Anti-Inflammatory Effects Exerted by 14-Methoxyalternate C from Antarctic Fungal Strain Pleosporales sp. SF-7343 via the Regulation of NF-κB and JAK2/STAT3 in HaCaT Human Keratinocytes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a profound negative impact on patients' quality of life. Four known secondary fungal metabolites were found in the chemical study of the Antarctic fungus Pleosporales sp. SF-7343, including 14-methoxyalternate C (1), 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (2), 3,8,10-trihydroxy-4-methoxy-6-methylbenzocoumarin (3), and alternariol monomethyl ether (4). Additionally, we identified the skin anti-inflammatory composition from the SF-7343 strain. Interleukin-8 and -6 Screening results showed that compound 1 inhibited IL-8 and IL-6 in tumor necrosis factor-α/interferon-γ stimulated HaCaT cells. Compound 1 showed inhibitory effects on MDC and RANTES. It also downregulated the expression of intercellular adhesion molecule-1 (ICAM-1) and upregulated the expression of involucrin. The results of the mechanistic study showed that compound 1 inhibited the nuclear translocation of nuclear factor-kappa B p65 and STAT3. In conclusion, this study demonstrates the potential of the Antarctic fungal strain SF-7343 as a bioactive resource to inhibit skin inflammation, such as AD.

Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia.

Microglia play a significant role in immune defense and tissue repair in the central nervous system (CNS). Microglial activation and the resulting neuroinflammation play a key role in the pathogenesis of neurodegenerative disorders. Recently, inflammation reduction strategies in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the anti-neuroinflammatory potential of compounds from the Antarctic fungi strain Aspergillus sp. SF-7402 in lipopolysaccharide (LPS)-stimulated BV2 cells. Four metabolites were isolated from the fungi through chemical investigations, namely, 5-methoxysterigmatocystin (1), sterigmatocystin (2), aversin (3), and 6,8-O-dimethylversicolorin A (4). Their chemical structures were elucidated by extensive spectroscopic analysis and HR-ESI-MS, as well as by comparison with those reported in literature. Anti-neuroinflammatory effects of the isolated metabolites were evaluated by measuring the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in LPS-activated microglia at non-cytotoxic concentrations. Sterigmatocystins (1 and 2) displayed significant effects on NO production and mild effects on TNF-α and IL-6 expression inhibition. The molecular mechanisms underlying this activity were investigated using Western blot analysis. Sterigmatocystin treatment inhibited NO production via downregulation of inducible nitric oxide synthase (iNOS) expression in LPS-stimulated BV2 cells. Additionally, sterigmatocystins reduced nuclear translocation of NF-κB. These results suggest that sterigmatocystins present in the fungal strain Aspergillus sp. are promising candidates for the treatment of neuroinflammatory diseases.

Antifungal and Larvicidal Activities of Phlorotannins from Brown Seaweeds.

Phlorotannins are secondary metabolites produced by brown seaweeds with antiviral, antibacterial, antifungal, and larvicidal activities. Phlorotannins' structures are formed by dibenzodioxin, ether and phenyl, ether, or phenyl linkages. The polymerization of phlorotannins is used to classify and characterize. The structural diversity of phlorotannins grows as polymerization increases. They have been characterized extensively with respect to chemical properties and functionality. However, review papers of the biological activities of phlorotannins have focused on their antibacterial and antiviral effects, and reviews of their broad antifungal and larvicidal effects are lacking. Accordingly, evidence for the effectiveness of phlorotannins as antifungal and larvicidal agents is discussed in this review. Online databases (ScienceDirect, PubMed, MEDLINE, and Web of Science) were used to identify relevant articles. In total, 11 articles were retrieved after duplicates were removed and exclusion criteria were applied. Phlorotannins from brown seaweeds show antifungal activity against dermal and plant fungi, and larvicidal activity against mosquitos and marine invertebrate larvae. However, further studies of the biological activity of phlorotannins against fungal and parasitic infections in aquaculture fish, livestock, and companion animals are needed for systematic analyses of their effectiveness. The research described in this review emphasizes the potential applications of phlorotannins as pharmaceutical, functional food, pesticide, and antifouling agents.

