title: Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats.
abstract: Chamomile (Matricaria chamomilla L., Asteraceae) is a medicinal plant widely used as remedy for pain and gastric disorders. The association of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase its antinociceptive activity, permit the use of lower doses and limit side effects. The aim was to isolate and identify the main chemical constituents of Matricaria chamomilla ethanolic extract (MCE) as well as to explore their activity as cyclooxygenase (COX) inhibitors in silico; besides, to examine the interaction between MCE and diclofenac on nociception in the formalin test by isobolographic analysis, and to determine the level of gastric injury in rats. Three terpenoids, α-bisabolol, bisabolol oxide A, and guaiazulene, were isolated and identified by (1)H NMR. Docking simulation predicted COX inhibitory activity for those terpenoids. Diclofenac, MCE, or their combinations produced an antinociceptive effect. The sole administration of diclofenac and the highest combined dose diclofenac-MCE produced significant a gastric damage, but that effect was not seen with MCE alone. An isobologram was constructed and the derived theoretical ED35 for the antinociceptive effect was significantly different from the experimental ED35; hence, the interaction between diclofenac and MCE that mediates the antinociceptive effect is synergist. The MCE contains three major terpenoids with plausible COX inhibitory activity in silico, but α-bisabolol showed the highest affinity. Data suggest that the diclofenac-MCE combination can interact at the systemic level in a synergic manner and may have therapeutic advantages for the clinical treatment of inflammatory pain.
authors.affiliation: Área Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico; Coordinación de Posgrado de la Universidad del Fútbol y Ciencias del Deporte, San Agustín Tlaxiaca, Hidalgo, Mexico.
authors.forename: Mario I
authors.initials: MI
authors.lastname: Ortiz
authors.affiliation: Área Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico. Electronic address: efernan@uaeh.edu.mx.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández-Martínez
authors.affiliation: Área Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico.
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Soria-Jasso
authors.affiliation: Área Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico.
authors.forename: Isaac
authors.initials: I
authors.lastname: Lucas-Gómez
authors.affiliation: Centro de Investigaciones Químicas del Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico.
authors.forename: Roberto
authors.initials: R
authors.lastname: Villagómez-Ibarra
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apdo. Postal 14-740, D.F., 07000, Mexico.
authors.forename: Martha P
authors.initials: MP
authors.lastname: González-García
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apdo. Postal 14-740, D.F., 07000, Mexico.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
authors.affiliation: Unidad Corporativa de Farmacovigilancia, Laboratorios Sanfer, S.A. de C.V. Mexico, D.F., Mexico.
authors.forename: Mireya
authors.initials: M
authors.lastname: Salinas-Caballero
mesh_terms: D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D008297:Male; D031168:Matricaria / Q000737:chemistry*; D062105:Molecular Docking Simulation; D009043:Motor Activity / Q000187:drug effects; D059225:Nociception / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar; D012015:Reference Standards; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D013816:Thermodynamics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D010936:Plant Extracts; D004008:Diclofenac
keywords: Cyclooxygenase docking; Diclofenac; Gastric damage; Matricaria chamomilla; Nociception; Synergism