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Kaurane diterpenes are considered important compounds in the development of new highly effective anticancer chemotherapeutic agents. Genotoxic effects of anticancer drugs in non-tumour cells are of special significance due to the possibility that they induce secondary tumours in cancer patients. In this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (KA), i.e. (-)-kaur-16-en-19-oic acid, isolated from Xylopia sericeae St. Hill, using several standard in vitro and in vivo protocols (comet, chromosomal aberration, micronucleus and Saccharomyces cerevisiae assays). Also, an analysis of structure-activity relationships was performed with two natural diterpenoid compounds, 14-hydroxy-kaurane (1) and xylopic acid (2), isolated from X. sericeae, and three semi-synthetic derivatives of KA (3-5). In addition, considering the importance of the exocyclic double bond (C16) moiety as an active pharmacophore of KA cytotoxicity, we also evaluated the hydrogenated derivative of KA, (-)-kauran-19-oic acid (KAH), to determine the role of the exocyclic bond (C16) in the genotoxic activity of KA. In summary, the present study shows that KA is genotoxic and mutagenic in human peripheral blood leukocytes (PBLs), yeast (S. cerevisiae) and mice (bone marrow, liver and kidney) probably due to the generation of DNA double-strand breaks (DSB) and/or inhibition of topoisomerase I. Unlike KA, compounds 1-5 and KAH are completely devoid of genotoxic and mutagenic effects under the experimental conditions used in this study, suggesting that the exocyclic double bond (C16) moiety may be the active pharmacophore of the genetic toxicity of KA., (2010 Elsevier B.V. All rights reserved.)

Guarana, a herbal extract from the seeds of Paullinia cupana Mart. has been evaluated in comparison with caffeine on mouse behaviour in forced swimming and open field tests. Guarana (25 and 50 mg/kg, p.o.) and caffeine (10 and 20 mg/kg, p.o.) each significantly reduced the duration of immobility in the forced swimming test suggesting an antidepressant-like effect in mice. At these doses, neither substance affected ambulation in the open field test. However, a high dose of guarana (100 mg/kg) and caffeine (30 mg/kg) significantly enhanced the locomotor activity in the open field test. Caffeine, but not guarana, could effectively block an adenosine agonist, cyclopentyl adenosine (CPA)-induced increase in swimming immobility suggesting that mechanism(s) other than the adenosinergic mechanism are involved in the antidepressant-like activity of guarana., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

The effects of guarana (Paullinia cupana) extract were analyzed in rats on acute gastric lesions induced by ethanol and indomethacin and were compared to those produced by caffeine, a methylxanthine. Guarana (50 and 100 mg/kg p.o.) pretreated animals showed a significant reduction in the severity of gastric lesions induced by absolute ethanol in a manner similar to caffeine (20 and 30 mg/kg p.o.). Against indomethacin-induced gastric ulceration, guarana at a higher dose offered significant protection but caffeine was ineffective at the doses tested. In 4 h pylorus-ligated rats, both guarana and caffeine caused significant diminution in the gastric secretory volume as well as the total acidity. Gastrointestinal transit in mice was not significantly affected by either of these agents. These findings indicate that guarana has a gastroprotective property that needs further elucidation as regards to its mechanism., (Copyright 2003 John Wiley & Sons, Ltd.)

The acetone soluble fraction from a crude methanol extract of Stryphnodendron adstringens stem bark (AFSAB) was evaluated in acute (ethanol, indomethacin and hypothermic restraint-stress) and chronic (acetic acid) models of gastric ulceration and on basal and bethanechol-stimulated gastric acid secretion in rats. Rats pretreated orally with AFSAB at doses of 400 and 800 mg/kg showed significant decreases of gastric lesion scores in ethanol (62% and 98%) and hypothermic restraint-stress (89% and 88%) models but exerted no significant influence on indomethacin-induced acute or acetic acid-induced chronic ulceration. In pylorus-ligated rats, AFSAB significantly decreased the basal as well as bethanechol-stimulated gastric secretory volume and the total acidity with an elevated pH value. AFSAB failed to modify the gastric mucus and the gastric wall nonprotein-sulphydryl content. These results point to a possible antisecretory effect of AFSAB which account for the observed antiulcer activity in ethanol and hypothermic restraint-stress induced models of acute gastric ulceration., (Copyright 2002 John Wiley & Sons, Ltd.)

The crude leaf extracts of Croton cajucara Benth. were studied for their antinociceptive property in chemical and thermal models of nociception in mice. All the tested extracts (hexanic, chloroformic and methanolic), at oral doses of 100 and 200 mg/kg demonstrated significant inhibition of acetic acid-induced writhing and the second phase response of formalin, but did not manifest a significant effect in hot-plate test.

The effects of oleo-resin obtained from the stem bark of Copaifera langsdorffii on ethanol, indomethacin and hypothermic restraint-stress induced gastric lesions were studied in rats. Oral administration of oleo-resin at doses of 200 and 400 mg/kg provided dose-dependent significant protection against gastric damage caused by ethanol and restraint stress, and at a dose of 400 mg/kg it also prevented the gastric ulceration induced by indomethacin. Further, in the 4 h pylorus ligated rats, the accumulation of gastric juice volume and the mucus secretion was significantly enhanced by oleo-resin whereas the total acidity was inhibited. These results highlight the gastroprotective potential of C. langsdorffii oleo-resin and the need for a systematic study on this traditional remedy.

In order to assess the use of Astronium urundeuva in folk medicine for treatment of diarrheal conditions, the alcoholic extract of its bark was tested on gastrointestinal transit in mice. The extract at oral doses of 100 and 200 mg/kg significantly inhibited physostigmine-induced gastrointestinal propulsion. Considering these data together with an in-vitro anti-acetylcholine effect reported earlier from this laboratory, we suggest that anti-cholinergic effects of the plant may account in part for its anti-diarrheal activity.

The anti-inflammatory activity of a purified fraction of the rhizome of Wilbrandia (cf) verticillata, which contains two novel norcucurbitacin glucosides, is reported. The increase of vascular permeability induced by acetic acid in mice (N = 5) was inhibited 69% and 90% by 50 and 100 mg/kg of the purified fraction, po (P less than 0.01). Acetylsalicylic acid (200 mg/kg), po, inhibited the response by 62% under the same conditions (P less than 0.05). The purified fraction (100 mg/kg, po) also significantly inhibited paw swelling in the rat formaldehyde-induced arthritis model on 8 of 10 days and reduced the swelling by 63% on day 10. Dexamethasone (1 mg/kg, ip) was more effective than the extract under the same conditions. These data partially characterize the anti-inflammatory activity of the purified fraction from this plant which is used in Brazilian folk medicine for the treatment of arthritis and related disorders.