Fucosterol of Marine Macroalgae: Bioactivity, Safety and Toxicity on Organism.

Fucosterol (24-ethylidene cholesterol) is a bioactive compound belonging to the sterol group that can be isolated from marine algae. Fucosterol of marine algae exhibits various biological activities including anti-osteoarthritic, anticancer, anti-inflammatory, anti-photoaging, immunomodulatory, hepatoprotective, anti-neurological, antioxidant, algicidal, anti-obesity, and antimicrobial. Numerous studies on fucosterol, mainly focusing on the quantification and characterization of the chemical structure, bioactivities, and health benefits of fucosterol, have been published. However, there is no comprehensive review on safety and toxicity levels of fucosterol of marine algae. This review aims to discuss the bioactivities, safety, and toxicity of fucosterol comprehensively, which is important for the application and development of fucosterol as a bioactive compound in nutraceutical and pharmaceutical industries. We used four online databases to search for literature on fucosterol published between 2002 and 2020. We identified, screened, selected, and analyzed the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method and identified 43 studies for review. Despite the potential applications of fucosterol, we identified the need to fill certain related research gaps. Fucosterol exhibited low toxicity in animal cell lines, human cell lines, and animals. However, studies on the safety and toxicity of fucosterol at the clinical stage, which are required before fucosterol is developed for the industry, are lacking.

Anti-Inflammatory Effects of Metabolites from Antarctic Fungal Strain Pleosporales sp. SF-7343 in HaCaT Human Keratinocytes.

Chemical investigation of the Antarctic fungi Pleosporales sp. SF-7343 revealed four known secondary fungal metabolites: alternate C (1), altenusin (2), alternariol (3), and altenuene (4). The compound structures were identified primarily by NMR and MS analyses. Atopic dermatitis, an inflammatory disease, is driven by the abnormal activation of T helper (Th) 2 cells and barrier dysfunction. We attempted to identify the anti-inflammatory components of SF-7343. Initial screening showed that compounds 1 and 3 inhibited the secretion of interleukin-8 and -6 in tumor necrosis factor-α/interferon-γ-treated HaCaT cells, and these compounds also showed inhibitory effects on CCL5 and CCL22. Compounds 1 and 3 also downregulated the protein expression levels of intercellular adhesion molecule-1 and upregulated the expression of filaggrin and involcurin. The mechanism study results showed that compounds 1 and 3 inhibited nuclear translocation of nuclear factor-kappa B p65 and the phosphorylation of STAT1 and STAT3. Compound 1, but not compound 3, significantly promoted the expression of heme oxygenase (HO)-1. The effects of compound 1 were partly reversed by co-treatment with a HO-1 inhibitor, tin protoporphyrin IX. Taken together, this study demonstrates the potential value of Antarctic fungal strain SF-7343 isolates as a bioresource for bioactive compounds to prevent skin inflammation.

PTP1B Inhibitory Secondary Metabolites from an Antarctic Fungal Strain Acremonium sp. SF-7394.

Chemical investigation of the Antarctic lichen-derived fungal strain Acremonium sp. SF-7394 yielded a new amphilectane-type diterpene, acrepseudoterin (1), and a new acorane-type sesquiterpene glycoside, isocordycepoloside A (2). In addition, three known fungal metabolites, (-)-ternatin (3), [D-Leu]-ternatin (4), and pseurotin A (5), were isolated from the EtOAc extract of the fungal strain. Their structures were mainly elucidated by analyzing their NMR and MS data. The absolute configuration of 1 was proposed by electronic circular dichroism calculations, and the absolute configuration of the sugar unit in 2 was determined by a chemical method. The inhibitory effects of the isolated compounds on protein tyrosine phosphatase 1B (PTP1B) were evaluated by enzymatic assays; results indicated that acrepseudoterin (1) and [D-Leu]-ternatin (4) dose-dependently inhibited the enzyme activity with IC50 values of 22.8 ± 1.1 µM and 14.8 ± 0.3 µM, respectively. Moreover, compound 1 was identified as a competitive inhibitor of PTP1B.

Terrein suppressed lipopolysaccharide-induced neuroinflammation through inhibition of NF-κB pathway by activating Nrf2/HO-1 signaling in BV2 and primary microglial cells.

