Marine Drugs最新文献

Cembranoid diterpenes are characteristic compounds of soft corals with diverse structures and significant activities, making them an important source of drug lead compounds. In this paper, five new cembranoid diterpenes, meijicrassolins A-E (1-5), were isolated from the soft coral Sarcophyton crassocaule, along with five previously reported compounds (6-10). The structures and absolute configuration for new compounds 1-5 were assigned by extensive spectroscopic analysis, single-crystal X-ray crystallography, quantum mechanical nuclear magnetic resonance (QM-NMR), and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Compounds 3, 4, and 9 showed moderate inhibition of nitric oxide generation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Overall, our research results have enriched the library of secondary metabolites from soft corals, providing more molecular entities for subsequent research and development of related compounds.

Majusculamide D, isolated from the marine cyanobacterium Moorea producens, is an anticancer lipopentapeptide consisting of fatty acid, tripeptide, and pyrrolyl proline moieties. In this work, by utilizing a convergent synthetic approach, late-stage modification, and bioisostere strategy, 26 majusculamide D analogues were synthesized, and two (1i and 1j) demonstrated IC₅₀ values < 1 nM against PANC-1 cancer cells. The results summarized a preliminary structure-activity relationship mainly at the C23, C4, C34, and C10 sites. A series of in vitro assays, including wound healing, transwell, clone formation, EdU, and western blot, confirmed that majusculamide D inhibited the migration, invasion, and proliferation of pancreatic cancer cells. The optimized fluorinated analogue 1n demonstrated a notable enhancement in stability during the mouse plasma assay (>50% left after 24 h), exhibited tumor-suppressive effects (51.5% at a dosage of 5 mg/kg), and successfully mitigated the severe toxicity (no mouse dead) observed in the group treated with majusculamide D (3 mice dead) in a xenografted mouse model.

This study explores the biocontrol potential of Pediococcus sp. M21F004, a lactic acid bacteria (LAB) isolated from marine environments, against several bacterial and fungal phytopathogens. Out of 50 marine bacterial isolates, Pediococcus sp. M21F004 was selected for its exceptional antimicrobial activity. The strain, isolated from the intestine of a starry flounder, was identified as Pediococcus sp. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that oleic acid (OA) is a key antimicrobial compound produced by Pediococcus sp. M21F004. In vitro assays showed that the culture broth (CB) of Pediococcus sp. M21F004, as well as OA, exhibited significant inhibitory effects against pathogens such as Fusarium oxysporum, Clarireedia homoeocarpa, and Pectobacterium carotovorum subsp. carotovorum. In vivo tests on cucumber Fusarium wilt, creeping bentgrass dollar spot, tomato bacterial wilt, and kimchi cabbage soft rot further demonstrated the strain's efficacy in reducing disease severity. Moreover, OA had the highest control value of 74% against tomato bacterial wilt, followed by 64.1% against cucumber fusarium wilt, 42.5% against kimchi cabbage soft rot, and 16.5% against creeping bentgrass dollar spot. These findings suggest that Pediococcus sp. M21F004 and its metabolite OA offer promising alternatives to chemical pesticides, contributing to sustainable plant disease management by promoting resistance induction and providing an eco-friendly approach to agriculture.

Cornea tissue engineering is strictly dependent on the development of biomaterials that fulfill the strict biocompatibility, biomechanical, and optical requirements of this organ. In this work, we generated novel biomaterials from the squid gladius (SG), and their application in cornea tissue engineering was evaluated. Results revealed that the native SG (N-SG) was biocompatible in laboratory animals, although a local inflammatory reaction was driven by the material. Cellularized biomaterials (C-SG) demonstrated that the SG provides an adequate substrate for cell attachment and growth, and corneal epithelial cells cultured on this biomaterial were able to express crystallin alpha, a marker for this type of cells. Biomechanical analyses showed that N-SG biomaterials have higher Young modulus and lower traction deformation than control native corneas (CTR), and C-SG showed a similar Young modulus than CTR. Analysis of the optical properties of these samples revealed that the diffuse transmittance of N-SG and C-SG were higher than CTR, with the diffuse reflectance showing the opposite behavior. These results confirm the putative usefulness of this abundant marine-derived biomaterial that can be obtained as a byproduct of the fishing industry.

