Cannabimimetic plants: are they new cannabinoidergic modulators?
- 536 Downloads
Phytochemicals and secondary metabolites able to interact with the endocannabinoid system (Cannabimimetics) have been recently described in a broad range of plants and fruits. These findings can open new alternative avenues to explore for the development of novel therapeutic compounds.
The cannabinoids regulate many physiological and pathological functions in both animals and plants. Cannabis sativa is the main plant that produces phytocannabinoids inside resins capable to defend the plant from the aggression of parasites and herbivores. Animals produce anandamide and 2-arachidonoyl glycerol, which thanks to binding with main receptors such as type-1 cannabinoid receptor (CB1R) and the type-2 cannabinoid receptor (CB2R) are involved in inflammation processes and several brain functions. Endogenous cannabinoids, enzymes for synthesis and degradation of cannabinoids, and CB1R and CB2R constitute the endocannabinoid system (ECS). Other plants can produce cannabinoid-like molecules such as perrottetinene extracted from Radula perrottetii, or anandamide and 2-arachidonoyl glycerol extracted from some bryophytes. Moreover, several other secondary metabolites can also interact with the ECS of animals and take the name of cannabimimetics. These phytoextracts not derived from Cannabis sativa can act as receptor agonists or antagonist, or enzyme inhibitors of ECS and can be involved in the inflammation, oxidative stress, cancer, and neuroprotection. Finally, given the evolutionary heterogeneity of the cannabimimetic plants, some authors speculated on the fascinating thesis of the evolutionary convergence between plants and animals regarding biological functions of ECS. The review aims to provide a critical and complete assessment of the botanical, chemical and therapeutic aspects of cannabimimetic plants to evaluate their spread in the world and medicinal potentiality.
This work was supported by “Research Grant from the University of Brescia EX60%MEMO” and “Petrus och Augusta Hedlunds Stiftelse; Loo och Hans Ostermans Stiftelse; Karolinska Institutet Research and Geriatrics Foundation; Gunvor och Josef Aners Stiftelse”.
- Chicca A, Schafroth MA, Reynoso-Moreno I, Erni R, Petrucci V, Carreira EM, Gertsch J (2018) Uncovering the psychoactivity of a cannabinoid from liverworts associated with a legal high. Sci Adv 4(10):eaat66Google Scholar
- Dhopeshwarkar AS, Jain S, Liao C, Ghose SK, Bisset KM, Nicholson RA (2011) The actions of benzophenanthridine alkaloids, piperonyl butoxide and (S)-methoprene at the G-protein coupled cannabinoid CB(1) receptor in vitro. Eur J Pharmacol 654(1):26–32. https://doi.org/10.1016/j.ejphar.2010.11.033 Google Scholar
- Gao J, Leon F, Radwan MM, Dale OR, Husni AS, Manly SP, Lupien S, Wang X, Hill RA, Dugan FM, Cutler HG, Cutler SJ (2011) Benzyl derivatives with in vitro binding affinity for human opioid and cannabinoid receptors from the fungus Eurotium repens. J Nat Prod 74(7):1636–1639. https://doi.org/10.1021/np200147c Google Scholar
- Granja AG, Carrillo-Salinas F, Pagani A, Gomez-Canas M, Negri R, Navarrete C, Mecha M, Mestre L, Fiebich BL, Cantarero I, Calzado MA, Bellido ML, Fernandez-Ruiz J, Appendino G, Guaza C, Munoz E (2012) A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis. J Neuroimmun Pharmacol 7(4):1002–1016. https://doi.org/10.1007/s11481-012-9399-3 Google Scholar
- He X, Yang L, Wang M, Zhuang X, Huang R, Zhu R, Wang S (2017) Targeting the endocannabinoid/CB1 receptor system for treating major depression through antidepressant activities of curcumin and dexanabinol-loaded solid lipid nanoparticles. Cell Physiol Biochem 42(6):2281–2294. https://doi.org/10.1159/000480001 Google Scholar
- Iijima M, Munakata R, Takahashi H, Kenmoku H, Nakagawa R, Kodama T, Asakawa Y, Abe I, Yazaki K, Kurosaki F, Taura F (2017) Identification and characterization of daurichromenic acid synthase active in anti-HIV biosynthesis. Plant Physiol 174(4):2213–2230. https://doi.org/10.1104/pp.17.00586 Google Scholar
