Network pharmacology, molecular docking, and molecular dynamics simulation analysis reveal the molecular mechanism of halociline against gastric cancer.

Halociline, a derivative of alkaloids, was isolated from the marine fungus Penicillium griseofulvum by our group. This remarkable compound exhibits promising antineoplastic activity, yet the precise molecular mechanisms underlying its anticancer properties remain enigmatic. To unravel these mechanisms, we employed an integrated approach of network pharmacology analysis, molecular docking simulations, and molecular dynamics simulations to explore halociline therapeutic targets for gastric cancer. The data from network pharmacology indicate that halociline targets MAPK1, MMP-9, and PIK3CA in gastric cancer cells, potentially mediated by diverse pathways including cancer, lipid metabolism, atherosclerosis, and EGFR tyrosine kinase inhibitor resistance. Notably, molecular docking and dynamics simulations revealed a high affinity between halociline and these targets, with free binding energies (ΔEtotal) of - 20.28, - 27.94, and - 25.97 kcal/mol for MAPK1, MMP-9, and PIK3CA, respectively. This study offers valuable insights into the potential molecular mechanism of halociline's inhibition of gastric cancer cells and serves as a valuable reference for future basic research efforts.

Marine Fungi: A Prosperous Source of Novel Bioactive Natural Products.

As the number of viruses, bacteria, and tumors that are resistant to drugs continues to rise, there is a growing need for novel lead compounds to treat them. Marine fungi, due to their unique secondary metabolic pathways and vast biodiversity, have become a crucial source for lead compounds in drug development. This review utilizes bibliometric methods to analyze the research status of natural products from marine fungi in the past decade, revealing the hotspots and trends in this field from Web of Science database. Furthermore, this review summarizes the biological activities and effects on molecular mechanisms of novel natural compounds isolated from marine fungi in the past five years. These novel compounds belong to six different structural classes, such as alkaloids, terpenoids, anthraquinones, polyketones, etc. They also exhibited highly potent biological properties, including antiviral, antitumor, antibacterial, antiinflammatory, and other properties. This review demonstrates the hotspots and trends of marine fungi research in recent years, as well as the variety of chemical structure and biological activities of their natural products, and it may provide guidance for those interested in discovering new drugs from marine fungi and specific targeting mechanisms.

Marine Bacteria: A Source of Novel Bioactive Natural Products.

Marine natural products have great pharmacological potential due to their unique and diverse chemical structures. The marine bacterial biodiversity and the unique marine environment lead to a high level of complexity and ecological interaction among marine species. This results in the production of metabolic pathways and adaptation mechanisms that are different from those of terrestrial organisms, which has drawn significant attention from researchers in the field of natural medicine. This review provides an analysis of the distribution and frequency of keywords in the literature on marine bacterial natural products as well as an overview of the new natural products isolated from the secondary metabolites of marine bacteria in recent years. Finally, it discusses the current research hotspots in this field and speculates on future directions and limitations.

Green Biosynthesis of Silver Nanoparticles Using Aqueous Extracts of Ageratum Conyzoides and Their Anti-Inflammatory Effects.

The NLRP3 inflammasome, which plays a central role in innate immunity, is linked to a variety of inflammatory diseases, and thus it may provide a new target for the treatment of those diseases. Biosynthesized silver nanoparticles (AgNPs), particularly those synthesized using medicinal plant extracts, have recently been shown to be a promising therapeutic option. Herein, the aqueous extract of Ageratum conyzoids was used to prepare a series of sized AgNPs (AC-AgNPs), in which the smallest mean particle size was 30 ± 1.3 nm with a polydispersity of 0.328 ± 0.009. The ζ potential value was -28.77 with a mobility of -1.95 ± 0.24 cm2/(v·s). Its main ingredient, elemental silver, accounted for about 32.71 ± 4.87% of its mass, and other ingredients included amentoflavone-7,7⁗-dimethyl ether, 1,3,5-tricaffeoylquinic acid, kaempferol 3,7,4'-triglucoside, 5,6,7,3',4',5'-hexamethoxyflavone, kaempferol, and ageconyflavone B. In LPS+ATP-stimulated RAW 264.7 and THP-1 cells, AC-AgNPs significantly inhibited the release of IL-1ß, IL-18, TNF-α, and caspase-1, indicating that AC-AgNPs can inhibit the activation of the NLRP3 inflammasome. The mechanistic study revealed that AC-AgNPs could decrease the phosphorylation levels of IκB-α and p65, resulting in decreased expression of NLRP3 inflammasome-related proteins, including pro-IL-1ß, IL-1ß, procaspase 1, caspase 1P20, NLRP3, and ASC, and also scavenge the level of intracellular ROS to prevent NLRP3 inflammasome assembly. Furthermore, AC-AgNPs attenuated the in vivo expression of inflammatory cytokines by suppressing NLRP3 inflammasome activation in a peritonitis mouse model. Our study provides evidence that the as-prepared AC-AgNPs can inhibit the inflammatory process by suppressing NLRP3 inflammasome activation and might be used to treat NLRP3 inflammasome-driven inflammatory diseases.

