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

Phytochemistry

Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, College of Pharmacy, College of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian, 116044, People's Republic of China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China. Electronic address:

Published: January 2022

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 (6R)3,7-dimethyl-6,7-dihydroxy-2(Z)-octenoic acid displayed a significant agonistic effect against the farnesoid X receptor (FXR) with an EC value of 0.43 μM, 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).

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http://dx.doi.org/10.1016/j.phytochem.2021.112974DOI Listing

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