Paullinia cupana: a multipurpose plant — a review

Abstract

Seeds of guarana (Paullinia cupana Kunth, Sapindaceae) feature diverse pharmacological functions, for example, antimicrobial, antioxidant, anticarcinogenic, stimulating, and cognitive functions, as well as liver protection and weight loss. Many of these actions are probably due to the high content of methylxanthines and tannins in its seeds. In Brazil, the world’s largest producer of guarana, the plant material is predominantly used in the soft drinks industry, although it is also used in the cosmetic and pharmaceutical industries. Although the Amazon region has the largest cropping area, the state of Bahia is the main guarana producer in Brazil (71%). This review focuses mainly on the possible pharmacological actions of guarana that have been investigated. Moreover, it discusses less-considered topics, such as the toxicology and quality control of seeds and extractives of guarana that will ultimately influence the safety of its use. In addition, it presents a detailed discussion of the methods used to prepare herbal drugs and their extracts, focusing on the importance of standardization and on the direct impact of preparatory factors, on the pharmacological properties of guarana extracts.

References

  1. Andersen, T., Fogh, J., 2001. Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients. J. Hum. Nutr. Dietet. 14, 243–250.

    CAS  Google Scholar 

  2. Andrade, L., Schenkel, E.P., Bergold, A.M., 1999. Estudo da metodologia de análise de cafeína em sementes de guarana (Paullinia cupana). Rev. Bras. Farm. 80, 7–9.

    CAS  Google Scholar 

  3. Angelucci, E., Tocchini, R.P., Lazarine, V.B., Prado, M.A.F., 1978. Caracterizac¸ ão química da semente de guarana (Paullinia cupana var. sorbilis Ducke). Bol. Inst. Tecnol. Alimentos 56, 183–192.

    CAS  Google Scholar 

  4. Antonelli-Ushirobira, T.M., Kaneshima, E.N., Gabriel, M., Audi, E.A., Marques, L.C., Mello, J.C.P., 2010. Acute and subchronic toxicological evaluation of the semipu-rified extract of seeds of guarana (Paullinia cupana) in rodents. Food Chem. Toxicol. 48, 1817–1820.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Antonelli-Ushirobira, T.M., Yamaguti, E., Uemura, L.M., Nakamura, C.V., Dias Filho, B.P., Mello, J.C.P., 2007. Chemical and microbiological study ofextract from seeds of guarana (Paullinia cupana var. sorbilis). Lat. Am. J. Pharm. 26, 5–9.

    CAS  Google Scholar 

  6. Antunes, E., Gordo, W.M., de Oliveira, J.F., Teixeira, C.E., Hyslop, S., De Nucci, G., 2001. The relaxation of isolated rabbit corpus cavernosum by the herbal medicine Catuama and its constituents. Phytother. Res. 15, 416–421.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Anvisa, 2001. RDC 12, Regulamento técnico sobre padrões microbiológicos para ali-mentos (in Portuguese). Agência Nacional de Vigilância Sanitária. Diário Oficial da União.

    Google Scholar 

  8. Anvisa, 2010. Farmacopeia brasileira, vol. 2., 5 ed. Agência Nacional de Vigilância Sanitária, Brasília.

  9. Aquino, S., Gonc¸alez, E., Reis, T.A., Sabundjian, I.T., Trindade, R.A., Rossi, M.H., Corrêa, B., Villavicencio, A.L.C.H., 2007. Effect of γ-irradiation on mycoflora of guarana (Paullinia cupana). Radiat. Phys. Chem., 1470–1473.

    Google Scholar 

  10. Arantes, L.P., Peres, T.V., Chen, P., Caito, S.W., Aschner, M., Soares, F.A.A., 2016. Guarana (Paullinia cupana Mart.) attenuates methylmercury-induced toxicity in Caenorhabditis elegans. Toxicol. Res. 5, 1629–1638.

    CAS  Google Scholar 

  11. Araújo, A.A.S., Mercuri, L.P., Seixas, S.R.S., Storpirtis, S., Matos, J.R., 2006. Determination of humidity and ash content of guarana commercial samples using conventional method and thermal analysis. Rev. Cienc. Farm. Básica Apl. 42, 269–277.

    Google Scholar 

  12. Armstrong, W.F., Johnson, P., Duhme, S., 2001. The effectofcommercial thermogenic weight loss supplement on body composition and energy expenditure in obese adults. J. Exerc. Physiol. Online 4, 28–35.

    Google Scholar 

  13. Audi, E.A., Mello, J.C.P., 2000. Efeito antidepressivo do extrato da droga vegetal guarana (Paullinia cupana var. sorbilis (Martius) Ducke), PI 0006638-9 (Patent). Universidade Estadual de Maringá, Brasil.

    Google Scholar 

  14. Audi, E.A., Roncon, C.M., Almeida, C.B., Mello, J.C.P., 2010. P.1.d.002 Effect of semipurified constituent from guarana seeds on performance of rats in elevated T maze. Eur. Neuropsychopharmacol 20, S274–S275.

    Google Scholar 

  15. Avato, P., Pesante, M.A., Fanizzi, F.P., Santos, C.A.M., 2003. Seed oil composition of Paullinia cupana var. sorbilis (Mart.) Ducke. Lipids 38, 773–780.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Babu, K.M., Church, R.J., Lewander, W., 2008. Energy drinks: the new eye-opener for adolescents. Clin. Ped. Emerg. Med. 9, 35–42.

    Google Scholar 

  17. Baghkhani, L., Jafari, M., 2002. Cardiovascular adverse reactions associated with guarana: is there a causal effect? J. Herb. Pharmacother. 2, 57–61.

    PubMed  PubMed Central  Google Scholar 

  18. Bara, M.T.F., Ribeiro, P.A.M., Arantes, M.C.B., Amorim, L.L.S.S., Paula, J.R., 2006. Determinac¸ão do teor do princípios ativos em matéria-primas vegetais. Rev. Bras. Farmacogn. 16, 211–215.

    Google Scholar 

  19. Barbosa, G.D.A., Mello, J.C.P., 2004. Clinical evaluation of the guarana extract on the dental plaque control. Rev. Paul. Odontol. 26, 28–30.

    Google Scholar 

  20. Basile, A., Ferrara, L., Del Pezzo, M., Mele, G., Sorbo, S., Bassi, P., Montesano, D., 2005. Antibacterial and antioxidant activities of ethanol extract from Paullinia cupana Mart. J. Ethnopharmacol. 102, 32–36.

    PubMed  PubMed Central  Google Scholar 

  21. Baumann, T.W., Schulthess, B.H., Hänni, K., 1995. Guarana (Paullinia cupana) rewards seed dispersers without intoxicating them by caffeine. Phytochemistry 39, 1063–1070.

