DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A(2A) receptor
Rangel L. Silva, Gabriela T. Silveira, Carlos W. Wanderlei, Nerry T. Cecilio, Alexandre G. M. Maganin, Marcelo Franchin, Lucas M. M. Marques, Norberto P. Lopes, Jose A. Crippa, Francisco S. Guimaraes, Jose C. F. Alves, Fernando Q. Cunha, Thiago M. Cunha
ARTIGO
Inglês
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...
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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 mu M concentration range: CBD (IC50 = 15 mu M) and DMH-CBD (IC50 = 38 mu M). However, the concentrations of CBD that mediated NF-kB inhibition were similar to those that cause cytotoxicity (LC50 = 58 mu M). 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 IkB alpha degradation or either p65 (NF-kB) translocation to the nucleus, although it decreased p38 MAP kinase phosphorylation. Additionally, 8-(3-Chlorostyryl) caffeine (CSC), an A(2A) 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 A(2A) receptor dependent-manner
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CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ
150955/2017-0; 466805/2014-4
FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP
2013/08216-2
Fechado
DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A(2A) receptor
Rangel L. Silva, Gabriela T. Silveira, Carlos W. Wanderlei, Nerry T. Cecilio, Alexandre G. M. Maganin, Marcelo Franchin, Lucas M. M. Marques, Norberto P. Lopes, Jose A. Crippa, Francisco S. Guimaraes, Jose C. F. Alves, Fernando Q. Cunha, Thiago M. Cunha
DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A(2A) receptor
Rangel L. Silva, Gabriela T. Silveira, Carlos W. Wanderlei, Nerry T. Cecilio, Alexandre G. M. Maganin, Marcelo Franchin, Lucas M. M. Marques, Norberto P. Lopes, Jose A. Crippa, Francisco S. Guimaraes, Jose C. F. Alves, Fernando Q. Cunha, Thiago M. Cunha
Fontes
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Toxicology and applied pharmacology Vol. 368 (Apr., 2019), p. 63-71 |