Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma
The flavonolignan silybin (isolated from the fruits of the milk thistle, Silybum marianum), is a mixture of two diastereoisomers and has anticancer, chemoprotective, hepatoprotective and dermatoprotective properties. This compound is largely used in various functional foods, nutraceutics and food su...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-04-01
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| Series: | Journal of Functional Foods |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464615000936 |
| _version_ | 1818384290702950400 |
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| author | Petr Marhol Petr Bednář Petra Kolářová Rostislav Večeřa Jitka Ulrichová Eva Tesařová Eva Vavříková Marek Kuzma Vladimír Křen |
| author_facet | Petr Marhol Petr Bednář Petra Kolářová Rostislav Večeřa Jitka Ulrichová Eva Tesařová Eva Vavříková Marek Kuzma Vladimír Křen |
| author_sort | Petr Marhol |
| collection | DOAJ |
| description | The flavonolignan silybin (isolated from the fruits of the milk thistle, Silybum marianum), is a mixture of two diastereoisomers and has anticancer, chemoprotective, hepatoprotective and dermatoprotective properties. This compound is largely used in various functional foods, nutraceutics and food supplements. The pharmacokinetic profiles of optically pure silybins (silybin A and silybin B) were monitored in rat plasma after the intragastric administration (200 mg⋅kg−1 of body weight) of each diastereoisomer. Free (unconjugated) and total (free + conjugated) silybins were monitored for 6 hours by HPLC-PDA. The metabolic profiles of each silybin diastereoisomer were completely different. Our results clearly demonstrate that silybin B (Cmax = 14.50 µg⋅mL−1, Tmax = 2.6 hours, T1/2 = 2.9 hours; total silybin B) was absorbed faster and in a substantially higher amount than silybin A (Cmax = 1.05 µg⋅mL−1, Tmax = 3.9 hours, T1/2 = 2.2 hours; total silybin A). The oral bioavailability of silybin B was estimated to be 0.3%. The AUC 0→6 h (area under the curve) value of total silybin B was 20-fold higher than that of silybin A. SPE-UPLC-MS/MS (solid phase extraction-ultra performance liquid chromatography) was used to identify glucuronides and sulfates (in several isomeric forms) as dominant metabolites of silybin B in rat plasma. Silybin B-7-O-β-glucuronide was the major plasma metabolite of silybin B. |
| first_indexed | 2024-12-14T03:19:55Z |
| format | Article |
| id | doaj.art-7c0855f118aa411bb18b2b243b913bef |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-12-14T03:19:55Z |
| publishDate | 2015-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-7c0855f118aa411bb18b2b243b913bef2022-12-21T23:19:03ZengElsevierJournal of Functional Foods1756-46462015-04-0114570580Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasmaPetr Marhol0Petr Bednář1Petra Kolářová2Rostislav Večeřa3Jitka Ulrichová4Eva Tesařová5Eva Vavříková6Marek Kuzma7Vladimír Křen8Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague 4, Czech Republic; Corresponding author. Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague 4, Czech Republic. Tel.: +420 296 442 510; fax: +420 296 442 509.Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, CZ 771 46 Olomouc, Czech RepublicInstitute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague 4, Czech Republic; Department of Analytical Chemistry, Faculty of Science, Charles University, Albertov 6, CZ 12843 Prague 2, Czech RepublicDepartment of Pharmacology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, CZ 775015 Olomouc, Czech RepublicDepartment of Medicinal Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, CZ 775015 Olomouc, Czech RepublicDepartment of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Albertov 6, CZ 12843 Prague 2, Czech RepublicInstitute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague 4, Czech RepublicInstitute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague 4, Czech RepublicInstitute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague 4, Czech Republic; Corresponding author. Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague 4, Czech Republic. Tel.: +420 296 442 510; fax: +420 296 442 509.The flavonolignan silybin (isolated from the fruits of the milk thistle, Silybum marianum), is a mixture of two diastereoisomers and has anticancer, chemoprotective, hepatoprotective and dermatoprotective properties. This compound is largely used in various functional foods, nutraceutics and food supplements. The pharmacokinetic profiles of optically pure silybins (silybin A and silybin B) were monitored in rat plasma after the intragastric administration (200 mg⋅kg−1 of body weight) of each diastereoisomer. Free (unconjugated) and total (free + conjugated) silybins were monitored for 6 hours by HPLC-PDA. The metabolic profiles of each silybin diastereoisomer were completely different. Our results clearly demonstrate that silybin B (Cmax = 14.50 µg⋅mL−1, Tmax = 2.6 hours, T1/2 = 2.9 hours; total silybin B) was absorbed faster and in a substantially higher amount than silybin A (Cmax = 1.05 µg⋅mL−1, Tmax = 3.9 hours, T1/2 = 2.2 hours; total silybin A). The oral bioavailability of silybin B was estimated to be 0.3%. The AUC 0→6 h (area under the curve) value of total silybin B was 20-fold higher than that of silybin A. SPE-UPLC-MS/MS (solid phase extraction-ultra performance liquid chromatography) was used to identify glucuronides and sulfates (in several isomeric forms) as dominant metabolites of silybin B in rat plasma. Silybin B-7-O-β-glucuronide was the major plasma metabolite of silybin B.http://www.sciencedirect.com/science/article/pii/S1756464615000936SilybinSilibininSilybin glucuronideSilybin sulfateSilymarinBenzofuranone |
| spellingShingle | Petr Marhol Petr Bednář Petra Kolářová Rostislav Večeřa Jitka Ulrichová Eva Tesařová Eva Vavříková Marek Kuzma Vladimír Křen Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma Journal of Functional Foods Silybin Silibinin Silybin glucuronide Silybin sulfate Silymarin Benzofuranone |
| title | Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma |
| title_full | Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma |
| title_fullStr | Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma |
| title_full_unstemmed | Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma |
| title_short | Pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma |
| title_sort | pharmacokinetics of pure silybin diastereoisomers and identification of their metabolites in rat plasma |
| topic | Silybin Silibinin Silybin glucuronide Silybin sulfate Silymarin Benzofuranone |
| url | http://www.sciencedirect.com/science/article/pii/S1756464615000936 |
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