Low Oral Bioavailability and Partial Gut Microbiotic and Phase II Metabolism of Brussels/Witloof Chicory Sesquiterpene Lactones in Healthy Humans

Abstract

Free and glycosylated sesquiterpene lactones (SLs), which are abundant in leafy vegetables including Brussels/witloof chicory, possess health-promoting effects in vivo. However, the pharmacokinetics of dietary source of SLs remain largely unknown. In this open-label and single-dose trial, sixteen healthy volunteers consumed 150 g of Brussels/witloof chicory juice containing 48.77 μmol SLs in 5 min. Blood, urine, and fecal samples were collected before and after chicory consumption in 24 h. No SLs were detected in the serum, urine, and fecal samples before chicory consumption in all of the participants. Chicory consumption increased lactucin, 11β,13-dihydrolactucin, and their glucuronide/sulfate conjugates, rather than lactucopicrin and 11β,13-dihydrolactucopicrin, as well as glycosylated SLs in biological samples. The peak concentration of total SLs in serum reached 284.46 nmol/L at 1 h, while, in urine, this peak was 220.3 nmol between 2 and 6 h. The recovery of total SLs in blood, urine, and feces was 7.03%, 1.13%, and 43.76% of the ingested dose, respectively. Human fecal suspensions with intestinal microbiota degraded glycosylated SLs in chicory, and converted lactucopicrin and 11β,13-dihydrolactucopicrin to lactucin and 11β,13-dihydrolactucin, respectively. Collectively, Brussels/witloof chicory SLs are poorly bioavailable and they undergo partial gut microbial and phase II metabolism in humans.

Bioactive, Mineral and Antioxidative Properties of Gluten-Free Chicory Supplemented Snack: Impact of Processing Conditions

“…Chicory sesquiterpene lactones have been reported to possess considerable biological activities and have been used in traditional medicines for centuries. Moreover, foods rich in SLs might be considered to be part of a healthy, balanced diet [ 37 ]. There is a noticeable lack of scientific studies that analyzed the content of SLs in food products, as well as the influence of processing conditions on the content of these bioactive compounds.…”

Evaluation of Activity of Sesquiterpene Lactones and Chicory Extracts as Acetylcholinesterase Inhibitors Assayed in Calorimetric and Docking Simulation Studies

“…The serum concentration of free lactucin and 11(S),13-dihydrolactucin after consumption of a serving of chicory juice containing 49 µmol of total SLs showed a Cmax of 0.143 and 0.116 µmol/L, respectively, and the Cmax of total SLs amounted to 0.284 µmol/L determined by Weng et al [37]. It suggests the in vivo efficacy of the tested extracts containing even about 200 µmol of total SLs converted to lactucin in a dosage of 2 g of extracts with approx.…”

Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

“…The concentrations upon which SL molecules are pharmacologically active are not well defined, and although SLs are described as poorly bioavailable [ 28 ], the aforementioned in vivo reports show that, in many cases, orally administered SLs are pharmacologically active against inflammation. These conclusions highlight the anti-inflammatory potential of orally administered SLs, thereby reinforcing the importance of studying their pharmacokinetic (ADME—Absorption, Distribution, Metabolism, Excretion) profile of these molecules.…”

“…In a study involving healthy volunteers, Weng et al [ 28 ] evaluated the absorption, metabolism, and excretion of SLs after the ingestion of a Brussels/witloof chicory juice. Although the largest percentage of consumed SLs (mainly lactucin and some derivatives) was recovered in the fecal samples (43.76%), 7.03% was detected in the blood samples and 1.13% in the urine samples, suggesting the systemic distribution of the compounds [ 28 ]. The authors also demonstrated that ingested SLs undergo phase II metabolism (glucuronidation and sulfation) and are metabolized by the gut microbiota in healthy humans [ 28 ].…”

“…Although the largest percentage of consumed SLs (mainly lactucin and some derivatives) was recovered in the fecal samples (43.76%), 7.03% was detected in the blood samples and 1.13% in the urine samples, suggesting the systemic distribution of the compounds [ 28 ]. The authors also demonstrated that ingested SLs undergo phase II metabolism (glucuronidation and sulfation) and are metabolized by the gut microbiota in healthy humans [ 28 ]. These results are consistent with those reported by García et al [ 100 ] for lactucin and lactucopicrin from escarole salad, which underwent dehydroxylation and hydrogenation by gut microbiota, as well as phase II metabolic reactions.…”