PMID- 24705672
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20181202
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 42
IP  - 6
DP  - 2014 Jun
TI  - Nigramide C is a natural agonist of human pregnane x receptor.
PG  - 1084-9
LID - 10.1124/dmd.114.057810 [doi]
AB  - Pregnane X receptor (PXR) is known as a xenosensor, playing a key role in 
      response to xenochemical stimuli. Activation of PXR enhanced expression of 
      various drug-metabolizing enzymes and transporters such as cytochrome P450 3A4 
      (CYP3A4). During a screening of a natural compounds library for novel ligands of 
      human xenosensing receptors by the mammalian one-hybrid assay, two 
      cyclohexene-type amide alkaloids were isolated, with nigramide C (NigC) showing 
      the most potent activation of human PXR (hPXR). NigC-mediated hPXR activation was 
      enhanced by overexpression of steroid receptor coactivator 1 (SRC1), peroxisome 
      proliferator-activated receptor gamma, coactivator 1alpha, and protein arginine 
      methyltransferase 1. A direct interaction between the ligand-binding domain of 
      hPXR and the receptor interaction domain of SRC1 was observed. NigC induced the 
      expression of endogenous CYP3A4 mRNA and protein in both cultured hepatoma cells 
      and primary hepatocytes. However, in primary hepatocytes, the relative agonist 
      activity of NigC was not as potent as that of rifampicin, probably because of 
      lower metabolic stability of NigC in these cells. In conclusion, NigC was found 
      to be an effective agonist of hPXR. NigC is a useful tool for investigation of 
      hPXR function.
FAU - Kanno, Yuichiro
AU  - Kanno Y
AD  - Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.
FAU - Yatsu, Tomofumi
AU  - Yatsu T
FAU - Li, Wei
AU  - Li W
FAU - Koike, Kazuo
AU  - Koike K
FAU - Inouye, Yoshio
AU  - Inouye Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140404
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Plant Extracts)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (Receptors, Steroid)
SB  - IM
MH  - Female
MH  - Hep G2 Cells
MH  - Hepatocytes/*drug effects/metabolism
MH  - Humans
MH  - Male
MH  - *Piper nigrum
MH  - Plant Extracts/chemistry/isolation & purification/*pharmacology
MH  - *Plant Roots
MH  - Pregnane X Receptor
MH  - Receptors, Steroid/*agonists/physiology
EDAT- 2014/04/08 06:00
MHDA- 2015/01/27 06:00
CRDT- 2014/04/08 06:00
PHST- 2014/04/08 06:00 [entrez]
PHST- 2014/04/08 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
AID - dmd.114.057810 [pii]
AID - 10.1124/dmd.114.057810 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2014 Jun;42(6):1084-9. doi: 10.1124/dmd.114.057810. Epub 2014 
      Apr 4.