Anxiolytic-like effects and toxicological studies of Brickellia cavanillesii (Cass.) A. Gray in experimental mice models.

ETHNOPHARMACOLOGICAL RELEVANCE: Brickellia cavanillesii (Asteraceae) (Cass.) A. Gray is one of the popular plants consumed in Central America and Mexico for the treatment of several diseases such as hypertension, diabetes and anxiety, among others. AIM OF THE STUDY: To determine the anxiolytic-like effect of B. Cavanillesii and the safety of its use through toxicological studies. MATERIAL AND METHODS: Anxiolytic-like effects of soluble-methanol extract of B. cavanillesii (MEBc) were evaluated in ambulatory activity (open-field test), hole-board test, cylinder of exploration, the elevated plus-maze and the potentiation of the sodium pentobarbital-induced hypnosis mice models. On the other hand, in vivo toxicological studies were conducted on acute and sub-acute mice models recommended by OECD. Active MEBc was subjected to phytochemical studies through conventional chromatographic techniques to isolate bioactive compounds. RESULTS: MEBc (100mg/Kg) showed significant anxiolytic-like effect on animal model used (p<0.05). The phytochemical analysis of MEBc allowed the isolation of two major compounds nicotiflorin and acacetin, among others. Both compounds were found to be partially responsible for the anxiolytic-like effects. Moreover, a median lethal dose (LD50) higher than 2000mg/Kg was determined in mice and sub-acute oral administration of MEBc (100mg/Kg) did not alter body weight, clinical chemistry parameters (ALT and AST) and it did not induce any toxic nor alteration in the liver, kidney and heart functions. CONCLUSIONS: In current investigation, we have shown that MEBc has a wide range of pharmacology-toxicology patterns. The results support further investigation of MEBc as a potential anxiolytic phytomedicinal agent.

Vasorelaxant mode of action of dichloromethane-soluble extract from Agastache mexicana and its main bioactive compounds.

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.

Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC) 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound) and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load) that may be caused by a high load of epiphytes than to damage caused by the xylophages.

Evaluation of the neuroprotective activity of stansin 6, a resin glycoside from Ipomoea stans.

Stansin 6 a tetrasaccharide resin glycoside isolated from the root of Ipomoea stans was evaluated as anticonvulsant and neuroprotective in kainic acid-induced seizures of rats. Intraperitoneal injection of kainic acid (10 mg/kg) induced typical behavioral seizures such as wet dog shakes and limbic seizures, and histopathological changes in the hippocampus (degeneration and loss of pyramidal cells in CA1 to CA4 areas). Stansin 6 (10-80 mg/kg) had no effect on the behavior of rats and did not induce hippocampal damage. Pretreatment with stansin 6 inhibited convulsions in rats from kainic acid-induced seizures, reduced the degeneration pattern in the CA3 region, decreased astrocytic reactivity, and reduced the expression of IL-1ß and TNF-α induced by kainic acid. These results suggest that stansin 6 possesses neuroprotective and anticonvulsant activities.

Active compounds against tinea pedis dermatophytes from Ageratina pichinchensis var. bustamenta.

Secondary metabolites 5-acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-2,3-dihydrobenzofurane (1), 5-acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-6-methoxy-2,3-dihydrobenzofurane (2), espeletone (3), encecalinol (4), O-methylencecalinol (5), encecalin (6), sonorol (7), taraxerol (8), (+)-beta-eudesmol (9), and a mixture of beta-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.