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.

Macrosphelides from Antarctic fungus Pseudogymnoascus sp. (strain SF-7351) and their neuroprotective effects on BV2 and HT22 cells.

Strategies for reducing inflammation in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the neuroprotective potential of fungal metabolites isolated from the Antarctic fungus Pseudogymnoascus sp. (strain SF-7351). The chemical investigation of the EtOAc extract of the fungal strain isolate revealed a novel naturally occurring epi-macrosphelide J (1), a novel secondary metabolite macrosphelide N (2), and three known compounds, namely macrosphelide A (3), macrosphelide B (4), and macrosphelide J (5). Their structures were established unambiguously using spectroscopic methods, such as one-dimensional and two-dimensional nuclear magnetic resonance (1D and 2D-NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and gauge-including atomic orbital (GIAO) NMR chemical shift calculations, with the support of the advanced statistical method DP4+. Among the isolated metabolites, the absolute configuration of epi-macrosphelide J (1) was further confirmed using single-crystal X-ray diffraction analysis. The neuroprotective effects of the isolated metabolites were evaluated in lipopolysaccharide (LPS)-induced BV2 and glutamate-stimulated HT22 cells. Only macrosphelide B (4) displayed substantial protective effects in both BV2 and HT22 cells. Molecular mechanisms underlying this activity were investigated using western blotting and molecular docking studies. Macrosphelide B (4) inhibited the inflammatory response by reducing the nuclear translocation of NF-κB (p65) in LPS-induced BV2 cells and induced the Nrf2/HO-1 signaling pathway in both BV2 and HT22 cells. The neuroprotective effect of macrosphelide B (4) is related to the interaction between Keap1 and p65. These results suggest that macrosphelide B (4), present in the fungus Pseudogymnoascus sp. (strain SF-7351), may serve as a candidate for the treatment of neurodegenerative diseases.

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.

The Effect of Combined Superheated Steam Roasting and Smoking on the Quality Characteristic of Alaska Pollack (Gadus chalcogrammus) Roe.

Alaska pollack roe (APR) is a protein source that is usually salted and fermented, containing a high salt content. Using a combination of superheated steam roasting and smoking, we developed a new low-salt ready-to-eat APR variant, whose quality characteristics we analyzed. The optimal conditions for roasting (216 °C for 4 min) and smoking (64 °C for 14 min) were obtained from sensorial attributes using response surface methodology. Under the optimal conditions, smoke-roasted APR had an overall acceptance (OA) score of 8.89. The combination of roasting and smoking significantly increased volatile basic nitrogen (VBN, 18.6%) and decreased the total bacterial count (TBC, 38.6%), while thiobarbituric acid reactive substances (TBARS) were not affected. Smoke-roasting APR also increased its nutritional content to 30% protein with 44% essential amino acids, and more than 40% DHA and EPA in 4.3% fat. During 30 days of storage, the OA, VBN, TBARS, and TBC values significantly changed with time and storage temperature (p < 0.05). The shelf life of the product was estimated to be 24 d. In conclusion, the combination of roasting and smoking APR could improve product quality and may be an alternative to diversify processed APR.

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.

Hizikia fusiformis: Pharmacological and Nutritional Properties.

The brown seaweed Hizikia fusiformis (syn. Sargassum fusiforme), commonly known as "Hijiki", has been utilized in traditional cuisine and medicine in East Asian countries for several centuries. H. fusiformis has attracted much attention owing to its rich nutritional and pharmacological properties. However, there has been no comprehensive review of the nutritional and pharmacological properties of H. fusiformis. The aim of this systematic review was to provide detailed information from the published literature on the nutritional and pharmacological properties of H. fusiformis. A comprehensive online search of the literature was conducted by accessing databases, such as PubMed, SpringerLink, ScienceDirect, and Google Scholar, for published studies on the nutritional and pharmacological properties of H. fusiformis between 2010 and 2021. A total of 916 articles were screened from all the databases using the preferred reporting items for systematic reviews and meta-analyses method. Screening based on the setdown criteria resulted in 59 articles, which were used for this review. In this review, we found that there has been an increase in the number of publications on the pharmacological and nutritional properties of H. fusiformis over the last 10 years. In the last 10 years, studies have focused on the proximate, mineral, polysaccharide, and bioactive compound composition, and pharmacological properties, such as antioxidant, anticancer, antitumor, anti-inflammatory, photoprotective, neuroprotective, antidiabetic, immunomodulatory, osteoprotective, and gastroprotective properties of H. fusiformis extracts. Overall, further studies and strategies are required to develop H. fusiformis as a promising resource for the nutrition and pharmacological industries.

