serratia marcescens ATCC 14764, Klebsiella pneumoniae ATCC 700603, Candida albicans ATCC 10231, and Fusarium oxysporum ATCC417. In vitro antioxidant activity assay was conducted using the ABTS [2,2'-Azino-bis (3-Ethylbenzthiazoline-6-Sulfonic Acid)] free radical scavenging method. EtOAc extracts of all isolated endophytic fungi showed antioxidant activities. This study would be one of the first reports to measure the antioxidant activity of Z. spina-christi (L.) Desf. endophytic fungi. Therefore, these isolated endophytic fungi can provide additional information for medicinal sources of natural antioxidants and antimicrobial agents.

Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.

Wound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employed in wound-repairing activities. This work investigates the mesenchymal stem cells in the combined capacity of the bone marrow (BMMSC) for wound healing and Cystoseira sp. Algae extract in immunosuppressed rats. High-resolution liquid chromatography / MS investigation of Cystoseira extract revealed the prevalence of fatty acids that have wound-soothing potential. From constructed PPI network for wound healing and further analysis through molecular docking and molecular dynamics (MD) simulation experiments suggested that cystalgerone metabolite may be responsible for the wound healing-promoting effect of Cystoseira extract. According to the CD marker characterization of the BMMSC, 98.21% of them expressed CD90, and 97.1% expressed CD105. Sixteen d after immunity suppression (by 40 mg/kg hydrocortisone daily), an incision was made in the dorsal skin of the rat. The treatments were applied for 16 d and samples were taken from the tested groups on the 8th, 14th, and 16th days. The BMMSCs / Cystoseira group showed significantly improved wound closure, thickness, density of new layers, and skin elasticity than the control group (p < 0.001). The BMMSCs / Cystoseira combination significantly reduced the oxidative indicators, pro-inflammatory cytokines, and immune markers, according to the RT-PCR gene expression study. In order to delve deeper into the complex interconnections among wound healing-related biological targets and pinpoint key factors in this complex process, we engaged in network pharmacology and computational research. Subsequently, we conducted a comprehensive computational analysis, including reverse docking, free energy (ΔG) computation, and molecular dynamics simulations, on the molecular structures of the annotated compounds. The purpose of this investigation was to identify potential new targets for these chemicals as well as any potential interactions they may have with different signaling pathways related to the wound healing process. Our research indicates that the primary compounds of Cystoseira holds potential wound healing therapeutic activity. Although more safety testing and clinical studies are required, the combination has great potential for regenerative medicine and could be a revolutionary advance in the healing of the wounds of immunosuppressed patients.

Antiplasmodial potential of phytochemicals from Citrus aurantifolia peels: a comprehensive in vitro and in silico study.

Phytochemical investigation of Key lime (Citrus aurantifolia L., F. Rutaceae) peels afforded six metabolites, known as methyl isolimonate acetate (1), limonin (2), luteolin (3), 3`-hydroxygenkwanin (4), myricetin (5), and europetin (6). The structures of the isolated compounds were assigned by 1D NMR. In the case of limonin (2), further 1- and 2D NMR experiments were done to further confirm the structure of this most active metabolite. The antiplasmodial properties of the obtained compounds against the pathogenic NF54 strain of Plasmodium falciparum were assessed in vitro. According to antiplasmodial screening, only limonin (2), luteolin (3), and myricetin (5) were effective (IC50 values of 0.2, 3.4, and 5.9 µM, respectively). We explored the antiplasmodial potential of phytochemicals from C. aurantifolia peels using a stepwise in silico-based analysis. We first identified the unique proteins of P. falciparum that have no homolog in the human proteome, and then performed inverse docking, ΔGBinding calculation, and molecular dynamics simulation to predict the binding affinity and stability of the isolated compounds with these proteins. We found that limonin (2), luteolin (3), and myricetin (5) could interact with 20S a proteasome, choline kinase, and phosphocholine cytidylyltransferase, respectively, which are important enzymes for the survival and growth of the parasite. According to our findings, phytochemicals from C. aurantifolia peels can be considered as potential leads for the development of new safe and effective antiplasmodial agents.

