Metabolites isolated from the human intestinal fungus Penicillium oxalicum SL2 and their agonistic effects on PXR and FXR. (January 2022)

• Record Type: Journal Article
• Authors: Zhao, Wen-Yu; Luan, Zhi-Lin; Sun, Cheng-Peng; Zhang, Bao-Jing; Jin, Ling-Ling; Deng, Sa; Zhang, Hou-Li; Yu, Zhen-Long; Wang, Chao; Ma, Xiao-Chi
• Is Part Of: Phytochemistry. Volume 193(2022)
• Publication Date: 2022-01
• Subjects: Penicillium oxalicum SL2 -- Trichocomaceae -- Metabolites -- FXR -- PXR; Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2021.112974
• Languages: English
• ISSNs: 0031-9422

Abstract

Abstract: Intestinal commensal fungi are vital to human health, and their metabolites play a key role in the reciprocal relationship. In the present work, eighteen alkaloids and seven monoterpenoids were isolated from the fermentation of the human intestinal fungus Penicillium oxalicum SL2, including seven undescribed alkaloids (penicilloxalines A-G), three undescribed monoterpenoids (penicilloxalines H-J), and fifteen reported compounds. The structures of the isolated compounds were identified by HRESIMS, 1D and 2D NMR, electronic circular dichroism spectra and quantum chemical calculations. Some metabolites displayed moderate agonistic effects against the pregnane X receptor (PXR), whereas (6 R )3, 7-dimethyl-6, 7-dihydroxy-2( Z )-octenoic acid displayed a significant agonistic effect against the farnesoid X receptor (FXR) with an EC50 value of 0.43 μ M, which was verified by investigating FXR downstream target genes and proteins, such as small heterodimer partner 1 (SHP1), fibroblast growth factor (FGF), and bile salt export pump (BSEP). Graphical abstract: 25 metabolites were identified from the human intestinal fungus Penicillium oxalicum SL2. Image 1 Highlights: Twenty-five metabolites were obtained from gut fungus Penicillium oxalicum. Seven undescribed alkaloids (penicilloxalines A-G) were identified. Three undescribed monoterpenoids (penicilloxalines H-J) were identified. Some metabolites activated pregnane X receptor significantly. One metabolite displayed agonistic effect against FXR (EC50 0.43 μM).