Three new nonenes from culture broth of marine-derived fungus Albifimbria verrucaria and their cytotoxic and anti-viral activities.

Three new nonenes, verrucanonenes A‒C (1‒3), were isolated from culture broth of marine-derived fungus Albifimbria verrucaria. These compounds were isolated using silica gel column chromatography, reversed-phase medium pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined using a spectroscopic method. Cytotoxicities of these isolated compounds to A549, DU145, HCT116, and HT1080 cancer cell lines were assessed. Compounds 1‒3 exhibited cytotoxicities to DU145 cancer cell line, with IC50 values of 23.4, 28.6, and 20.1 µM, respectively. Compound 2 decreased H1N1-induced cytopathic effects on MDCK cells in a dose-dependent manner.

Three new phthalide derivatives from culture broth of Dentipellis fragilis and their cytotoxic activities.

Three new phthalide derivatives (1‒3) together with two known compounds, erinaceolactone B (4) and hericerin III (5), were isolated from the culture broth of Dentipellis fragilis. The chemical structures of 1‒5 were determined by analyses of their 1D-, 2D-NMR, and MS. The absolute configuration of 1 was determined by CD analysis. The isolated compounds were assessed for their cytotoxic activities against A549, DU145, HCT116, and HT1080 cancer cell lines. Compounds 1‒5 showed strong cytotoxic activities against DU145, with IC50 values ranging from 14.3 to 16.1 µM. Additionally, all compounds showed moderate or weak cytotoxic activities against all cell lines except for compounds 4 and 1 which showed no cytotoxic activities against A549 and HCT116 cancer cell lines, respectively. Against HT1080 cancer cell line, only compound 2 displayed moderate cytotoxic activity.

Anti-Inflammatory Effects of Alphitolic Acid Isolated from Agrimonia coreana Nakai Extracts Are Mediated via the Inhibition of ICRAC Activity in T Cells.

Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai-a naturally growing species in South Korea-and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases.

Formanilides from the culture broth of Perenniporia fraxinea.

A new formanilide dimer, fraxinin (1), and three known formanilides (2‒4) were isolated from the culture broth of Perenniporia fraxinea using silica gel and Sephadex LH-20 column chromatographies, medium-pressure liquid chromatography (MPLC), and preparative HPLC. The structures of these compounds were determined by spectroscopic methods, such as NMR and mass analysis, and by comparison of the spectra with previously reported data. The free radical scavenging activities of the isolated compounds were assessed using 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Compounds 1‒3 exhibited ABTS radical scavenging activity with IC50 values in the range of 57.2-250.2 µM. Compounds 2 and 4 marginally reduced disease incidence of powdery mildew with a control value of 42% at 1.0 mg ml-1 in cucumber leaf disk assay.

Pullusurfactins A‒C, new biosurfactants produced by Aureobasidium pullulans A11231-1-58 from Chrysanthemum boreale Makino.

Biosurfactants have found widespread use across multiple industrial fields, including medicine, food, cosmetics, detergents, pulp, and paper, as well as the degradation of oil and fat. The culture broth of Aureobasidium pullulans A11231-1-58 isolated from flowers of Chrysanthemum boreale Makino exhibited potent surfactant activity. Surfactant activity-guided fractionation led to the isolation of three new biosurfactants, pullusurfactins A‒C (1‒3). Their chemical structures were established through the use of spectroscopic techniques, predominantly 1D and 2D NMR, in conjunction with mass measurements. We evaluated the surface tension activities of isolated compounds. At 1.0 mg l-1, these compounds showed high degrees of surfactant activity (31.15 dyne/cm, 33.75 dyne/cm, and 33.83 dyne/cm, respectively).

Chemical constituents of the culture broth of Dentipellis fragilis and their anti-inflammatory activities.

Seven undescribed compounds, dentipellinones A‒D (1, 2, 5, and 6), dentipellinol (3), methoxyerinaceolactone B (4), and erinaceolactomer A (7), were isolated from the culture broth of Dentipellis fragilis. Chemical structures of these isolated compounds were determined by analyses of 1D and 2D-NMR and MS data in comparison with data reported in the literature. Absolute configurations of 1‒7 were also determined by Electronic Circular Dichroism calculations. The isolated compounds were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokines levels in LPS-stimulated RAW264.7 cells. Compounds 5 and 7 were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokine levels in LPS-stimulated RAW264.7 cells. They exhibited inhibitory effects on LPS-induced NO production in a dose-dependent manner, and significantly reduced the levels of inflammatory-related cytokines such as IL-1ß and IL-6. TNF-α was not involved in the anti-inflammatory effects of these compounds. Finally, compounds 5 and 7 showed significant anti-inflammatory effects.

