Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease.
OBJECTIVE
Orally administered rutin reportedly ameliorates 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis of rats. We investigated the metabolic and pharmacological properties of rutin underlying the rutin-mediated amelioration of the rat colitis.


METHODS
Apparent partition coefficients of rutin and its aglycone quercetin were compared. The biochemical/chemical stability of rutin was examined in the contents of various segments of gastrointestinal tracts of rats. Inflammatory indices were determined in the colitis rats after oral administration of rutin or rectal administration of quercetin. In human colon epithelial cells, the effect of quercetin on tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor kappa B (NFkappaB) activation was examined.


RESULTS
The sugar residue in rutin greatly lowered the apparent partition coefficient and was rapidly deglycosylated to liberate quercetin in the cecal contents, whereas it was stable in the contents of the upper intestine. Not only oral administration of rutin but also rectal administration of quercetin remarkably ameliorated TNBS-induced colitis rats, indicating that quercetin liberated from rutin is therapeutically active. Furthermore, quercetin dose-dependently inhibited an inflammatory signal TNF-alpha-dependent NFkappaB activation.


CONCLUSIONS
Our data suggest that rutin acted as a quercetin deliverer to the large intestine and its anti-inflammatory action in TNBS-induced colitis rats may be through quercetin-mediated inhibition of TNF-alpha-induced NFkappaB activation.
Kim
Heejung
H
Laboratory of Biomedicinal Chemistry, College of Pharmacy, Pusan National University, Jangjeon-Dong, Keumjung-Gu, Pusan 609-735, Republic of Korea.
Kong
Hyesik
H
Choi
Boim
B
Yang
Youngwook
Y
Kim
Youngmi
Y
Lim
Mi Jung
MJ
Neckers
Len
L
Jung
Yunjin
Y
D000818:Animals; D002460:Cell Line; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D011794:Quercetin / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000493:pharmacokinetics / Q000627:therapeutic use*
D012431:Rutin; D011794:Quercetin