Antinociceptive, genotoxic and histopathological study of Heliopsis longipes S.F. Blake in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: H. longipes S.F. Blake (Asteraceae) is a Mexican plant, whose roots are traditionally used as a condiment, as a mouth anesthetic, and as an antiparasitic. Affinin is the alkamide present in higher amounts in the roots of H. longipes. AIM OF THE STUDY: To date, there are no published studies regarding the relation between the analgesic properties, in vivo cytotoxicity, and DNA-damaging potential of H. longipes ethanol extract (HLEE). MATERIALS AND METHODS: The HLEE was chromatographically fingerprinted to validate its affinin contents. Biological evaluation was conducted in sets of 6-8 CD1(+) mice. Antinociceptive effect was evaluated using the writhing and hot-plate tests, and mutagenic and cytotoxic effects were evaluated with micronucleous test in CD1(+) mice. For histopathological studies, biological samples from liver, heart, kidneys, spleen, lung, and brain were collected and stained. RESULTS: Oral administration of HLEE (3-100 mg/kg) produced a dose-dependent antinociceptive effect in both assays. In micronucleus assay, the variability in the number of micronucleated polychromatic erythrocytes (MNPE) induced, and PE/NE index, the ratio of polychromatic erythrocytes with respect to the number of normochromatic erythrocytes induced by HLEE in the evaluated schedule, were small and nonsignificant. After histopathological results, HLEE showed polioencephalomalacia with 1000 mg/kg dose. CONCLUSIONS: This work provides evidence that HLEE exerts analgesic effects, with no genotoxic effects in vivo. These findings would be an important contribution to explain the use of H. longipes root as an effective analgesic in traditional medicine, and to establish for the first time the absence of genotoxic and cytotoxic effects of the root in bioactive doses in vivo.

Interaction between Heliopsis longipes extract and diclofenac on the thermal hyperalgesia test.

Heliopsis longipes is an herbaceous plant found in Mexico, used traditionally for its analgesic and anesthetic activities. Plant extracts in combined use with synthetic drugs may represent a therapeutic advantage for the clinical treatment of pain, allowing the use of lower doses, and limiting side-effects. Therefore, the main objective of this study was to determine the possible pharmacological interaction between Heliopsis longipes ethanolic extract (HLEE) and diclofenac in the Hargreaves model of thermal hyperalgesia in the mouse. HLEE, diclofenac or fixed-dose ratio HLEE-diclofenac combinations were administered systemically to mice and the antihyperalgesic effect was evaluated using the thermal hyperalgesia test. All treatments produced a dose-dependent antihyperalgesic effect. ED(30) values were estimated for all the treatments and an isobologram was constructed. The derived theoretical ED(30) value for the HLEE-diclofenac combination was 54.4+/-9.4 mg/kg body wt, significantly higher than the actually observed experimental ED(30) value, 8.6+/-4.0 mg/kg body wt. This result corresponds to synergistic interaction between HLEE and diclofenac in the Hargreaves model of thermal hyperalgesia. Data suggest that low doses of the HLEE-diclofenac combination can interact synergistically at the systemic level and that this association may therefore represent a therapeutic advantage for the clinical treatment of inflammatory pain.

Antimutagenicity of Stevia pilosa and Stevia eupatoria evaluated with the Ames test.

Stevia pilosa and Stevia eupatoria are plants used for various purposes in traditional medicine. In this report we studied the antimutagenic effect of methanolic extracts obtained from leaves, root, and flowers of the two species using the Ames test with and without metabolic activation. We tested the effect of the extracts on the damage induced by three mutagens with the following results: 1 - we found an inhibitory effect of both species on the mutagenicity induced by 2-aminoanthracene in the strain TA98. The best antimutagenic effect was obtained with leaves of both species and the flowers of S. eupatoria (99%), 2 - the mutations induced with N-ethyl-N'-nitro-N-nitrosoguanidine in the strain TA100 was also reduced. The flowers of S. pilosa and the root of S. eupatoria showed about 93% of inhibition, 3 - finally, the mutations induced by mitomycin-C on the strain TA102 had a reduction of 87% with the leaves of S. eupatoria. Besides, we determined the radical scavenging potential of the extracts with the DPPH method, and found a potent effect produced by all extracts, with an efficacy of more than 90%. The present study showed both antimutagenic and antioxidant potential of the tested extracts, and suggest the pertinence to confirm these effects in other models, and to accurately determine their mechanism of action.