Production of a New Biosurfactant by a New Yeast Species Isolated from Prunus mume Sieb. et Zucc.

Biosurfactants reduce surface and interfacial tension due to their amphiphilic properties and are an eco-friendly alternative for chemical surfactants. In this study, a new yeast strain JAF-11 that produces a biosurfactant was selected using drop collapse method, and the properties of the extracts were investigated. The nucleotide sequences of the strain were compared with closely related strains and identified based on the D1/D2 domain of the large subunit ribosomal DNA (LSU) and internal transcribed spacer (ITS) regions. Neodothiora populina CPC 39399T, the closest species with strain JAF-11, showed a sequence similarity of 97.75% for LSU and 94.27% for ITS, respectively. The result suggests that the strain JAF-11 represents a distinct species that cannot be assigned to any existing genus or species in the family Dothideaceae. Strain JAF-11 produced a biosurfactant reducing the surface tension of water from 72 mN/m to 34.5 mN/m on the sixth day of culture and the result of measuring the critical micelle concentration (CMC) by extracting the crude biosurfactant was found to be 24 mg/l. The molecular weight 502 of the purified biosurfactant was confirmed by measuring the fast atom bombardment mass spectrum. The chemical structure was analyzed by measuring 1H nuclear magnetic resonance (NMR), 13C NMR, and two-dimensional NMRs of the compound. The molecular formula was C26H46O9, and it was composed of one octanoyl group and two hexanoyl groups to myo-inositol moiety. The new biosurfactant is the first report of a compound produced by a new yeast strain, JAF-11.

Identification of Loliolide with Anti-Aging Properties from Scenedesmus deserticola JD052.

Herein, different extracts of Scenedesmus deserticola JD052, a green microalga, were evaluated in vitro as a potential anti-aging bioagent. Although post-treatment of microalgal culture with either UV irradiation or high light illumination did not lead to a substantial difference in the effectiveness of microalgal extracts as a potential anti-UV agent, the results indicated the presence of a highly potent compound in ethyl acetate extract with more than 20% increase in the cellular viability of normal human dermal fibroblasts (nHDFs) compared with the negative control amended with DMSO. The subsequent fractionation of the ethyl acetate extract led to two bioactive fractions with high anti-UV property; one of the fractions was further separated down to a single compound. While electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy analysis identified this single compound as loliolide, its identification has been rarely reported in microalgae previously, prompting thorough systematic investigations into this novel compound for the nascent microalgal industry.

A new antibiotic from the culture broth of Dentipellis fragilis.

During the search for natural antibiotics from fungal metabolites, a new cyathane diterpenoid, fragilicine A (1), and three known cyathane diterpenoids, erinacines I, A, and B (2-4) were isolated from the culture broth of Dentipellis fragilis. Chemical structures of 1-4 were determined by analyses of 1D- and 2D-NMR and MS data and by comparisons with data of those reported in the literature. These isolated compounds were assessed for their antimicrobial activities against Bacillus subtilis, B. atrophaeus, B. cereus, Listeria monocytogenes, Fusarium oxysporum, Diaporthe sp., and Rhizoctonia solani. These compounds showed weak antimicrobial activities.

p-Terphenyl glucosides from the culture broth of Phlebiopsis castanea.

A new p-terphenyl derivative, hydroxystrepantibin D (1), was isolated along with two known p-terphenyls (2 and 3) from the culture broth of Phlebiopsis castanea. These compounds were isolated using silica gel column chromatography, reversed-phase medium-pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined based on spectroscopic methods. These compounds exhibited free radical scavenging activities with IC50 values in the range from 22.2 to 158.4 µM against 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and in the range from 161.1 to 356.1 µM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.

Neodothiora pruni sp. nov., a Biosurfactant-Producing Ascomycetous Yeast Species Isolated from Flower of Prunus mume.

A yeast strain, designated as JAF-11T, was isolated from flower of Prunus mume Sieb. et Zucc. in Gwangyang, Republic of Korea. Phylogenetic analysis showed that strain JAF-11T was closely related to Neodothiora populina CPC 39399T with 2.07 % sequence divergence (12 nucleotide substitutions and three gaps in 581 nucleotides) in the D1/D2 domain of the large subunit (LSU) rRNA gene, and Rhizosphaera macrospora CBS 208.79T with 4.66 % sequence divergence (25 nucleotide substitutions and five gaps in 535 nucleotides) in the internal transcribed spacer (ITS) region. Further analysis based on the concatenated sequences of the D1/D2 domain of the LSU rRNA gene and the ITS region confirmed that strain JAF-11T was well-separated from Neodothiora populina CPC 39399T. In addition to the phylogenetic differences, strain JAF-11T was distinguished from its closest species, Neodothiora populina CPC 39399T and Rhizosphaera macrospora CBS 208.79T belonging to the family Dothioraceae by its phenotypic characteristics, such as assimilation of carbon sources. Hence, the name Neodothiora pruni sp. nov. is proposed with type strain JAF-11T (KACC 48808T; MB 850034).