    CAS  Google Scholar 

  22. Beck, H.T., 2005. Caffeine, alcohol, and sweeteners. In: Prance, G.T. (Ed.), The Cultural History of Plants. Routledge, New York.

    Google Scholar 

  23. Bektas, E., Daferera, D., Sokmen, M., Serdar, G., Erturk, M., Polissiou, M.G., Sokmen, A., 2016. In vitro antimicrobial, antioxidant, and antiviral activities of the essential oil and various extractsfrom Thymus nummularis M. Bieb. Indian J. Tradit. Knowl. 15, 403–410.

    Google Scholar 

  24. Bentes, J.L.S., Neto, P.Q.C., 2011. Variabilidade genética de Colletotrichum guaranicola usando marcadores AFLP. Acta Amaz. 41, 251–256.

    Google Scholar 

  25. Bentes, J.L.S., Matsuoka, K., 2002. Histology of Colletotrichum guaranicola and Paullinia cupana var. sorbilis on resistant and susceptible clones. Fitopatol. Bras. 27, 71–77.

    Google Scholar 

  26. Bérubé-Parent, S., Pelletier, C., Doré, J., Tremblay, A., 2005. Effects of encapsulated green tea and guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24h energy expenditure and fat oxidation in men. Br. J. Nutr. 94, 432–436.

    PubMed  PubMed Central  Google Scholar 

  27. Bittencourt, L.S., Zeidán-Chuliá, F., Yatsu, F.K.J., Schnorr, C.E., Moresco, K.S., Kolling, E.A., Gelain, D.P., Bassani, V.L., Moreira, J.C.F., 2014. Guarana (Paullinia cupana Mart.) prevents β-amyloid aggregation, generation of advanced glycation-end products (AGEs), and acrolein-induced cytotoxicity on human neuronal-like cells. Phytother. Res. 28, 1615–1624.

    CAS  Google Scholar 

  28. Bittencourt, L.S., Machado, D.C., Machado, M.M., Dos Santos, G.F.F., Algarve, T.D., Marinowic, D.R., Ribeiro, E.E., Soares, F.A.A., Barbisan, F., Athayde, M.L., Cruz, I.B.M., 2013. The protective effects of guarana extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside. Food Chem. Toxicol. 53, 119–125.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Bogas, A.C., Ferreira, A.J., Araujo, W.L., Astolfi, S., Kitajima, E.W., Lacava, P.T., Azevedo, J.L., 2015. Endophytic bacterial diversity in the phyllosphere of Amazon Paullinia cupana associated with asymptomatic and symptomatic anthracnose. Springer-Plus 4, 258.

    PubMed  PubMed Central  Google Scholar 

  30. Bona, E., Cantamessa, S., Massa, N., Manassero, P., Marsano, F., Copetta, A., Lingua, G., D’Agostino, G., Gamalero, E., Berta, G., 2017. Arbuscular myc-orrhizal fungi and plant growth-promoting pseudomonads improve yield, quality and nutritional value of tomato: a field study. Mycorrhiza 27, http://dx.doi.org/10.1007/s00572-016-0727-y.

  31. Bonadiman, B.D.R., Cadona, F.C., Assmann, C.E., Weis, G.C.C., Alves, A.D., Durte, M.F., Chaves, C.M., Chaves, C.D., Motta, K.M.D., Ribeiro, E.E., Bagatini, M.D., da Cruz, I.B.M., 2017. Guarana (Paullinia cupana): cytoprotective effects on age-related eye dysfunction. J. Funct. Food. 36, 375–386.

    Google Scholar 

  32. Boozer, C.N., Nasser, J.A., Heymsfield, S.B., Wang, V., Chen, G., Solomon, J.L., 2001. An herbal supplement containing Ma Huang-guarana for weight loss: a randomized, double-blind trial. Int. J. Obes. 25, 316–324.

    CAS  Google Scholar 

  33. Borgo, J., Xavier, C.A.G., Moura, D.J., Richter, M.F., Suyenaga, E.S., 2010. The Influence of drying processes on flavonoid level and the antioxidant activity of Baccharis articulata (Lam.) extracts. Rev. Bras. Farmacogn. 20, 12–17.

    CAS  Google Scholar 

  34. Boullata, J.I., Nace, A.M., 2000. Safety issues with herbal medicine. Pharmacotherapy 20, 257–269.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Brenelli, E.C.S., 2003. Caffeine extraction from stimulating beverages: a new approach for a classic organic chemistry experiment. Quim. Nova 26, 136–138.

    CAS  Google Scholar 

  36. Bugno, A., Almodovar, A.A.B., Pereiral, T.C., Pinto, T.J.A., Sabino, M., 2006. Occurrence of toxigenic fungi in herbal drugs. Braz.J. Microbiol. 37, 47–51.

    Google Scholar 

  37. Bulku, E., Zinkovsky, D., Patel, P., Javia, V., Lahoti, T., Khodos, I., Stohs, S.J., Ray, S.D., 2010. A novel dietary supplement containing multiple phytochemicals and vita mins elevates hepatorenal and cardiac antioxidant enzymes in the absence of significant serum chemistry and genomic changes. Oxid. Med. Cell. Longev. 3, 129–144.

    PubMed  PubMed Central  Google Scholar 

  38. Bydlowski, S.P., D’Amico, E.A., Chamone, D.A.F., 1991. An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Braz. J. Med. Biol. Res. 24, 421–424.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Bydlowski, S.P., Yunker, R.L., Subbiah, M.T., 1988. A novel property of an aqueous guarana extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo. Braz. J. Med. Biol. Res. 21, 535–538.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Cadona, F.C., Machado, A.K., Azzolin, V.F., Barbisan, F., Dornelles, E.B., Glanzner, W., Goncalves, P.B.D., Assmann, C.E., Ribeiro, E.E., da Cruz, I.B.M., 2016. Guarana caffeine-rich food increases oxaliplatin sensitivity of colorectal HT-29 cells by apoptosis pathway modulation. Anti-Cancer Agents Med. Chem. 16, 1055–1065.

    CAS  Google Scholar 

  41. Camargo, M.C.R., Tfouni, S.A.V., Vitorino, S.H.P., Menegário, T.F., Toledo, M.C.F., 2006. Detemination of polycyclic aromatic hydrocarbons (PAHS) in guarana powder (Paullinia cupana). Cienc. Tecnol. Aliment. 26, 230–234.

