PMID- 8347144
OWN - NLM
STAT- MEDLINE
DCOM- 19930908
LR  - 20220316
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 46
IP  - 2
DP  - 1993 Jul 20
TI  - Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver 
      and small intestine of rat and guinea pig in vitro by piperine.
PG  - 229-38
AB  - The effects of piperine, a major ingredient of black pepper, on UDP-glucose 
      dehydrogenase (UDP-GDH) and glucuronidation potentials of rat and guinea pig 
      liver and intestine were studied. Piperine caused a concentration-related strong 
      inhibition of UDP-GDH (50% at 10 microM) reversibly and equipotently, in both 
      tissues. Partially purified rat liver UDP-GDH was used to obtain the kinetic 
      values at pH optima of 9.4 and 8.6. At pH 9.4: KmUDP-glucose = 15 microM, Vmax = 
      5.2 nmol NADH/min/mg protein, Ki = 6 microM. With NAD, a Ki of 16 microM was 
      obtained. At pH 8.6: Km = 35 microM, Vmax = 7.5 nmol, Ki = 15 microM. In all of 
      these cases, piperine caused non-competitive inhibition. Data from 
      structure-activity comparisons of piperine analogs indicated that the presence of 
      conjugated double bonds in the side chain of the molecule is a factor in piperine 
      inhibition. However, the UDP-glucuronic acid (UDPGA) contents were decreased less 
      effectively by piperine in isolated rat hepatocytes compared with enterocytes of 
      guinea pig small intestine. Piperine at 50 microM caused a marginal decrease of 
      UDPGA in hepatocytes when the rate of glucuronidation of 3-hydroxybenzo[a]pyrene 
      (3-OH-BP) decreased by about 40%. The decrease obtained at 10 microM piperine in 
      intestinal cells was comparable to that obtained at 50-100 microM in hepatocytes. 
      UDP-glucuronosyltransferase (UGT) activities towards 3-OH-BP (UGT1A1) and 
      4-OH-biphenyl (UGT2B1) were also determined. Piperine did not affect the rate of 
      glucuronidation of 4-OH-biphenyl in rat liver, whereas that of 3-OH-BP was 
      impaired significantly. In guinea pig small intestine, both these activities were 
      inhibited significantly requiring less than 25 microM piperine to produce a more 
      than 50% inhibition of UGT(s). The results suggested that (i) piperine is a 
      potent inhibitor of UDP-GDH, (ii) inhibition is offered exclusively by the 
      conjugated double bonds of the molecule, and (iii) piperine exerts stronger 
      effects on intestinal glucuronidation than in rat liver.
FAU - Reen, R K
AU  - Reen RK
AD  - Biochemistry Section, Council of Scientific and Industrial Research (CSIR), Jammu 
      Tawi, India.
FAU - Jamwal, D S
AU  - Jamwal DS
FAU - Taneja, S C
AU  - Taneja SC
FAU - Koul, J L
AU  - Koul JL
FAU - Dubey, R K
AU  - Dubey RK
FAU - Wiebel, F J
AU  - Wiebel FJ
FAU - Singh, J
AU  - Singh J
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Alkaloids)
RN  - 0 (Benzodioxoles)
RN  - 0 (Piperidines)
RN  - 0 (Polyunsaturated Alkamides)
RN  - EC 1.1.1.22 (Uridine Diphosphate Glucose Dehydrogenase)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - U71XL721QK (piperine)
SB  - IM
MH  - *Alkaloids
MH  - Animals
MH  - Benzodioxoles
MH  - Cells, Cultured
MH  - Glucuronidase/*metabolism
MH  - Guinea Pigs
MH  - Intestine, Small/*enzymology
MH  - Kinetics
MH  - Liver/*enzymology
MH  - Male
MH  - Microsomes, Liver/enzymology
MH  - Piperidines/*pharmacology
MH  - Polyunsaturated Alkamides
MH  - Rats
MH  - Structure-Activity Relationship
MH  - Uridine Diphosphate Glucose Dehydrogenase/analysis/*antagonists & inhibitors
EDAT- 1993/07/20 00:00
MHDA- 1993/07/20 00:01
CRDT- 1993/07/20 00:00
PHST- 1993/07/20 00:00 [pubmed]
PHST- 1993/07/20 00:01 [medline]
PHST- 1993/07/20 00:00 [entrez]
AID - 0006-2952(93)90408-O [pii]
AID - 10.1016/0006-2952(93)90408-o [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1993 Jul 20;46(2):229-38. doi: 10.1016/0006-2952(93)90408-o.