Two Novel Biosurfactants Produced by Aureobasidium pullulans A11211-4-57 from a Fleabane, Erigeron annus (L.) pers.

Biosurfactants have been widely used in various industrial fields including medicine, food, cosmetics, detergent, pulp and paper, and oil and fat degradation. The culture broth of Aureobasidium pullulans A11211-4-57 using glucose as carbon source exhibited potent surfactant activity. The culture broth was separated by column chromatographies using ODS, silica gel, and Sephadex LH-20 resins, consecutively, to provide two biosurfactants. Based on mass and NMR measurements, their structures were determined as myo-inositol lipids and named pullusurfactans F and G. These compounds showed a high degree of activity, with 27.25 mN/m and 24.07 mN/m, respectively, at 1.0 mg l-1, which is useful for washing and cleaning agents.

Dihydroconiferyl Ferulate Isolated from Dendropanax morbiferus H.Lév. Suppresses Stemness of Breast Cancer Cells via Nuclear EGFR/c-Myc Signaling.

Breast cancer is the leading cause of global cancer incidence and breast cancer stem cells (BCSCs) have been identified as the target to overcome breast cancer in patients. In this study, we purified a BCSC inhibitor from Dendropanax morbiferus H.Lév. leaves through several open column and high-performance liquid chromatography via activity-based purification. The purified cancer stem cell (CSC) inhibitor was identified as dihydroconiferyl ferulate using nuclear magnetic resonance and mass spectrometry. Dihydroconiferyl ferulate inhibited the proliferation and mammosphere formation of breast cancer cells and reduced the population of CD44high/CD24low cells. Dihydroconiferyl ferulate also induced apoptosis, inhibited the growth of mammospheres and reduced the level of total and nuclear EGFR protein. It suppressed the EGFR levels, the interaction of Stat3 with EGFR, and c-Myc protein levels. Our findings show that dihydroconiferyl ferulate reduced the level of nuclear epidermal growth factor receptor (EGFR) and induced apoptosis of BCSCs through nEGFR/Stat3-dependent c-Myc deregulation. Dihydroconiferyl ferulate exhibits potential as an anti-CSC agent through nEGFR/Stat3/c-Myc signaling.

Isopanepoxydone inhibits oxidative damage in murine alveolar macrophages via NRF2 and NLRP3 inflammasome.

BACKGROUND: Respiratory diseases due to particulate matter are a serious health issue. We sought to investigate the efficacy of isopanepoxydone (ISO) isolated from the Panus rudis as a therapeutic against particulate matter-induced respiratory complications. MATERIALS AND METHODS: ISO was isolated from a culture broth of Panus rudis using solvent partition, silica gel, and column chromatography, and high-performance liquid chromatography. Its chemical structure was determined spectroscopically. Murine alveolar macrophages (MH-S) were treated with ISO to investigate the inhibition of nitric oxide (NO) while cytotoxicity was investigated via a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The expression of pro-inflammatory mediators, cytokines, and protein expression levels in the oxidative protective and inflammasome pathway were also investigated. Reactive oxygen species in MH-S cells were investigated using 2',7'-dichlorofluorescein diacetate while immunofluorescence was performed to investigate the expression of activated apoptosis-associated speck-like proteins (ASC) containing a caspase recruitment domain in MH-S cells. RESULTS: ISO effectively inhibited CFA-induced NO production with no cytotoxicity on MH-S cells and pro-inflammatory mediators and cytokines were also inhibited (except tumor necrosis factor α and interleukin-6). ISO enhanced the protein expression of nuclear factor erythroid 2-related factor 2, while suppressing proteins in the inflammasome pathway, but did not suppress the expression of nuclear factor-kappa B. ISO also reduced detectable ROS other than preventing the activation of ASC. CONCLUSION: Pathways of action of ISO in MH-S cells that prevent oxidative damage and suppress the expression of proteins in the inflammasome pathway were investigated. ISO may be developed as a treatment for respiratory inflammation.

Anti-Inflammatory Effects of (9Z,11E)-13-Oxooctadeca-9,11-dienoic Acid (13-KODE) Derived from Salicornia herbacea L. on Lipopolysaccharide-Stimulated Murine Macrophage via NF-kB and MAPK Inhibition and Nrf2/HO-1 Signaling Activation.

