Zhiming Liu , Le Ba Vinh , Nguyen Quoc Tuan , Hwan Lee , Eunae Kim , Youn-Chul Kim , Jae Hak Sohn , Joung Han Yim , Ha-Jin Lee , Dong-Sung Lee , Hyuncheol Oh
{"title":"南极真菌Pseudogymnoascus sp.（菌株SF-7351）的巨大水螅及其对BV2和HT22细胞的神经保护作用。","authors":"Zhiming Liu , Le Ba Vinh , Nguyen Quoc Tuan , Hwan Lee , Eunae Kim , Youn-Chul Kim , Jae Hak Sohn , Joung Han Yim , Ha-Jin Lee , Dong-Sung Lee , Hyuncheol Oh","doi":"10.1016/j.cbi.2023.110718","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Strategies for reducing inflammation in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the </span>neuroprotective potential of fungal metabolites isolated from the Antarctic fungus </span><em>Pseudogymnoascus</em> sp. (strain SF-7351). The chemical investigation of the EtOAc extract of the fungal strain isolate revealed a novel naturally occurring <em>epi</em>-macrosphelide J (<strong>1</strong><span>), a novel secondary metabolite macrosphelide N (</span><strong>2</strong>), and three known compounds, namely macrosphelide A (<strong>3</strong>), macrosphelide B (<strong>4</strong>), and macrosphelide J (<strong>5</strong><span><span>). 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 </span>atomic orbital (GIAO) NMR chemical shift calculations, with the support of the advanced statistical method DP4+. Among the isolated metabolites, the absolute configuration of </span><em>epi</em>-macrosphelide J (<strong>1</strong><span>) 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 (</span><strong>4</strong><span>) 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 (</span><strong>4</strong>) 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 (<strong>4</strong>) is related to the interaction between Keap1 and p65. These results suggest that macrosphelide B (<strong>4</strong>), present in the fungus <em>Pseudogymnoascus</em> sp. (strain SF-7351), may serve as a candidate for the treatment of neurodegenerative diseases.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110718"},"PeriodicalIF":4.7000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Macrosphelides from Antarctic fungus Pseudogymnoascus sp. (strain SF-7351) and their neuroprotective effects on BV2 and HT22 cells\",\"authors\":\"Zhiming Liu , Le Ba Vinh , Nguyen Quoc Tuan , Hwan Lee , Eunae Kim , Youn-Chul Kim , Jae Hak Sohn , Joung Han Yim , Ha-Jin Lee , Dong-Sung Lee , Hyuncheol Oh\",\"doi\":\"10.1016/j.cbi.2023.110718\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>Strategies for reducing inflammation in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the </span>neuroprotective potential of fungal metabolites isolated from the Antarctic fungus </span><em>Pseudogymnoascus</em> sp. (strain SF-7351). The chemical investigation of the EtOAc extract of the fungal strain isolate revealed a novel naturally occurring <em>epi</em>-macrosphelide J (<strong>1</strong><span>), a novel secondary metabolite macrosphelide N (</span><strong>2</strong>), and three known compounds, namely macrosphelide A (<strong>3</strong>), macrosphelide B (<strong>4</strong>), and macrosphelide J (<strong>5</strong><span><span>). 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 </span>atomic orbital (GIAO) NMR chemical shift calculations, with the support of the advanced statistical method DP4+. Among the isolated metabolites, the absolute configuration of </span><em>epi</em>-macrosphelide J (<strong>1</strong><span>) 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 (</span><strong>4</strong><span>) 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 (</span><strong>4</strong>) 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 (<strong>4</strong>) is related to the interaction between Keap1 and p65. These results suggest that macrosphelide B (<strong>4</strong>), present in the fungus <em>Pseudogymnoascus</em> sp. 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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.
期刊介绍：
Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.
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