Melanoma is an aggressive skin cancer with a high risk of cancer-related deaths, and inducing apoptosis in melanoma cells is a promising therapeutic strategy. This study investigates the anti-tumor potential of a novel lucknolide derivative LA-UC as a therapeutic candidate for melanoma. Lucknolide A (LA), a tricyclic ketal-lactone metabolite isolated from marine-derived Streptomyces sp., was chemically modified by introducing a 10-undecenoyl group to synthesize LA-UC. LA-UC preferentially inhibited the proliferation of melanoma cells, including B16F10, while exerting minimal effects on normal melanocytes or other tumor cell types, indicating the selective action of LA-UC against melanoma cells. LA-UC decreased G2/M checkpoint proteins, including cyclin B1 and Cdc2, while activating caspase-3 and caspase-9, resulting in G2/M cell cycle arrest and inducing apoptotic cell death in B16F10 cells. The addition of a pan-caspase inhibitor confirmed the caspase-dependent mechanism of LA-UC-induced cell death. Additionally, LA-UC elevated mitochondrial ROS levels, leading to mitochondrial membrane disruption, upregulation of pro-apoptotic proteins, and DNA damage in melanoma cells. The ROS scavenger N-acetylcysteine reduced LA-UC-induced mitochondrial ROS accumulation, mitochondrial membrane disruption, DNA damage, and apoptosis. Collectively, these findings suggest that LA-UC induces G2/M cell cycle arrest and caspase-dependent apoptosis in B16F10 cells through excessive mitochondrial ROS generation, membrane impairment, and DNA damage, highlighting its potential as a promising therapeutic candidate for melanoma treatment.

Triglochin maritima, a salt-tolerant plant, has demonstrated antioxidant effects, the ability to prevent prostate enlargement, antifungal properties, and skin moisturizing benefits. This study aimed to explore the anti-melanogenic potential of the 70% ethanol extract of T. maritima (TME) along with its ethyl acetate (TME-EA) and water (TME-A) fractions. TME (10-200 µg/mL), TME-EA (1-15 µg/mL), and TME-A (100-1000 µg/mL) were prepared and applied to B16F10 cells with or without α-MSH for 72 h. MTT assays were used to assess cytotoxicity, and anti-melanogenesis activity was determined by measuring melanin content, conducting a tyrosinase activity assay, and evaluating the expression of melanogenesis-related genes and proteins via RT-PCR and Western blotting. HPLC-PDA was used to analyze TME and TME-EA. The IC₂₀ cytotoxicity values of TME, TME-A, and TME-EA without α-MSH, were 198.426 μg/mL, 1000 μg/mL, and 18.403 μg/mL, respectively. TME and TME-EA significantly decreased melanin and tyrosinase activity in α-MSH-stimulated B16F10 cells, with TME-EA showing comparable effects to arbutin, while TME-A showed no influence. TME-EA down-regulated melanogenesis genes (Tyr, Trp1, Dct, Mitf, Mc1r) and reduced CREB, p-38, and JNK phosphorylation while increasing ERK phosphorylation, suggesting the CREB/MAPK pathway's role in the anti-melanogenic effect. Luteolin was identified as a potential active ingredient. TME-EA may serve as an effective cosmeceutical for hyperpigmentation improvement due to its anti-melanogenic properties.

Tetrodotoxin (TTX) is a neurotoxin that binds to sodium channels and blocks sodium conduction. Importantly, TTX has been increasingly detected in edible aquatic organisms. Because of this and the lack of specific antidotes, TTX poisoning is now a major threat to public health. However, it is of note that ultra-low dose TTX is an excellent analgesic with great medicinal value. These contradictory effects highlight the need for further research to elucidate the impacts and functional mechanisms of TTX. This review summarizes the latest research progress in relation to TTX sources, analogs, mechanisms of action, detection methods, poisoning symptoms, therapeutic options, biosynthesis pathways, and mechanisms of transport and accumulation in pufferfish. This review also provides a theoretical basis for reducing the poisoning risks associated with TTX and for establishing an effective system for its use and management to ensure the safety of fisheries and human health.