    Google Scholar 

  42. Campos, A.R., Barros, A.I.S., Albuquerque, F.A.A., Leal, L.K.A.M., Rao, V.S.N., 2005. Acute effects of guarana (Paullinia cupana Mart.) on mouse behaviour in forced swimming and open field tests. Phytother. Res. 19, 441–443.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Campos, A.R., Barros, A.I.S., Santos, F.A., Rao, V.S.N., 2003. Guarana (Paullinia cupana Mart.) offers protection against gastric lesions induced by ethanol and indomethacin in rats. Phytother. Res. 17, 1199–1202.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Campos, M.M., Fernandes, E.S., Ferreira, J., Bortolanza, L.B., Santos, A.R., Calixto, J.B., 2004. Pharmacological and neurochemical evidence forantidepressant-like effects ofthe herbal product Catuama. Pharmacol. Biochem. Behav. 78, 757–764.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Campos, M.P.d.O., Riechelmann, R., Casa, L.B.A., Hassan, B.J., Casa, F.B.A., Giglio, A.D., 2011. Guarana (Paullinia cupana) improves fatigue in breast cancer patients undergoing systemic chemotherapy. J. Altern. Complement. Med. 17, 505–512.

    Google Scholar 

  46. Carlini, E.A., 2003. Plants and the central nervous system. Pharmacol. Biochem. Behav. 75, 501–512.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Carlini, E.A., Rodrigues, E., Mendes, F.R., Tabach, R., Gianfratti, B., 2006. Treatment of drug dependence with brazilian herbal medicines. Rev. Bra. Farmacogn. 16, 690–695.

    Google Scholar 

  48. Carlson, M., Thompson, R.D., 1998. Liquid chromatographic determination of methylxanthines and catechins in herbal preparations containing guarana. J. AOAC Int. 81, 691–701.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Carvalho, L.M., Costa, J.A.M., Carnelossi, M.A.G., 2010. Qualidade em plantas medic-inais. Embrapa, Aracaju.

    Google Scholar 

  50. Carvalho, L.V.N., Cordeiro, M.F., Lins, T.U.L., Sampaio, M.C.P.D., Mello, G.S.V., Costa, V.C.M., Marques, L.LM., Klein, T., Mello, J.C.P., Cavalcanti, I.M.F., Pitta, I.R., Pitta, M.G.R., Rêgo, M.J.B.M., 2016. Evaluation of antibacterial, antineoplastic, and immunomodulatory activity of Paullinia cupana seeds crude extract and ethyl-acetate fraction. Evid. Based Complement. Altern. Med., https://doi.org/10.1155/2016/1203274.

    Google Scholar 

  51. Chiste, R.C., Benassi, M.D., Mercadante, A.Z., 2014. Efficiency of different solvents on the extraction of bioactive compounds from the Amazonian fruit Caryocar villosum and the effect on its antioxidant and colour properties. Phytochem. Anal. 25, 364–372.

    CAS  Google Scholar 

  52. Chorilli, M., Ribeiro, M.C.A.P., Pires-de-Campos, M.S.M., Leonardi, G.R., Polacow, M.L.O., 2004. Emulsion effect containing dry extract of guarana over the blood vessels of the papillary dermis of rats. Saúde Rev. 6, 7–12.

    Google Scholar 

  53. Corrêa, M.P., 1984. Dicionário das plantas úteis do Brasil e das exóticas cultivadas. Ministério da Agricultura, Instituto Brasileiro de Desenvolvimento Florestal, Rio de Janeiro.

    Google Scholar 

  54. Couto, R.O., Martins, F.S., Chaul, L.T., Conceição, E.C., Freitas, L.A.P., Bara, M.T.F., Paula, J.R., 2013. Spray drying of Eugenia dysenterica extract: effects of in-process parameters on product quality. Rev. Bras. Farmacogn. 23, 115–123.

    Google Scholar 

  55. da Fonseca, C.A., Leal, J., Costa, S.S., Leitao, A.C., 1994. Genotoxic and mutagenic effects of guarana (Paullinia cupana) in prokaryotic organisms. Mutat. Res. 321, 165–173.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. da Silva, G.S., Canuto, K.M., Ribeiro, P.R.V., de Brito, E.S., Nascimento, M.M., Zocolo, G.J., Coutinho, J.P., de Jesus, R.M., 2017. Chemical profiling of guarana seeds (Paullinia cupana) from different geographical origins using UPLC-QTOF-MS combined with chemometrics. Food Res. Int. 102, 700–709.

    PubMed  PubMed Central  Google Scholar 

  57. Dalonso, N., Petkowicz, C.L.d.O., 2012. Guarana powder polysaccharides: characterisation and evaluation of the antioxidant activity of a pectic fraction. Food Chem. 134, 1804–1812.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. de Aquino, J.C., Souza, C.F.C., Santos, J.R.D., Joachim-Bravo, I.S., 2016. Adding guarana powdertomedflydiets:analternativeforimprovingthesterileinsecttechnique. Sci. Agric. 73, 294–298.

    Google Scholar 

  59. de Gois, J.S., Almeida, T.S., de Andrade, R.M., Toaldo, I.M., Bordignon-Luiz, M.T., Borges, D.L.G., 2016. Direct solid analysis for the determination of Mn, Ni, Rb and Srinpowderedstimulantplantsusinghigh-resolutioncontinuum source atomic absorption spectrometry followed by chemometric classification based on elemental composition, polyphenol content and antioxidant activity. Microchem. J. 124, 283–289.

    Google Scholar 

  60. de Menezes-Júnior, J.B.F., 1942. Do exame microscópico do guarana em bromatologia. Rev. Inst. Adolfo Lutz 2, 45–68.

    Google Scholar 

  61. de Oliveira, D.M., Barreto, G., Galeano, P., Romero, J.I., Holubiec, M.I., Badorrey, M.S., Capani, F., Alvarez, L.D.G., 2011. Paullinia cupana Mart. var. sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Hum. Exp. Toxicol. 30, 1382–1391.

    PubMed  PubMed Central  Google Scholar 

  62. de Oliveira, J.F., Avila, A.S., Braga, A.C., de Oliveira, M.B., Boasquevisque, E.M., Jales, R.L., Cardoso, V.N., Bernardo-Filho, M., 2002. Effect of extract of medicinal plants on the labelingofblood elementswith Technetium-99m andonthemorphology of red blood cells: I–a study with Paullinia cupana. Fitoterapia 73, 305–312.

    PubMed  PubMed Central  Google Scholar 

  63. del Giglio, A.B., Cubero, D.I.G., Lerner, T.G., Guariento, R.T., de Azevedo, R.G., Paiva, H., Goldman, C., Carelli, B., Cruz, F.M., Schindler, F., Pianowski, L., de Matos, L.L., del Giglio, A., 2013. Purified dry extract of Paullinia cupana (guarana) (PC-18) for chemotherapy-related fatigue in patients with solid tumors: an early discontinuation study. J. Diet. Suppl. 10, 325–334.

