ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The high frequency of poisoning by sting or bite from venomous animals has begun to be a serious public health problem in Mexico where scorpion sting is the most common. Because of this, there is the need to seek active substances in plant species with an antagonistic effect against neurotropic activity of scorpion venom. The aim of this work was to demonstrate which of the compounds contained in the n-hexane extract from Aristolochia elegans roots display activity against scorpion venom. MATERIAL AND METHODS: Antagonist activity displayed by extract, fractions and isolated compounds obtained from Aristolochia elegans was guided by the inhibition of smooth muscle contraction induced by scorpion venom (Centruroides limpidus limpidus) in a model of isolated guinea pig ileum. The neolignans obtained from this extract were isolated and analyzed by chromatographic methods including HPLC. The chemical characterization of these compounds was performed by the analysis of (1)H and (13)C NMR spectra. RESULTS: The bio-guided chromatographic fractionation allowed us to isolate 4 known neolignans: Eupomatenoid-7 (1), licarin A (2), licarin B (3), eupomatenoid-1 (4) and other new neolignan which was characterized as 2-(3'-hydroxy-4'-methoxyphenyl)-3-methyl-5-[(E)-α-propen-γ-al]-7-methoxy-benzo [b] furan (5). This compound was named as eleganal. Compounds 1 and 2 were purified from the most active fraction AeF3 (EC50 of 149.9µg/mL, Emax of 65.66%). A doses-response analysis of eupomatenoid-7(1) and licarin A(2) allowed us to establish EC50 values (65.96µg/mL and 51.96µg/mL) respectively. CONCLUSIONS: The antagonistic effect against Centuroides limpidus limpidus scorpion venom displayed by the n-hexane extract from Aristolochia elegans roots is due to the presence of neolignans 1-2 contained in the fraction AeF3. Chemical analysis of fraction AeF2 allowed the isolation of a new compound which was identified as 2-(3'-hydroxy-4'-methoxyphenyl)-3-methyl-5-[(E)-α-propen-γ-al]-7-methoxy-benzo[b]furan (5), denominated as eleganal.
Subject(s)
Antivenins/pharmacology , Aristolochia/chemistry , Lignans/pharmacology , Scorpion Venoms/antagonists & inhibitors , Animals , Antivenins/administration & dosage , Antivenins/isolation & purification , Bites and Stings/drug therapy , Chromatography, High Pressure Liquid/methods , Dose-Response Relationship, Drug , Guinea Pigs , Lignans/administration & dosage , Lignans/isolation & purification , Magnetic Resonance Spectroscopy , Male , Mexico , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/metabolism , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Roots , ScorpionsABSTRACT
We evaluated the immune response of healthy control and stressed Wistar rats submitted to hypothalamic-pituitary-adrenal (HPA) axis activation. Rats were treated with Ginkgo biloba extract (EGb 761) orally (100 mg/kg per day for 7 days). EGb 761 stimulated the digestion index of peritoneal and alveolar macrophages (PM and AM) of stressed rats. Likewise, the cellular immune response measured using the delayed-type hypersensitivity response to sheep red blood cells (SRBC) and the humoral immune response (measured through an anti-SRBC response), were also restored in stressed rats. Thus, this G. biloba extract possesses immunostimulatory activity in addition to its broad spectrum of pharmacological effects.
