Pharmacokinetics and Metabolic Profile of Free, Conjugated, and Total Silymarin Flavonolignans in Human Plasma after Oral Administration of Milk Thistle Extract

Abstract

ABSTRACT:Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is composed mainly of silychristin, silydianin, silybin A, silybin B (SB B ), isosilybin A (ISB A ), and isosilybin B. In this study, the plasma concentrations of free (unconjugated), conjugated (sulfated and glucuronidated), and total (free and conjugated) silymarin flavonolignans were measured using liquid chromatography-electrospray ionization-mass spectrometry, after a single oral dose of 600 mg of standardized milk thistle extracts to three healthy volunteers. Pharmacokinetic analysis indicated that silymarin flavonolignans were rapidly eliminated with short half-lives (1-3 and 3-8 h for free and conjugated, respectively). The AUC 03ؕ values of the conjugated silymarin flavonolignans were 4-to 30-fold higher than those of their free fractions, with SB B (mean AUC 03ؕ ‫؍‬ 51 and 597 g ⅐ h/l for free and conjugated, respectively) and ISB A (mean AUC 03ؕ ‫؍‬ 30 and 734 g ⅐ h/l for free and conjugated, respectively) exhibiting higher AUC 03ؕ values in comparison with other flavonolignans. Near the plasma peak times (1-3 h), the free, sulfated, and glucuronidated flavonolignans represented approximately 17, 28, and 55% of the total silymarin, respectively. In addition, the individual silymarin flavonolignans exhibited quite different plasma profiles for both the free and conjugated fractions. These data suggest that, after oral administration, silymarin flavonolignans are quickly metabolized to their conjugates, primarily forming glucuronides, and the conjugates are primary components present in human plasma.

Comparative Efficacy of Silymarin and Choline Chloride (Liver Tonics) in Preventing the Effects of Aflatoxin B1 in Bovine Calves

“…Silymarin (Silybum marianum), the polyphenolic fraction from Milk Thistle is used for hepatoprotection in humans (Flora et al 1998, Jacobs et al 2002, Fraschini et al 2002, Ladas and Kelly, 2003, Wen et al 2007) and demonstrated good protection in various toxic paradigms of experimental liver diseases in small laboratory animals (Radko and Cybulski 2007). Silymarin functions as an antioxidant, which absorbs and regulates the intracellular glutathione.…”

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

“…As with other flavolignans, limitations of silybin use include low water solubility, low bioavailability, and poor intestinal absorption [14]. Derivatives of silybin with improved solubility may surmount these pharmacologic limitations [15,16].…”

Rumen degradability and whole tract digestibility of flavonolignans from milk thistle (Silybum marianum) fruit expeller in dairy cows

“…As reported by Rickling et al (1995) or Wen et al (2008), silymarin flavonolignans after oral administration were quickly metabolized to their conjugates, primarily forming glucuronides, and the conjugates were primary components present in human plasma. Wen et al (2008) further demonstrated that all six silymarin flavonolignans were rapidly eliminated, and the conjugated silymarin flavonolignans had relatively longer half-lives than their free forms.…”

“…Wen et al (2008) further demonstrated that all six silymarin flavonolignans were rapidly eliminated, and the conjugated silymarin flavonolignans had relatively longer half-lives than their free forms. In our study, plasma conjugated Silymarin complex digestibility (%) SB was determined at all sampling times in period B with the highest plasma concentration at the last sampling time (13:00 h), it was approximately 6 h after feeding.…”