The alkaloid Epi-aszonalenin A (EAA), isolated and purified from the secondary metabolites of coral symbiotic fungi, has shown, in our earlier studies, favorable effects on atherosclerosis and anti-angiogenic activity. An intensive examination of antiangiogenic activity's mechanism of action against tumor metastasis and invasion is undertaken in the present study. Invasive metastatic pairs serve as a defining characteristic of malignancy, and the spreading of tumor cells represents the most threatening aspect of tumor formation. EAA's impact on HT1080 cell migration and invasion, as measured by cell wound healing and Transwell assays, demonstrates its effective interference with PMA-induced processes. EAA treatment, as assessed by Western blot and ELISA, led to a reduction in MMPs and VEGF activity, along with a decrease in N-cadherin and HIF-1 expression. This was achieved by regulating the phosphorylation of downstream MAPK, PI3K/AKT, and NF-κB pathways. Analysis of molecular docking results indicated a stable interaction between the EAA and MMP-2/-9 molecules, fostered by mimic coupling. By investigating EAA's effect on tumor metastasis, this research provides a foundation for future studies, supporting prior research and showcasing the drug potential of this compound class in treating angiogenesis-related illnesses and potentially expanding the availability of coral symbiotic fungi.
Marine bivalves, a source of the polyunsaturated fatty acid docosahexaenoic acid (DHA), recognized for its positive impact on human health, yet its capacity to shield shellfish from the toxicity of diarrhetic shellfish toxins (DSTs) remains poorly understood. By utilizing LC-MS/MS, RT-qPCR, and histological examination, we aimed to understand DHA's impact on the DST response of the Perna viridis bivalve. 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's addition significantly increased the esterification of DSTs and augmented the expression of genes and enzyme activities related to the Nrf2 signaling pathway, thereby mitigating the damage to digestive glands caused by DSTs. The observed results supported the hypothesis that DHA may be instrumental in the esterification of DSTs and the activation of Nrf2 signaling within P. viridis, providing a protective mechanism for mussels exposed to DSTs. This study's contribution could potentially offer new insights into how bivalves react to DSTs and provide a foundation for investigating the importance of DHA in the environmental adaptation of bivalves.
Conotoxins, a type of peptide toxin found in the venom of marine cone snails, are characterized by their disulfide-rich composition, while other conopeptides are also present. 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. Employing a bibliometric approach, we examine the literature on cone snail toxins published between 2000 and 2022 to fill this existing gap. 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. Globally and in a collaborative fashion, the research, according to the data, is conducted, underscoring the communal foundation of discoveries. Examining the keywords attached to each article disclosed research trends, their development throughout the study period, and key milestones. Keywords associated with pharmacology and medicinal chemistry are the most commonly employed. 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. This research article on conopeptides boasts a high citation count, positioning it among the top ten most cited in the field. From the date of the article's appearance, medicinal chemistry research into conopeptide engineering for neuropathic pain treatment experienced substantial growth, highlighted by the intensified focus on topological modifications (such as cyclization), electrophysiology experiments, and structural biological studies.
A significant rise in allergic diseases has been observed globally in recent years, with more than 20% of the population affected. The current first-line strategy for anti-allergic treatment comprises topical corticosteroids and supplemental antihistamine medications; however, prolonged application can induce adverse side effects and result in drug resistance. Importantly, the pursuit of alternative anti-allergic agents from natural products is a priority. 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. The information presented in this review concerns anti-allergic secondary metabolites, featuring a range of chemical structures such as polyphenols, alkaloids, terpenoids, steroids, and peptides. These substances are principally sourced from fungi, bacteria, macroalgae, sponges, mollusks, and fish. A molecular docking simulation, performed using MOE, further explores the potential mechanism of action for representative marine anti-allergic natural products against the H1 receptor. This review unveils the structures and anti-allergic mechanisms of marine-origin natural products, thereby offering a significant reference for understanding their immunomodulatory properties.
