title: Pure Δ9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages.
abstract: 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 CB1and CB2receptors, and inhibited, via CB2but not CB1cannabinoid 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 CB1receptors, 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 CB2receptor activation - inhibits nitrite production in macrophages. The effect of this phytocannabinoid was associated with a down-regulation of CB1, but not CB2or TRP channel mRNA expression.
authors: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy. Electronic address: barbara.romano@unina.it.
authors: Barbara
authors: B
authors: Romano
authors: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
authors: Ester
authors: E
authors: Pagano
authors: Endocannabinoid Research Group, Italy; Institute of Protein Biochemistry, National Research Council, Pozzuoli, Naples, Italy; Institute of Applied Sciences & Intelligent Systems of National Research Council, Pozzuoli, Naples, Italy.
authors: Pierangelo
authors: P
authors: Orlando
authors: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
authors: Raffaele
authors: R
authors: Capasso
authors: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
authors: Maria Grazia
authors: MG
authors: Cascio
authors: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
authors: Roger
authors: R
authors: Pertwee
authors: Endocannabinoid Research Group, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy.
authors: Vincenzo Di
authors: VD
authors: Marzo
authors: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
authors: Angelo A
authors: AA
authors: Izzo
authors: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy. Electronic address: francesca.borrelli@unina.it.
authors: Francesca
authors: F
authors: Borrelli
mesh_terms: D000818:Animals; D016466:CHO Cells; D002186:Cannabinoids / Q000494:pharmacology*; D002188:Cannabis / Q000737:chemistry*; D002460:Cell Line; D003412:Cricetulus; D051546:Cyclooxygenase 2 / Q000378:metabolism; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002186:Cannabinoids; D008070:Lipopolysaccharides; D009573:Nitrites; D010936:Plant Extracts; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D050051:Transient Receptor Potential Channels; C003403:tetrahydrocannabivarin 9; D009569:Nitric Oxide; D013759:Dronabinol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Cannabinoid receptors; Cannabis; Inflammation; Phytocannabinoids; Transient receptor potential (TRP) channels