Pure Δ⁹-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ⁹-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages

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• 作者：Barbara Romano^a ; ^b ; ^{barbara.romano@unina.it" class="auth_mail" title="E-mail the corresponding author} ; Ester Pagano^a ; ^b ; Pierangelo Orlando^b ; ^c ; ^d ; Raffaele Capasso^a ; ^b ; Maria Grazia Cascio^e ; Roger Pertwee^e ; Vincenzo Di Marzo^b ; ^f ; Angelo A. Izzo^a ; ^b ; Francesca Borrelli^a ; ^b ; ^{francesca.borrelli@unina.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BSA ; albumin bovine serum ; CB1 ; cannabinoid receptor type 1 ; CB2 ; cannabinoid receptor type 2 ; CBC ; cannabichromene ; CBD ; cannabidiol ; CBG ; cannabigerol ; COX-2 ; cyclooxygenase-2 ; DAN ; 2 ; 3-diaminonaphthalene ; DMSO ; dimethyl sulfoxide (DMSO) ; DTT ; 1 ; 4-dithiothreitol ; EDTA ; ethylenediaminetetraacetic acid ; EGTA ; ethylene glycol tetracetic acid ; ELISA ; enzyme-linked immunosorbent assay ; FBS ; fetal bovine serum ; hCB1/hCB2-CHO cells ; Chinese hamster ovarian stably transfected with complementary DNA en
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：113
• 期：part_PA
• 页码：199-208
• 全文大小：2348 K

文摘

Historical and scientific evidence suggests that Cannabis use has immunomodulatory and anti-inflammatory effects. We have here investigated the effect of the non-psychotropic phytocannabinoid Δ⁹-tetrahydrocannabivarin (THCV) and of a Cannabis sativa extract with high (64.8%) content in THCV (THCV-BDS) on nitric oxide (NO) production, and on cannabinoid and transient receptor potential (TRP) channel expression in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages.

THCV-BDS and THCV exhibited similar affinity in radioligand binding assays for CB₁ and CB₂ receptors, and inhibited, via CB₂ but not CB₁ cannabinoid receptors, nitrite production evoked by LPS in peritoneal macrophages. THCV down-regulated the over-expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin 1β (IL-1β) proteins induced by LPS. Furthermore, THCV counteracted LPS-induced up-regulation of CB₁ receptors, without affecting the changes in CB₂, TRPV2 or TRPV4 mRNA expression caused by LPS. Other TRP channels, namely, TRPA1, TRPV1, TRPV3 and TRPM8 were poorly expressed or undetectable in both unstimulated and LPS-challenged macrophages.

It is concluded that THCV − via CB₂ receptor activation − inhibits nitrite production in macrophages. The effect of this phytocannabinoid was associated with a down-regulation of CB₁, but not CB₂ or TRP channel mRNA expression.