Flavonoids are polyphenolic phytochemicals
present extensively in our dailydiet, medicinal plants and herbal remedies. Since
2001, with the continuous support of RGC grants and CUHK Direct Grants, a series of
investigations on Baicalein (B), a bioactive flavonoid isolated from the root of
Scutellaria baicalensis Georgi, and related flavonoids have been conducted in our research
group. Previous studies from us and others have indicated that extensive intestinal
first-pass
metabolism, mainly glucuronidation catalyzed by UDP-glucuronsyltransferase
(UGT) isozymes, and a subsequent unfavorable efflux transport mediated by multidrug
resistance associated protein (MRP) are the two major reasons responsible for the low
oral bioavailability of B. The current study is a continuous mechanistic investigation
on the potential interactions between UGT isoenzymes and MRP transporters during the
absorption of flavonoids. Both in vitro Caco-2 cell culture model and rat single pass
in situ intestinal perfusion model were used.
It was found that inhibitions on either the efflux transport mediated by MRP transporters
or UGT isozymes would lead to reduction in formation and transport of glucuronide
and sulfate conjugates of B. Once the interactions between UGT isoenzymes and
MRP transporters have been confirmed from the in vitro and in situ model, their impacts
on the overall bioavailability of B were conducted in rats. In vivo
studies in rats suggested that co-administered inhibitors
of either MRP transporters or UGT isozymes would lead to increased absorption of B and
reduced formation of its glucuronide and sulfate conjugated metabolites of B. In order
to apply such mechanistic findings to herbdrug/herb-herb interaction
investigations, we have studied interactions between B and a
series of herbal components or western
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drugs,
which mechanistically share similar metabolic
and transport pathways as B. It was found
that Wogonin and Oroxylin A, the two major
co-occurring components of B in the Radix
Scutellariae, were sharing the similar metabolic
and transport pathway as B. Co-administration of these components together with B would
lead to enhanced oral bioavailabilities of each component and reduced formation of their
corresponding glucuronides and sulfates metabolites. Comparison between in vitro
and in vivo results indicated that the trend of
changes in B absorption is more significant in vitro than that
in vivo. The current findings on
B could also apply to other flavonoids, which would enable us to recognize or even
predict potential herb/herb or herb/drug interactions
so as to effectively avoid their occurrence.
In addition to 3 full papers published in
international peer reviewed journals, 4 conference abstracts (one of them has
obtained the First Place in Poster Award for Postdoctoral Fellow Category), 2
manuscripts under review, the project has trained 1 Postdoctoral fellow, 1 PhD student and 1
undergraduate student. Recently, due to our established reputations in flavonoids
research, we were able to attract international student exchange via
the "Global Scholarship
Programme for Research Excellence–CNOOC Grants for
2009-10" to further our
international collaborative research in novel flavonoids.
Prof Zhong Zuo
School of Pharmacy
The Chinese University of Hong Kong
joanzuo@cuhk.edu.hk
Prof Ge Lin
School of Biomedical Sciences
The Chinese University of Hong Kong
linge@cuhk.edu.hk
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