Biotransformation of Silymarin Flavonolignans by Human Fecal Microbiota.

Kateřina Valentová,Lucie Petrásková,Kristýna Káňová,Jaroslav Havlík,Vladimír Křen,Jitka Ulrichová,Barbora Papoušková,José Diógenes Jaimes,Pavel Kosina

doi:10.3390/metabo10010029

Abstract

Flavonolignans occur typically in Silybum marianum (milk thistle) fruit extract, silymarin, which contains silybin, isosilybin, silychristin, silydianin, and their 2,3-dehydroderivatives, together with other minor flavonoids and a polymeric phenolic fraction. Biotransformation of individual silymarin components by human microbiota was studied ex vivo, using batch incubations inoculated by fecal slurry. Samples at selected time points were analyzed by ultrahigh-performance liquid chromatography equipped with mass spectrometry. The initial experiment using a concentration of 200 mg/L showed that flavonolignans are resistant to the metabolic action of intestinal microbiota. At the lower concentration of 10 mg/L, biotransformation of flavonolignans was much slower than that of taxifolin, which was completely degraded after 16 h. While silybin, isosilybin, and 2,3-dehydrosilybin underwent mostly demethylation, silychristin was predominantly reduced. Silydianin, 2,3-dehydrosilychristin and 2,3-dehydrosilydianin were reduced, as well, and decarbonylation and cysteine conjugation proceeded. No low-molecular-weight phenolic metabolites were detected for any of the compounds tested. Strong inter-individual differences in the biotransformation profile were observed among the four fecal-material donors. In conclusion, the flavonolignans, especially at higher (pharmacological) doses, are relatively resistant to biotransformation by gut microbiota, which, however, depends strongly on the individual structures of these isomeric compounds, but also on the stool donor.

Highlights

Flavonolignans are plant secondary metabolites belonging to the group of polyphenols formed by the coupling of a flavonoid with a phenylpropanoid; they occur typically in Silybum marianum (L.) Gaertn fruits
The crude extract denoted silymarin is used in a plethora of nutraceutical preparations and drugs, mainly for its hepatoprotective action [1]; it exerts a number of other pharmacological activities, it exerts a number of other pharmacological activities, such as cardioprotective [2], such as cardioprotective [2], hypocholesterolemic [3], and antidiabetic [4,5] activities
Major constituents of silymarin are as constituents of silymarin are as follows: flavonolignans silybin A and B; isosilybin A and B; follows: flavonolignans silybin A and B; isosilybin A and B; silychristin A; silydianin; the flavanol silychristin A; silydianin; the flavanol (+)-taxifolin [7]; and ca 30% of a polyphenolic fraction

Summary

Introduction

Flavonolignans are plant secondary metabolites belonging to the group of polyphenols formed by the coupling of a flavonoid with a phenylpropanoid (lignan); they occur typically in Silybum marianum (L.) Gaertn (milk thistle, Asteraceae) fruits (cypselae). Flavonolignans are plant secondary metabolites belonging to the group of polyphenols formed by the coupling of a flavonoid with a phenylpropanoid (lignan); they occur typically in Silybum Metabolites. The crude extract denoted silymarin is used in a plethora of nutraceutical preparations and drugs, mainly for its hepatoprotective action [1]; it exerts a number of other pharmacological activities, it exerts a number of other pharmacological activities, such as cardioprotective [2], such as cardioprotective [2], hypocholesterolemic [3], and antidiabetic [4,5] activities. Studies have shown its great potential in the treatment of have shown its great potential in the treatment of Alzheimer’s disease [11], as well as in cancer

Objectives

Methods

Results

Conclusion