PMID- 9714315
OWN - NLM
STAT- MEDLINE
DCOM- 19980914
LR  - 20220321
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 55
IP  - 12
DP  - 1998 Jun 15
TI  - In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer 
      preventive natural product with anti-inflammatory properties.
PG  - 1955-62
AB  - Curcumin is a naturally occurring, dietary polyphenolic phytochemical that is 
      under preclinical trial evaluation for cancer preventive drug development and 
      whose working pharmacological actions include anti-inflammation. With respect to 
      inflammation, in vitro, it inhibits the activation of free radical-activated 
      transcription factors, such as nuclear factor kappaB (NFkappaB) and AP-1, and 
      reduces the production of pro-inflammatory cytokines such as tumor necrosis 
      factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), and interleukin-8. 
      Inducible nitric oxide synthase (iNOS) is an inflammation-induced enzyme that 
      catalyzes the production of nitric oxide (NO), a molecule that may lead to 
      carcinogenesis. Here, we report that in ex vivo cultured BALB/c mouse peritoneal 
      macrophages, 1-20 microM of curcumin reduced the production of iNOS mRNA in a 
      concentration-dependent manner. Furthermore, we demonstrated that, in vivo, two 
      oral treatments of 0.5 mL of a 10-microM solution of curcumin (92 ng/g of body 
      weight) reduced iNOS mRNA expression in the livers of 
      lipopolysaccharide(LPS)-injected mice by 50-70%. Although many hold that curcumin 
      needs to be given at dosages that are unattainable through diet to produce an in 
      vivo effect, we were able to obtain potency at nanomoles per gram of body weight. 
      This efficacy is associated with two modifications in our preparation and feeding 
      regimen: 1) an aqueous solution of curcumin was prepared by initially dissolving 
      the compound in 0.5 N NaOH and then immediately diluting it in PBS; and 2) mice 
      were fed curcumin at dusk after fasting. Inhibition was not observed in mice that 
      were fed ad lib., suggesting that food intake may interfere with the absorption 
      of curcumin.
FAU - Chan, M M
AU  - Chan MM
AD  - Department of Biomedical Sciences, Pennsylvania College of Podiatric Medicine, 
      Philadelphia 19107, USA. chan@biology.rutgers.edu
FAU - Huang, H I
AU  - Huang HI
FAU - Fenton, M R
AU  - Fenton MR
FAU - Fong, D
AU  - Fong D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (DNA Primers)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*pharmacology
MH  - Curcumin/administration & dosage/*pharmacology
MH  - DNA Primers
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Liver/drug effects/metabolism
MH  - Macrophages, Peritoneal/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nitric Oxide Synthase/*biosynthesis/genetics
MH  - Nitric Oxide Synthase Type II
MH  - Polymerase Chain Reaction
EDAT- 1998/08/26 00:00
MHDA- 1998/08/26 00:01
CRDT- 1998/08/26 00:00
PHST- 1998/08/26 00:00 [pubmed]
PHST- 1998/08/26 00:01 [medline]
PHST- 1998/08/26 00:00 [entrez]
AID - S0006295298001142 [pii]
AID - 10.1016/s0006-2952(98)00114-2 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1998 Jun 15;55(12):1955-62. doi: 
      10.1016/s0006-2952(98)00114-2.