Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites

PloS One
Yang-Ji KimChang Hwa Jung

Abstract

Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH) or N-acetylcysteine (NAC) and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesi...Continue Reading

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Citations

Jul 4, 2017·International Journal of Molecular Sciences·Lalita SubediSun Yeou Kim
Jan 19, 2018·Molecular Nutrition & Food Research·Chia-Wen LoLei Wan
Jan 5, 2018·International Journal of Molecular Sciences·Md Abu SayeedLory Santarelli
Apr 20, 2018·The Journal of Veterinary Medical Science·Jeongtae KimTaekyun Shin
Jun 14, 2018·Molecular Nutrition & Food Research·Teresa OlivieroMatthijs Dekker
Dec 31, 2017·Molecular Nutrition & Food Research·Ahmad Faizal Abdull RazisCostas Ioannides
Jan 25, 2017·Current Pharmaceutical Design·Edoardo CapuanoTeresa Oliviero
Nov 4, 2020·Journal of Agricultural and Food Chemistry·Jinxin XieRi-Yuan Tang

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Methods Mentioned

BETA
histone acetylation
column chromatography
NMR

Software Mentioned

PK solution
Borwin chromatography
GraphPad
ImageJ
Xcalibur
Prism5
PK Solutions

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