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In vitro hepatotoxicity of Petasites hybridus extract (Ze 339) depends on the concentration, the cytochrome activity of the cell system, and the species used
Author(s) -
Forsch Kristina,
Schöning Verena,
Assmann Greta Marie,
Moser Christin,
Siewert Beate,
Butterweck Veronika,
Drewe Jürgen
Publication year - 2020
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6516
Subject(s) - glutathione , biochemistry , cytotoxicity , cytochrome p450 , chemistry , in vitro , cytochrome , cytochrome c , cell culture , liver cell , pharmacology , enzyme , biology , mitochondrion , medicine , genetics
Ze 339, a CO 2 extract prepared from the leaves of Petasites hybridus, possesses antispasmodic and anti‐inflammatory effects and is proven to be effective in the treatment of allergic rhinitis. To study possible hepatotoxic effects of Ze 339, its main constituents and metabolites, a series of in vitro investigations were performed. Furthermore, different reconstituted fractions of extract (petasins and fatty acid fraction) were examined in three in vitro test systems using hepatocytes: Two human cell lines, with lower and higher activity of cytochrome P450 enzymes (HepG2, HepaRG) as well as a rodent cell line with high cytochrome P450 activity (H‐4‐II‐E), were used. Metabolic activity, assessed by the WST‐1 assay, was chosen as indicator of cytotoxicity. To assess potential bioactivation of Ze 339 compounds, metabolic experiments using S9 fractions from rats, dogs, and humans and isolated cytochromes (human/rat) were performed, and the formation of reactive metabolites was assessed by measuring cellular concentrations of glutathione and glutathione disulphide. Our data revealed that the cytotoxicity of Ze 339, its single constituents, and main metabolites depends on the concentration, the cytochrome activity of the cell system, and the species used.