Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Chemical Composition and In Vitro Neuroprotective Activity of Fibre-Type Cannabis sativa L. (Hemp)

Author(s): Lorenzo Corsi, Federica Pellati*, Virginia Brighenti, Nicolò Plessi and Stefania Benvenuti

Volume 15, Issue 2, 2019

Page: [201 - 210] Pages: 10

DOI: 10.2174/1573407214666180809124952

Price: $65

Abstract

Background: Fibre-type Cannabis sativa L. (hemp) usually contains cannabidiolic acid and cannabidiol as the main non-psychoactive cannabinoids. Even though there is evidence of the neuroprotective activity of pure cannabidiol, no in vitro studies have reported so far the role of hemp extracts on neuroprotection. The objective of this study was to evaluate the neuroprotective effect of hemp extracts in in vitro cellular models of neurotoxicity.

Methods: One extract was obtained from raw hemp inflorescences, while the other was prepared from the same plant material submitted to a decarboxylation process. The composition of both these extracts was evaluated by HPLC-UV/DAD. Human neuroblastoma SH-SY5Y and microglial BV-2 cell lines treated with rotenone were selected as the model of neurodegeneration. The neuroprotection of hemp extracts was assessed also in serum-free conditions both in the presence and in the absence of rotenone as the toxic agent by using the same cell lines. The neuroprotective potential of cannabidiol was tested in parallel.

Results: The decarboxylated hemp extract possesses a mild neuroprotective activity on BV-2 cells treated with rotenone, higher than that of pure cannabidiol. As regards serum-free experiments, the nondecarboxylated hemp extract was the most effective neuroprotective agent toward SH-SY5Y cells, while BV-2 cells were better protected from the toxic insult by the decarboxylated extract and cannabidiol.

Conclusion: Both hemp extracts and pure cannabidiol displayed a moderate neuroprotective activity in the neurotoxicity models considered in this study; in addition, they showed a trophic effect on SHSY5Y cells.

Keywords: Cannabis sativa L., hemp, cannabinoids, cannabidiol, HPLC, neuroprotection, SH-SY5Y, BV-2.