    PubMed  PubMed Central  Google Scholar 

  64. Donadio, V., Bonsi, P., Zele, I., Monari, L., Liguori, R., Vetrugno, R., Albani, F., Montagna, P., 2000. Myoglobinuria after ingestion of extracts of guarana, Ginkgo biloba and kava. Neurol. Sci. 21, 124.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Duarte, M.L.R., Albuquerque, F.C., Corrêa, M.P.F., 1995. Variações morfológicas e fisiológicas em isolamentos de Colletotrichum guaranicola. Fitopatol. Bras. 20, 141–144.

    Google Scholar 

  66. Duke, J.A., 1987. Handbook of Medicinal Herbs, 2 ed. CRC Press LLC, Florida.

    Google Scholar 

  67. Edwards, H.G.M., Farwell, D.W., Oliveira, L.F.C., Alia, J.-M., Hyaric, M.L., Ameida, M.V., 2005. FT-Ramanspectroscopic studiesofguarana andsome extracts. Anal. Chim. Acta 532, 177–186.

    CAS  Google Scholar 

  68. Escobar, J.R., Correa, M.P.F., Aguilera, F.J.P., 1984. Estruturas florais, floração e técnicas para a polinização controlada do guaranazeiro. I. Simpósio Brasileiro do Guaraná–Anais. Embrapa-UEPAE, Manaus, p. 222.

    Google Scholar 

  69. Espinola, E.B., Dias, R.F., Mattei, R., Carlini, E.A., 1997. Pharmacological activity of guaraná (Paullinia cupana Mart.) in laboratory animals. J. Ethnopharmacol. 55, 223–229.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Farmacopeia Brasileira, 1977. 3 ed. Atheneu, São Paulo.

    Google Scholar 

  71. Forzza, R.C., 2010. Lista de espécies Flora do Brasil. Jardim Botânico do Rio de Janeiro, Rio de Janeiro, Published on the Internet. http://floradobrasil.jbrj.gov.br/2010/ (accessed 16.06.18).

    Google Scholar 

  72. Freitas, R.S., Moreno, S.R.F., Lima-Filho, G.L., Fonseca, A.S., Bernardo-Filho, M., 2007. Effect of a commercial extract of Paullinia cupana (guarana) on the binding of 99mTc-DMSA on blood constituents: an in vivo study. Appl. Radiat. Isot. 65, 528–533.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Fukumasu, H., Avanzo, J.L., Heidor, R., Silva, T.C., Atroch, A., Moreno, F.S., Dagli, M.L.Z., 2006a. Protective effects of guarana (Paullinia cupana Mart. var. sor-bilis) against DEN-induced DNA damageon mouse liver. Food Chem. Toxicol. 44, 862–867.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Fukumasu, H., Avanzo, J.L., Nagamine, M.K., Barbuto, J.A., Rao, K.V., Dagli, M.L.Z., 2008. Paullinia cupana Mart var. sorbilis, guarana, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice Braz. J. Med. Biol. Res. 41, 305–310.

    CAS  Google Scholar 

  75. Fukumasu, H., Latorre, A.O., Zaidan-Dagli, M.L., 2011. Paullinia cupana Mart. var. sorbilis, guarana, increases survival of Ehrlich ascites carcinoma (EAC) bearing mice by decreasing cyclin-D1 expression and inducing a G0/G1cell cycle arrest in EAC cells. Phytother. Res. 25, 11–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Fukumasu, H., Silva, T.C.d., Avanzo, J.L., Lima, C.E.d., Mackwiak, I.I., Atroch, A., Spinosa, H.d.S., Moreno, F.S., Dagli, M.L.Z., 2006b. Chemopreventive effects of Paullinia cupana Mart. var. sorbilis, the guarana, on mouse hepatocarcinogenesis. Cancer Lett. 233, 158–164.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Funasaki, M., Barroso, H.D., Fernandes, V.L.A., Menezes, I.S., 2016. Amazon rainforest cosmetics: chemical approach for quality control. Quim. Nova 39, 194–209.

    CAS  Google Scholar 

  78. Funk, V.A., Berry, P.E., Alexander, S.N., Hollowell, T.H., Kelloff, C.L., 2007. Checklist of the plants of the Guiana shield (Venezuela: Amazonas, Bolivar, Delta Amacuro; Guyana, Surinam, French Guiana). Contr. U.S. Natl. Herb. 55, 1–584.

    Google Scholar 

  79. Galduróz, J.C.F., Carlini, E.A., 1994. Acute effects of the Paullinia cupana, “guarana” on the cognition of normal volunteers. São Paulo Med. J. 112, 607–611.

    PubMed  PubMed Central  Google Scholar 

  80. Galduróz, J.C.F., Carlini, E.A., 1996. The effectsoflong-term administrationof guarana on the cognitionofnormal, elderly volunteers. São Paulo Med. J. 114, 1073–1078.

    PubMed  PubMed Central  Google Scholar 

  81. Gobbo-Neto, L., Lopes, N.P., 2007. Medicinal plants: factors of influence on the content of secondary metabolites. Quim. Nova 30, 374–381.

    CAS  Google Scholar 

  82. Gouveia, V.F., Rossil, A.P., Rossi, A.P., Rocha, V.d.F., Ribeiro, L.F.C., 2012. Profile of the producers of guarana (Paullinia cupana) of Alta Floresta-MT. Rev. Conexão UEPG 8, 300–312.

    Google Scholar 

  83. Greene, J.C., Vermillion, J.R., 1964. The simplified oral hygiene index. J. Am. Dent. Assoc. 68, 7–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Haller, C.A., Jacob, P., Benowitz, N.L., 2005. Short-term metabolic and hemody-namic effects of ephedra and guarana combinations. Clin. Pharmacol. Ther. 77, 560–571.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Hamerski, L., Somner, G.V., Tamaio, N., 2013. Paullinia cupana Kunth (Sapindaceae): a review of its ethnopharmacology, phytochemistry and pharmacology. J. Med. Plants Res. 7, 2221–2229.

    Google Scholar 

  86. Haskell, C.F., Kennedy, D.O., Wesnes, K.A., Milne, A.L., Scholey, A.B., 2007. A doubleblind, placebo-controlled, multi-dose evaluationof the acute behavioural effects of guarana in humans. J. Psychopharmacol. 21, 65–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Heard, C.M., Johnson, S., Moss, G., Thomas, C.P., 2006. In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia cupana. Int. J. Pharm. 317, 26–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Henman, A.R., 1982. Guarana (Paullinina cupana var. sorbilis): ecological and social perspectives on an economic plant of the central amazon basin. J. Ethnopharmacol. 6, 311–338.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Hertz, E., Cadoná, F.C., Machado, A.K., Azzolin, V., Holmrich, S., Assmann, C., Ledur, P., Ribeiro, E.E., Filho, O.C.d.S., Mânica-Cattani, M.F., Cruz, I.B.M.d., 2015. Effect of Paullinia cupana on MCF-7 breast cancer cell response to chemotherapeutic drugs. Mol. Clin. Oncol. 3, 37–43.

