Cytotoxic clerodane diterpenes from Casearia rupestris.

Four new clerodane diterpenes, casearupestrins A-D (1-4), were isolated from the leaves of Casearia rupestris. Compounds 1 and 4 were acetylated to yield 2,7-di-O-acetylcasearupestrin A (5) and 2,6-di-O-acetylcasearupestrin D (6). All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Casearupestrin A (1) exhibited the most potent activity against MDA/MB-435 (human melanoma) and SF-295 (human glioblastoma) cells, superior to that of the standard drug doxorubicin.

Atividade antibacteriana de plantas úteis e constituintes químicos da raiz de Copernicia prunifera / Antibacterial activity of useful plants and chemical constituents of the roots of Copernicia prunifera

Extratos etanólicos de Qualea grandiflora e Copernicia prunifera e extrato hexânico de Dipteryx lacunifera foram avaliados quanto a atividade antibacteriana, utilizando ensaios de difusão a partir de orifício e concentração inibitória mínima (CIM), frente a cepas Gram positivas e Gram-negativas, incluindo espécies multidroga resistentes. O extrato de Q. grandiflora apresentou atividade moderada para as cepas de Staphylococcus epidermidis (CIM = 500 µg/mL) e atividade fraca sobre as demais bactérias Gram-positivas testadas e inativo sobre bactérias Gram-negativas. Os resultados obtidos com S. epidermidis apesar de moderados são importantes, uma vez que este microorganismo é o principal causador de bacteremias e sepse associada com dispositivos médicos implantados. gama-Tocoferol e a mistura de sitosterol e estigmasterol foram isolados do extrato etanólico de raiz de C. prunifera e as estruturas destes compostos foram identificadas com base na análise dos dados espectrais de RMN e comparação com a literatura.

Ethanol extracts of Qualea grandiflora and Copernicia prunifera and hexane extract of Dipteryx lacunifera were evaluated by diffusion in agar and minimum inhibitory concentration (MIC) against Gram-positive and Gram-negative bacteria including multiresistant drug strains. The extract of Q. grandiflora presented moderate activity for Staphylococcus epidermidis (MIC = 500 µg/mL) and weak activity against other Gram-positive strains and inactive for Gram-negative species. The results obtained for S. epidermidis despite being moderate are important because this pathogen is often recovered from bacteremia and sepsis from infections of implanted devices. gamma-Tocopherol and the mixture of sitosterol and stigmasterol were isolated from the ethanol extract of the roots of C. prunifera. The structures of these compounds were identified by NMR spectroscopy and comparison with literature data.

Gastroprotective effect of the mixture of alpha- and beta-amyrin from Protium heptaphyllum: role of capsaicin-sensitive primary afferent neurons.

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.

Pentacyclic triterpenoids, alpha,beta-amyrins, suppress the scratching behavior in a mouse model of pruritus.

In the search for natural compounds useful against pruritus, alpha,beta-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 alpha,beta-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 alpha,beta-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 alpha,beta-amyrins (100 mg/kg) or ketotifen (1 mg/kg), a known mast cell stabilizer. In the open-field test, alpha,beta-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 alpha,beta-amyrins and suggest that this effect may be related to a stabilizing action on mast cell membrane.

Gastroprotective and anti-inflammatory effects of resin from Protium heptaphyllum in mice and rats.

The natural resin collected from the trunk wood of Protium heptaphyllum is used in folk medicine to treat inflammatory conditions and to hasten wound repair. In the search of new potential anti-inflammatory agents with gastroprotective property, the present study evaluated its effects in experimental models of gastric ulcer and inflammation. In mice, the resin (200 and 400 mg/kg) significantly attenuated the gastric damage induced by ethanol or acidified ethanol (HCl/ethanol), in a manner similar to N-acetyl-L-cysteine (NAC), a replenisher of sulfhydryls. Unlike NAC the resin failed to restore the ethanol-induced depletion of non-protein sulfhydryl content, indicating a different mechanism of gastroprotection. However, in 4-h pylorus-ligated rats, the resin significantly reduced the total acidity without much change in gastric secretory volume. In rats, at similar doses the resin did not modify the hind-paw edema induced by carrageenan, but effectively reduced the formation of cotton pellet-induced granuloma, suggesting its inhibitory effect on collagen formation but not on acute edema. Furthermore, the vascular permeability increase induced by acetic acid was significantly reduced in mice that received 400 mg/kg resin. The resin demonstrated no overt toxicity in mice up to an oral dose of 5 g/kg. Phytochemical analysis revealed the presence of alpha- and beta-amyrins as principal triterpenoid constituents of resin, which were previously described to have anti-ulcer property. These findings indicate the potential gastroprotective and anti-inflammatory property of P. heptaphyllum resin and further support its popular use in gastrointestinal disorders.