Graphical Abstract

[1]
Hartsel, J.A.; Eads, B.; Hickory, B.; Makriyannis, A. Cannabis sativa and hemp. In: Nutraceuticals: efficacy, safety and toxicity; Ramesh C. , Gupta., Ed.; Elsevier Inc.: London, 2016; pp. 735-754.
[2]
Aizpurua-Olaizola, O.; Soydaner, U.; Öztürk, E.; Schibano, D.; Simsir, Y.; Navarro, P.; Etxebarria, N.; Usobiaga, A. Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes. J. Nat. Prod., 2016, 79(2), 324-331.
[3]
Regulation (EU) No 1307/2013 of the European parliament and of the council of 17 december 2013 establishing rules for direct payments to farmers under support schemes within the framework of the common agricultural policy and repealing Council Regulation (EC) No 637/2008 and Council Regulation (EC) No 73/2009.
[4]
Bossong, M.G.; Niesink, R.J.M. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog. Neurobiol., 2010, 92(3), 370-385.
[5]
Schönhofen, P.; de Medeiros, L.M.; Bristot, I.J.; Lopes, F.M.; De Bastiani, M.A.; Kapczinski, F.; Crippa, J.A.S.; Castro, M.A.A.; Parsons, R.B.; Klamt, F. Cannabidiol exposure during neuronal differentiation sensitizes cells against redox-active neurotoxins. Mol. Neurobiol., 2015, 52(1), 26-37.
[6]
Bergamaschi, M.M.; Queiroz, R.H.; Zuardi, A.W.; Crippa, J.A. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr. Drug Saf., 2011, 6(4), 237-249.
[7]
Campos, A.C.; Fogaça, M.V.; Sonego, A.B.; Guimarães, F.S. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol. Res., 2016, 112, 119-127.
[8]
Pisanti, S.; Malfitano, A.M.; Ciaglia, E.; Lamberti, A.; Ranieri, R.; Cuomo, G.; Abate, M.; Faggiana, G.; Proto, M.C.; Fiore, D.; Laezza, C.; Bifulco, M. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol. Ther., 2017, 175, 133-150.
[9]
Vilela, L.R.; Lima, I.V.; Kunsch, É.B.; Pinto, H.P.P.; de Miranda, A.S.; Vieira, É.L.M.; de Oliveira, A.C.P.; Moraes, M.F.D.; Teixeira, A.L.; Moreira, F.A. Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels. Epilepsy Behav., 2017, 75, 29-35.
[10]
Ramer, R.; Hinz, B. Cannabinoids as anticancer drugs. Adv. Pharmacol., 2017, 80, 397-436.
[11]
Campos, A.C.; Fogaça, M.V.; Scarante, F.F.; Joca, S.R.L.; Sales, A.J.; Gomes, F.V.; Sonego, A.B.; Rodrigues, N.S.; Galve-Roperh, I.; Guimarães, F.S. Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders. Front. Pharmacol., 2017, 8, 269.
[12]
Alexander, S.P.H. Therapeutic potential of cannabis-related drugs. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2016, 64, 157-166.
[13]
McLoughlin, B.C.; Pushpa-Rajah, J.A.; Gillies, D.; Rathbone, J.; Variend, H.; Kalakouti, E.; Kyprianou, K. Cannabis and schizophrenia. Cochrane Database Syst. Rev., 2014, 10(10), CD004837.
[14]
Fernández-Ruiz, J.; Sagredo, O.; Pazos, M.R.; García, C.; Pertwee, R.; Mechoulam, R.; Martínez-Orgado, J. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? Br. J. Clin. Pharmacol., 2013, 75(2), 323-333.
[15]
Borges, R.S.; Batista, J., Jr; Viana, R.B.; Baetas, A.C.; Orestes, E.; Andrade, M.A.; Honório, K.M.; da Silva, A.B.F. Understanding the molecular aspects of tetrahydrocannabinol and cannabidiol as antioxidants. Molecules, 2013, 18(10), 12663-12674.
[16]
Schröder, N.; da Silva, V.K.; Hallak, J.E.C.; Zuardi, A.W.; de Souza Crippa, J.A. Cannabidiol and neuroprotection: evidence from pre-clinical studies. In: Handbook of Cannabis and related pathologies. Biology, pharmacology, diagnosis and treatment; Victor R. , Preedy, Ed.; Academic Press: London, 2017; pp. 802-812.
[17]
Janefjord, E.; Mååg, J.L.V.; Harvey, B.S.; Smid, S.D. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell. Mol. Neurobiol., 2014, 34(1), 31-42.
[18]
Fernández-Ruiz, J.; Moreno-Martet, M.; Rodríguez-Cueto, C.; Palomo-Garo, C.; Gómez-Cañas, M.; Valdeolivas, S.; Guaza, C.; Romero, J.; Guzmán, M.; Mechoulam, R.; Ramos, J.A. Prospects for cannabinoid therapies in basal ganglia disorders. Br. J. Pharmacol., 2011, 163(7), 1365-1378.
[19]
Lastres-Becker, I.; Molina-Holgado, F.; Ramos, J.A.; Mechoulam, R.; Fernández-Ruiz, J. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson’s disease. Neurobiol. Dis., 2005, 19(1-2), 96-107.
[20]
Radio, N.M.; Mundy, W.R. Developmental neurotoxicity testing in vitro: models for assessing chemical effects on neurite outgrowth. Neurotoxicology, 2008, 29(3), 361-376.
[21]
Harvey, B.S.; Ohlsson, K.S.; Mååg, J.L.V.; Musgrave, I.F.; Smid, S.D. Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro. Neurotoxicology, 2012, 33(1), 138-146.
[22]
Mori, M.A.; Meyer, E.; Soares, L.M.; Milani, H.; Guimarães, F.S.; de Oliveira, R.M.W. Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2017, 75, 94-105.
[23]
Lopes, F.M.; Schröder, R.; da Frota, M.L., Jr; Zanotto-Filho, A.; Müller, C.B.; Pires, A.S.; Meurer, R.T.; Colpo, G.D.; Gelain, D.P.; Kapczinski, F.; Moreira, J.C. Fernandes, Mda.C.; Klamt, F. Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies. Brain Res., 2010, 1337, 85-94.
[24]
Korecka, J.A.; van Kesteren, R.E.; Blaas, E.; Spitzer, S.O.; Kamstra, J.H.; Smit, A.B.; Swaab, D.F.; Verhaagen, J.; Bossers, K. Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One, 2013, 8(5), e63862.
[25]
Lopes, F.M.; Londero, G.F.; de Medeiros, L.M.; da Motta, L.L.; Behr, G.A.; de Oliveira, V.A.; Ibrahim, M.; Moreira, J.C.; Porciúncula, L.O.; da Rocha, J.B.; Klamt, F. Evaluation of the neurotoxic/neuroprotective role of organoselenides using differentiated human neuroblastoma SH-SY5Y cell line challenged with 6-hydroxydopamine. Neurotox. Res., 2012, 22(2), 138-149.
[26]
Henn, A.; Lund, S.; Hedtjärn, M.; Schrattenholz, A.; Pörzgen, P.; Leist, M. The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation. ALTEX, 2009, 26(2), 83-94.
[27]
Valdeolivas, S.; Satta, V.; Pertwee, R.G.; Fernández-Ruiz, J.; Sagredo, O. Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington’s disease: role of CB1 and CB2 receptors. ACS Chem. Neurosci., 2012, 3(5), 400-406.
[28]
Brighenti, V.; Pellati, F.; Steinbach, M.; Maran, D.; Benvenuti, S. Development of a new extraction technique and HPLC method for the analysis of non-psychoactive cannabinoids in fibre-type Cannabis sativa L. (hemp). J. Pharm. Biomed. Anal., 2017, 143, 228-236.
[29]
Flockhart, I.R.; Wheatley, G.W.; Dring, S.; Archer, L. Methods of preparing cannabinoids from plant material. U.S. Patent 8, 846, 409 B2 2014.
[30]
Rimmerman, N.; Ben-Hail, D.; Porat, Z.; Juknat, A.; Kozela, E.; Daniels, M.P.; Connelly, P.S.; Leishman, E.; Bradshaw, H.B.; Shoshan-Barmatz, V.; Vogel, Z.; Rimmerman, N. Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: A novel mechanism for cannabinoid-induced cell death. Cell Death Dis., 2013, 4, e949.
[31]
Juknat, A.; Kozela, E.; Kaushansky, N.; Mechoulam, R.; Vogel, Z. Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol - studies in BV-2 microglia and encephalitogenic T cells. J. Basic Clin. Physiol. Pharmacol., 2016, 27(3), 289-296.
[32]
Yadava, N.; Nicholls, D.G. Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone. J. Neurosci., 2007, 27(27), 7310-7317.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy