title: Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages.
abstract: Inflammatory response plays an important role in the activation and progress of many debilitating diseases. Natural products, like cannabidiol, a constituent of Cannabis sativa, and moringin, an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucomoringin present in Moringa oleifera seeds, are well known antioxidants also endowed with anti-inflammatory activity. This is due to a covalent-based mechanism for ITC, while non-covalent interactions underlie the activity of CBD. Since these two mechanisms are distinct, and the molecular endpoints are potentially complementary, we investigated in a comparative way the protective effect of these compounds alone or in combination on lipopolysaccharide-stimulated murine macrophages. Our results show that the cannabidiol (5μM) and moringin (5μM) combination outperformed the single constituents that, at this dosage had only a moderate efficacy on inflammatory (Tumor necrosis factor-α, Interleukin-10) and oxidative markers (inducible nitric oxide synthase, nuclear factor erythroid 2-related factor 2, nitrotyrosine). Significant upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3 was observed in cells treated with cannabidiol-moringin combination. Treatment with the transient receptor potential vanilloid receptor 1 antagonist was detrimental for the efficacy of cannabidiol, while no effect was elicited by cannabinoid receptor 1 and cannabinoid receptor 2 antagonists. None of these receptors was involved in the activity of moringin. Taken together, our in vitro results testify the anti-inflammatory, antioxidative, and anti-apoptotic effects of the combination of cannabidiol and moringin.
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, contrada Casazza, 98124 Messina, Italy.
authors.forename: Thangavelu Soundara
authors.initials: TS
authors.lastname: Rajan
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, contrada Casazza, 98124 Messina, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Giacoppo
authors.affiliation: Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di Ricerca per le Colture Industriali (CREA-CIN), Via Di Corticella 133, Bologna 40128, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Iori
authors.affiliation: Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di Ricerca per le Colture Industriali (CREA-CIN), Via Di Corticella 133, Bologna 40128, Italy.
authors.forename: Gina Rosalinda
authors.initials: GR
authors.lastname: De Nicola
authors.affiliation: Council for Research and Experimentation in Agriculture-Research Centre for Industrial Crops (CRA-CIN), Rovigo, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Grassi
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pollastro
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, contrada Casazza, 98124 Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, contrada Casazza, 98124 Messina, Italy. Electronic address: emazzon.irccs@gmail.com.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D029587:Moringa / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D017879:Isothiocyanates; D008070:Lipopolysaccharides; C000614007:moringin; D002185:Cannabidiol; C037152:isothiocyanic acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Anti-inflammation; Cannabidiol; Combination therapy; LPS; Macrophages; Moringin