Effects of Vacuum Frying on the Preparation of Ready-to-Heat Batter-Fried and Sauced Chub Mackerel (Scomber japonicus).

Chub mackerel (CM) is a commercial fish in Korea, owing to its availability and nutritional values. This study aimed to develop a ready-to-heat (RTH) Korean preparation of CM, known as Godeungo gangjeong. We utilized vacuum frying technology to fry the CM and evaluated its quality. Conventional frying with a deep fryer was performed in parallel to assess the superiority of the vacuum fryer. We optimized the frying conditions of vacuum frying (VBF) and deep frying (DBF) using response surface methodology. At optimum conditions of 95 °C for 7 min 42 s, VBF produced better sensory, chemical, and microbial properties than DBF at 190 °C for 5 min 30 s. The nutritional values, including amino acid and fatty acid contents, were investigated and found to be higher in VBF than in DBF. Sensory properties also showed better scores on VBF than DBF, especially in appearance, aroma, taste, and overall acceptability. The VBF produced lower volatile basic nitrogen (VBN), thiobarbituric acid reactive substances (TBARS), and total bacterial count (TBC) than DBF. The findings confirmed that vacuum frying is a better option to produce RTH Godeungo gangjeong, since it provides less oxidation and maintains the product quality. Using the Arrhenius approach, the product was concluded to preserve both quality and safety for 9 months of storage at -18 °C.

Development of a Home Meal Replacement Product Containing Braised Mackerel (Scomber japonicus) with Radish (Raphanus sativus).

The coronavirus disease pandemic has contributed to increasing convenience in food preferences. Home meal replacement (HMR) products are ready-to-eat, -cook, or -heat foods, providing convenience for consumers. We developed a HMR product containing mackerel as a protein- and lipid-rich source using various food-processing technologies to maintain its nutritional content and prolong shelf life. The HMR product contained mackerel, radish, and sauce in a ratio of 5:1:4. Raw frozen mackerels were thawed by using a high-frequency defroster before being braised using a superheated steam roaster. Response surface methodology was employed to obtain the optimal heating conditions of 181 °C for 9 min. The final test HMR product was packed in a polypropylene plastic bowl prior to freezing at -35 °C for 1 h using a quick freezing system. The HMR product developed using these technologies exhibited stable microbiological and chemical properties for 90 days of storage. Sensory scores gradually decreased with increasing storage temperature and time. Protein content in the HMR product was 13%, 40% of which comprised essential amino acids; lipid content was 13.4%, 18% of which was composed of docosahexaenoic acid. The HMR product can preserve its quality and is considered safe for consumption for up to 40 months of storage at -18 °C.

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.

Effects of Phlorotannins on Organisms: Focus on the Safety, Toxicity, and Availability of Phlorotannins.

Phlorotannins are polyphenolic compounds produced via polymerization of phloroglucinol, and these compounds have varying molecular weights (up to 650 kDa). Brown seaweeds are rich in phlorotannins compounds possessing various biological activities, including algicidal, antioxidant, anti-inflammatory, antidiabetic, and anticancer activities. Many review papers on the chemical characterization and quantification of phlorotannins and their functionality have been published to date. However, although studies on the safety and toxicity of these phlorotannins have been conducted, there have been no articles reviewing this topic. In this review, the safety and toxicity of phlorotannins in different organisms are discussed. Online databases (Science Direct, PubMed, MEDLINE, and Web of Science) were searched, yielding 106 results. Following removal of duplicates and application of the exclusion criteria, 34 articles were reviewed. Phlorotannins from brown seaweeds showed low toxicity in cell lines, invertebrates, microalgae, seaweeds, plants, animals (fish, mice, rats, and dogs), and humans. However, the safety and toxicity of phlorotannins in aquaculture fish, livestock, and companion animals are limited. Further studies in these organisms are necessary to carry out a systematic analysis of the safety and toxicity of phlorotannins and to further identify the potential of phlorotannins as functional foods, feeds, and pharmaceuticals.