- Iwata N, Kitanaka S (2011) New cannabinoid-like chromane and chromene derivatives from Rhododendron anthopogonoides. Chem Pharm Bull 59(11):1409–1412Google Scholar
- Lazzari P, Pau A, Tambaro S, Asproni B, Ruiu S, Pinna G, Mastinu A, Curzu MM, Reali R, Bottazzi ME, Pinna GA, Murineddu G (2012) Synthesis and pharmacological evaluation of novel 4-alkyl-5-thien-2′-yl pyrazole carboxamides. Cent Nerv Syst Agents Med Chem 12(4):254–276Google Scholar
- Lazzari P, Serra V, Marcello S, Pira M, Mastinu A (2017) Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds co-administration in female rats. Eur Neuropsychopharmacol 27(7):667–678. https://doi.org/10.1016/j.euroneuro.2017.03.010 Google Scholar
- Liu X, Yang D, Liu J, Ren N (2015) Analysis of essential oils from Voacanga africana seeds at different hydrodistillation extraction stages: chemical composition, antioxidant activity and antimicrobial activity. Nat Prod Res 29(20):1950–1953. https://doi.org/10.1080/14786419.2015.1012716 Google Scholar
- Mahgoub M, Keun-Hang SY, Sydorenko V, Ashoor A, Kabbani N, Al Kury L, Sadek B, Howarth CF, Isaev D, Galadari S, Oz M (2013) Effects of cannabidiol on the function of alpha7-nicotinic acetylcholine receptors. Eur J Pharmacol 720(1–3):310–319. https://doi.org/10.1016/j.ejphar.2013.10.011 Google Scholar
- Manca I, Mastinu A, Olimpieri F, Falzoi M, Sani M, Ruiu S, Loriga G, Volonterio A, Tambaro S, Bottazzi ME, Zanda M, Pinna GA, Lazzari P (2013) Novel pyrazole derivatives as neutral CB(1) antagonists with significant activity towards food intake. Eur J Med Chem 62:256–269. https://doi.org/10.1016/j.ejmech.2012.12.056 Google Scholar
- Marques DD, Graebner IB, de Lemos TL, Machado LL, Assuncao JC, Monte FJ (2010) Triterpenes from Protium hebetatum resin. Nat Prod Commun 5(8):1181–1182Google Scholar
- Mechoulam R, Gaoni Y (1965) Hashish. IV. The isolation and structure of cannabinolic cannabidiolic and cannabigerolic acids. Tetrahedron 21(5):1223–1229Google Scholar
- Navarro G, Varani K, Reyes-Resina I, Sanchez de Medina V, Rivas-Santisteban R, Sanchez-Carnerero Callado C, Vincenzi F, Casano S, Ferreiro-Vera C, Canela EI, Borea PA, Nadal X, Franco R (2018) Cannabigerol action at cannabinoid CB1 and CB2 receptors and at CB1-CB2 heteroreceptor complexes. Front Pharmacol 9:632. https://doi.org/10.3389/fphar.2018.00632 Google Scholar
- Palit P, Mukherjee D, Mahanta P, Shadab M, Ali N, Roychoudhury S, Asad M, Mandal SC (2018) Attenuation of nociceptive pain and inflammatory disorders by total steroid and terpenoid fraction of Euphorbia tirucalli Linn root in experimental in vitro and in vivo model. Inflammopharmacology 26(1):235–250. https://doi.org/10.1007/s10787-017-0403-7 Google Scholar
- Quaghebeur K, Coosemans J, Toppet S, Compernolle F (1994) Cannabiorci- and 8-chlorocannabiorcichromenic acid as fungal antagonists from Cylindrocarpon olidum. Phytochemistry 37(1):159–161Google Scholar
- Refolo MG, D’Alessandro R, Malerba N, Laezza C, Bifulco M, Messa C, Caruso MG, Notarnicola M, Tutino V (2015) Anti proliferative and pro apoptotic effects of flavonoid quercetin are mediated by CB1 receptor in human colon cancer cell lines. J Cell Physiol 230(12):2973–2980. https://doi.org/10.1002/jcp.25026 Google Scholar
- Romano B, Borrelli F, Fasolino I, Capasso R, Piscitelli F, Cascio M, Pertwee R, Coppola D, Vassallo L, Orlando P, Di Marzo V, Izzo A (2013) The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis. Br J Pharmacol 169(1):213–229. https://doi.org/10.1111/bph.12120 Google Scholar
- Ruiu S, Anzani N, Orru A, Floris C, Caboni P, Maccioni E, Distinto S, Alcaro S, Cottiglia F (2013) N-Alkyl dien- and trienamides from the roots of Otanthus maritimus with binding affinity for opioid and cannabinoid receptors. Bioorg Med Chem 21(22):7074–7082. https://doi.org/10.1016/j.bmc.2013.09.017 Google Scholar
- Weidner C, de Groot JC, Prasad A, Freiwald A, Quedenau C, Kliem M, Witzke A, Kodelja V, Han CT, Giegold S, Baumann M, Klebl B, Siems K, Muller-Kuhrt L, Schurmann A, Schuler R, Pfeiffer AF, Schroeder FC, Bussow K, Sauer S (2012) Amorfrutins are potent antidiabetic dietary natural products. Proc Natl Acad Sci USA 109(19):7257–7262. https://doi.org/10.1073/pnas.1116971109 Google Scholar