Glasswort (Salicornia herbacea L.) is a halophyte that exhibits antioxidant and antidiabetic effects. Only a few studies have been conducted on its antioxidant effects. Here, we isolated an antioxidant using an activity-based purification method, and the resulting compound was identified as (9Z,11E)-13-Oxooctadeca-9,11-dienoic acid (13-KODE). We investigated its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide-stimulated RAW 264.7 macrophage cells. We studied the anti-inflammatory effects of 13-KODE derived from S. herbacea L on RAW 264.7 macrophages. 13-KODE inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production by suppressing inducible NO synthase and suppressed LPS-induced tumor necrosis factor and interleukin-1ß expression in RAW 264.7 macrophages. LPS-mediated nuclear localization of NF-κB and mitogen-activated protein kinase activation were inhibited by 13-KODE. 13-KODE significantly reduced LPS-induced production of reactive oxygen species and increased the expression of nuclear factor erythroid-2 like 2 (Nfe2I2) and heme oxygenase 1. Overall, our results indicate that 13-KODE may have potential for treating inflammation.

Daldinans D‒G, new isoindolinone antioxidants isolated from the ascomycete Daldinia concentrica.

Four new isoindolinone derivatives, daldinans D‒G (3‒6), together with two known compounds, daldinans A and B (1 and 2), were isolated from the stroma of the ascomycete Daldinia concentrica. Chemical structures of the isolated compounds were determined by spectroscopic methods. All of these compounds exhibited antioxidant activities with IC50 values of 3.21 to 39.67 µM in the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay.

New antioxidants from the culture broth of Coprinopsis echinospora.

During the search for natural antioxidants from fungal metabolites, three new sesquiterpene derivatives (1-3) have been isolated from the culture broth of Coprinopsis echinospora. Their structures were determined by spectroscopic methods, mainly NMR and mass spectrometric analyses. These compounds exhibited antioxidant activity with IC50 values in the range of 34.4-144.5 µM in the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assay.

Inhibitory Effect of Phellinus baumii Extract on CFA-Induced Inflammation in MH-S Cells through Nuclear Factor-κB and Mitogen-Activated Protein Kinase Signaling Pathways.

Phellinus baumii is a mushroom utilized as a traditional medicine for a wide range of human ailments, including diabetes, hypertension, hypercholesterolemia, and cancer, in Asia. The purpose of this study was to find out whether Phellinus baumii extract (PBE) could reduce inflammation caused by coal fly ash (CFA) in alveolar macrophages (MH-S). The anti-inflammatory effect of PBE was evaluated by measuring the nitric oxide (NO) concentration after the onset of CFA-stimulated inflammation in MH-S cells. Polymerase chain reaction (PCR) was used to examine inflammatory gene expression. Western blotting and immunofluorescence (IF) studies were used to investigate the inflammatory mechanism in MH-S cells. According to our results, the PBE suppressed CFA-induced NO generation in the MH-S cells dose-dependently. Furthermore, PBE inhibited the proinflammatory mediators and cytokines generated by exposure to CFA, including cyclooxygenase 2 (COX-2) and inducible NO synthase (iNOS), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α). Real-time PCR was also used to determine the inhibiting effect of the PBE on proinflammatory factors such as COX-2, iNOS, IL-1ß, IL-6, and TNF-α. Moreover, Western blot was used to assess the effects of the PBE on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in the CFA-stimulated MH-S cells. The suppressive effect of the PBE on phosphorylated (p)-NF-κB translocation was also investigated using IF analysis. This study showed that the PBE suppressed the CFA-induced inflammation in the MH-S cells by suppressing the NF-κB and MAPK signaling pathways, which suggests its potential usefulness in reducing lung inflammation.

Consoramides A-C, New Zwitterionic Alkaloids from the Fungus Irpex consors.

In our ongoing search for new secondary metabolites from fungi, a basidiomycete fungus Irpex consors was selected for mycochemical investigation, and three new zwitterionic alkaloids (1-3) and five known compounds (4-8) were isolated from the culture broth (16 l) of I. consors. The culture filtrate was fractionated by a series of column chromatography including Diaion HP-20, silica gel, and Sephadex LH-20, Sep-Pak C18 cartridge, medium pressure liquid chromatography (MPLC), and high pressure liquid chromatography (HPLC) to yield eight compounds (1-8). The structures of the isolated compounds were elucidated by the interpretation of nuclear magnetic resonance (NMR) spectra and high-resolution mass spectrometry (HR-MS). Their antioxidant and antibacterial activities were examined. The zwitterionic structures of three new sesquiterpene alkaloids (1-3) were determined together with five known compounds identified as stereumamide E (4), stereumamide G (5), stereumamide H (6), stereumamide D (7), and sterostrein H (8). This is the first report of the zwitterionic alkaloids in the culture broth of I. consors. Three new zwitterionic alkaloids were named as consoramides A-C (1-3).