    PubMed  PubMed Central  Google Scholar 

  90. Higgins, J.P., Tuttle, T.D., Higgins, C.L., 2010. Energy beverages: content and safety. Mayo Clin. Proc. 85, 1033–1041.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Homma, A.K.O., 2014. Guaraná: passado, presente e futuro. In: Homma, A.K.O. (Ed.), Extrativismo vegetal naAmazônia: história, ecologia, economiae domesticação. Embrapa, Brasília, p. 472.

    Google Scholar 

  92. IBGE, 2017. Levantamento sistemático da produção agrícola. In: Coagro. Instituto Brasileiro de Geografia e Estatística-IBGE, Rio de Janeiro, pp. 1–113.

    Google Scholar 

  93. Iyadurai, S.J., Chung, S.S., 2007. New-onset seizures in adults: possible association with consumption of popular energy drinks. Epilepsy Behav. 10, 504–508.

    PubMed  PubMed Central  Google Scholar 

  94. Jippo, T., Kobayashi, Y., Sato, H., Hattori, A., Takeuchi, H., Sugimoto, K., Shigekawa, M., 2009. Inhibitory effects of guarana seed extract on passive cutaneous anaphylaxis and mast cell degranulation. Biosci. Biotechnol. Biochem. 73, 2110–2112.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Kalia, K., Sharma, K., Singh, H.P., Singh, B., 2008. Effects of extraction methods on phenolic contents and antioxidant activity in aerial parts of Potentilla atrosan-guinea Lodd. and quantification of its phenolic constituents by RP-HPLC. J. Agric. Food Chem. 56, 10129–10134.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Kennedy, D.O., Haskell, C.F., Robertson, B., Reay, J., Brewster-Maund, J.C., Luedemann, J., Maggini, S., Ruf, M., Zangara, A., Scholey, A.B., 2008. Improved cognitive performance and mentalfatigue followingamulti-vitamin and mineralsupplement with added guarana (Paullinia cupana). Appetite 50, 506–513.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Kennedy, D.O., Haskell, C.F., Wesnes, K.A., Scholey, A.B., 2004. Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng. Pharmacol. Biochem. Behav. 79, 401–411.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Klein, T., Longhini, R., Bruschi, M.L., Mello, J.C.P., 2013. Development of tablets containing semipurified extract ofguarana (Paullinia cupana). Rev. Bras. Farmacogn. 23, 186–193.

    Google Scholar 

  99. Klein, T., Longhini, R., Bruschi, M.L., Mello, J.C.P., 2015. Microparticles containing guarana extract obtained by spray-drying technique: development and characterization. Rev. Bras. Farmacogn. 25, 292–300.

    CAS  Google Scholar 

  100. Klein, T., Longuini, R., Mello, J.C.P., 2012. Development of an analytical method using reversed-phase HPLC-PDA for a semipurified extract of Paullinia cupana var. sorbilis (guarana). Talanta 88, 502–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Kneifel, W., Czech, E., Kopp, B., 2001. Microbial contamination of medicinal plants–a review. Planta Med. 68, 5–15.

    Google Scholar 

  102. Kober, H., Tatsch, E., Torbitz, V.D., Cargnin, L.P., Sangoi, M.B., Bochi, G.V., da Silva, A.R.H., Barbisan, F., Ribeiro, E.E., da Cruz, I.B.M., Moresco, R.N., 2016. Genoprotec-tive and hepatoprotective effects of guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats. Drug. Chem. Toxicol. 39, 48–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Kofink, M., Papagiannopoulos, M., Galensa, R., 2007. Enantioseparation of catechin and epicatechin in plant food by chiral capillary electrophoresis. Eur. Food Res. Technol. 225, 569–577.

    CAS  Google Scholar 

  104. Krewer, C.C., Ribeiro, E.E., Ribeiro, E.A.M., Moresco, R.N., da Rocha, M.I.U.M., Montagner, G.F.F.S., Machado, M.M., Viegas, K., Brito, E., da Cruz, I.B.M., 2011. Habitual intake of guarana and metabolic morbidities: an epidemiological study of an elderly Amazonian population. Phytother. Res. 25, 1367–1374.

    CAS  Google Scholar 

  105. Kuri, C.M.B., 2008. The guarana industry in Brazil. Int. Bus. Econ. Res. J. 7, 87–98.

    Google Scholar 

  106. Lapa, A.J., Souccar, C., Lima-Landman, M.T., Godinho, R.O., Lima, T.C.M., 2010. Farma-cologia e toxicologia de produtos naturais (in Portuguese). In: Simões, C.M.O., Schenkel, E.P., Gosmann, G., Mello, J.C.P., Mentz, L.A., Petrovick, P.R. (Eds.), Farmacognosia: da planta ao medicamento. UFRGS/UFSC, Porto Alegre, Flori-anópolis, pp. 247–262.

    Google Scholar 

  107. Leite, R.P., Predes, F.S., Monteiro, J.C., Freitas, K.M., Wada, R.S., Dolder, H., 2013. Advantage of guarana (Paullinia cupana Mart.) supplementation on cadmium-induced damages in testis of adult wistar rats. Toxicol. Pathol. 41, 73–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Leite, R.P., Wada, R.S., Monteiro, J.C., Predes, F.S., Dolder, H., 2011. Protective effect of guarana (Paullinia cupana var. sorbilis) pre-treatment on cadmium-induced damages in adult Wistar testis. Biol. Trace Elem. Res. 141, 262–274.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Lima, N.D., Numata, E.D., Mesquita, L.M.D., Dias, P.H., Vilegas, W., Gambero, A., Ribeiro, M.L., 2017. Modulatory effects of guarana (Paullinia cupana) on adipogenesis. Nutrients 9, https://doi.org/10.3390/nu9060635.

  110. Lima, N.D., Teixeira, L., Gambero, A., Ribeiro, M.L., 2018. Guarana (Paullinia cupana) stimulates mitochondrial biogenesis in mice fed high-fat diet. Nutrients 10, https://doi.org/10.3390/nu10020165.

  111. Lima, R.B.S., Silva, L., Melo, M.R.S., Costa, J.S., Picanco, N.S., Lima, E.S., Vasconcellos, M.C., Boleti, A.P.A., Santos, J.M.P., Amorim, R.C.N., Chaves, F.C.M., Coutinho, J.P., Tadei, W.P., Krettli, A.U., Pohlit, A.M., 2015. In vitro and in vivo anti-malarial activity of plants from the Brazilian Amazon. Malar. J. 14, https://doi.org/10.1186/s12936-015-0999-2.