In the course of our continuous investigation on the bioactive marine-derived fungal metabolites, terrein was isolated from marine-derived fungal strain Penicillium sp. SF-7181. Terrein inhibited the overproduction of pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated BV2 and primary microglial cells. This compound also repressed the LPS-induced production of pro-inflammatory cytokines, interleukin (IL)-1ß and IL-6. These inhibitory effects of terrein were associated with the inactivation of the nuclear factor kappa B (NF-κB) pathway through suppression of the translocation of p65/p50 heterodimer into the nucleus, the phosphorylation and degradation of inhibitor kappa B (IκB)-α and the DNA binding activity of the p65 subunit. In addition, terrein induced the protein expression of heme oxygenase (HO)-1 through the activation of nuclear transcription factor erythroid-2 related factor 2 (Nrf2) in BV2 and primary microglial cells. The anti-inflammatory effect of terrein was blocked by pre-treatment with a selective HO-1 inhibitor, suggesting that its anti-neuroinflammatory effect is mediated by HO-1 induction.

Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123.

A chemical investigation of the marine-derived fungal strain Penicillium glabrum (SF-7123) revealed a new citromycetin (polyketide) derivative (1) and four known secondary fungal metabolites, i.e, neuchromenin (2), asterric acid (3), myxotrichin C (4), and deoxyfunicone (5). The structures of these metabolites were identified primarily by extensive analysis of their spectroscopic data, including NMR and MS data. Results from the initial screening of anti-inflammatory effects showed that 2, 4, and 5 possessed inhibitory activity against the excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC50 values of 2.7 µM, 28.1 µM, and 10.6 µM, respectively. Compounds 2, 4, and 5 also inhibited the excessive production of NO, with IC50 values of 4.7 µM, 41.5 µM, and 40.1 µM, respectively, in LPS-stimulated RAW264.7 macrophage cells. In addition, these compounds inhibited LPS-induced overproduction of prostaglandin E2 in both cellular models. Further investigation of the most active compound (2) revealed that these anti-inflammatory effects were associated with a suppressive effect on the over-expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, we showed that the anti-inflammatory effects of compound 2 were mediated via the downregulation of inflammation-related pathways such as those dependent on nuclear factor kappa B and p38 mitogen-activated protein kinase in LPS-stimulated BV2 and RAW264.7 cells. In the evaluation of the inhibitory effects of the isolated compounds on protein tyrosine phosphate 1B (PTP1B) activity, compound 4 was identified as a noncompetitive inhibitor of PTP1B, with an IC50 value of 19.2 µM, and compound 5 was shown to inhibit the activity of PTP1B, with an IC50 value of 24.3 µM, by binding to the active site of the enzyme. Taken together, this study demonstrates the potential value of marine-derived fungal isolates as a bioresource for bioactive compounds.

Anti-inflammatory effect of 3,7-dimethyl-1,8-hydroxy-6-methoxyisochroman via nuclear factor erythroid 2-like 2-mediated heme oxygenase-1 expression in lipopolysaccharide-stimulated RAW264.7 and BV2 cells.

Objective: The isochroman-type fungal metabolite 3,7-dimethyl-1,8-hydroxy-6-methoxyisochroman (DMHM) was isolated from the extracts of a marine-derived fungal strain of Penicillium sp. SF-6013. In this study, we investigated the effect of DMHM on inflammatory response. Materials and methods: Anti-inflammatory effects of DMHM were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells. We observed their anti-inflammatory effects by ELISA, qRT-PCR, and western blot analysis. Results: DMHM revealed that it suppressed the production of prostaglandin E2 (PGE2), nitric oxide (NO), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) in LPS-stimulated RAW264.7 and BV2 cells. Furthermore, DMHM decreased the mRNA expression of pro-inflammatory cytokines including interleukin (IL)-1ß and IL-6. Therefore, DMHM was further investigated to elucidate the mechanisms of its anti-inflammatory properties; the results indicated that its effect was mediated by the suppression of the nuclear factor (NF)-κB and c-Jun N-terminal kinase (JNK) MAPK pathways. Furthermore, the anti-inflammatory activity of DMHM correlated with its induction of heme oxygenase-1 (HO)-1 expression via activation of the nuclear factor erythroid 2-like 2 (Nrf2) pathway. Discussion and conclusions: Collectively, the results of this study suggest that DMHM inhibited several inflammatory pathways including the NF-κB and MAPK pathways, and induced Nrf2-mediated HO-1 expression, demonstrating its potential usefulness for treating inflammatory and neuroinflammatory diseases.

