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Pure Δ9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages.
Pharmacol Res 2016; 113(Pt A):199-208PR

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 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.

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    Authors+Show Affiliations

    Romano B
    Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy. Electronic address: barbara.romano@unina.it.
    Pagano E
    Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
    Orlando P
    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.
    Capasso R
    Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
    Cascio MG
    School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
    Pertwee R
    School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
    Marzo VD
    Endocannabinoid Research Group, Italy; Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy.
    Izzo AA
    Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
    Borrelli F
    Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy. Electronic address: francesca.borrelli@unina.it.

    MeSH

    AnimalsCHO CellsCannabinoidsCannabisCell LineCricetulusCyclooxygenase 2DronabinolLipopolysaccharidesMacrophages, PeritonealMaleMiceMice, Inbred ICRNitric OxideNitric Oxide Synthase Type IINitritesPlant ExtractsRNA, MessengerReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Transient Receptor Potential ChannelsUp-Regulation

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    27498155

    Citation

    Romano, Barbara, et al. "Pure Δ9-tetrahydrocannabivarin and a Cannabis Sativa Extract With High Content in Δ9-tetrahydrocannabivarin Inhibit Nitrite Production in Murine Peritoneal Macrophages." Pharmacological Research, vol. 113, no. Pt A, 2016, pp. 199-208.
    Romano B, Pagano E, Orlando P, et al. Pure Δ9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages. Pharmacol Res. 2016;113(Pt A):199-208.
    Romano, B., Pagano, E., Orlando, P., Capasso, R., Cascio, M. G., Pertwee, R., ... Borrelli, F. (2016). Pure Δ9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages. Pharmacological Research, 113(Pt A), pp. 199-208. doi:10.1016/j.phrs.2016.07.045.
    Romano B, et al. Pure Δ9-tetrahydrocannabivarin and a Cannabis Sativa Extract With High Content in Δ9-tetrahydrocannabivarin Inhibit Nitrite Production in Murine Peritoneal Macrophages. Pharmacol Res. 2016;113(Pt A):199-208. PubMed PMID: 27498155.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Pure Δ9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages. AU - Romano,Barbara, AU - Pagano,Ester, AU - Orlando,Pierangelo, AU - Capasso,Raffaele, AU - Cascio,Maria Grazia, AU - Pertwee,Roger, AU - Marzo,Vincenzo Di, AU - Izzo,Angelo A, AU - Borrelli,Francesca, Y1 - 2016/08/03/ PY - 2016/04/19/received PY - 2016/07/28/revised PY - 2016/07/31/accepted PY - 2016/10/21/pubmed PY - 2017/12/21/medline PY - 2016/8/8/entrez KW - Cannabinoid receptors KW - Cannabis KW - Inflammation KW - Phytocannabinoids KW - Transient receptor potential (TRP) channels SP - 199 EP - 208 JF - Pharmacological research JO - Pharmacol. Res. VL - 113 IS - Pt A N2 - 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. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/27498155/Pure_Δ9_tetrahydrocannabivarin_and_a_Cannabis_sativa_extract_with_high_content_in_Δ9_tetrahydrocannabivarin_inhibit_nitrite_production_in_murine_peritoneal_macrophages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(16)30339-5 DB - PRIME DP - Unbound Medicine ER -