Improvement of Sensorial, Physicochemical, Microbiological, Nutritional and Fatty Acid Attributes and Shelf Life Extension of Hot Smoked Half-Dried Pacific Saury (Cololabis saira).

Half-dried Pacific saury of Cololabis saira (HDPS) is a fatty fish of high nutritional value with remarkable consumer interest in the Asia Pacific region, however, it undergoes various deteriorative changes associated with browning, bacterial contamination, oxidation, and decreased sensory attributes while marketed in various processed forms. To withstand these complications, research aimed to investigate the hot smoking technology to improve physicochemical, microbiological, and sensory attributes of HDPS with prolonged shelf life in storage conditions. The HDPS fillets were processed with hot smoking (70 °C) using various sawdust materials of Apple, Chestnut, Oak, Cherry, and Walnut, wherein the smoke time was set at different time points of 0, 20, 25, and 30 min. The results indicated that 25 min of smoking time with the selective Oak sawdust showed better sensorial characteristics, physicochemical properties, and microbiological qualities. Moreover, HDPS possessed higher nutritional value and valuable functional fatty acids, particularly docosahexaenoic acid and eicosapentaenoic acid, having a storage ability of up to 30 days at 10 °C. The processed HDPS offered a reduced level of Trimethylamine-N-oxide and Benzo[a]pyrene contents, indicating the acceptable and safe for human consumption. Therefore, HDPS with hot smoking could likely be a promising technique for preserving the premium quality of the product by providing desired characteristics of health and nutrition to end-point consumers.

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.

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.

Identification and characterization of novel antioxidant peptides from mackerel (Scomber japonicus) muscle protein hydrolysates.

Antioxidant peptides are commonly used as functional ingredient in the pharmaceutical industries. Here, we characterized the antioxidant peptides from mackerel muscle protein hydrolysates (MPHs). MPHs showing higher bioactivities were separated into seven groups by FPLC. MPH-3 which exhibited significantly higher (p < 0.05) DPPH scavenging activity (32.12 ± 3.01%) was fractionated using RP-HPLC to obtain purified fractions A and B, which were further subjected to MALDI-TOF/TOF-MS for mass fingerprinting. Fraction A exhibited the highest (p < 0.05) DPPH scavenging activity (34.11 ± 1.52%), and it contained 21 peptides characterized by LC-MS/MS-. Ten peptides were synthesized, and their antioxidant activities were evaluated; one of the peptides, ALSTWTLQLGSTSFSASPM, showed the highest (p < 0.05) DPPH scavenging activity (36.34 ± 4.64%) and another peptide, LGTLLFIAIPI, exhibited the highest (p < 0.05) SOD-like activity (28.94 ± 4.19%). The results of this study indicate that MPHs could serve as a suitable source of antioxidant peptides.

Protein tyrosine phosphatase 1B inhibitors from a marine-derived fungal strain aspergillus sp. SF-5929.

In the course of our continuing investigation of bioactive secondary metabolites from marine-derived fungal strains, a racemate of a novel diphenolic derivative named (±)-tylopilusin D (1) along with ten previously known secondary metabolites (2-11) were isolated from a marine-derived fungal strain Aspergillus sp. SF-5929. Their structures were elucidated mainly by analysis of NMR and MS data. In addition, the inhibitory effects of the isolated compounds against protein tyrosine phosphatase 1B (PTP1B) activity were evaluated, and compounds 1, 2, and 5-7 inhibited PTP1B activity with IC50 values ranging from 3.3 to 8.1 µM. Kinetics studies suggested that compounds 1, 2, and 5 had noncompetitive inhibitory effects against PTP1B.

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.

New preaustinoids from a marine-derived fungal strain Penicillium sp. SF-5497 and their inhibitory effects against PTP1B activity.

Chemical investigation of the marine-derived fungal isolate Penicillium sp. SF-5497 resulted in the isolation of two new preaustinoid-related meroterpenoids, named preaustinoid A6 (1) and preaustinoid A7 (2), along with three known metabolites (3-5). Their structures were elucidated by extensive spectroscopic analyses, such as 1D and 2D NMR and MS data. Among these, compounds 1 and 3 inhibited PTP1B activity in a dose-dependent manner, with IC50 values of 17.6 and 58.4 µM, respectively. Furthermore, kinetic analyses indicated that compound 1 inhibited PTP1B in a noncompetitive manner, with the Ki value of 17.0 µM.