  112. Lima, W.P., Carnevali, J.L.C., Eder, R., Rosa, L.F.B.P.C., Bacchi, E.M., Seelaender, M.C.L., 2005. Lipid metabolism in trained rats: effect of guarana (Paullinia cupana Mart.) supplementation. Clin. Nutr. 24, 1019–1028.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Liu, X., Zhao, M., Wang, J., Luo, W., 2007. Antimicrobial and antioxidant activity of emblica extracts obtained by supercritical carbon dioxide extraction and methanol extraction. J. Food Biochem. 33, 307–330.

    Google Scholar 

  114. Lude, S., Vecchio, S., Sinno-Tellier, S., Dopter, A., Mustonen, H., Vucinic, S., Jonsson, B., Muller, D., Fruchtengarten, L.V., Hruby, K., Nascimento, E.D., Di Lorenzo, C., Restani, P., Kupferschmidt, H., Ceschi, A., 2016. Adverse effects of plant food supplements and plants consumed as food: results from the poisons centres-based plantLIBRA study. Phytother. Res. 30, 988–996.

    PubMed  PubMed Central  Google Scholar 

  115. Lunguinho, L.G., 2007. Florescimento em guaranazeiro (Paullinia cupana var. sorbilis). Dissertação de Mestrado (Biotecnologia). Universidade Federal do Amazonas, Manaus, p. 86. http://200.129.163.131:8080/handle/tede/2244/ (accessed 19.08.18).

    Google Scholar 

  116. Machado, A.K., Canodá, F.C., Azzolin, V.F., Dornelles, E.B., Barbisan, F., Ribeiro, E.E., Mânica-Cattani, M.F., Duarte, M.M.M.F., Saldanha, J.R.P., Cruz, I.B.M., 2015. Guarana (Paullinia cupana) improves the proliferation and oxidative metabolim of senescent adipocyte stem cells derived from human lipoaspirates. Food Res. Int. 67, 426–433.

    CAS  Google Scholar 

  117. Machado, K.N., Freitas, A.A.d., Cunha, L.H., Faraco, A.A.G., Pádua, R.M.d., Braga, F.C., Vianna-Soares, C.D., Castilho, R.O., 2018. A rapid simultaneous determination of methylxanthines and proanthocyanidins in Brazilian guaraná (Paullinia cupana Kunth.). Food Chem. 239, 180–188.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Machado, O., 1946. Contribuição ao estudo das plantas medicinais do Brasil–o guarana (in Portuguese). Rodriguesia 9, 89–110.

    Google Scholar 

  119. Majhenic, L., Skerget, M., Knez, Z., 2007. Antioxidant and antimicrobial activity of guarana seed extracts. Food Chem. 104, 1258–1268.

    CAS  Google Scholar 

  120. Marques, L.L.M., Panizzon, G.P., Aguiar, B.A.A., Simionato, A.S., Cardozo-Filho, L., Andrade, G., Oliveira, A.G.d., Guedes, T.A., Mello, J.C.P., 2016. Guarana (Paullinia cupana) seeds: selective supercritical extraction of phenolic compounds. Food Chem. 212, 703–711.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Martins, M., Kluczkovski, A.M., Santos, A.C.S., Fernandes, O.C.C., Scussel, V.M., 2014. Evaluation of ochratoxin A and fungi in powdered guarana (Paullinia cupana Kunth), a caffeine rich product from Amazon forest. Afr. J. Microbiol. Res. 8, 545–550.

    Google Scholar 

  122. Marx, F., 1990. Analysis of guarana seeds. II. Studies on the composition of the tannin fraction Z. Lebensm. Unters. Forsch. 190, 429–431.

    CAS  Google Scholar 

  123. Marx, F., Maia, J.G., 1990. Analysis of guarana (Paullinia cupana var, sorbilis). III. Identification and determination of guaraná beverages by HPLC analysis of caffeine anda theophylline. Quim. Nova 13, 285–286.

    CAS  Google Scholar 

  124. Matsuura, E., Godoy, J.S.R., Bonfim-Mendonça, P.S., Mello, J.C.P., Svidzinski, T.I.E., Gasparetto, A., Maciel, S.M., 2015. In vitro effect of Paullinia cupana (guarana) on hydrophobicity, biofilm formation, and adhesion of Candida albicans to polystyrene, composites, and buccal epithelial cells. Arch. Oral Biol. 60, 471–478.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Mattei, R., Dias, R.F., Espinola, E.B., Carlini, E.A., Barros, S.B.M., 1998. Guarana (Paullinia cupana): toxic behavioral effects inlaboratory animals and antioxidant activity in vitro. J. Ethnopharmacol. 60, 111–116.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. McGuire, S., 2014. Institute of Medicine. 2014. Caffeine in food and dietary supplements: examining safety-workshop summary. Washington, DC: The National Academies Press, 2014. Adv. Nutr. 5, 585–586.

    PubMed  PubMed Central  Google Scholar 

  127. Mehr, C.B., Biswal, R.N., Collins, J.L., 1996. Supercritical carbon dioxide extraction of caffeine from guarana. J. Supercrit. Fluids 9, 185–191.

    CAS  Google Scholar 

  128. Mello, J.C.P., Ito, L.A., 2012. Aplicação da eletroforese capilar na análise de produtos naturais. In: Souza, G.H.B., Mello, J.C.P., Lopes, N.P. (Eds.), Revisões em Processos e TécnicasAvançadasdeIsolamentoeDeterminação Estrutural Ativosde Plantas Medicinais. UFOP, Ouro Preto, pp. 209–242.

    Google Scholar 

  129. Mello, J.R.B., Mello, F.B., Langeloh, A., 2010. Pre-clinic toxicity of a phytoter-apic containing Anemopaegma mirandum, Cola nitida, Passiflora alata, Paullinia cupana, Ptychopetalum olacoides and thiamin chlorhydrate. Lat. Am. J. Pharm. 29, 1431–1435.

    Google Scholar 

  130. Meurer-Grimes, B., Berkov, A., Beck, H., 1998. Theobromine, theophylline, and caffeine in 42 samples and products of Guarana (Paullinia cupana, Sapindaceae). Econ. Bot. 52, 293–301.

    Google Scholar 

  131. Mingori, M.R., Heimfarth, L., Ferreira, C.F., Gomes, H.M., Moresco, K.S., Delgado, J., Roncato, S., Zeidan-Chulia, F., Gelain, D.P., Moreira, J.C.F., 2017. Effect of Paullinia cupana Mart. commercial extract during the aging of middle age Wistar rats: differential effects on the hippocampus and striatum. Neurochem. Res. 42, 2257–2273.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Miranda, V.C., Trufelli, D.C., Fêde, A.B.S., Martins, F.D., Saad, L.S., Oliveira, V., Trindade, T.Z.C., Riechelmann, R., Giglio, A.D., 2008. Guarana (Paullinia cupana) for chemotherapy-related fatigue. Einstein 6, 195–199.

