A Patent-Pending Ointment Containing Extracts of Five Different Plants Showed Antinociceptive and Anti-Inflammatory Mechanisms in Preclinical Studies
Juan Carlos Barragan-Galvez,
Maria Leonor Gonzalez-Rivera,
Juan C. Jiménez-Cruz,
Araceli Hernandez-Flores,
Guadalupe de la Rosa,
Martha L. Lopez-Moreno,
Eunice Yañez-Barrientos,
Michelle Romero-Hernández,
Martha Alicia Deveze-Alvarez,
Pedro Navarro-Santos,
Claudia Acosta-Mata,
Mario Alberto Isiordia-Espinoza,
Angel Josabad Alonso-Castro
Affiliations
Juan Carlos Barragan-Galvez
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36200, Mexico
Maria Leonor Gonzalez-Rivera
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36200, Mexico
Juan C. Jiménez-Cruz
Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCyT)-Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolas de Hidalgo, Morelia 58030, Mexico
Araceli Hernandez-Flores
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36200, Mexico
Guadalupe de la Rosa
División de Ciencias e Ingenierías, Universidad de Guanajuato, Campus León, León 37150, Mexico
Martha L. Lopez-Moreno
Chemistry Department, University of Puerto Rico at Mayagüez, 259 Boulevard Alfonso Valdez, Mayagüez 00681, Puerto Rico
Eunice Yañez-Barrientos
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36200, Mexico
Michelle Romero-Hernández
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36200, Mexico
Martha Alicia Deveze-Alvarez
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36200, Mexico
Pedro Navarro-Santos
Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCyT)-Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolas de Hidalgo, Morelia 58030, Mexico
Claudia Acosta-Mata
Laboratorio de Patología Clínica, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Guanajuato 36000, Mexico
Mario Alberto Isiordia-Espinoza
Clinics Department, University of Guadalajara, Tepatitlan 47620, Mexico
Angel Josabad Alonso-Castro
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36200, Mexico
Background/Objectives: The antinociceptive and anti-inflammatory effects of a patent-pending ointment containing plant extracts from Eucalyptus globulus, Curcuma longa, Hamamelis virginiana, Echinacea purpurea, and Zingiber officinale were evaluated. Methods: Plant extracts were chemically characterized by gas chromatography–mass spectroscopy. The antinociceptive activity of the ointment was assessed using the hot plate, tail flick, and formalin tests, whereas the anti-inflammatory activity was measured using the acute and chronic TPA-induced ear edema tests. Mechanisms of action were evaluated using inhibitors from signaling pathways related to pain response and by using histological analysis and assessing the expression and activity of pro-inflammatory mediators. Results: The ointment showed antinociceptive and anti-inflammatory effects like those observed with diclofenac gel (1.16% v/v) and ketoprofen gel (2.5% v/v). The antinociceptive actions of the ointment are mediated by the possible participation of the opiodergic system and the nitric oxide pathway. The anti-inflammatory response was characterized by a decrease in myeloperoxidase (MPO) activity and by a reduction in ear swelling and monocyte infiltration in the acute inflammation model. In the chronic model, the mechanism of action relied on a decrease in pro-inflammatory mediators such as COX-2, IL-1β, TNF-α, and MPO. An in-silico study with myristic acid, one of the compounds identified in the ointment’s plant mixture, corroborated the in vivo results. Conclusions: The ointment showed antinociceptive activities mediated by the decrease in COX-2 and NO levels, and anti-inflammatory activity due to the reduction in IL-1β and TNFα levels, a reduction in MPO activity, and a decrease in NF-κB and COX-2 expression.
