Download PDF
Planta Med 2022; 88(13): 1223-1232
DOI: 10.1055/a-1628-2299
Natural Product Chemistry and Analytical Studies
Original Papers

Chemical Analysis by LC-MS of Cannabis sativa Root Samples from Northeast Brazil and Evaluation of Antitussive and Expectorant Activities

Pedro Modesto Nascimento Menezes
1   Pós-graduação em Biotecnologia – RENORBIO, Universidade Federal Rural de Pernambuco– UFRPE, Recife/PE – Brasil
,
Emanuella Chiara Valença Pereira
1   Pós-graduação em Biotecnologia – RENORBIO, Universidade Federal Rural de Pernambuco– UFRPE, Recife/PE – Brasil
,
Kátia Simoni Bezerra Lima
2   Universidade Federal do Vale do São Francisco – UNIVASF, Colegiado de Enfermagem (CENF), Petrolina/PE – Brasil
,
Bismarques Augusto Oliveira da Silva
3   Pós-graduação em Biotecnologia – PPGBIOTEC, Universidade Estadual de Feira de Santana – UEFS, Feira de Santana/BA – Brasil
,
Mariana Coelho Brito
3   Pós-graduação em Biotecnologia – PPGBIOTEC, Universidade Estadual de Feira de Santana – UEFS, Feira de Santana/BA – Brasil
,
Tarcísio Cícero de Lima Araújo
4   Pós-graduação em Biociências – PGB, Universidade Federal do Vale do São Francisco – UNIVASF, Petrolina/PE – Brasil
,
Janaine Almeida Neto
4   Pós-graduação em Biociências – PGB, Universidade Federal do Vale do São Francisco – UNIVASF, Petrolina/PE – Brasil
,
Luciano Augusto de Araujo Ribeiro
5   Universidade Federal do Vale do São Francisco – UNIVASF, Colegiado de Farmácia (CFARM), Petrolina/PE – Brasil
,
Fabrício Souza Silva
3   Pós-graduação em Biotecnologia – PPGBIOTEC, Universidade Estadual de Feira de Santana – UEFS, Feira de Santana/BA – Brasil
5   Universidade Federal do Vale do São Francisco – UNIVASF, Colegiado de Farmácia (CFARM), Petrolina/PE – Brasil
,
Larissa Araújo Rolim 
1   Pós-graduação em Biotecnologia – RENORBIO, Universidade Federal Rural de Pernambuco– UFRPE, Recife/PE – Brasil
4   Pós-graduação em Biociências – PGB, Universidade Federal do Vale do São Francisco – UNIVASF, Petrolina/PE – Brasil
5   Universidade Federal do Vale do São Francisco – UNIVASF, Colegiado de Farmácia (CFARM), Petrolina/PE – Brasil
› Author AffiliationsSupported by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 001
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 315231/2018-1
› Further Information
Also available at
    Permissions and Reprints

Abstract

Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots: p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolitesʼ variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.