Cytotoxic metabolites from Sinularia levi supported by network pharmacology.

The in-vitro anti-proliferative evaluation of Sinularia levi total extract against three cell lines revealed its potent effect against Caco-2 cell line with IC50 3.3 µg/mL, followed by MCF-7 and HepG-2 with IC50 6.4 µg/mL and 8.5 µg/mL, respectively, in comparison to doxorubicin. Metabolic profiling of S. levi total extract using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealed the presence of phytoconstituents clusters consisting mainly of steroids and terpenoids (1-20), together with five metabolites 21-25, which were additionally isolated and identified through the phytochemical investigation of S. levi total extract through various chromatographic and spectroscopic techniques. The isolated metabolites included one sesquiterpene, two steroids and two diterpenes, among which compounds prostantherol (21) and 12-hydroperoxylsarcoph-10-ene (25) were reported for the first time in Sinularia genus. The cytotoxic potential evaluation of the isolated compounds revealed variable cytotoxic effects against the three tested cell lines. Compound 25 was the most potent with IC50 value of 2.13 ± 0.09, 3.54 ± 0.07 and 5.67 ± 0.08 µg/mL against HepG-2, MCF-7 and Caco-2, respectively, followed by gorgosterol (23) and sarcophine (24). Additionally, network analysis showed that cyclin-dependent kinase 1 (CDK1) was encountered in the mechanism of action of the three cancer types. Molecular docking analysis revealed that CDK1 inhibition could possibly be the reason for the cytotoxic potential.

Apium extract alleviates indomethacin-induced gastric ulcers in rats via modulating the VEGF and IK-κB/NF-κB p65 signaling pathway: insights from in silico and in vivo investigations.

BACKGROUND: Gastric ulcers represent a worldwide health problem, characterized by erosions that affect the mucous membrane of the stomach and may even reach the muscular layer, leading to serious complications. Numerous natural products have been assessed as anti-ulcerogenic agents, and have been considered as new approaches for treatment or prevention of gastric ulcers. The present research investigated the preventive benefits of Apium graveolens L. (Apiaceae), known as celery, seed extract towards indomethacin-induced ulceration of the stomach in rats. METHODS: Metabolomic profiling, employing liquid chromatography coupled to high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), was implemented with the aim of investigating the chemical profile of the seeds. Histopathological analysis of gastric tissues, as well as assessment of numerous inflammatory cytokines and oxidative stress indicators, confirmed the in vivo evaluation. RESULTS: The prior treatment with A. graveolens seed extract resulted in a substantial reduction in the ulcer index when compared to the indomethacin group, indicating an improvement in stomach mucosal injury. Moreover, the gastroprotective effect was demonstrated through examination of the oxidative stress biomarkers which was significantly attenuated upon pre-treatment with A. graveolens seed extract. Vascular endothelial growth factor (VEGF), a fundamental angiogenic factor that stimulates angiogenesis, was markedly inhibited by indomethacin. A. graveolens seed extract restored this diminished level of VEGF. The dramatic reductions in NF-κB protein levels indicate a considerable attenuation of the indomethacin-induced IKκB/NF-κB p65 signaling cascade. These activities were also correlated to the tentatively featured secondary metabolites including, phenolic acids, coumarins and flavonoids, previously evidenced to exert potent anti-inflammatory and antioxidant activities. According to our network pharmacology study, the identified metabolites annotated 379 unique genes, among which only 17 genes were related to gastric ulcer. The PTGS2, MMP2 and PTGS1 were the top annotated genes related to gastric ulcer. The top biological pathway was the VEGF signaling pathway. CONCLUSION: A. graveolens seed extract possesses significant anti-ulcer activity, similar to famotidine, against gastric lesions induced by indomethacin in rats. It is worth highlighting that the extract overcomes the negative effects of conventional chemical anti-secretory drugs because it does not lower stomach acidity.

