| Full text | |
| Author(s): Show less - |
Silva, Rangel L.
[1]
;
Silveira, Gabriela T.
[1]
;
Wanderlei, Carlos W.
[2, 1]
;
Cecilio, Nerry T.
[1]
;
Maganin, Alexandre G. M.
[1]
;
Franchin, Marcelo
[3]
;
Marques, Lucas M. M.
[4]
;
Lopes, Norberto P.
[4]
;
Crippa, Jose A.
[5]
;
Guimaraes, Francisco S.
[1]
;
Alves, Jose C. F.
[1]
;
Cunha, Fernando Q.
[1]
;
Cunha, Thiago M.
[1]
Total Authors: 13
|
| Affiliation: | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil
[2] Univ Fed Ceara, Fac Med, Dept Physiol & Pharmacol, Fortaleza, Ceara - Brazil
[3] Univ Estadual Campinas, Piracicaba Dent Sch, BR-13414903 Piracicaba, SP - Brazil
[4] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Phys Chem, Ribeirao Preto - Brazil
[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Ribeirao Preto - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Toxicology and Applied Pharmacology; v. 368, p. 63-71, APR 1 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |