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

Hui Weng,Xiuping Liu,Jiakun Zheng,Qing Li,Dongliang Wang,Luanying He

doi:10.3390/nu12123675

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.

Highlights

Sesquiterpene lactones (SLs) are a colorless, bitter, and stable subfamily of terpenes [1].Over 5000 structures of SLs are widely distributed within the plant kingdom, most of which are derived from the family Asteraceae [2]
The in vitro fermentation of lactucopicrin, 11β,13-dihydrolactucopicrin, or Brussels/witloof chicory SLs by human fecal suspensions with or without intestinal microbiota was carried out as we have previously described for the fermentation of Brussels/witloof chicory phenolic acids [17]
Representative high-performance liquid chromatography (HPLC) chromatograms of free or glycosylated SL extracts from Brussels/witloof chicory are shown in Figure 1A,B, respectively

Summary

Introduction

Over 5000 structures of SLs are widely distributed within the plant kingdom, most of which are derived from the family Asteraceae [2]. Lettuce and chicory (Lactuca sativa and Chicorium intybus L.) that belong to the family Asteraceae are the leading sources of SLs in the human diet [3]. Lactucopicrin, and 11β,13-dihydrolactucin have been reported to possess considerable analgesic and sedative activities in mice [6]. These capacities were comparable to ibuprofen, which is a widely used nonsteroidal anti-inflammatory drug [6]. We recently found that SLs-rich Brussels/witloof chicory We recently found that SLs-rich Brussels/witloof chicory (Chicorium intybus L. var. foliosum), one variety of chicory, is able to slow down the progression

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Results

Conclusion