    Google Scholar 

  133. Miranda, V.C., Trufelli, D.C., Santos, J., Campos, M.P., Nobuo, M., Miranda, M.C., Schlinder, F., Riechelmann, R., Giglio, A.D., 2009. Effectiveness of guarana (Paullinia cupana) for postradiation fatigue and depression: results of a pilot double-blind randomized study. J. Altern. Complement. Med. 15, 431–433.

    Google Scholar 

  134. Miura, T., Tatara, M., Nakamura, K., Suzuki, I., 1998. Effect of guarana on exercise in normal and epinephrine-induced glycogenolytic mice. Biol. Pharm. Bull. 21, 646–648.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Moaddeb, J., Tofade, T.S., Bevins, M.B., 2011. Hypertensive urgency associated with Xenadrine EFX use. J. Pharm. Pract. 24, 400–403.

    Google Scholar 

  136. Moraes, M.L.L., Micke, G.A., Fujyia, N.M., Tavares, M.F.M., 2003. Separação e análise de metilxantinas em extratos de guarana e erva mate por eletroforese capilar. Rev. Anal. 5, 44–50.

    Google Scholar 

  137. Mottram, D.R., Chester, N., 2015. Drugs in Sport, 6 ed. Taylor & Francis, New York, pp. 351.

    Google Scholar 

  138. Moure, A., Cruz, J.M., Franco, D., Domínguez, J.M., Sineiro, J., Domínguez, H., Núnez, M.J., Parajó, J.C., 2001. Natural antioxidants from residual sources–review. Food Chem. 72, 145–171.

    CAS  Google Scholar 

  139. Murugan, R., Parimelazhagan, T., 2014. Comparative evaluation of different extraction methods for antioxidant and anti-inflammatory properties from Osbeckia parvifolia Arn.–an in vitro approach. J. King Saud Univ. Sci. 26, 267–275.

    Google Scholar 

  140. Nawrot, P., Jordan, S., Eastwood, J., Rotstein, J., Hugenholtz, A., Feeley, M., 2003. Effects of caffeine on human health. Food Addit. Contam. A 20, 1–30.

    CAS  Google Scholar 

  141. Nazaré, R.F.R., 1998. Processamento de guarana em pó solúvel. Embrapa, Belém, PA, Brazil, p. 24.

    Google Scholar 

  142. Nazaré, R.F.R., Figueiredo, F.J.C., 1982. Contribuição ao estudo do guarana. Embrapa Amazônia Oriental, Belém, p. 41.

    Google Scholar 

  143. Nguyen, V.T., Pham, H.N.T., Bowyer, M.C., van Altena, I.A., Scarlett, C.J., 2016. Influence of solvents and novel extraction methods on bioactive compounds and antioxidant capacity of Phyllanthus amarus. Chem. Pap. 70, 556–566.

    CAS  Google Scholar 

  144. Nicoletti, M.A., Oliveira-Junior, M.A., Bertasso, C.C., Coporossi, P.Y., Tavares, A.P.L., 2007. Principais interações no uso de medicamentos fitoterápicos. Infarma 19, 32–40.

    Google Scholar 

  145. Nyska, A., Murphy, E., Foley, J.F., Collins, B.J., Petranka, J., Howden, R., Hanlon, P., Dunnick, J.K., 2005. Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine. Toxicol. Sci. 83, 388–396.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Oliveira, A.N., Oliveira, L.A., 2005. Seasonal dynamics of arbuscular mycorrhizal fungi in plants of Theobroma grandiflorum Schum and Paullinia cupana Mart. of aN agroforestry system in Central Amazonia, Amazonas State, Brazil. Braz. J. Microbiol. 36, 262–270.

    Google Scholar 

  147. Oliveira, C.H., Moraes, M.E.A., Moraes, M.O., Bezerra, F.A.F., Abib, E., De Nucci, G., 2005. Clinical toxicology study of anherbal medicinal extractof Paullinia cupana, Trichilia catigua, Ptychopetalum olacoides and Zingiber oficinale (Catuama®) in healthy volunteers. Phytother. Res. 19, 54–57.

    PubMed  PubMed Central  Google Scholar 

  148. Oliveira, D.M., Barreto, G., Galeano, P., Romero, J.I., Holubiec, M.I., Badorrey, M.S., Capani, F., Alvarez, L.D.G., 2011. Paullinia cupana Mart. var. sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Hum. Exp. Toxicol. 30, 1382–1391.

    PubMed  PubMed Central  Google Scholar 

  149. Oliveira, S.S., Giglio, A.B., Lerner, T.G., Zanellato, R.M., Tiemi, L., Reifur, L., Santi, P.X., Giglio, A., 2013. Paullinia cupana for control of hot flashes in breast cancer patients: a pilot study. Einstein 11, 435–438.

    PubMed  PubMed Central  Google Scholar 

  150. Onakpoya, I., Ernst, E., 2012. Safety of guarana-containing weight loss supplements: a mini-review. J. Naturol. Complemen. Ther. 1, 45–50.

    Google Scholar 

  151. Opala, T., Rzymski, P., Pischel, I., Wilczak, M., Wozniak, J., 2006. Efficacy of 12 weeks supplementation of a botanical extract-based weight loss formula on body weight, body composition and blood chemistryinhealthy, overweight subjects-a randomised double-blind placebo-controlled clinical trial. Eur. J. Med. Res. 11, 343–350.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Otobone, F.J., Sanches, A.C., Nagae, R.L., Martins, J.V.C., Obici, S., Mello, J.C.P., Audi, E.A., 2005. Effect of crude extract and its semi purifies constituents from guarana seeds (Paullinia cupana var. sorbilis (Mart.)) Lucke on cognitive performance in morris water maze in rats. Braz. Arch. Biol. Technol. 48, 723–728.

    Google Scholar 

  153. Otobone, F.J., Sanches, A.C.C., Magae, R.L., Martins, J.V.C., Sela, V.R., Mello, J.C.P., Audi, E.A., 2007. Effect off liophilized extracts from guarana seeds [Paullinia cupana var. sorbilis (Mart.) Ducke] on behavioral profiles in rats. Phytother. Res. 21, 531–535.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Pagliarussi, R.S., Bastos, J.K., Freitas, L.A.P., 2006. Fluid bed drying of guarana (Paullinia cupana HBK) extract: effectofprocess factors oncaffeine content. AAPS Pharm. Sci. Tech. 7, E1–E7.

  155. Pagliarussi, R.S., Freitas, L.A.P., Bastos, J.K., 2002. A quantitative method for the analysis of xanthine alkaloids in Paullinia cupana (guarana) by capillary column gas chromatography. J. Sep. Sci. 25, 1–6.

