Comparative pharmacokinetics of purified flaxseed and associated mammalian lignans in male Wistar rats

Abstract

Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG , SECO , ED; volume of distribution, SDG , SECO , ED; half-life, SDG , ED , SECO. The percentage of oral bioavailability was 0, 25 and , 1 % for SDG, SECO and ED, respectively.

Pharmacokinetics and Tissue Distribution of Anwuligan in Rats after Intravenous and Intragastric Administration by Liquid Chromatography-Mass Spectrometry

“…Meanwhile, it is reported that the structural analog of anwuligan, was given to rat i.v. at a dose of 20 mg/kg for pharmacokinetic study [27,28], was given to rat i.g. at a dose of 40 mg/kg for pharmacokinetic study [28].…”

“…at a dose of 20 mg/kg for pharmacokinetic study [27,28], was given to rat i.g. at a dose of 40 mg/kg for pharmacokinetic study [28]. The intravenous dosage of another piece of literature is 20 mg/kg for pharmacological activity study [29].…”

Cereal Lignans, Natural Compounds of Interest for Human Health?

“…oily matrices versus cereal bran), lignans are converted to enterolignans by the gut microbiota [20]. Following metabolization, enterodiol and enterolactone may reach a level high enough for signal pathway regulation in the liver, lung, kidney, heart and brain tissues [83] and pharmacokinetic studies show that these microbial metabolites have high systemic clearance and short halflives in the blood circulation, before being excreted as hepatic conjugates with the urine [85]. Dietary consumption of probiotics and limited digestible or indigestible food constituents such as oligosaccharides (prebiotics) and polyphenols or both (synbiotics), regulate the numbers and types of microbes which can influence energy utilization from the diet and regulate energy expenditure and storage.…”

Short communication: The mammalian lignan enterolactone is absorbed by newborn dairy calves fed enterolactone-enriched milk

“…The AEA 0-12 h of EL was <2% and tended (P = 0.08) to be lower in H-EL (1.31%) than L-EL calves (1.85%) as shown in Table 1. Interestingly, the oral bioavailability of ED averaged <1% in Wistar rats (Mukker et al, 2015). Low bioavailability of enterolignans may be attributed to poor intestinal permeability or high first-pass metabolism and systemic clearance (Mukker et al, 2015).…”

“…Interestingly, the oral bioavailability of ED averaged <1% in Wistar rats (Mukker et al, 2015). Low bioavailability of enterolignans may be attributed to poor intestinal permeability or high first-pass metabolism and systemic clearance (Mukker et al, 2015). Guglielmini et al (2012), reported an association between serum EL concentration ≥10 nmol/L and decreased mortality risk (all-causes and breast cancer-specific) in women after breast cancer surgery.…”