Key words

Cannabaceae - Cannabis sativa - cough - marijuana - mucolytic - phenol red


Publication History

Received: 07 June 2021

Accepted after revision: 22 August 2021

Article published online:
29 October 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Ren M, Tang Z, Wu X, Spengler R, Jiang H, Yang Y, Boivin N. The origins of cannabis smoking: Chemical residue evidence from the first millennium BCE in the Pamirs. Science Advances 2019; 5: 1-9
    CrossrefPubMedSearch in Google Scholar
  • 2 Pisanti S, Bifulco M. Modern history of medical cannabis: From widespread use to prohibitionism and back. Trends Pharmacol Sci 2017; 38: 195-198
    CrossrefPubMedSearch in Google Scholar
  • 3 ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A. Phytochemistry of Cannabis sativa L. Prog Chem Org Nat Prod 2017; 103: 1-36
    CrossrefPubMedSearch in Google Scholar
  • 4 Schofs L, Sparo MD, Bruni SFS. The antimicrobial effect behind Cannabis sativa . Pharmacol Res Perspect 2021; 9: e00761
    CrossrefPubMedSearch in Google Scholar
  • 5 Pellati F, Borgonetti V, Brighenti V, Biagi M, Benvenutti S, Corsi L. Cannabis sativa L. and nonpsychoactive cannabinoids: Their chemistry and role against oxidative stress, inflammation, and cancer. Biomed Res Int 2018; 1691428: 1-15
    CrossrefPubMedSearch in Google Scholar
  • 6 Gahlinger P. Illegal Drugs: A complete Guide to their History, Chemistry, Use, and Abuse. 2nd edition. Montgomery, IL, U.S.A.: Plume; 2004: 488pp
    Search in Google Scholar
  • 7 Zuardi AW. History of cannabis as a medicine: A review. Rev Bras Psiquiatr 2006; 28: 153-157
    CrossrefPubMedSearch in Google Scholar
  • 8 Ryz NR, Remillard DJ, Russo EB. Cannabis roots: A traditional therapy with future potential for treating inflammation and pain. Cannabis Cannabinoid Res 2017; 2: 210-216
    CrossrefPubMedSearch in Google Scholar
  • 9 Lima KSB, Silva MEGDC, Araújo TCL, Silva CPDF, Santos BL, Ribeiro LAA, Menezes PMN, Silva MG, Lavor ÉM, Silva FS, Nunes XP, Rolim LA. Cannabis roots: Pharmacological and toxicological studies in mice. J Ethnopharmacol 2021; 271: 113868
    CrossrefPubMedSearch in Google Scholar
  • 10 Menezes PMN, Araújo TCL, Pereira ECV, Neto JA, Silva DS, Brito MC, Lima KSB, Monte APO, Matos MHT, Lima RS, Ribeiro LAA, Silva FS, Rolim LA. Investigation of antinociceptive, antipyretic, antiasthmatic and spasmolytic activities of Brazilian Cannabis sativa L. roots in rodents. J Ethnopharmacol 2021; 278: 114259
    CrossrefPubMedSearch in Google Scholar
  • 11 Bramness JG, Soest T. A longitudinal study of cannabis use increasing the use of asthma medication in young Norwegian adults. BMC Pulm Med 2019; 19: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 12 Tetrault JM, Crothers K, Moore BA, Mehra R, Concato J, Fiellin DA. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med 2007; 167: 221-228
    CrossrefPubMedSearch in Google Scholar
  • 13 Tashkin DP. Effects of Marijuana Smoking on the Lung. Ann Am Thorac Soc 2013; 10: 239-247
    Search in Google Scholar
  • 14 Makwana R, Venkatasamy R, Spina D, Page C. The effect of phytocannabinoids on airway hyper responsiveness, airway inflammation, and cough. J Pharmacol Exp Ther 2015; 353: 169-180
    CrossrefPubMedSearch in Google Scholar
  • 15 Galarce-Bustos O, Pavón-Perez J, Henríquez-Aedo K, Aranda M. An improved method for a fast screening of α-glucosidase inhibitors in cherimoya fruit (Annona cherimola Mill.) applying effect-directed analysis via high-performance thin-layer chromatography-bioassay-mass spectrometry. J Chromatogr A 2019; 1608: 460415 1–9