Anti-Inflammatory Effects of Curvularin-Type Metabolites from a Marine-Derived Fungal Strain Penicillium sp. SF-5859 in Lipopolysaccharide-Induced RAW264.7 Macrophages.

Chemical study on the extract of a marine-derived fungal strain Penicillium sp. SF-5859 yielded a new curvularin derivative (1), along with eight known curvularin-type polyketides (2-9). The structures of these metabolites (1-9) were established by comprehensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). In vitro anti-inflammatory effects of these metabolites were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Among these metabolites, 3-9 were shown to strongly inhibit LPS-induced overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) with IC50 values ranging from 1.9 µM to 18.1 µM, and from 2.8 µM to 18.7 µM, respectively. In the further evaluation of signal pathways involved in these effects, the most active compound, (10E,15S)-10,11-dehydrocurvularin (8) attenuated the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 macrophages. Furthermore, compound 8 was shown to suppress the upregulation of pro-inflammatory mediators and cytokines via the inhibition of the nuclear factor-κB (NF-κB) signaling pathway, but not through the mitogen-activated protein kinase (MAPK) pathway. Based on the comparisons of the different magnitude of the anti-inflammatory effects of these structurally-related metabolites, it was suggested that the opening of the 12-membered lactone ring in curvularin-type metabolites and blocking the phenol functionality led to the significant decrease in their anti-inflammatory activity.

Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus Aspergillus sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines.

In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus Aspergillus sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS) as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS) generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO)-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.

Dihydroisocoumarin Derivatives from Marine-Derived Fungal Isolates and Their Anti-inflammatory Effects in Lipopolysaccharide-Induced BV2 Microglia.

Chemical investigation of the EtOAc extracts of marine-derived fungal isolates Aspergillus sp. SF-5974 and Aspergillus sp. SF-5976 yielded a new dihydroisocoumarin derivative (1) and 12 known metabolites. The structures of the isolated metabolites were established by extensive spectroscopic analyses, including 1D and 2D NMR spectra and MS data. Among the metabolites, the absolute configuration of 5'-hydroxyasperentin (6) was determined by single-crystal X-ray diffraction analysis. The in vitro antineuroinflammatory effects of the metabolites were also evaluated in lipopolysaccharide (LPS)-stimulated microglial cells. Among the isolated metabolites, dihydroisocoumarin derivatives 1-6 (10-80 µM) were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated BV2 microglia. Further, 1 (20-80 µM) was found to suppress the phosphorylation of the inhibitor of nuclear factor kappa B-α (IκB-α), interrupt the nuclear translocation of nuclear factor kappa B (NF-κB), and decrease the activation of p38 mitogen-activated protein kinase (MAPK).

Penicillium jejuense sp. nov., isolated from the marine environments of Jeju Island, Korea.

Three strains of an unidentified Penicillium species were isolated during a fungal diversity survey of marine environments in Korea. These strains are described here as a new species following a multigene phylogenetic analyses of nuc rDNA internal transcribed spacer barcodes (ITS1-5.8S-ITS2), genes for ß-tubulin, calmodulin and RNA polymerase II second largest subunit, and observation of macro-and micromorphological characters. Phylogenetic analyses revealed that the three strains formed a strongly supported monophyletic group distinct from previously reported species of section Aspergilloides. Morphologically this species can be distinguished from its sister species, P. crocicola, by the reverse color on Czapek yeast autolysate agar, abundant production of sclerotia on malt extract agar and colony characters on yeast extract sucrose agar. We name this new species P. jejuense, after the locality where it was discovered. At 25 C for 7 d, P. jejuense colonies grew to 55-60 mm on CYA, 45-48 mm on MEA, 48-52 mm on YES and 23-26 mm on CREA. Conidia (2.2-3.4 × 2.0-2.6 µm) and sclerotia (160-340 × 125-210 µm) were globose to ellipsoidal.

