A potential role for the vanilloid receptor TRPV1 in the therapeutic effect of curcumin in dinitrobenzene sulphonic acid-induced colitis in mice.
A protective role of the transient potential vanilloid receptor 1 (TRPV1) in intestinal inflammation induced by dinitrobenzene sulphonic acid (DNBS) has been recently demonstrated. Curcumin, the major active component of turmeric, is also able to prevent and ameliorate the severity of the damage in DNBS-induced colitis. We evaluated the possibility that curcumin (45 mg kg(-1) day p.o. for 2 days before and 5 days after the induction of colitis) was able to reduce DNBS-induced colitis in mice, by acting as a TRPV1 agonist. Macroscopic damage score, histological damage score and colonic myeloperoxidase (MPO) activity were significantly lower (by 71%, 65% and 73%, respectively; P < 0.01), in animals treated with curcumin compared with untreated animals. Capsazepine (30 mg kg(-1), i.p.), a TRPV1 receptor antagonist, completely abolished the protective effects of curcumin. To extend these data in vitro, Xenopus oocytes expressing rat TRPV1 were examined. Capsaicin-evoked currents (3.3 micromol L(-1)) disappeared subsequent either to removal of the agonist or subsequent to the addition of capsazepine. However, curcumin (30 micromol L(-1)) was ineffective both as regard direct modification of cell membrane currents and as regard interference with capsaicin-mediated effects. As sensitization of the TRPV1 receptor by mediators of inflammation in damaged tissues has been shown previously, our results suggest that in inflamed, but not in normal tissue, curcumin can interact with the TRPV1 receptor to mediate its protective action in DNBS-induced colitis.
Martelli
L
L
Department of Pharmacology and Anaesthesiology, Universitá di Padova, 2 Largo Menenghetti, I-35131 Padua, Italy.
Ragazzi
E
E
di Mario
F
F
Martelli
M
M
Castagliuolo
I
I
Dal Maschio
M
M
Palù
G
G
Maschietto
M
M
Scorzeto
M
M
Vassanelli
S
S
Brun
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001557:Benzenesulfonates; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D003474:Curcumin / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009865:Oocytes / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D012720:Severity of Illness Index; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D014981:Xenopus
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001557:Benzenesulfonates; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C007488:dinitrobenzenesulfonic acid; D009195:Peroxidase; D003474:Curcumin; C071423:capsazepine; D002211:Capsaicin