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

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

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

Chem Biol Interact. 2023 Nov 1:385:110718. doi: 10.1016/j.cbi.2023.110718. Epub 2023 Sep 28.

Authors

Zhiming Liu¹, Le Ba Vinh², Nguyen Quoc Tuan³, Hwan Lee⁴, Eunae Kim⁵, Youn-Chul Kim⁶, Jae Hak Sohn⁷, Joung Han Yim⁸, Ha-Jin Lee⁹, Dong-Sung Lee¹⁰, Hyuncheol Oh¹¹

Affiliations

¹ College of Pharmacy, Chosun University, Dong-gu, Gwangju, 61452, South Korea. Electronic address: lzmqust@126.com.
² Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, 54538, South Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, 54538, South Korea. Electronic address: vinhrooney@gmail.com.
³ Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, 54538, South Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, 54538, South Korea. Electronic address: quoctuan301281@gmail.com.
⁴ College of Pharmacy, Chosun University, Dong-gu, Gwangju, 61452, South Korea. Electronic address: ghksdldi123@hanmail.net.
⁵ College of Pharmacy, Chosun University, Dong-gu, Gwangju, 61452, South Korea. Electronic address: eunaekim@chosun.ac.kr.
⁶ Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, 54538, South Korea. Electronic address: yckim@wku.ac.kr.
⁷ College of Medical and Life Sciences, Silla University, Busan, 46958, South Korea. Electronic address: jhsohn@silla.ac.kr.
⁸ Division of Polar Life Sciences, Korea Polar Research Institute, Incheon, 21990, South Korea. Electronic address: jhyim@kopri.re.kr.
⁹ Division of Chemistry and Bio-Environmental Sciences, Seoul Women's University, Seoul, 01797, South Korea. Electronic address: hajinlee@swu.ac.kr.
¹⁰ College of Pharmacy, Chosun University, Dong-gu, Gwangju, 61452, South Korea. Electronic address: dslee2771@chosun.ac.kr.
¹¹ Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, 54538, South Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, 54538, South Korea. Electronic address: hoh@wku.ac.kr.

PMID: 37777167
DOI: 10.1016/j.cbi.2023.110718

Abstract

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.

Keywords: Antarctic fungi; Macrosphelides; Molecular docking; NF-κB; Neuroprotection; Nrf2.