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.

Metabolomic profiling and biological evaluations of Spongia irregularis-associated actinomycetes supported by multivariate statistical analysis.

AIM: Metabolomic analysis using LC-HRESIMS of 12 extracts of Spongia irregularis-associated actinomycetes for dereplication purposes in addition to evaluation of cytotoxic and antiviral activities of the extracts. METHODS AND RESULTS: In this study, three actinomycetes belonging to the genera Micromonospora, Streptomyces, and Rhodococcus were recovered from the marine sponge Spongia irregularis. Applying the OSMAC approach, each strain was fermented on four different media, resulting in 12 extracts. All extracts were subjected to metabolomic analysis using LC-HRESIMS for dereplication purposes. Multivariate data statistical analysis was carried out for the differentiation between extracts. Additionally, the cytotoxic and anti-hepatitis C virus (anti-HCV) potentials of extracts were evaluated. Most of extracts showed strong to moderate cytotoxicity effects against HepG-2, CACO-2, and MCF-7 cell lines with a general IC50 range of 2.8-8.9 µg/ml. Moreover, the extracts of Micromonospora sp. UR44 using ISP2 and OLIGO media and Streptomyces sp. UR32 using ISP2 medium exhibited anti-HCV activity with IC50 of 4.5 ± 0.22, 3.8 ± 0.18, and 5.7 ± 0.15 µM, respectively. CONCLUSION: Metabolomic analysis of 12 extracts of S. irregularis-associated actinomycetes led to the identification of a large number of secondary metabolites. Morever, investigation of cytotoxic and antiviral activities of the extracts revealed that only three extracts exhibited antiviral activity and seven extracts exhibited cytotoxic activity.

NS3 helicase inhibitory potential of the marine sponge Spongia irregularis.

In the current study, an investigation of the activity of the total extract of the marine sponge Spongia irregularis and its different fractions against the hepatitis C virus (HCV) was pursued. The results revealed that the ethyl acetate fraction exhibited the highest anti-HCV activity, with an IC50 value of 12.6 ± 0.05 µg ml-1. Chromatographic resolution of the ethyl acetate fraction resulted in the isolation of four known compounds, 1,3,7-trimethylguanine (1), 3,5-dihydroxyfuran-2(5H)-one (2), thymidine (3), and 1H-indazole (4). By using LC-HR-ESI-MS metabolic profiling, compounds 5-14 were also identified in the same fraction. Molecular docking calculations revealed the high binding affinity of compound 14 against the allosteric pocket of HCV NS3-NS4A and the active site of HCV NS3 helicase (-10.1 and -7.4 kcal mol-1, respectively). Molecular dynamics simulations, followed by molecular mechanics-generalized Born surface area energy calculations, demonstrated the structural and energetic stability of compound 14 in complex with HCV targets.

The Red Sea marine sponge Spongia irregularis: metabolomic profiling and cytotoxic potential supported by in silico studies.

The current study discusses the chemical composition of the marine sponge Spongia irregularis using LC-HRESIMS. The metabolomic profiling resulted in the annotation of 17 metabolites of different chemical classes. Additionally, evaluation of the cytotoxic activities of the total extract and different fractions were carried out against three different cell lines where the n-butanol fraction exhibited the highest cytotoxic effects against HepG-2, MCF-7 and CACO-2 cell lines with IC50 values of 9.6 ± 0.02, 4.3 ± 0.10 and 5.6 ± 0.03 µg/mL, respectively. Also, the study was supported by docking study of the identified compounds for binding affinity to MSK1.

Marine natural products from sponges (Porifera) of the order Dictyoceratida (2013 to 2019); a promising source for drug discovery.

Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities. Sponges which belong to the order Dictyoceratida are distinctly classified into 5 families: Dysideidae, Irciniidae, Spongiidae, Thorectidae, and Verticilliitidae. In this review, compounds isolated from Dictyoceratida sponges were discussed with their biological potential within the period 2013 to December 2019. Moreover, analysis of the physicochemical properties of these marine natural products was investigated and the results showed that 78% of the compounds have oral bioavailability potential. This review highlights sponges of the order Dictyoceratida as exciting source for discovery of new drug leads.