title: Neolignans from Aristolochia elegans as antagonists of the neurotropic effect of scorpion venom.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Southern Biomedical Research, Mexican Institute of Social Security, Argentina No. 1, Col. Centro, 62790 Xochitepec, Morelos, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zamilpa
authors.affiliation: Southern Biomedical Research, Mexican Institute of Social Security, Argentina No. 1, Col. Centro, 62790 Xochitepec, Morelos, Mexico.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Abarca-Vargas
authors.affiliation: Development Center Biotic Products. Instituto Politécnico Nacional (IPN), 62761 Yautepec, Morelos, Mexico.
authors.forename: Elsa
authors.initials: E
authors.lastname: Ventura-Zapata
authors.affiliation: Southern Biomedical Research, Mexican Institute of Social Security, Argentina No. 1, Col. Centro, 62790 Xochitepec, Morelos, Mexico.
authors.forename: Lidia
authors.initials: L
authors.lastname: Osuna-Torres
authors.affiliation: Departament of Biological Systems, UAM-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, México, DF 04960 Mexico.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Zavala
authors.affiliation: Southern Biomedical Research, Mexican Institute of Social Security, Argentina No. 1, Col. Centro, 62790 Xochitepec, Morelos, Mexico.
authors.forename: Maribel
authors.initials: M
authors.lastname: Herrera-Ruiz
authors.affiliation: Southern Biomedical Research, Mexican Institute of Social Security, Argentina No. 1, Col. Centro, 62790 Xochitepec, Morelos, Mexico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Jiménez-Ferrer
authors.affiliation: Southern Biomedical Research, Mexican Institute of Social Security, Argentina No. 1, Col. Centro, 62790 Xochitepec, Morelos, Mexico. Electronic address: gmanases2000@gmail.com.
authors.forename: Manasés
authors.initials: M
authors.lastname: González-Cortazar
mesh_terms: D000818:Animals; D000997:Antivenins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D030022:Aristolochia / Q000737:chemistry*; D001733:Bites and Stings / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D017705:Lignans / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008800:Mexico; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D018517:Plant Roots; D012604:Scorpion Venoms / Q000037:antagonists & inhibitors*; D012605:Scorpions
chemical_list: D000997:Antivenins; D017705:Lignans; D010936:Plant Extracts; D012604:Scorpion Venoms
keywords: Aristolochia elegans; Aristolochiaceae; Centruroides limpidus limpidus; neolignans; scorpion venom