    CrossrefPubMedSearch in Google Scholar
  • 16 Yamamoto I, Matsunaga T, Kobayashi H, Watanabe K, Yoshimura H. Analysis and pharmacotoxicity of feruloyltyramine as a new constituent and p-coumaroyltyramine in Cannabis sativa L. Pharmacol Biochem Behav 1991; 40: 465-469
    CrossrefPubMedSearch in Google Scholar
  • 17 Avula B, Bae J, Majrashi T, Wu T, Wang Y, Wang M, Ali Z, Wu Y, Khan IA. Targeted and non-targeted analysis of annonaceous alkaloids and acetogenins from Asimina and Annona species using UHPLC-QToF-MS. J Pharm Biomed Anal 2018; 159: 548-566
    CrossrefPubMedSearch in Google Scholar
  • 18 Nascimento IR. Identificação química em nível molecular de amostras de maconha por ESI-FT-ICR MS [Dissertation]. Vitória: Universidade Federal do Espírito Santo; 2014
    PubMedSearch in Google Scholar
  • 19 Turner CE, Hsu MH, Knapp JE, Schiff jr. PL, Slatkin DJ. Isolation of cannabisativine, an alkaloid, from Cannabis sativa L. root. J Pharm Sci 1976; 65: 1084-1085
    CrossrefPubMedSearch in Google Scholar
  • 20 ElSohly MA, Turner CE, Phoebe jr. CH, Knapp JE, Schiff jr. PL, Slatkin DJ. Anhydrocannabisativine, a new alkaloid from Cannabis sativa L. J Pharm Sci 1978; 67: 124
    CrossrefPubMedSearch in Google Scholar
  • 21 Radwan MM, Chandra S, Gul S, ElSohly MA. Cannabinoids, phenolics, terpenes and alkaloids of Cannabis . Molecules 2021; 26: 2774
    CrossrefPubMedSearch in Google Scholar
  • 22 Elhendawy MA, Wanas AS, Radwan MM, Azzaz NA, Toson ES, ElSohly MA. Chemical and biological studies of Cannabis sativa roots. Med Cannabis Cannabinoids 2019; 1: 104-111
    CrossrefPubMedSearch in Google Scholar
  • 23 Kornpointner C, Martinez AS, Marinovic S, Haselmair-Gosch C, Jamnik P, Schröder K, Löfke C, Halbwirth H. Chemical composition and antioxidant potential of Cannabis sativa L. roots. Ind Crops Prod 2021; 165: 113422
    CrossrefPubMedSearch in Google Scholar
  • 24 Holeski LM, Hillstrom ML, Whitham TG, Lindroth RL. Relative importance of genetic, ontogenetic, induction, and seasonal variation in producing a multivariate defense phenotype in a foundation tree species. Oecologia 2012; 170: 695-707
    CrossrefPubMedSearch in Google Scholar
  • 25 Lomba A, Alves P, Honrado J. Endemic sand dune vegetation of the Northwest Iberian peninsula: Diversity, dynamics, and significance for bioindication and monitoring of coastal landscapes. J Coast Res 2008; 24: 113-121
    CrossrefPubMedSearch in Google Scholar
  • 26 Mossi AJ, Cansian RL, Leontiev-Orlov O, Zanin EM, Oliveira CH, Cechet ML, Carvalho AZ, Echeverrigaray S. Intra and inter populational genetic variability in Maytenus ilicifolia Mart. ex Reiss. 1861, through RAPD markers. Rev Bras Biol 2007; 67: 957-961
    CrossrefPubMedSearch in Google Scholar
  • 27 Dicpinigaitis PV. Chronic cough due to asthma: ACCP evidence-based clinical practice guidelines. Chest 2006; 129: 75S-79S
    CrossrefPubMedSearch in Google Scholar
  • 28 Niimi A. Cough and Asthma. Curr Respir Med Rev 2011; 7: 47-54
    CrossrefPubMedSearch in Google Scholar
  • 29 Belvisi MG, Hele DJ. Cough: Citric acid and nerves. Drug Discov Today Dis Models 2006; 3: 237-241
    CrossrefPubMedSearch in Google Scholar
  • 30 Lai Y, Wu L, Lin T, Lin C. The role of mast cells in citric acid-induced airway constriction and cough. Chin J Physiol 2009; 52: 332-338
    CrossrefPubMedSearch in Google Scholar
