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Artigo Produção Nacional Revisado por pares
BIBTEX RIS

DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A2A receptor

2019; Elsevier BV; Volume: 368; Linguagem: Inglês

10.1016/j.taap.2019.02.011

ISSN

1096-0333

Autores

Rangel L. Silva, Gabriela T. Silveira, Carlos W. Wanderlei, Nerry T. Cecílio, Alexandre G.M. Maganin, Marcelo Franchin, Lucas Maciel Mauriz Marques, Norberto Peporine Lopes, José A. Crippa, Francisco Silveira Guimarães, José Carlos Farias Alves-Filho, Fernando Q. Cunha, Thiago M. Cunha,

Tópico(s)

Immune Cell Function and Interaction

Resumo

Cannabidiol (CBD) is a natural compound with psychoactive therapeutic properties well described. Conversely, the immunological effects of CBD are still poorly explored. In this study, the potential anti-inflammatory effects and underlying mechanisms of CBD and its analog Dimethyl-Heptyl-Cannabidiol (DMH-CBD) were investigated using RAW 264.7 macrophages. CBD and DMH-CBD suppressed LPS-induced TNF production and NF-kB activity in a concentration-dependent manner. Both compounds reduced the NF-kB activity in a μM concentration range: CBD (IC50 = 15 μM) and DMH-CBD (IC50 = 38 μM). However, the concentrations of CBD that mediated NF-kB inhibition were similar to those that cause cytotoxicity (LC50 = 58 μM). Differently, DMH-CBD inhibited the NF-kB activation without cytotoxic effects at the same concentrations, although it provokes cytotoxicity at long-term exposure. The inhibitory action of the DMH-CBD on NF-kB activity was not related to the reduction in IkBα degradation or either p65 (NF-kB) translocation to the nucleus, although it decreased p38 MAP kinase phosphorylation. Additionally, 8-(3-Chlorostyryl) caffeine (CSC), an A2A antagonist, reversed the effect of DMH-CBD on NF-kB activity in a concentration-dependent manner. Collectively, our results demonstrated that CBD reduces NF-kB activity at concentrations intimately associated with those that cause cell death, whereas DMH-CBD decreases NF-kB activity at non-toxic concentrations in an A2A receptor dependent-manner.

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