The aqueous extracts of Ageratum conyzoides inhibit inflammation by suppressing NLRP3 inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ageratum conyzoides L. (Asteraceae), a well-known and widely distributed traditional tropical medicinal herb, has been used to treat diverse diseases. Our preliminary research has shown that aqueous extracts of A. conyzoides leaf (EAC) have anti-inflammatory activity. However, the detailed underlying anti-inflammatory mechanism of EAC is still unclear. AIM OF THE STUDY: To determine the anti-inflammatory mechanism of action of EAC. MATERIALS AND METHODS: The major constituents of EAC were identified by ultra-performance liquid chromatography (UPLC) combined with quadrupole-time-of-flight mass/mass spectrometry (UPLC-Q-TOF-MS/MS). LPS and ATP were used to activate the NLRP3 inflammasome in two types of macrophages (RAW 264.7 and THP-1 cells). The cytotoxicity of EAC was measured by the CCK8 assay. The levels of inflammatory cytokines and NLRP3 inflammasome-related proteins were detected by ELISA and western blotting (WB), respectively. The oligomerization of NLRP3 and ASC and the resulting inflammasome complex formation were observed by immunofluorescence. The intracellular reactive oxygen species (ROS) level was measured by flow cytometry. Finally, an MSU-induced peritonitis model was established to evaluate the anti-inflammatory effects of EAC in vivo. RESULTS: Twenty constituents were identified in the EAC. Kaempferol 3,7-diglucoside, 1,3,5-tricaffeoylquinic acid, and kaempferol 3,7,4'-triglucoside were found to be the most potent ingredients. EAC significantly reduced the levels of IL-1ß, IL-18, TNF-α, and caspase-1 in the two types of activated macrophages, implying that EAC can inhibit the activation of the NLRP3 inflammasome. A mechanistic study revealed that EAC inhibited NLRP3 inflammasome activation by blocking NF-κB signalling pathway activation and scavenging the level of intracellular ROS to prevent NLRP3 inflammasome assembly in macrophages. Furthermore, EAC attenuated the in vivo expression of inflammatory cytokines by suppressing NLRP3 inflammasome activation in a peritonitis mouse model. CONCLUSION: Our results demonstrated that EAC inhibited inflammation by suppressing NLRP3 inflammasome activation, highlighting that this traditional herbal medicine might be used to treat NLRP3 inflammasome-driven inflammatory diseases.

Investigation of the bactericidal mechanism of Penicilazaphilone C on Escherichia coli based on 4D label-free quantitative proteomic analysis.

There is an urgent need to find new antibiotics to fight against the increasing drug resistance of microorganisms. A novel natural compound, Penicilazaphilone C (PAC), was isolated from a marine-derived fungus. It has displayed broad bactericidal activities against Gram-negative and Gram-positive bacteria. However, its bactericidal mechanism is still unknown. Herein, time-kill assays verified that PAC is a fast and efficient bactericidal agent. Furthermore, data from 4D label-free quantitative proteome assays revealed that PAC significantly influences over 898 proteins in Escherichia coli. Combining the results of biofilm formation, ß-galactosidase measurement, TEM observation, soft agar plate swimming, reactive oxygen species measurement, qRT-PCR, and west-blotting, the mode of PAC action against E. coli was to block respiration, inhibit assimilatory nitrate reduction and dissimilar sulfur reduction, facilitate assimilatory sulfate reduction, suppress cysteine and methionine biosynthesis, down-regulate antioxidant protein expression and induced intracellular ROS accumulation, weaken bacterial chemotaxis, destroy flagellar assembly, etc., and finally cause the bacteria's death. Our findings suggest that PAC could have a multi-target regulatory effect on E. coli and could be used as a new antibiotic in medicine.