Anti-inflammatory effect of α,ß-amyrin, a triterpene from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice.

OBJECTIVE: To evaluate the anti-inflammatory effect of α,ß-amyrin, a pentacyclic triterpenoid from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced in Swiss mice by five intraperitoneal injections of cerulein (50 µg/kg), at 1 h intervals. Mice received α,ß-amyrin (10, 30 and 100 mg/kg), thalidomide (200 mg/kg), or vehicle (3% Tween 80) orally 1 h before and 12 h after the cerulein challenge. The severity of pancreatitis was evaluated 24 h after cerulein by assessing serum pro-inflammatory cytokines and amylase activity, pancreatic myeloperoxidase (MPO), and thiobarbituric acid-reactive substances (TBARS), as well as by histology. RESULTS: α,ß-Amyrin and thalidomide significantly attenuated the cerulein-induced increase in tumor necrosis factor (TNF)-α, interleukin-6, lipase, amylase, MPO, and TBARS. Moreover, α,ß-amyrin greatly suppressed the pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and expressions of TNFα and inducible nitric oxide synthase. CONCLUSIONS: α,ß-Amyrin ameliorates cerulein-induced acute pancreatitis by acting as an anti-inflammatory and antioxidant agent.

Oleanolic acid, a pentacyclic triterpene attenuates capsaicin-induced nociception in mice: possible mechanisms.

The anti-inflammatory pentacyclic triterpene, oleanolic acid (OA) was examined on acute nociception induced by intraplantar injection of capsaicin in mice. OA administered orally to mice at 10, 30 and 100 mgkg(-1), significantly attenuated the paw-licking response to capsaicin (1.6 microg/paw) by 53%, 68.5% and 36.6%, respectively. Ruthenium red (3 mgkg(-1), s.c.), a non-competitive vanilloid receptor (V1, TRPV1)-antagonist also suppressed the capsaicin nociception by 38.6%. The maximal antinociception produced by 30 mgkg(-1) OA was significantly blocked in animals pre-treated with naloxone (2 mgkg(-1), i.p.), the opioid antagonist; l-arginine (600 mgkg(-1), i.p.), the substrate for nitric oxide synthase; or glibenclamide (2 mgkg(-1), i.p.), the K(ATP)-channel blocker, but was unaffected by yohimbine (2 mgkg(-1), i.p.), an alpha(2)-adrenoceptor antagonist. In open-field and rota-rod tests that detect motor deficits, mice received 30 mgkg(-1) OA did not manifest any effect per se, indicating that the observed antinociception is not a consequence of motor abnormality. These data suggest that OA inhibits capsaicin-evoked acute nociception due to mechanisms possibly involving endogenous opioids, nitric oxide, and K(ATP)-channel opening.

12-Acetoxyhawtriwaic acid lactone, a diterpene from Egletes viscosa, attenuates capsaicin-induced ear edema and hindpaw nociception in mice: possible mechanisms.

The diterpene, 12-acetoxyhawtriwaic acid lactone (AHAL, tanabalin) isolated from the flower buds of Egletes viscosa Less. (Asteraceae) was evaluated on capsaicin-induced ear edema and hindpaw nociception in mice. AHAL (12.5, 25 and 50 mg/kg, P. O.) significantly attenuated the ear edema response to topically applied capsaicin (250 microg), in a dose-related manner. At similar doses, AHAL also suppressed the nocifensive paw-licking behavior induced by intraplantar injection of capsaicin (1.6 microg). These responses to capsaicin were also greatly inhibited by ruthenium red (3 mg/kg, S. C.), a non-competitive capsaicin receptor (TRPV1) antagonist. The anti-edema effect of AHAL (50 mg/kg) seems unrelated to either blockade of mast cell degranulation or to histamine and serotonin receptor antagonism since AHAL did not modify the paw edema response induced by intraplantar injections of compound 48/80, histamine or serotonin. However, the hindpaw edema induced by substance P and vascular permeability increase induced by intraperitoneal acetic acid were significantly suppressed by AHAL. The antinociceptive effect of AHAL (50 mg/kg) was unaffected by naloxone pretreatment but was significantly antagonized by theophylline and glibenclamide, the respective blockers of adenosine and K(ATP)-channels. AHAL (50 mg/kg, P. O.) did not impair the ambulation or motor coordination of mice in open-field and rota-rod tests. These data suggest that AHAL inhibits acute neurogenic inflammation possibly involving capsaicin-sensitive TRPV1-receptors, endogenous adenosine and ATP-sensitive potassium channels.