PMID- 26348140
OWN - NLM
STAT- MEDLINE
DCOM- 20160208
LR  - 20220818
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 289
IP  - 1
DP  - 2015 Nov 15
TI  - Identification and characterization of naturally occurring inhibitors against 
      UDP-glucuronosyltransferase 1A1 in Fructus Psoraleae (Bu-gu-zhi).
PG  - 70-8
LID - S0041-008X(15)30077-6 [pii]
LID - 10.1016/j.taap.2015.09.003 [doi]
AB  - As an edible traditional Chinese herb, Fructus psoraleae (FP) has been widely 
      used in Asia for the treatment of vitiligo, bone fracture and osteoporosis. 
      Several cases on markedly elevated bilirubin and acute liver injury following 
      administration of FP and its related proprietary medicine have been reported, but 
      the mechanism in FP-associated toxicity has not been well investigated yet. This 
      study aimed to investigate the inhibitory effects of FP extract and its major 
      constituents against human UDP-glucuronosyltransferase 1A1 (UGT1A1), the key 
      enzyme responsible for metabolic elimination of bilirubin. To this end, 
      N-(3-carboxy propyl)-4-hydroxy-1,8-naphthalimide (NCHN), a newly developed 
      specific fluorescent probe for UGT1A1, was used to evaluate the inhibitory 
      effects of FP extract or its fractions in human liver microsomes (HLM), while 
      LC-UV fingerprint and UGT1A1 inhibition profile were combined to identity and 
      characterize the naturally occurring inhibitors of UGT1A1 in FP. Our results 
      demonstrated that both the extract of FP and five major components of FP 
      displayed evident inhibitory effects on UGT1A1 in HLM. Among these five 
      identified naturally occurring inhibitors, bavachin and corylifol A were found to 
      be strong inhibitors of UGT1A1 with the inhibition kinetic parameters (Ki) values 
      lower than 1 muM, while neobavaisoflavone, isobavachalcone, and bavachinin 
      displayed moderate inhibitory effects against UGT1A1 in HLM, with the Ki values 
      ranging from 1.61 to 9.86muM. These findings suggested that FP contains natural 
      compounds with potent inhibitory effects against human UGT1A1, which may be one 
      of the important reasons for triggering FP-associated toxicity, including 
      elevated bilirubin levels and liver injury.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Wang, Xin-Xin
AU  - Wang XX
AD  - Liaoning Medical University, Jinzhou, Liaoning, China; Laboratory of 
      Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese 
      Academy of Sciences, Dalian 116023, China.
FAU - Lv, Xia
AU  - Lv X
AD  - Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences, Dalian 116023, China.
FAU - Li, Shi-Yang
AU  - Li SY
AD  - Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences, Dalian 116023, China.
FAU - Hou, Jie
AU  - Hou J
AD  - Dalian Medical University, Dalian 116044, China.
FAU - Ning, Jing
AU  - Ning J
AD  - Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences, Dalian 116023, China; Dalian Medical 
      University, Dalian 116044, China.
FAU - Wang, Jia-Yue
AU  - Wang JY
AD  - Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences, Dalian 116023, China.
FAU - Cao, Yun-Feng
AU  - Cao YF
AD  - Liaoning Medical University, Jinzhou, Liaoning, China; Laboratory of 
      Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese 
      Academy of Sciences, Dalian 116023, China.
FAU - Ge, Guang-Bo
AU  - Ge GB
AD  - Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: 
      geguangbo@dicp.ac.cn.
FAU - Guo, Bin
AU  - Guo B
AD  - Liaoning Medical University, Jinzhou, Liaoning, China. Electronic address: 
      jyguobin@126.com.
FAU - Yang, Ling
AU  - Yang L
AD  - Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences, Dalian 116023, China; Jiangxi University of 
      Traditional Chinese Medicine, Nanchang 330006, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150905
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Chalcones)
RN  - 0 (Flavones)
RN  - 0 (Flavonoids)
RN  - 0 (Isoflavones)
RN  - 0 (Plant Extracts)
RN  - 0 (bavachin)
RN  - 0 (corylifol A)
RN  - 0 (neobavaisoflavone)
RN  - 20784-50-3 (isobavachalcone)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - RFM9X3LJ49 (Bilirubin)
RN  - VL3EV483SZ (bavachinin)
SB  - IM
MH  - Bilirubin/metabolism
MH  - Chalcones/toxicity
MH  - Chemical and Drug Induced Liver Injury/pathology
MH  - Dose-Response Relationship, Drug
MH  - Flavones/toxicity
MH  - Flavonoids/toxicity
MH  - Fruit/chemistry
MH  - Glucuronosyltransferase/*antagonists & inhibitors/metabolism
MH  - Humans
MH  - Isoflavones/toxicity
MH  - Liver/drug effects/metabolism
MH  - Microsomes, Liver/drug effects/metabolism
MH  - Plant Extracts/*toxicity
MH  - Psoralea/*chemistry
OTO - NOTNLM
OT  - Fructus psoraleae
OT  - Inhibitory effects
OT  - LC-UV fingerprint
OT  - NCHN
OT  - UDP-glucuronosyltransferase 1A1
EDAT- 2015/09/09 06:00
MHDA- 2016/02/09 06:00
CRDT- 2015/09/09 06:00
PHST- 2015/07/01 00:00 [received]
PHST- 2015/08/19 00:00 [revised]
PHST- 2015/09/01 00:00 [accepted]
PHST- 2015/09/09 06:00 [entrez]
PHST- 2015/09/09 06:00 [pubmed]
PHST- 2016/02/09 06:00 [medline]
AID - S0041-008X(15)30077-6 [pii]
AID - 10.1016/j.taap.2015.09.003 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2015 Nov 15;289(1):70-8. doi: 10.1016/j.taap.2015.09.003. 
      Epub 2015 Sep 5.