Tanzawaic acid derivatives from a marine isolate of Penicillium sp. (SF-6013) with anti-inflammatory and PTP1B inhibitory activities.

Chemical investigation of a marine-derived fungus Penicillium sp. SF-6013 resulted in the discovery of a new tanzawaic acid derivative, 2E,4Z-tanzawaic acid D (1), together with four known analogues, tanzawaic acids A (2) and D (3), a salt form of tanzawaic acid E (4), and tanzawaic acid B (5). Their structures were mainly determined by analysis of NMR and MS data, along with chemical methods. Preliminary screening for anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglial BV-2 cells showed that compounds 1, 2, and 5 inhibited the production of nitric oxide (NO) with IC50 values of 37.8, 7.1, and 42.5 µM, respectively. Compound 2 also inhibited NO production in LPS-stimulated RAW264.7 murine macrophages with an IC50 value of 27.0 µM. Moreover, these inhibitory effects correlated with the suppressive effect of compound 2 on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 and BV2 cells. In addition, compounds 2 and 5 significantly inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with the same IC50 value (8.2 µM).

Marine-derived Penicillium in Korea: diversity, enzyme activity, and antifungal properties.

The diversity of marine-derived Penicillium from Korea was investigated using morphological and multigene phylogenetic approaches, analyzing sequences of the internal transcribed spacer region, ß-tubulin gene, and RNA polymerase subunit II gene. In addition, the biological activity of all isolated strains was evaluated. We tested for the extracellular enzyme activity of alginase, endoglucanase, and ß-glucosidase, and antifungal activity against two plant pathogens (Colletotrichum acutatum and Fusarium oxysporum). A total of 184 strains of 36 Penicillium species were isolated, with 27 species being identified. The most common species were Penicillium polonicum (19.6 %), P. rubens (11.4 %), P. chrysogenum (11.4 %), and P. crustosum (10.9 %). The diversity of Penicillium strains isolated from soil (foreshore soil and sand) and marine macroorganisms was higher than the diversity of strains isolated from seawater. While many of the isolated strains showed alginase and ß-glucosidase activity, no endoglucanase activity was found. More than half the strains (50.5 %) showed antifungal activity against at least one of the plant pathogens tested. Compared with other strains in this study, P. citrinum (strain SFC20140101-M662) showed high antifungal activity against both plant pathogens. The results reported here expand our knowledge of marine-derived Penicillium diversity. The relatively high proportion of strains that showed antifungal and enzyme activity demonstrates that marine-derived Penicillium have great potential to be used in the production of natural bioactive products for pharmaceutical and/or industrial use.

Inhibitory effects of benzaldehyde derivatives from the marine fungus Eurotium sp. SF-5989 on inflammatory mediators via the induction of heme oxygenase-1 in lipopolysaccharide-stimulated RAW264.7 macrophages.

Two benzaldehyde derivatives, flavoglaucin (1) and isotetrahydro-auroglaucin (2), were isolated from the marine fungus Eurotium sp. SF-5989 through bioassay- and 1H NMR-guided investigation. In this study, we evaluated the anti-inflammatory effects of these compounds in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We demonstrated that compounds 1 and 2 markedly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression without affecting cell viability. We also demonstrated that the compounds reduced the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Furthermore, compounds 1 and 2 inhibited LPS-induced nuclear factor-κB (NF-κB) activation by suppressing phosphorylation of IkappaB (IκB). These results indicated that the anti-inflammatory effects of these benzaldehyde derivatives in LPS-stimulated RAW264.7 macrophages were due to the inactivation of the NF-κB pathway. In addition, compounds 1 and 2 induced heme oxygenase-1 (HO-1) expression through the nuclear transcription factor-E2-related factor 2 (Nrf2) translocation. The inhibitory effects of compounds 1 and 2 on the production of pro-inflammatory mediators and on NF-κB binding activity were reversed by HO-1 inhibitor tin protoporphyrin (SnPP). Thus, the anti-inflammatory effects of compounds 1 and 2 also correlated with their ability of inducing HO-1 expression.

