In search of novel gastroprotective agents, mangiferin, a naturally occurring glucosylxanthone from Mangifera indica L. (Anacardiaceae), was evaluated in mice on gastric injury induced by ethanol and ...indomethacin. The effects of mangiferin on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area or ulcer score in mice and on gastric secretory volume and total acidity in 4-h pylorus-ligated rats. Mangiferin (3, 10 and 30 mg/kg, P. O.) significantly attenuated the gastric damage induced by ethanol by 30, 35, and 63 %, and of indomethacin by 22, 23 and 57 %, respectively. N-Acetylcysteine (750 mg/kg, I. P.) and lansoprazole (30 mg/kg, P. O.) used as positive controls in these ulcerogenic models resulted in 50 % and 76 % suppression of gastric injury, respectively. In 4-h pylorus-ligated rats, intraduodenally applied mangiferin (30 mg/kg) caused significant diminutions in gastric secretory volume and total acidity. In addition, like N-acetylcysteine, a donor of sulfhydryls, mangiferin effectively prevented the ethanol-associated depletion of gastric mucosal non-protein sulfhydryl content in mice, suggesting an antioxidant action. These findings provide evidence that mangiferin affords gastroprotection against gastric injury induced by ethanol and indomethacin most possibly through the antisecretory and antioxidant mechanisms of action.
Cariniana rubra Miers (Lecythidaceae), popularly known as "jequitibá-vermelho'', is a large Brazilian tree whose bark is used in infusion and decoction for the treatment of inflammatory conditions. ...This study aims to assess the anti-inflammatory, antinociceptive, and antipyretic effects of Cariniana rubra methanolic stem bark extract (EM Cr) using experimental animals. Anti-inflammatory activity of EM Cr was tested on carrageenan and dextran-induced rat paw edema, carrageenan-induced pleurisy in rats and acetic acid-increase vascular permeability in mice. Antinociceptive and antipyretic activities were evaluated using acetic acid-induced writhing, formalin and hot-plate tests in mice, as well as brewer's yeast-induced pyrexia in rats. The extract inhibitied carrageenan and dextran-induced edema, reduced exudate volume and leukocyte migration on the carrageenan-induced pleurisy and on the vascular permeability increase induced by acetic acid. The EM Cr inhibited nociception on the acetic acid-induced writhing and in the second phase of formalin test, and decreased rectal temperature. It was, however, inactive against thermal nociception.Phytochemical analysis with EM Cr showed the occurrence of saponins, triterpenes, sterols and phenolic compounds. Phytosterols (β-sitosterol, stigmasterol), pentacyclic triterpenes (α- and β-amyrin as a mixture), arjunolic acid, a phytosterol glycoside (sitosterol 3-O-β-D-glucopyranoside), and triterpenoid saponins (28-β-glucopyranosyl-23-O-acetyl arjunolic acid; 3-O-β-glucopyranosyl arjunolic acid and 28-O-α-L-Rhamnopyranosyl-(1→2)-β-glucopyranosyl-23- O-acetyl arjunolic acid) were the main identified compounds. It can be presumed that EM Cr caused their effects by inhibiting the liberation and/or action of different inflammatory mediators. These findings support the traditional use of Cariniana rubra preparations to treat inflammation.
Anti-inflammatory effect of the ethanolic extract from Bowdichia virgilioides H.B.K stem bark Barros, Wander M.(Universidade Federal de Mato Grosso FCM Departamento de Ciências Básicas em Saúde); Rao, Vietla S.N.(Universidade Federal do Ceará Faculdade de Medicina Departamento de Fisiologia e Farmacologia); Silva, Regilane M.(Universidade Federal de Mato Grosso FCM Departamento de Ciências Básicas em Saúde) ...