  • 31 Gordon R, Gordon RJ, Sofia D. Antitussive activity of some naturally occurring cannabinoids in anesthetized cats. Eur J Pharmacol 1976; 35: 309-313
    CrossrefPubMedSearch in Google Scholar
  • 32 Calignano A, Kátona I, Désarnaud F, Giuffrida A, La Rana G, Mackie K, Freund TF, Piomelli D. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature 2000; 408: 96-101
    CrossrefPubMedSearch in Google Scholar
  • 33 Jia Y, Mcleod RL, Wang X, Parra LE, Egan RW, Hey JA. Anandamide induces cough in conscious guinea-pigs through VR1 receptors. Br J Pharmacol 2002; 137: 831-836
    CrossrefPubMedSearch in Google Scholar
  • 34 Evans CM, Kima K, Tuvim MJ, Dickey BF. Mucus hypersecretion in asthma: Causes and effects. Curr Opin Pulm Med 2009; 15: 4-11
    CrossrefPubMedSearch in Google Scholar
  • 35 Rogers DF, Barnes PJ. Treatment of airway mucus hypersecretion. Ann Med 2006; 38: 116-125
    CrossrefPubMedSearch in Google Scholar
  • 36 Balsamo R, Lanata L, Egan CG. Mucoactive drugs. Eur Respir Rev 2010; 19: 127-133
    CrossrefPubMedSearch in Google Scholar
  • 37 Decramer M, Janssens W. Mucoactive therapy in COPD. Eur Respir Rev 2010; 19: 134-140
    CrossrefPubMedSearch in Google Scholar
  • 38 Engler H, Szelenyi I. Tracheal phenol red secretion, a new method for screening mucosecretolytic compounds. J Pharmacol Methods 1984; 11: 151-157
    CrossrefPubMedSearch in Google Scholar
  • 39 Menezes PMN, Brito MC, Sá PGS, Ribeiro LAA, Rolim LA, Silva FS. Analytical and pharmacological validation of the quantification of phenol red in a mouse model: An optimized method to evaluate expectorant drugs. J Pharmacol Toxicol Methods 2019; 98: 106586
    CrossrefPubMedSearch in Google Scholar
  • 40 Rubin BK. Mucolytics, expectorants, and mucokinetic medications. Respir Care 2007; 52: 859-865
    PubMedSearch in Google Scholar
  • 41 Albrecht HH, Dicpinigaitis PV, Guenin EP. Role of guaifenesin in the management of chronic bronchitis and upper respiratory tract infections. Multidiscip Respir Med 2017; 12: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 42 Macleod J, Robertson R, Copeland L, McKenzie J, Elton R, Reid P. Cannabis, tobacco smoking, and lung function: A cross-sectional observational study in a general practice population. Br J Gen Pract 2015; 65: e89-e95
    CrossrefPubMedSearch in Google Scholar
  • 43 Touw M. The religious and medicinal uses of cannabis in China, India and Tibet. J Psychoactive Drugs 1981; 13: 23-34
    CrossrefPubMedSearch in Google Scholar
  • 44 Popp JR, Petrakis EA, Angelis A, Halabalaki M, Bonn GK, Stuppner H, Skaltsounis LA. Rapid isolation of acidic cannabinoids from Cannabis sativa L. usingpH-zone-refining centrifugal partition chromatography. J Chromatogr A 2019; 1599: 196-202
    CrossrefPubMedSearch in Google Scholar
  • 45 Kamei J, Nakanishi Y, Asato M, Ikeda H. Fentanyl enhances the excitability of rapidly adapting receptors to cause cough via the enhancement of histamine release in the airways. Cough 2013; 9: 1-6
    CrossrefPubMedSearch in Google Scholar
  • 46 Tanaka M, Maruyama K. Mechanisms of capsaicin- and citric-acid-induced cough reflexes in guinea pigs. J Pharmacol Sci 2005; 99: 77-82
    CrossrefPubMedSearch in Google Scholar
  • 47 Wang D, Wang S, Chen X, Xu X, Zhu J, Nie L, Long X. Antitussive, expectorant and anti-inflammatory activities of four alkaloids isolated from Bulbus of Fritillaria wabuensis . J Ethnopharmacol 2012; 139: 189-193
    CrossrefPubMedSearch in Google Scholar