Cancer-derived small extracellular vesicles (sEVs) act as vital messengers in the process of cellular dialogue. Unique marine-derived alkaloid Manzamine A (MA), possessing various bioactivities, demonstrates anti-cancer activity against multiple tumor types; however, its effect on breast cancer cells is still unknown. This study provides evidence that MA inhibits MDA-MB-231 and MCF-7 cell proliferation, migration, and invasion, exhibiting a notable effect that is both time- and dose-dependent. MA's effect on breast cancer cells includes the stimulation of autophagosome formation, coupled with a suppression of their degradation. 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). Through its mechanistic action, MA decreases the expression levels of RIP1, the essential upstream regulator of the autophagic pathway, and lowers the pH of lysosomes. Overexpression of RIP1 led to the activation of the AKT/mTOR pathway, resulting in a decrease in MA-induced autophagy and the subsequent secretion of autophagy-associated sEVs. The data collectively indicate that MA potentially inhibits autophagy by hindering autophagosome turnover, and RIP1 is involved in mediating MA-induced secretory autophagy, which could be beneficial for breast cancer treatment.
The marine-derived fungus, belonging to the Acremonium genus, served as the source of Marinobazzanan (1), a novel bazzanane-type sesquiterpenoid. Employing NOESY data analysis, the relative configurations of 1 were established, with NMR and mass spectroscopic data illuminating its chemical structure. selleck products Employing a combination of the modified Mosher's method and vibrational circular dichroism (VCD) calculations, the absolute configurations of molecule 1 were ascertained as 6R, 7R, 9R, and 10R. Experiments demonstrated that compound 1 exhibited no cytotoxicity towards human cancer cell lines, such as A549 (lung), AGS (gastric), and Caco-2 (colorectal), at concentrations below 25 micromoles per liter. Soft agar colony formation, cancer cell migration, and invasion were all noticeably decreased by compound 1, present in concentrations from 1 to 5 M. This was a consequence of reduced KITENIN expression and elevated KAI1 expression. Suppression of -catenin-mediated TOPFLASH activity, and its downstream targets, occurred in AGS, A549, and Caco-2 cells following treatment with Compound 1, alongside a modest reduction in the Notch signaling pathway within these three cancer cell lines. selleck products In the same vein, I also reduced the frequency of metastatic nodules in the intraperitoneal xenograft mouse model.
From the fermentation broth of the marine fungus *Phaeosphaeriopsis sp.*, five new isocoumarin compounds, named phaeosphaerins A to E (1-5), were isolated. Isocoumarin 68-dihydroxy-7-methoxy-3-methylisocoumarin (6), along with the well-characterized diterpenes diaporthein A (7) and diaporthein B (8), were also found alongside WP-26. Employing NMR experiments in conjunction with X-ray diffraction analysis and a comparison of experimental and computed ECD curves, their structural features were characterized. Compounds 1-7 revealed a muted neuroprotective response to H2O2-induced damage in the SH-SY5Y cell line. selleck products Compound 8 was cytotoxic to BEL-7402, SGC-7901, K562, A549, and HL-60 cellular lines, respectively.
Physical injuries commonly involve excisional wounds, ranking among the most prevalent. We are investigating the effects of a nanophytosomal formulation containing a dried hydroalcoholic extract of Spirulina platensis on the rate of excisional wound healing in this study. Concerning particle size (59840 ± 968 nm), zeta potential (-198 ± 049 mV), entrapment efficiency (6276 ± 175%), and Q6h (7400 ± 190%), the Spirulina platensis nanophytosomal formulation (SPNP) containing 100 mg PC and 50 mg CH exhibited optimal physicochemical characteristics. This particular HPMC gel (SPNP-gel) was selected for preparation. Thirteen compounds were discovered through metabolomic profiling of the algal extract. Analysis of the binding of identified compounds to HMGB-1's active site via molecular docking demonstrated 1213-DiHome achieving the highest score, reaching -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.