LC-HRMS Profiling and Cytotoxic Potential of Actinomycetes Associated with the Red Sea Soft Coral Sarcophyton glaucum: In vitro and In silico Studies.

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC50 =3.3, 4.2 and 6.8 µg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well.

Expression of concern: The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches.

Expression of concern for 'The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches' by Abeer H. Elmaidomy et al., RSC Adv., 2022, 12, 11769-11785, https://doi.org/10.1039/D2RA01340A.

Niosomes as promising approach for enhancing the cytotoxicity of Hemimycale sp. total crude extract supported with in-silico studies.

The crude extract of Hemimycale sp. marine sponge was evaluated as a cytotoxic drug against different cell lines; whereas it exhibited promising selective activity toward the breast cancer cell line only with IC50 value 199.6 ± 0.00512 µg/ml. Moreover, its cytotoxic activity against the breast cancer cell line was reevaluated upon forming total extract-loaded niosomes. This revealed an IC50 value of 44.35 ± 0.011128 µg/ml, indicating the potential contribution of niosomes in boosting cell penetration and activity as a result. Owing to highlight the bioactive constituents responsible for the cytotoxic activity, metabolomics profiling of Hemimycale sp. was performed using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealing tentative identification of phytoconstituents clusters like as, diterpenes, sesterterpenes and sterols. Additionally, the cytotoxic activity of the crude extract was explained on the molecular level, whereas the dereplicated compounds were evaluated in silico against the Epidermal Growth Factor Receptor tyrosine kinase (EGFR). The sesterterpenoid derivatives phorbaketal A acetate (12) and secoepoxy ansellone A (13) together with mycalol-522 (17) showed the best binding energy.

Targeting antimalarial metabolites from the actinomycetes associated with the Red Sea sponge Callyspongia siphonella using a metabolomic method.

Malaria is a persistent illness that is still a public health issue. On the other hand, marine organisms are considered a rich source of anti­infective drugs and other medically significant compounds. Herein, we reported the isolation of the actinomycete associated with the Red Sea sponge Callyspongia siphonella. Using "one strain many compounds" (OSMAC) approach, a suitable strain was identified and then sub-cultured in three different media (M1, ISP2 and OLIGO). The extracts were evaluated for their in-vitro antimalarial activity against Plasmodium falciparum strain and subsequently analyzed by Liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS). In addition, MetaboAnalyst 5.0 was used to statistically analyze the LC-MS data. Finally, Molecular docking was carried out for the dereplicated metabolites against lysyl-tRNA synthetase (PfKRS1). The phylogenetic study of the 16S rRNA sequence of the actinomycete isolate revealed its affiliation to Streptomyces genus. Antimalarial screening revealed that ISP2 media is the most active against Plasmodium falciparum strain. Based on LC-HR-MS based metabolomics and multivariate analyses, the static cultures of the media, ISP2 (ISP2-S) and M1 (M1-S), are the optimal media for metabolites production. OPLS-DA suggested that quinone derivatives are abundant in the extracts with the highest antimalarial activity. Fifteen compounds were identified where eight of these metabolites were correlated to the observed antimalarial activity of the active extracts. According to molecular docking experiments, saframycin Y3 and juglomycin E showed the greatest binding energy scores (-6.2 and -5.13) to lysyl-tRNA synthetase (PfKRS1), respectively. Using metabolomics and molecular docking investigation, the quinones, saframycin Y3 (5) and juglomycin E (1) were identified as promising antimalarial therapeutic candidates. Our approach can be used as a first evaluation stage in natural product drug development, facilitating the separation of chosen metabolites, particularly biologically active ones.

Evaluation of the anti-infective potential of the seed endophytic fungi of Corchorus olitorius through metabolomics and molecular docking approach.

