Silybin is the main component of silymarin, a standardized extract obtained from the seeds of milk thistle (Silybum marianum). Flavonolignan silybin has antioxidant, hepatoprotective, chemoprotective and antitumor activities. Natural silybin occurs as an approximately equimolar mixture of two diastereoisomers - silybin A and silybin B. Analytical separation of these diastereoisomers is possible but preparative separation is complicated. The biological activity of the silybin A is different from the silybin B. Silybin diastereoisomers are mainly conjugated to glucuronides and sulfates in organism. A mixture of both silybin diasteroisomers is used in the majority of reported biological, chemical and pharmacokinetic studies. For the first time, optically pure silybin A and silybin B were used for pharmacokinetic study in this thesis. The object of this work was determination of the concentration of free and total silybin in rats plasma in relation to time. Theoretical introduction describes the current state of the problem of chemistry, pharmacology and pharmacokinetics of silybin diastereoisomers. Second part is focused on the selection of appropriate analytical column, chromatographic method and suitable procedure for preparation of biological samples for the determination of the silybin...

No description available.

Natural flavonoids and flavonolignans feature beneficial properties for living organisms such as antioxidant and hepatoprotective effects, anticancer, chemoprotective, dermatoprotective and hypocholesterolemic activities. Their metabolism in mammals is complex, the exact structure of their metabolites still remains partly unclear and the standards are usually not commercially available. Hence, this project focused on the preparation of potential and defined biotransformation Phase II sulfated metabolites of silymarin flavonolignans: silybin, 2,3-dehydrosilybin, isosilybin, silychristin, silydianin and flavonoids quercetin, taxifolin, rutin and isoquercitrin. Pure sulfated derivatives were prepared using aryl sulfotransferase from Desulfitobacterium hafniense and aryl sulfotransferase from rat liver. Using heterologously expressed PAPS (3'-phosphoadenosine-5'-phosophosulfate) - independent arylsulfotransferase from Desulfitobacterium hafniense and cheap p-nitrophenyl sulfate as sulfate donor, sulfated flavonolignans and flavonoids were obtained in high yields. Silymarin flavonolignans afforded exclusively monosulfates at the position C-20 (C-19 in the case of silychristin), except 2,3-dehydrosilybin that yielded also the 7,20-O-disulfated derivative. Isoquercitrin and rutin were selectively sulfated...

Natural bioactive compounds have drawn the interest of many researchers worldwide in their effort to find novel treatments, including prostate cancer (PC) treatment which is estimated to be 13.1% of all new cancer cases in the U.S. in 2021. Many of these bioactive compounds have been identified from treatments in traditional Chinese medicine (TCM), that often have multiple bioactive compounds present. However, in vitro studies frequently focus on the compounds in isolation, or in simple combinations of two compounds. We used mixture design response surface methodology (MDRSM) to assess changes in PC cell viability after 48 hours of treatment to identify the optimal mixture of all 35 three-compound combinations of seven bioactive compounds from TCM. We used Berberine, Wogonin, Shikonin, Curcumin, Triptolide, Emodin, and Silybin to treat PC-3, DU145, and LNCaP human PC cells, and a drug-resistant PC-3 cell line. Berberine and Wogonin most frequently contributed to the optimal combination to reduce cell viability in PC-3 and LNCaP cells; DU145 cells more frequently responded best to a single compound.