Anais da Academia Brasileira de Ciências,
09/2010, Letnik:
82, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Bowdichia virgilioides H.B.K stem bark (Fabaceae), locally known as "sucupira-preta", is a reputed folk-remedy to treat some inflammatory disorders. To validate its traditional claim, the ethanolic ...extract from B. virgilioides was evaluated in several animal models of inflammation and nociception. The extract at oral doses of 100 to 1000 mg/kg body weight caused a significant inhibition of carrageenan-induced hind paw oedema, suppression of exudate volume and leukocyte immigration in rat pleurisy induced by carrageenan, and reduction of granuloma weights in the model of subcutaneous granulomas promoted by cotton pellets. In addition, the plant extract significantly inhibited the vascular permeability increase induced by intraperitoneal acetic acid. It also showed marked antinociceptive effect in acetic acid-induced writhing test and in the second phase of formalin test in mice. These findings evidence the anti-inflammatory potential of Bowdichia virgilioides bark and supports its traditional use in inflammatory conditions.
A casca do caule de Bowdichia virgilioides H.B.K (Fabaceae), conhecida localmente como sucupira-preta, é um remédio popular muito utilizado para tratar inflamações. Com o objetivo de validar sua crença popular, o extrato etanólico de B. virgilioides foi avaliado em vários modelos experimentais de inflamação e nocicepção. O extrato administrado, via oral, em doses de 100 a 1000 mg/kg de peso corporal produziu inibição significativa no edema de pata induzido por carragenina, no aumento na permeabilidade vascular induzido por acido acético, no volume de exudato e na migração leucocitária no teste de pleurisia induzida por carragenina, bem como no peso de granulomas induzidos por pelotas de algodão, em ratos. Em camundongos, o EE Bv reduziu o número de contorções abdominais induzidas por ácido acético e a lambedura da pata na segunda fase do teste da formalina. Esses resultados validam o potencial anti-inflamatório da casca de Bowdichia virgilioides e referendam seu uso tradicional em condições inflamatórias.
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
mg
kg
−1, significantly attenuated the paw-licking response to capsaicin (1.6
μg/paw) by 53%, 68.5% and 36.6%, respectively. Ruthenium red (3
mg
kg
−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
mg
kg
−1 OA was significantly blocked in animals pre-treated with naloxone (2
mg
kg
−1, i.p.), the opioid antagonist;
l-arginine (600
mg
kg
−1, i.p.), the substrate for nitric oxide synthase; or glibenclamide (2
mg
kg
−1, i.p.), the K
ATP-channel blocker, but was unaffected by yohimbine (2
mg
kg
−1, i.p.), an α
2-adrenoceptor antagonist. In open-field and rota-rod tests that detect motor deficits, mice received 30
mg
kg
−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.
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.
In the search for natural compounds useful against pruritus, α,β-amyrins, the pentacyclic triterpenes isolated from the resin of popular medicinal plant
Protium heptaphyllum were examined on ...scratching behavior induced by dextran T40 and compound 48/80 in mice. The animals were pretreated orally with α,β-amyrins (50, 100 and 200 mg/kg) or cyproheptadine (10 mg/kg), an antagonist of histamine and serotonin receptors and 2 h later, they were given subcutaneous injections of dextran T40 (75 mg/kg) or compound 48/80 (3 mg/kg) into the rostral back, and scratching was quantified for 20 min. The scratching behavior induced by dextran T40 and compound 48/80 was significantly inhibited in mice pretreated with α,β-amyrins (100 and 200 mg/kg) or cyproheptadine (10 mg/kg), In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells (ex vivo) was also markedly reduced in animals pretreated with α,β-amyrins (100 mg/kg) or ketotifen (1 mg/kg), a known mast cell stabilizer. In the open-field test, α,β-amyrins (100 and 200 mg/kg)-pretreated mice showed no impairment of spontaneous locomotion, suggesting that these triterpenoids possess no sedative activity that could account for suppression of scratching behavior. These results clearly indicate the antipruritic effect of α,β-amyrins and suggest that this effect may be related to a stabilizing action on mast cell membrane.
