Our prior studies have established that Epi-aszonalenin A (EAA), an alkaloid derived from the secondary metabolites of coral symbiotic fungi, effectively intervenes in atherosclerotic processes and inhibits angiogenesis. The present study's intensive investigation of antiangiogenic activity focuses on its mechanism of action in combating tumor metastasis and invasion. Invasive metastatic pairs are a characteristic of malignancy, and tumor cell dispersion stands as the most dangerous event in the genesis of tumors. The results of the Transwell chamber assay and cell wound healing experiments indicate that EAA effectively counteracted the effects of PMA on the migration and invasion of HT1080 cells. Results from Western blot and ELISA assays showed that EAA suppressed MMP and VEGF activity and prevented the expression of N-cadherin and HIF-1. Phosphorylation of downstream MAPK, PI3K/AKT, and NF-κB pathways was responsible for this regulation. A stable interaction was found through mimic coupling in the molecular docking results involving EAA and MMP-2/-9 molecules. This study's results on EAA's tumor metastasis inhibition form a research basis, supporting prior findings and highlighting the therapeutic potential of these compounds for angiogenesis-related diseases and simultaneously improving access to coral symbiotic fungi.
Docosahexaenoic acid (DHA), a significant polyunsaturated fatty acid found in marine bivalves and advantageous for human health, however, its protective function against diarrhetic shellfish toxins (DSTs) in shellfish remains elusive. To explore DHA's role in the DST response of Perna viridis, we combined LC-MS/MS, RT-qPCR, and histological evaluation. Within the digestive gland of the mussel P. viridis, subjected to a 96-hour exposure to the DST-producing dinoflagellate Prorocentrum lima, a noteworthy decrease in DHA content was measured, particularly after DST esterification. DHA supplementation demonstrably augmented the esterification levels in DSTs, resulting in elevated expression of Nrf2-related genes and enzymes, thereby reducing the damage inflicted by DSTs on the digestive glands. DHA's potential involvement in the esterification of DSTs and the subsequent activation of the Nrf2 signaling pathway in P. viridis was suggested by these results, offering a protective mechanism against DST toxicity for mussels. This research project might provide novel knowledge regarding bivalve responses to DSTs, establishing the framework for the role DHA plays in the environmental acclimatization of bivalve species.
Disulfide-rich conotoxins are a specific class of conopeptides, which themselves are a major component of the venom produced by marine cone snails. The widespread interest in conopeptides, as reported in numerous publications, largely stems from their potent and selective activity, a phenomenon yet to be formally quantified in the field. To illuminate this area, we present a bibliometric analysis of the literature on cone snail toxins, encompassing the years from 2000 to 2022. Research in the conopeptide field, as revealed by our study encompassing 3028 research articles and 393 reviews, exhibits a considerable output, averaging 130 research articles per year. Collaboratively and globally, the research, as the data show, consistently occurs, solidifying the community-driven nature of discoveries. The keywords embedded in each article indicated research trends, their development during the period examined, and significant points of progress. Frequently utilized keywords are predominantly in the fields of pharmacology and medicinal chemistry. A notable shift in keyword trends occurred during 2004, highlighted by the FDA's approval of ziconotide, the first conopeptide-based peptide toxin drug, for treating persistent and severe pain. The research article concerning conopeptides is recognized for its impact, securing a place among the top ten most cited. Since the release of that article, there was a marked escalation in medicinal chemistry research directed at modifying conopeptides to alleviate neuropathic pain, as demonstrated by an increased dedication to topological alterations (e.g., cyclization), electrophysiological analyses, and structural biological characterization.
More than 20% of the global population has been impacted by the frequent occurrence of allergic diseases in recent years. Anti-allergic drug therapy often includes topical corticosteroids as a first-line treatment, in tandem with antihistamines as adjunctive therapy; this approach, however, may lead to adverse side effects and drug resistance with prolonged use. Consequently, the need for alternative anti-allergic agents derived from natural sources is paramount. The combination of high pressure, low temperatures, and inadequate light within marine ecosystems leads to the formation of a highly functionalized and diverse spectrum of natural products. This review encompasses a compilation of information regarding anti-allergic secondary metabolites, displaying a variety of chemical structures, including polyphenols, alkaloids, terpenoids, steroids, and peptides. These metabolites are sourced mainly from fungi, bacteria, macroalgae, sponges, mollusks, and fish. By employing molecular docking simulation within MOE, the potential mechanism of action for selected marine anti-allergic natural products interacting with the H1 receptor is further investigated. This review delves into the structural makeup and anti-allergic potential of marine-sourced natural compounds, simultaneously offering a valuable resource for those investigating the immunomodulatory functions of these natural products.