Anti-inflammatory effect of methylpenicinoline from a marine isolate of Penicillium sp. (SF-5995): inhibition of NF-κB and MAPK pathways in lipopolysaccharide-induced RAW264.7 macrophages and BV2 microglia.

In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS) in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2) production by suppressing cyclooxygenase-2 (COX-2) expression in a concentration-dependent manner (from 10 µM to 80 µM) without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1ß (IL-1ß). In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB) activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α), thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK) pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases.

Single-dose oral toxicity of fermented rice extracts (FREs): a 14-day observation.

The aim of present research was to determine the acute oral toxicity of fermented rice extracts (FREs), in female and male ICR mice. To investigate the toxicity and identify target organs, FREs were orally administered once to male and female ICR mice at doses of 0 (vehicle control), 500, 1000, or 2000 mg/kg body weight (BW). Effects on mortality, BW, and clinical signs were monitored over 14 days, including changes in the weights and histopathological characteristics of 14 organs, as described in the Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). No treatment-related mortality was observed during the 14-day observation period in either gender. In addition, no FRE-related change was observed in BW or organ weight (OW), clinical indicators, or histopathological findings in this study. Our results suggest that the FRE is non-toxic in mice and is therefore likely to be safe for clinical use. The approximate LD and LD50 in mice after single oral dose of FRE are greater than 2000 mg/kg in female and male ICR mice. Additionally, no specific target organ or negative clinical indicator was detected in this study.

Nutritional Composition and Safety Aspects of Deep-Sea Whelks (Buccinum tenuissimum Kuroda).

The deep-sea whelk Buccinum tenuissimum Kuroda is highly sought-after as food in East Asian countries, notably, Korea and Japan. However, it lacks official recognition as a food product in Korea. This study aimed to assess its nutritional composition and safety for the potential development of seafood products. The nutritional analysis revealed high protein (13.54-20.47 g/100 g whelk), fat (0.85-8.59 g/100 g whelk), carbohydrate (1.55-12.81 g/100 g whelk), and dietary fiber (1.25-1.95 g/100 g whelk) contents in both muscle and gut samples, with energy contents ranging from 339.11 ± 1.64 to 692.00 ± 3.21 kJ/100 g. Key minerals, including iron, potassium, calcium, and sodium, and essential fatty acids, including eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, omega-3, and omega-6 fatty acids, were abundant, making it a potential supplementary food. Notably, heavy metal levels met the Korean standards for seafood safety. No trans fats, radioactivity concerning the radioactive isotopes 134Cs/137Cs and 131I, or pathogenic bacteria were detected. This confirms the safety and nutritional value of deep-sea whelks, suggesting their potential for developing seafood products rich in beneficial components, which could enhance nutrition and food security while contributing to economic growth.

PTP1B inhibitory and anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungus Penicillium sp. JF-55.

Protein tyrosine phosphatase 1B (PTP1B) plays a major role in the negative regulation of insulin signaling, and is thus considered as an attractive therapeutic target for the treatment of diabetes. Bioassay-guided investigation of the methylethylketone extract of marine-derived fungus Penicillium sp. JF-55 cultures afforded a new PTP1B inhibitory styrylpyrone-type metabolite named penstyrylpyrone (1), and two known metabolites, anhydrofulvic acid (2) and citromycetin (3). Compounds 1 and 2 inhibited PTP1B activity in a dose-dependent manner, and kinetic analyses of PTP1B inhibition suggested that these compounds inhibited PTP1B activity in a competitive manner. In an effort to gain more biological potential of the isolated compounds, the anti-inflammatory effects of compounds 1-3 were also evaluated. Among the tested compounds, only compound 1 inhibited the production of NO and PGE2, due to the inhibition of the expression of iNOS and COX-2. Penstyrylpyrone (1) also reduced TNF-α and IL-1ß production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of penstyrylpyrone (1) on the pro-inflammatory mediators and NF-κB DNA binding activity were associated with the HO-1 expression. Therefore, these results suggest that penstyrylpyrone (1) suppresses PTP1B activity, as well as the production of pro-inflammatory mediators via NF-κB pathway, through expression of anti-inflammatory HO-1.