This study represents the first investigation into the ultrasonic and microwave extraction of bioactive metabolites from Jania rubens (J. rubens) (red seaweed) and Sargassum. muticum (S. muticum) (brown seaweed), with a focus on their biological activities. The research compares ultrasound-assisted extraction (UAE) with microwave-assisted extraction (MAE) utilizing a hydromethanolic solvent to evaluate their effects on these seaweeds' bioactive compounds and biological activities. The assessment included a series of antioxidant essays: DPPH, ABTS, phenanthroline, and total antioxidant capacity, followed by enzyme inhibition activities: alpha-amylase and urease. Results revealed significant proportions of phenolic compounds, ranging from 48.31 ± 0.32 to 74.42 ± 0.80 μg GAE/mg, depending on the extraction method. The extracts demonstrated a high antioxidant activity, with IC₅₀ values ranging from 26.58 ± 0.39 to 87.55 ± 0.69 μg/mL. Notably, the MAE extract of S. muticum showed a value of 48.11 ± 2.75 μg/mL for alpha-amylase inhibition, which is strictly superior to the reference acarbose with an IC₅₀ equal to 3431.01 μg/mL. UPLC-ESI-MS/MS analysis identified 14 bioactive compounds. The proportion of riboflavin with MAE was 70.58% and 59.11% for J. rubens and S. muticum fractions, respectively. These findings underscore the critical influence of extraction technique selection on bioactive compounds' yield and efficiency, highlighting the potential of algal biomass as a sustainable alternative in various applications.

Peritoneal dialysis (PD) serves as a home-based kidney replacement therapy with increasing utilization across the globe. However, long-term use of high-glucose-based PD solution incites repeated peritoneal injury and inevitable peritoneal fibrosis, thus compromising treatment efficacy and resulting in ultrafiltration failure eventually. In the present study, we utilized human mesothelial MeT-5A cells for the in vitro experiments and a PD mouse model for in vivo validation to study the pathophysiological mechanisms underneath PD-associated peritoneal fibrosis. High-glucose PD solution (Dianeal 4.25%, Baxter) increased protein expression of mesothelial-mesenchymal transition (MMT) markers, such as N-cadherin and α-SMA in MeT-5A cells, whereas it decreased catalase expression and stimulated the production of reactive oxygen species (ROS). Furthermore, macrophage influx and increased serum pro-inflammatory cytokines, such as IL-1β, MCP-1, and TNF-α, were observed in the PD mouse model. Interestingly, we discovered that oligo-fucoidan, an oligosaccharide extract from brown seaweed, successfully prevented PD-associated peritoneal thickening and fibrosis through antioxidant effect, downregulation of MMT markers, and attenuation of peritoneal and systemic inflammation. Hence, oligo-fucoidan has the potential to be developed into a novel preventive strategy for PD-associated peritoneal fibrosis.

Sulphated polysaccharides (SPs) are negatively charged compounds found in the cell wall of seaweeds or marine macro algae. These compounds exhibit a range of pharmacological activities, including anti-obesity effects. The aim of this systematic review as well as meta-analysis was to assess the potentials of seaweed-derived SPs to mitigate obesity through a systematic review and meta-analysis of animal model-based studies. A comprehensive summary of the included articles was conducted, focusing on the following obesity-related parameters: food intake, body weight gain, epididymal fat size, adipocyte size, liver weight, serum alanine transaminase (ALT) and aspartate transaminase (AST), insulin and tumour necrosis factor-α (TNF-α), and the lipid profile (total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c)). The systematic review demonstrated that seaweed-derived SPs exhibit ameliorative effects against obesity, as evidenced by reductions in food intake, body weight gain, epididymal fat and adipocyte size, liver weight, ALT and AST levels, serum insulin and TNF-α, LDL-c, total cholesterol, and triglycerides and an increase in HDL-c in obese rats administered with seaweed-derived SPs. However, the meta-analysis revealed statistically significant anti-obesity effects of seaweed-derived SPs for most, but not all the parameters tested. Further research in human subjects is necessary not only to ascertain the results of preclinical studies but also to provide conclusive evidence of the anti-obesity potential of SPs in humans.