By acting as key communicators, cancer-derived small extracellular vesicles (sEVs) regulate interactions between cells. The marine-derived alkaloid, Manzamine A (MA), with a unique array of biological activities, shows anti-cancer properties against diverse tumor types, but its action against breast cancer cells is yet to be fully determined. We found MA to effectively impede the growth, movement, and invasion of both MDA-MB-231 and MCF-7 cancer cells in a manner influenced by both time and dose. Simultaneously, MA promotes the formation of autophagosomes, yet it hinders their degradation within breast cancer cells. Notably, our results demonstrated that MA facilitates the secretion of sEVs and enhances the accumulation of autophagy-related proteins in secreted sEVs, an effect that is further amplified by the presence of the autophagy inhibitor chloroquine (CQ). The mechanistic action of MA entails a decrease in the expression of RIP1, a key upstream regulator of the autophagic pathway, and a reduction in the pH of the lysosomes. Increased RIP1 expression activated the AKT/mTOR signaling pathway, causing a reduction in the autophagy response initiated by MA and the secretion of associated sEVs. MA may be a potential autophagy inhibitor, according to these data, preventing autophagosome turnover. RIP1 mediates MA-induced secretory autophagy, a potential approach to breast cancer treatment.
Within a marine-derived fungus of the Acremonium genus, a novel bazzanane-type sesquiterpenoid, identified as Marinobazzanan (1), was isolated. Through the combined application of NMR and mass spectrometry, the chemical structure of 1 was elucidated; the relative configurations were deduced from NOESY data analysis. click here Spectral analyses, including vibrational circular dichroism (VCD), and the modified Mosher's method, led to the determination that the absolute configurations of 1 are 6R, 7R, 9R, and 10R. It was determined that compound 1 displayed no cytotoxic effects on human cancer cells, encompassing A549 (lung), AGS (gastric), and Caco-2 (colorectal), at concentrations below 25 microM. Compound 1's ability to decrease cancer cell migration, invasion, and soft agar colony formation was observed at concentrations from 1 to 5 M, correlating with decreased KITENIN levels and increased KAI1 levels. Compound 1's treatment resulted in a suppression of -catenin-mediated TOPFLASH activity and its associated downstream targets across AGS, A549, and Caco-2 cells, coupled with a minor attenuation of the Notch signaling pathway in these three cancer cell types. click here Moreover, I also mitigated the number of metastatic nodules found in the intraperitoneal xenograft of mice.
Five new isocoumarins, namely phaeosphaerins A through E (1-5), were isolated from the fermentation culture of the marine fungus *Phaeosphaeriopsis sp*. Identified alongside WP-26 were the isocoumarin, 68-dihydroxy-7-methoxy-3-methylisocoumarin (6), and the two established pimarane-type diterpenes, diaporthein A (7) and diaporthein B (8). Through the combined efforts of NMR experiments, X-ray diffraction analysis, and a comparison of experimental and computed ECD curves, their structures were elucidated. H2O2-caused cellular damage in SH-SY5Y cells was not significantly mitigated by the neuroprotective actions of compounds 1 through 7. click here Compound 8's cytotoxicity was evident in BEL-7402, SGC-7901, K562, A549, and HL-60 cell lines.
Excisional wounds are often observed as one of the most common types of physical trauma. The current study endeavors to explore the potential of a nanophytosomal formulation containing a dried hydroalcoholic extract of S. platensis in fostering excisional wound healing. The Spirulina platensis nanophytosomal formulation (SPNP) with 100 mg of PC and 50 mg of CH showed ideal physicochemical properties: 59840 ± 968 nm particle size, -198 ± 49 mV zeta potential, 6276 ± 175% entrapment efficiency, and 7400 ± 190% Q6h value. The chosen method for the creation of an HPMC gel (SPNP-gel) was selected. The algal extract, when subjected to metabolomic profiling, resulted in the identification of thirteen compounds. The molecular docking procedure, applied to the identified compounds interacting with the HMGB-1 protein's active site, identified 1213-DiHome with the highest docking score, amounting to -7130 kcal/mol. SPNP-gel's effectiveness in wound closure and improvement of histopathological features exceeded that of the standard MEBO ointment and S. platensis gel treatments in wounded Sprague-Dawley rats.