Active Compounds in Zingiber officinale as Possible Redox Inhibitors of 5-Lipoxygenase Using an In Silico Approach

International Journal of Molecular Sciences

Maribel Jiménez-Fernández¹  Oscar García-Barradas²  Jaqueline Stephanie Ley-Martínez³  Jose Erick Ortega-Valencia³  Jacqueline Oliva-Ramírez³  Carlos Iván Vencedor-Meraz⁴  Esmeralda Uribe-Lam⁵ 

[1] Centro de Investigación y Desarrollo en Alimentos, Universidad Veracruzana, Av. Dr. Luis Castelazo s/n, Col. Industrial-Animas, Xalapa Enríquez 91190, Veracruz, Mexico;Instituto de Química Aplicada, Universidad Veracruzana, Av. Dr. Luis Castelazo s/n, Col. Industrial-Animas, Xalapa Enríquez 91190, Veracruz, Mexico;Laboratorio de Ingeniería de Superficies, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, Av. Lago de Guadalupe Km. 3.5, Margarita Maza de Juárez, Ciudad López Mateos 52926, Mexico, Mexico;Research and Development Department, Genolife-Información de vida S.A.P.I de C.V., Blvd. Paseo Rio Sonora, Hermosillo 83270, Sonora, Mexico;Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, México, Epigmenio González 500, Fraccionamiento San Pablo, Querétaro 76130, Querétaro, Mexico;

关键词: 5-Lipooxygenase;    6-shogaol;    6-gingerol;    inflammation;    leukotrienes;   

DOI  :  10.3390/ijms23116093

来源: DOAJ

【 摘 要 】

5-Lipoxygenase (5-LOX) converts arachidonic acid to lipidic inflammatory mediators such as leukotrienes (LTs). In diseases such as asthma, LTs contribute to a physiopathology that could be reverted by blocking 5-LOX. Natural products with anti-inflammatory potential such as ginger have been used as nutraceuticals since ancient times. 6-Gingerol and 6-shogaol are the most abundant compounds in the ginger rhizome; they possess anti-inflammatory, antioxidant, and chemopreventive properties. In the present study, 6-gingerol and 6-shogaol structures were analyzed and compared with two commercial 5-LOX inhibitors (zileuton and atreleuton) and with other inhibitor candidates (3f, NDGA, CP 209, caffeic acid, and caffeic acid phenethyl ester (CAPE)). The pharmacokinetics and toxicological properties of 6-gingerol, 6-shogaol, and the other compounds were evaluated. Targeted molecular coupling was performed to identify the optimal catalytic pocket for 5-LOX inhibition. The results showed that 6-gingerol and 6-shogaol follow all of the recommended pharmacokinetic parameters. These compounds could be inhibitors of 5-LOX because they present specific interactions with the residues involved in molecular inhibition. The current study demonstrated the potential of 6-gingerol and 6-shogaol as anti-inflammatory agents that inhibit 5-LOX, as they present a high level of performance in the toxicological analysis and could be catabolized by the cytochrome p450 enzymatic complex; however, 6-gingerol was superior in safety compared to 6-shogaol.

【 授权许可】

Unknown