Antiulcerogenic activity of four extracts obtained from the bark wood of Quassia amara L. (Simaroubaceae).

Quassia amara L., a neotropical forest shrub of the Simaroubaceae family, is widely used in Caribbean folk medicine and in some northern states of Brazil for the treatment of gastric ulcers. This plant is a source of numerous compounds including both beta-carbonile and cantin-6 alkaloids as well as, primarily, the bitter compounds known as quassinoids. We analyzed the possible antiulcerogenic activities of four extracts of different polarities: 70% ethanol (70% EtOH), 100% EtOH, 100% dichloromethane (DCM), and 100% hexane (HEX) obtained from Quassia amara bark. All extracts, administered at doses of 5000 mg/kg orally and 1000 mg/kg intraperitoneally, caused neither toxicity or death. In the indomethacin/bethanechol-induced gastric ulcer, 70% EtOH, 100% EtOH, DCM and HEX extracts, 100 mg/kg, p.o., inhibited the gastric ulcer (22.5, 23.4, 50.5, 46.8%, respectively). 70% EtOH, 100% EtOH, DCM, and HEX extracts reduced the gastric injury induced by the hypothermic restraint-stress test in mice (70.7, 80, 60, 82.7%, respectively). In the pylorus ligature of the mouse stomach, following pre-treatment with a single intraduodenal administration of 100 mg/kg of each extract, only 70% EtOH did not change the biochemical parameters of gastric juice. 100% EtOH, DCM and HEX extracts presented decreased gastric juice content, increased pH values and decreased acid output. We also determined the antiulcerogenic activity on HCl-EtOH-induced gastric ulcers in mice at four doses (25, 50, 75, 100 mg/kg, p.o.), then evaluated the possible dose-dependent relation and calculated the ED50 values. Except for 70% EtOH at a dose of 25 mg/kg, the other extracts showed significantly activity (p<0.05). The free mucous amount in the gastric stomach content was also evaluated. All extracts showed significant increases (p<0.05) of free mucous. This effect was abolished when the animals were pre-treated with indomethacin. Prostaglandin synthesis was evaluated by the administration of HEX extracts by the oral route (100 mg/kg). Prostaglandin synthesis was significantly, increased by 52.3% (p<0.05), and this effect was abolished with prior administration of indomethacin. We concluded that Quassia amara is a probable source for a new drug to treat gastric ulcers, and the mechanism of its activity relates to cytoprotective factors, such as mucous and prostaglandins, but there is still the possibility that antisecretory activity is involved in its antiulcerogenic effect.

Natural trans-crotonin: the antiulcerogenic effect of another diterpene isolated from the bark of Croton cajucara Benth.

The nor-clerodane diterpene trans-crotonin isolated from the bark of Croton cajucara BENTH. was investigated for its ability to prevent the formation of gastric-mucosa ulceration in different experimental models in mice. The results obtained from crotonin were compared with those obtained with another diterpene, DHC (trans-dehydrocrotonin) in the same models. When previously administered (p.o.) at the dose of 100 mg/kg, crotonin, as well as DHC, significantly reduced (p<0.05) gastric injury induced by stress (72, 67%), indomethacin/bethanechol (78, 29%) and pylorus ligature (35, 30%). In the HCl/ethanol-induced gastric ulcer model, at oral doses of 100 and 250 mg/kg, crotonin significantly prevented (p<0.05) the formation of gastric lesions by 51 and 56%, respectively, when compared to the control group. Gastric injury was also of significantly less magnitude in the DHC treatment group (p<0.05). In the pylorus-ligature model, crotonin (p.o.), like cimetidine, increased the volume of gastric juice when compared to the control group (p<0.05). No significant modifications where found in gastric parameters such as pH or total acid content after oral crotonin treatment. However, systemic alterations were observed when crotonin (100 mg/kg) was previously administered intraduodenally to mice. We observed significant changes (p<0.001) in gastric-juice parameters such as an increase in volume and a decrease in gastric acidity. Those pre-treated with crotonin as well as with DHC did not increase free mucus production (p>0.05). The results suggest that crotonin presents a significant anti-ulcer effect when assessed in these ulcer-induced models. As with DHC, the antiulcerogenic effects of crotonin are probably related to anti-secretory or/and gastroprotective properties of this substance. In light of results obtained with DHC and natural trans-crotonin in the present study, we concluded that the A-ring of both diterpenes is not directly involved in the antiulcerogenic activity.

Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the Turneraceae as a new source of antiulcerogenic drugs.

Turnera ulmifolia is a plant belonging to the family Turneraceae, popularly known in Brazil as chanana. This species is distributed from Guyana to southern Brazil where it is considered a weed. The plant occurs in tropical rain forest, fields, and gardens. Chanana tea is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric dysfunction including gastric and duodenal ulcers. In this study, the ability of a lyophilized infusion, as an aqueous fraction (AqF) of the aerial parts of T. ulmifolia, was investigated for its ability to prevent ulceration of the gastric and duodenal mucosa was examined in mice and rats, respectively. The AqF significantly reduced the formation of lesions associated with HCl/ethanol administration by 39% and 46%, respectively, at doses of 500 mg/kg and 1000 mg/kg, p.o. The AqF also significantly reduced the incidence of gastric lesions induced by a combination of indomethacin and bethanechol by 58% and 72% at doses of 500 mg/kg and 1000 mg/kg, respectively. In stress-induced gastric ulcer, the inhibition by the AqF was 48%, 57%, and 58% at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg, respectively (p<0.05). A pyloric ligature experiment showed that the highest dose of the AqF significantly affected the gastric juice parameters by increasing the pH from 2.5 (control) to 5.3 and decreasing the acid output from 11.3 (control) to 3.7 mEq/ml/4 h. The AqF had no significant effect on duodenal ulcers induced by cysteamine. Preliminary phytochemical screening confirmed that flavonoids were the major constituents of the AqF of T. ulmifolia. These results indicate that this extract has a significant antiulcerogenic effect, as popularly believed.