Gallic and ellagic acids: two natural immunomodulator compounds solve infection of macrophages by Leishmania major.

Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC50) values 16.4 and 9.8 µg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC50 values 126.6 and 23.8 µg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC50 values 5.0 and 0.9 µg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca2+i] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.

Estudo do creme de buriti (Mauritia flexuosa L.) no processo de cicatrização / Study of buriti (Mauritia flexuosa L.) cream in the healing process

Objetivo: Avaliar o efeito do creme de buriti (Mauritia flexuosa L .) na cicatrização de lesões cutâneas em camundongos. Métodos: Cinquenta e seis camundongos foram submetidos ao procedimento cirúrgico de exérese da pele na região dorsal. Após a cirurgia, os grupos foram tratados com solução fisiológica 0,9%, creme de buriti a 5% e a 10% e Fibrase®. Resultados: No sétimo dia, foi observada uma redução significativa da área da ferida nos animais tratados com creme de buriti 5% e Fibrase® em relação ao controle. Não foram observadas diferenças entre os grupos no 14º dia de tratamento. A análise histológica demonstrou a presença de tecido de granulação mais evoluído, fibras colágenas e fibroblastos nas amostras do creme de buriti a 5% e Fibrase a partir do sétimo dia de tratamento. Conclusão: O creme de óleo de buriti a 5% apresentou capacidade aceleração do processo de cicatrização.

Objective: To evaluate the effect of buriti (Mauritia flexuosa L.) cream on the healing of skin lesions in mice. Methods: Fifty-six mice underwent surgical procedure of excision of the skin in the dorsal region. After surgery, the groups were treated with saline 0.9%, buriti cream 5% and 10% and Fibrase®. Results: On the seventh day was observed a significant reduction of the wound area in the animals treated with cream buriti 5% and Fibrase® when compared to control. No differences were observed between groups on the 14 th day of treatment. Histological examination showed the presence of granulation issue more evolved, fibroblasts and collagen fibers in the samples buriti cream 5% and Fibrase® from the seventh day of treatment. Conclusion: The buriti cream 5% is able to accelerate the healing process.

Vitamin E ameliorates high dose trans-dehydrocrotonin-associated hepatic damage in mice.

trans-Dehydrocrotonin (t-DCTN), the diterpenoid from Croton cajucara Bentham, exhibits hypoglycemic and hypolipidemic activities, but in high doses is associated with a discrete hepatotoxicity. In the search for measures to mitigate this, pretreatment with the antioxidants N-acetylcysteine and vitamin E has been examined. Mice that received a high dose t-DCTN (100 mg/kg) manifested hepatic damage, as evidenced by significant elevations in serum ALT and AST, and hepatic GSH, and histological alterations, which could be obliterated by pretreatment with vitamin E, but not with N-acetylcysteine, possibly by creating an effective antioxidant balance.

Estudo farmacológico dos efeitos gastrointestinais e comportamentais do lupeol e da dilactona do ácido valonéico, isolados de Cenostigma macrophyllum Tul., em roedores [manuscrito] / Study of the pharmacological and behavioral effects of gastrointestinal lupeol and the dilactone valonéico acid, isolated Cenostigma macrophyllum Tul., in rodents [manuscript]

O triterpeno lupeol e o tanino hidrolisável dilactona do ácido valonéico (DAV), componentes majoritários de Cenostigma macrophyllum Tul. (Leguminoseae), foram avaliados no modelo experimental de lesão gástrica induzida por etanol e em modelos comportamentais. O lupeol (3, 10 e 30 mg/kg, v.o.) e a DAV (3, 10 e 30 mg/kg, i.p.) atenuaram significativamente (p < 0,05) as lesões gástricas induzidas por etanol. No estudo mecanístico, o lupeol (30 mg/kg) e a DAV (10 mg/kg) mostraram ação antioxidante, prevenindo a depleção de grupos sulfidrilas não protéicos e a participação do óxido nítrico, de prostaglandinas, de canais de potássio ATP-dependentes e canais de cálcio. Foi observada ainda a participação de receptores alfa-adrenérgicos, mas não de receptores opióides, no mecanismo gastroprotetor das substâncias. Tanto o lupeol (30 mg/kg) quanto a DAV (10 mg/kg) reduziram a acidez gástrica total sem alterar o volume secretório gástrico no modelo de ligadura do piloro. Na avaliação sobre a motilidade intestinal normal, o tratamento com lupeol (3, 10 e 30 mg/kg) não alterou o percentual de trânsito em relação ao controle, contudo a DAV (3, 10 e 30 mg/kg) reduziu de forma significativa (p < 0,05) o percentual de trânsito, por um mecanismo que não envolve receptores opióides ou adrenérgicos...

Gastroprotective mechanisms of centipedic acid, a natural diterpene from Egletes viscosa LESS.

This study was aimed to clarify the mechanisms of gastroprotection by centipedic acid (CPA), a natural diterpene from Egletes viscosa LESS. (Asteraceae) using ethanol-induced gastric mucosal damage in mice and gastric secretion in 4-h pylorus-ligated rats as model systems. In mice, intragastrically administered CPA (25, 50, 100 mg/kg) greatly reduced the mucosal lesions induced by 96% ethanol (0.2 ml, p.o.) by 18, 53, and 79%, respectively, whereas N-acetylcysteine (NAC, 300 mg/kg, i.p.), the reference compound produced a 50% inhibition. In 4-h pylorus-ligated rats, CPA (50 mg/kg) applied intraduodenally decreased both gastric secretory volume and total acidity. Similar to NAC, the plant diterpene effectively prevented the ethanol associated decrease in non-proteic sulfhydryls (NP-SH) and the elevated thiobarbituric acid-reactive substances (TBARS) in gastric tissue, suggesting that these compounds exert an antioxidant effect. Pretreatment of mice with indomethacin, the cyclooxygenase inhibitor but not with capsazepine, the transient receptor potential vanilloid-1 (TRPV1)-receptor antagonist greatly suppressed the gastroprotective effect of CPA. Furthermore, CPA gastroprotection was significantly attenuated in mice pretreated with L-NAME or glibenclamide the respective inhibitors of nitric oxide synthase and K(+)(ATP) channel activation. These data suggest that CPA affords gastroprotection by different and complementary mechanisms, which include a sparing effect on NP-SH reserve, and roles for endogenous prostaglandins, nitric oxide, and TRPV1-receptor and K(+)(ATP) channel activation.