Heliopsis longipes is used as analgesic in Mexican traditional medicine. The present study assesses the possible antinociceptive effect of Heliopsis longipes and describes the pharmacological mechanism of action of the antinociceptive effect of affinin, identified as the one active principle in Heliopsis longipes acetone extract. Intraperitoneal administration of H. longipes extract and affinin produced a dose-dependent antinociceptive effect when assessed in mice submitted to acetic acid and capsaicin tests. Affinin-induced antinociception (30 mg/kg, i. p.) was blocked by naltrexone (1 mg/kg, s. c.), p-chlorophenylalanine (80 mg/kg, i. p.) and flumazenil (5 mg/kg, s. c.) suggesting that its pharmacological effect could be due to the activation of opiodergic, serotoninergic and GABAergic systems. In addition, the antinociceptive effect of affinin was attenuated by pretreatment with 1H-[1,2,4]oxadiazolo[1,2-a]quinoxalin-1-one (1 mg/kg, s. c.) and glibenclamide (10 mg/kg, s. c.) suggesting that the nitric oxide-K⁺ channels pathway could be involved in its mechanism of action. These results suggest that affinin itself or its derivatives may have potential antinociceptive effects.

Context: Agastache mexicana (Kunth) Lint & Epling (Lamiaceae) is a plant used in Mexican traditional medicine for the treatment of hypertension, anxiety and so on. Objective: To determine the vasorelaxant effect and functional mode of action of dichloromethane-soluble extract from A. mexicana (DEAm) and isolate the constituents responsible for the pharmacological activity. Materials and methods: Extracts were prepared from the aerial parts of A. mexicana (225.6 g) by successive maceration with hexane, dichloromethane and methanol (three times for 72 h at room temperature), respectively. DEAm (0.01–1000 μg/mL), fractions (at 174.27 μg/mL), acacetin and ursolic acid (UA) (0.5–500 μM) were evaluated to determine their vasorelaxant effect on ex vivo rat aorta ring model. In vivo UA antihypertensive action was determined on spontaneously hypertensive rats. Results and discussion: DEAm induced a significant vasorelaxant effect in concentration-dependent and endothelium-independent manners (EC₅₀=174.276 ± 5.98 μg/mL) by a calcium channel blockade and potassium channel opening. Bio-guided fractionation allowed to isolate acacetin (112 mg), UA (2.830 g), acacetin/oleanolic acid (OA) (M1) (155 mg) and acacetin/OA/UA (M2) (1.382 g) mixtures, which also showed significant vasodilation. UA significantly diminished diastolic (80 mmHg) and systolic blood pressure (120 mmHg), but heart rate was not modified. Conclusion: DEAm produced significant vasorelaxant action by myogenic control cation. The presence of acacetin, OA and UA into the extract was substantial for the relaxant activity of DEAm. In vivo antihypertensive action of UA corroborates the use of A. mexicana as an antihypertensive agent on Mexican folk medicine.

Secondary metabolites 5-acetyl-3β-angeloyloxy-2β-(1-hydroxyisopropyl)-2,3-dihydrobenzofurane (1), 5-acetyl-3β-angeloyloxy-2β-(1-hydroxyisopropyl)-6-methoxy-2,3-dihydrobenzofurane (2), espeletone (3), encecalinol (4), O-methylencecalinol (5), encecalin (6), sonorol (7), taraxerol (8), (+)-β-eudesmol (9), and a mixture of β-sitosterol and stigmasterol, were isolated from the aerial parts of Ageratina pichinchensis var. bustamenta. The antimicrobial activity of compounds 6, 8 and 9, together with derivatives 9a and 9b against the most important dermatophytes responsible for tinea pedis infection, Trichophyton rubrum and T. mentagrophytes, and against Candida albicans and Aspergillus niger were determined, showing that the three natural products were active against both Trichophyton species. Ageratina pichinchensis var. bustamenta is used in folk medicine to treat skin infections and wounds, and this study confirms that the n-hexane extract contains metabolites which are responsible for these utilities.