BACKGROUND: Endophytic fungi are very rich sources of natural antibacterial and antifungal compounds. The main aim of this study is to isolate the fungal endophytes from the medicinal plant Corchorus olitorius seeds (F. Malvaceae), followed by antimicrobial screening against various bacterial and fungal strains. RESULTS: Seven endophytic fungal strains belonging to different three genera were isolated, including Penicillium, Fusarium, and Aspergillus. The seven isolated endophytic strains revealed selective noticeable activity against Escherichia coli (ATCC25922) with varied IC50s ranging from 1.19 to 10 µg /mL, in which Aspergillus sp. (Ar 6) exhibited the strongest potency against E. coli (ATCC 25,922) and candida albicans (ATCC 10,231) with IC50s 1.19 and 15 µg /mL, respectively. Therefore, the chemical profiling of Aspergillus sp. (Ar 6) crude extract was performed using LC-HR-ESI-MS and led to the dereplication of sixteen compounds of various classes (1-16). In-silico analysis of the dereplicated metabolites led to highlighting the compounds responsible for the antimicrobial activity of Aspergillus sp. extract. Moreover, molecular docking showed the potential targets of the metabolites; Astellatol (5), Aspergillipeptide A (10), and Emericellamide C (14) against E. coli and C. albicans. CONCLUSION: These results will expand the knowledge of endophytes and provide us with new approaches to face the global antibiotic resistance problem and the future production of undiscovered compounds different from the antibiotics classes.

Phytochemical analysis and anti-infective potential of fungal endophytes isolated from Nigella sativa seeds.

Endophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungi Aspergillus sp. SA1, Aspergillus sp. SA2, and Aspergillus sp. SA3, cultivated from Nigella sativa seeds against Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 13883), MRSA (ATCC 33591), and human pathogen Candida albicans (ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1-26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally, in-silico interactions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.

New cytotoxic dammarane type saponins from Ziziphus spina-christi.

Cancer is the world's second-leading cause of death. Drug development efforts frequently focus on medicinal plants since they are a valuable source of anticancer medications. A phytochemical investigation of the edible Ziziphus spina-christi (F. Rhamnaceae) leaf extract afforded two new dammarane type saponins identified as christinin E and F (1, 2), along with the known compound christinin A (3). Different cancer cell lines, such as lung cancer (A549), glioblastoma (U87), breast cancer (MDA-MB-231), and colorectal carcinoma (CT-26) cell lines, were used to investigate the extracted compounds' cytotoxic properties. Our findings showed significant effects on all the tested cell lines at varying concentrations (1, 5, 10, and 20 µg/mL). The three compounds exhibited potent activity at low concentrations (< 10 µg/mL), as evidenced by their low IC50 values. To further investigate the complex relationships between these identified cancer-relevant biological targets and to identify critical targets in the pathogenesis of the disease, we turned to network pharmacology and in silico-based investigations. Following this, in silico-based analysis (e.g., inverse docking, ΔG calculation, and molecular dynamics simulation) was performed on the structures of the isolated compounds to identify additional potential targets for these compounds and their likely interactions with various signalling pathways relevant to this disease. Based on our findings, Z. spina-christi's compounds showed promise as potential anti-cancer therapeutic leads in the future.

Paralemnalia thyrsoides-associated fungi: phylogenetic diversity, cytotoxic potential, metabolomic profiling and docking analysis.

