Neuroprotective Secondary Metabolite Produced by an Endophytic Fungus, Neosartorya fischeri JS0553, Isolated from Glehnia littoralis

Abstract

Roots of Glehnia littoralis have been used to heal stroke as a traditional medicine. Even though many studies on this plant have been conducted, the secondary metabolites produced by its endophytes and their bioactivities have not been investigated thus far. Therefore, a new meroditerpenoid named sartorypyrone E (1) and eight known compounds (2−9) were isolated from extracts of cultured Neosartorya fischeri JS0553, an endophyte of G. littoralis. The isolated metabolites were identified using spectroscopic methods and chemical reaction, based on a comparison to literature data. Relative and absolute stereochemistries of compound 1 were also elucidated. To identify the protective effects of isolated compounds (1−9) in HT22 cells against glutamate-induced cytotoxicity, we assessed inhibition of cell death, intracellular reactive oxygen species (ROS) accumulation, and calcium ion (Ca 2+ ) influx. Among the isolates, compound 8, identified as fischerin, showed significant neuroprotective activity on glutamate-mediated HT22 cell death through inhibition of ROS, Ca 2+ influx, and phosphorylation of mitogen-activated protein kinase, including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38. The results suggested that the metabolites produced by the endophyte N. fischeri JS0553 might be related to the neuroprotective activity of its host plant, G. littoralis.

Classification of Aspergillus, Penicillium, Talaromyces and related genera (Eurotiales): An overview of families, genera, subgenera, sections, series and species

“…Extrolites in sect. Fumigati (with its eight families): ardeemins, asnovolins, aszonalenins, avenaciolides, cephalimycins, chaetominines, chevalones, chrysogines, clavatols, cycloechinulins, cyclopiazonic acids, cytochalasins, expansolides, fiscalins, fischerins, fumagillins,fumicyclins, fumigaclavines, fumigatins, fumigatonins, fumiquinazolines, fumitremorgins, gangicins, glabramycins, gliotoxins, helvolic acids, lentulins, neosartorins, novoamaauromins, novobenzomalvins, pseurotins, pyripyropenes, sartorypyrones, sphingofungins terreins trypacidins, tryprostatins, tryptoquivalines, viridicatumtoxins, viriditoxins, wortmannins and several more (see above) ( Hong et al., 2005 , Larsen et al., 2007 , Samson et al., 2007a , Hong et al., 2008 , Hubka et al., 2013b , Hubka et al., 2017 , Hubka et al., 2018a , Frisvad and Larsen, 2015 , Tamiya et al., 2015 , Bessa et al., 2016 , May Zin et al., 2016 , Rajachan et al., 2016 , Yu et al., 2016 , Bang et al., 2019 , Xu et al., 2019a , Yu et al., 2019 ). Among these, the aszonalenin biosynthetic family (BF) is shared by six species, the pyrones (aszonapyrone, chavalones, sartorypyrones) are shared by five species, the helvolic acid biosynthetic family is shared by five species, the pyripyropene BF is shared by four species, the gliotoxin BF is shared by four species, the fumigatin BF is shared by 4 species and the tryptoquivaline BF is shared by four species.…”

Bioactive Compounds from Terrestrial and Marine-Derived Fungi of the Genus Neosartorya †

“…Compound 8 was isolated from a culture extract of: N. pseudofischeri IFM 52672, which was cultured in moist rice [ 24 ]; N. ficheri KUFC6344, isolated from coastal forest soil at Samaesarn island, Chonburi Province, Thailand, and cultured in a cooked rice solid medium [ 25 ]; N. fischeri CGMCC3.5378, obtained from the Chinese Academy of Science, and cultured in a solid medium containing moist corn germ [ 26 ]; N. fischeri JS0553, an endophytic fungus isolated from the plant Glehnia littoralis (family Apiaceae), which was collected in a swamp area of Suncheon, South Korea, and cultured in a solid rice medium [ 27 ]; N. tatenoi KKU-2NK23, collected from forest soil in Khon Kaen province, Thailand, and cultured in a liquid medium containing potato dextrose broth [ 28 ]; the marine-derived N. takakii KUFC 7898, isolated from the alga Amphiroa sp., which was collected in Samaesarn Island in the Gulf of Thailand and cultured in a cooked rice solid medium [ 29 ], the marine-derived N. glabra , isolated from a marine sponge Mycale sp., which was collected from the coral reef of Samaesarn Island, in the Gulf of Thailand, and cultured in a cooked rice solid medium [ 23 ]; and the marine sponge-associated N. fenelliae KUFA 0811, isolated from the marine sponge Clathria reinwardtii, which was collected from Samaesarn Island in the Gulf of Thailand and cultured in a cooked rice solid medium [ 30 ]. Compound 9a was reported only from N. ficheri KUFC6344 [ 25 ], N. fischeri CGMCC3.5378 [ 26 ], an endophytic fungus, N. fischeri JS0553 [ 27 ], and N. fischeri TJ 403-CA8 [ 20 ], whereas the unreported 6-hydroxyacetylaszonalenin ( 9b ) ( Figure 2 ) was also isolated from a culture extract of the insect-derived N. fischeri TJ403-CA8 [ 20 ]. The indole 6-Hydroxyaszonalenin ( 10 ) ( Figure 2 ) was also isolated from a culture extract of N. fischeri CGMCC3.5378 [ 26 ] and the insect-derived N. fischeri TJ 403-CA8 [ 20 ], whereas 1-formyl-5-hydroxyaszonalenin ( 11 ) ( Figure 2 ) was obtained from a culture extract of N. fischeri KUFC 6344 [ 25 ].…”

“…Compounds 18 – 20 were also isolated from the insect-derived N. fischeri TJ403-CA8 [ 20 ], while 12β-hydroxyverruculagen TR-2 ( 23 ) ( Figure 3 ) was isolated from a culture extract of N. fischeri NRRL 181, purchased from DSMZ (DE-Braunschweig), and was cultured in potato dextrose agar medium [ 33 ]. Compound 20 was also isolated, together with fumitremorgin B ( 24 ) ( Figure 3 ), from the endophytic fungus, N. fischeri JS0553 [ 27 ]. Compound 24 was also isolated from N. fischeri var.…”

“…Fumitremorgin A ( 26 ) ( Figure 4 ), a hexacyclic 1,4-diketopiperazine-containing prenylated indole with a peroxide-containing eight-membered ring formed by two prenyl groups, was reported from the endophytic fungus N. fischeri JS0553 [ 27 ], N. fischeri NRRL 18 [ 33 ], and N. fischeri var. fischeri CBM-FA-0156 [ 34 ].…”

Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study

“…An endophytic fungus, Neosartorya fifischeri JS0553, was isolated from G. littoralis plant. From the fungus, a new meroditerpenoid named sartorypyrone E 77 (Figure 3) was isolated [34]. Two new oxoindolo diterpene epimers, anthcolorin G 78 (Figure 3) and anthcolorin H 79 (Figure 3), isolated for the first time from a natural source, were isolated from the solid rice culture of the endophytic fungus Aspergillus versicolor [35].…”