In vitro pharmacokinetic characterization of mulberroside A, the main polyhydroxylated stilbene in mulberry (Morus alba L.), and its bacterial metabolite oxyresveratrol in traditional oral use.
Mulberroside A (MulA) is one of the main bioactive constituents in mulberry (Morus alba L.). This study examined the determining factors for previously reported oral pharmacokinetic profiles of MulA and its bacterial metabolite oxyresveratrol (OXY) on in vitro models. When incubated anaerobically with intestinal bacteria, MulA underwent rapid deglycosylation and generated two monoglucosides and its aglycone OXY sequentially. MulA exhibited a poor permeability and predominantly traversed Caco-2 cells via passive diffusion; yet, the permeation of OXY across Caco-2 cells was much more rapid and involved efflux (both p-glycoprotein and MRPs)-mediated mechanisms. Moreover, OXY underwent extensive hepatic glucuronidation; yet, the parent MulA was kept intact in liver subcellular preparations. There was insignificant species difference in intestinal bacterial conversion of MulA and the extent of OXY hepatic glucuronidation between humans and rats, while OXY exhibited a distinct positional preference of glucuronidation in the two species. Overall, these findings revealed a key role of intestinal bacterial conversion in absorption and systemic exposure of MulA and its resultant bacterial metabolite OXY in oral route in humans and rats and warranted further investigational emphasis on OXY and its hepatic metabolites for understanding the benefits of mulberry.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
Mei
M
Mei
Jian-Qing
JQ
Ruan
Wen-Jin
WJ
Wu
Rui-Na
RN
Zhou
Jacky Pui-Cheong
JP
Lei
Hai-Yu
HY
Zhao
Ru
R
Yan
Yi-Tao
YT
Wang
D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D004187:Disaccharides / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines / Q000382:microbiology; D008099:Liver / Q000378:metabolism; D031625:Morus / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D013045:Species Specificity; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D004187:Disaccharides; D020719:Glucuronides; D010936:Plant Extracts; D013267:Stilbenes; C420606:mulberroside A; C034912:puag-haad