In the search for novel natural compounds effective against visceral nociception, the triterpenoid mixture alpha- and beta-amyrin, isolated from Protium heptaphyllum resin, was assessed in two ...established mouse models of visceral nociception. Mice were pretreated orally with alpha- and beta-amyrin (3, 10, 30, and 100 mg/kg) or vehicle, and the pain-related behavioral responses to intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed. The triterpenoid mixture showed a dose-related significant antinociception against the cyclophosphamide-induced bladder pain, and at 100 mg/kg, the nociceptive behavioral expression was almost completely suppressed. Intracolonic mustard oil-induced nociceptive behaviors were maximally inhibited by 10 mg/kg alpha- and beta-amyrin mixture in a naloxone-reversible manner. While pretreatment with ruthenium red (3 mg/kg, s. c.), a non-specific transient receptor potential cation channel V1 (TRPV1) antagonist, also caused significant inhibition, the alpha (2)-adrenoceptor antagonist, yohimbine (2 mg/kg, s. c.), showed no significant effect. The triterpene mixture (10 mg/kg, p. o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rotarod tests, respectively, indicating the absence of sedative or motor abnormalities that could account for its antinociception. These results indicate that the antinociceptive potential of alpha- and beta-amyrin possibly involves the opioid and vanilloid (TRPV1) receptor mechanisms and further suggests that it could be useful to treat visceral pain of intestinal and pelvic origins.
In recent years, there has been a renewed interest in the search for novel natural substances active against erectile dysfunction. Plants that belong to the genus Aspidosperma (Apocyanaceae) are ...known to be very rich in indole alkaloids and have an ethnomedical history of use as traditional remedies for erectile dysfunction. This study examined whether the indole alkaloidal rich fraction (F3–5) from Aspidosperma ulei Markgr. root bark could manifest penile erection-related behavioral responses (penile erection, erection-like and genital grooming) in mice. Intraperitoneal injection of F3–5 (25 and 50mg/kg) elicited all the three different behavioral responses in a manner similar to yohimbine (2mg/kg, i.p.), a known indole alkaloid. Seventy-five percent of mice treated with yohimbine or F3–5 showed penile erections, which were completely blocked by clonidine, an alpha-2-adrenoceptor agonist and haloperidol, a dopaminergic antagonist and as well as by l-NAME, a nitric oxide synthase inhibitor. These results point out that F3–5 facilitates penile erection in mice possibly through the activation of central dopamine and blockade of presynaptic alpha-2 adrenoceptors with a subsequent enhancement in nitric oxide release from the penile nerves and arteries. This study further supports the traditional use of extracts from Aspidosperma species in erectile dysfunction.
The effects of 1,8‐cineole on d‐galactosamine/lipopolysaccharide (GalN/LPS)‐induced shock model of liver injury was investigated in mice. The co‐administration of GalN (700 mg kg−1, i.p.) and LPS (5 ...μg kg−1, i.p.) greatly elevated serum concentrations of tumour necrosis factor‐α (TNF‐α), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8‐cineole (400 mg kg−1, p.o.) and dexamethasone (1 mg kg−1, s.c.),60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF‐α and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8‐cineole and dexamethasone treatment. The results indicate that 1,8‐cineole protects mice against GalN/LPS‐induced liver injury through the inhibition of TNF‐α production, and suggest that 1,8‐cineole may be a promising agent to combat septic‐shock‐associated pathologies.
This investigation evaluated the role of capsaicin-sensitive afferent neurons in the gastroprotective effect of alpha- and beta-amyrin, a triterpenoid mixture isolated from Protium heptaphyllum ...resin. Gastric mucosai damage was induced in mice by intragastric ethanol and assessed by planimetry. Mice pretreated orally with the amyrin mixture (50 and 100 mg/kg) or capsaicin (2.5 and 5 mg/kg), the pungent principle from red hot peppers, showed a significantly lower intensity of ethanol-associated gastric mucosal damage, in relation to vehicle-treated controls. At higher doses both these agents produced either a diminished protection or no significant effect. The maximal gastroprotection that was observed at the dose of 100 mg/kg amyrin mixture was almost abolished in mice with their sensory afferents chemically ablated by a neurotoxic dose of capsaicin, suggesting that the gastro-protective mechanism of alpha- and beta-amyrin mixture involves at least in part the activation of capsaicin-sensitive primary afferent neurons.
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