BACKGROUND: Cancer continues to be one of the biggest causes of death that affects human health. Chemical resistance is still a problem in conventional cancer treatments. Fortunately, numerous natural compounds originating from different microbes, including fungi, possess cytotoxic characteristics that are now well known. This study aims to investigate the anticancer prospects of five fungal strains that were cultivated and isolated from the Red Sea soft coral Paralemnalia thyrsoides. The in vitro cytotoxic potential of the ethyl acetate extracts of the different five isolates were evaluated using MTS assay against four cancer cell lines; A549, CT-26, MDA-MB-231, and U87. Metabolomics profiling of the different extracts using LC-HR-ESI-MS, besides molecular docking studies for the dereplicated compounds were performed to unveil the chemical profile and the cytotoxic mechanism of the soft coral associated fungi. RESULTS: The five isolated fungal strains were identified as Penicillium griseofulvum (RD1), Cladosporium sphaerospermum (RD2), Cladosporium liminiforme (RD3), Penicillium chrysogenum (RD4), and Epicoccum nigrum (RD5). The in vitro study showed that the ethyl acetate extract of RD4 exhibited the strongest cytotoxic potency against three cancer cell lines A549, CT-26 and MDA-MB-231 with IC50 values of 1.45 ± 8.54, 1.58 ± 6.55 and 1.39 ± 2.0 µg/mL, respectively, also, RD3 revealed selective cytotoxic potency against A549 with IC50 value of 6.99 ± 3.47 µg/mL. Docking study of 32 compounds dereplicated from the metabolomics profiling demonstrated a promising binding conformation with EGFR tyrosine kinase that resembled its co-crystallized ligand albeit with better binding energy score. CONCLUSION: Our results highlight the importance of soft coral-associated fungi as a promising source for anticancer metabolites for future drug discovery.

Anti-leishmanial and cytotoxic compounds isolated from marine sponge Hemimycale sp.

The methanolic extract of the marine sponge Hemimycale sp. yielded two new compounds; 1-(2'-methyl heptadecyl) phenol (1) and a new pyrazole derivative; 4-(hydroxymethyl)-1H-pyrazol-3-ol (2), together with previously isolated (2'R)-2'-hydroxy-N-((2S,3S,4R)-1,3,4-trihydroxy-16-methylpentadecan-2-yl)docosanamide (3), cholesterol (4), 5, 8-epi-dioxycholest-6-en-3-ol (5) and 3-acetylsesterstatin 3 (6), which were firstly reported from family Hymedesmiidae. Their structure elucidation was based on extensive nuclear magnetic resonance spectroscopy and high resolution-electrospray ionization-mass spectrometry. The isolated compounds were evaluated for their anti-leishmanial and cytotoxic activities. Compound 5 showed remarkable anti-leishmanial activity with IC50 value of 15.8 ± 0.92 µg/mL comparable with the standard miltefosine (IC50 = 3.2 ± 0.07 µg/mL), while compound 3 exhibited noteworthy cytotoxicity against A594 cell line with IC50 value of 29.6 ± 1.68 µg/mL compared to etoposide (IC50 = 10.9 ± 1.30 µg/mL).

Emerging trends and applications of metabolomics in food science and nutrition.

The study of all chemical processes involving metabolites is known as metabolomics. It has been developed into an essential tool in several disciplines, such as the study of plant physiology, drug development, human diseases, and nutrition. The field of food science, diagnostic biomarker research, etiological analysis in the field of medical therapy, and raw material quality, processing, and safety have all benefited from the use of metabolomics recently. Food metabolomics includes the use of metabolomics in food production, processing, and human diets. As a result of changing consumer habits and the rising of food industries all over the world, there is a remarkable increase in interest in food quality and safety. It requires the employment of various technologies for the food supply chain, processing of food, and even plant breeding. This can be achieved by understanding the metabolome of food, including its biochemistry and composition. Additionally, Food metabolomics can be used to determine the similarities and differences across crop kinds, as an indicator for tracking the process of ripening to increase crops' shelf life and attractiveness, and identifying metabolites linked to pathways responsible for postharvest disorders. Moreover, nutritional metabolomics is used to investigate the connection between diet and human health through detection of certain biomarkers. This review assessed and compiled literature on food metabolomics research with an emphasis on metabolite extraction, detection, and data processing as well as its applications to the study of food nutrition, food-based illness, and phytochemical analysis. Several studies have been published on the applications of metabolomics in food but further research concerning the use of standard reproducible procedures must be done. The results published showed promising uses in the food industry in many areas such as food production, processing, and human diets. Finally, metabolome-wide association studies (MWASs) could also be a useful predictor to detect the connection between certain diseases and low molecular weight biomarkers.