    Google Scholar 

  156. Peixoto, H., Roxo, M., Röhrig, T., Richling, E., Wang, X., Wink, M., 2017. Anti-aging and antioxidant potential of Paullinia cupana var. sorbilis: findings in Caenorhabditis elegans indicate a new utilization for roasted seeds of guarana. Medicines 4, http://dx.doi.org/10.3390/medicines4030061.

  157. Pelozo, M.I.G., Cardoso, M.L.C., Mello, J.C.P., 2008. Spectrophotometric determination of tannins and caffeine in preparations from Paullinia cupana var. sorbilis. Braz. Arch. Biol. Technol. 51, 447–451.

    CAS  Google Scholar 

  158. Pinelo, M., Ruiz-Rodríguez, A., Sineiro, J., Sen˜oráns, F.J., Reglero, G., Núnez, M.J., 2007. Supercritical fluid and solid–liquid extraction of phenolic antioxidants from grape pomace: a comparative study. Eur. Food Res. Technol. 226, 199–205.

    CAS  Google Scholar 

  159. Pittler, M.H., Schimidt, K., Ernst, E., 2005. Adverse events of herbal food supplements for body weight reduction: systematic review. Obes. Rev. 6, 93–111.

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Pomportes, L., Brisswalter, J., Casini, L., Hays, A., Davranche, K., 2017. Cognitive performance enhancement induced by caffeine, carbohydrate and guarana mouth rinsing during submaximal exercise. Nutrients 9, http://dx.doi.org/10.3390/nu9060589.

  161. Pomportes, L., Davranche, K., Brisswalter, I., Hays, A., Brisswalter, J., 2015a. Heart rate variability and cognitive function following a multi-vitamin and mineral supplementation with added guarana (Paullinia cupana). Nutrients 7, 196–208.

    Google Scholar 

  162. Pomportes, L., Davranche, K., Hays, A., Brisswalter, J., 2015b. Effect of a creatine-guarana complex on muscular power and cognitive performance in high-level athletes. Sci. Sports 30, 188–195.

    Google Scholar 

  163. Portella, R.L., Barcelos, R.P., Rosa, E.J.F., Ribeiros, E.E., Cruz, I.B.M., Suleiman, L., Soares, F.A.A., 2013. Guarana (Paullinia cupana Kunth) effects on LDL oxidation in elderly people: an in vitro and in vivo study. Lipids Health Dis. 12, 1–9.

    Google Scholar 

  164. Prance, G.T., Nesbitt, M., 2005. The Cultural History of Plants. Routledge, New York; London.

    Google Scholar 

  165. Rangel, M.P., Mello, J.C.P., Audi, E.A., 2013. Evaluation of neurotransmitters involved in the anxiolytic and panicolytic effect ofthe aqueous fraction of Paullinia cupana (guarana) in elevated T maze. Rev. Bras. Farmacogn. 23, 358–365.

    Google Scholar 

  166. Ravi Subbiah, M.T., 2005. Guarana consumption: a review of health benefits and risks. Alternat. Complement. Ther. 11, 212–213.

    Google Scholar 

  167. Ribeiro, B.D., Coelho, M.A.Z., 2012. Production of caffeine-rich guarana extracts using. Braz. J. Food Technol. 15, 261–270.

    CAS  Google Scholar 

  168. Richardson, W.H., Slone, C.M., Michels, J.E., 2007. Herbal drugs ofabuse:an emerging problem. Emerg. Med. Clin. North Am. 25, 435–457.

    PubMed  PubMed Central  Google Scholar 

  169. Rodrigues, M., Alves, G., Lourenco, N., Falcao, A., 2012. Herbdrug interaction of Paullinia cupana (guarana) seed extract on the pharmacoki-netics of amiodarone in rats. Evid. Based Complement. Alternat. Med., http://dx.doi.org/10.1155/2012/428560.

    Google Scholar 

  170. Roggia, I., Ziegler, S., Cruz, I.B.M., Ourique, A.F., Gomes, P., 2016. A derivativeUV spec-trophotometric method for the determination of methylxanthines and tannins in guarana bulk (Paullinia cupana) Int. J. Pharm. Sci. Res. 7, 2334–2342.

    CAS  Google Scholar 

  171. Roncon, C.M., De Almeida, C.B., Klein, T., Mello, J.C.P., Audi, E.A., 2011. Anxiolytic effects of a semipurified constituent of guarana seeds on rats in the elevated T-maze test. Planta Med. 77, 236–241.

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Ruchel, J.B., Braun, J.B.S., Adefegha, S.A., Manzoni, A.G., Abdalla, F.H., de Oliveira, J.S., Trelles, K., Signor, C., Lopes, S.T.A., da Silva, C.B., Castilhos, L.G., Rubin, M.A., Leal, D.B.R., 2017. Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain. Physiol. Behav. 168, 11–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Ruchel, J.B., Rezer, J.F.P., Thorstenberg, M.L., dos Santos, C.B., Cabral, F.L., Lopes, S.T.A., da Silva, C.B., Machado, A.K., da Cruz, I.B.M., Schetinger, M.R.C., Goncalves, J.F., Leal, D.B.R., 2016. Hypercholesterolemia and ecto-enzymes of purinergic system: effects of Paullinia cupana. Phytother. Res. 30, 49–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Ruxton, C.H.S., Kirkwood, L., McMillan, B., John, D.S., Evans, C.E.L., 2007. Effectiveness of a herbal supplement (ZotrimTM) for weight management. Brit. Food J. 109, 416–428.

    Google Scholar 

  175. Saldan˜a, M.D.A., Zetzl, C., Mohamed, R.S., Brunner, G., 2002. Extraction of methylx-anthines from guaraná seeds, mate leaves, and cocoa beans using supercritical carbon dioxide and ethanol. J. Agric. Food Chem. 50, 4820–4826.

    Google Scholar 

  176. Santa Maria, A., Lopez, A., Diaz, M.M., Munhoz-Mingarro, D., Pozuleo, J.M., 1998. Evaluation of the toxicity of guarana with in vitro bioassays. Ecotoxicol. Environ. Safe 39, 164–167.

    CAS  Google Scholar 

  177. Santos, L.P., 2014. Sistema mecanizado de processamento pós-colheita de guaraná: nova tecnologia. In: Comunicado Técnico. Embrapa, Manaus, p. 12.

    Google Scholar 

  178. Schimpl, F.C., da Silva, J.F., Goncalves, J.F., Mazzafera, P., 2013. Guarana: revisiting a highly caffeinated plant from the Amazon. J. Ethnopharmacol. 150, 14–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Schimpl, F.C., Kiyota, E., Mayer, J.L., Goncalves, J.F., da Silva, J.F., Mazzafera, P., 2014. Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit. Phytochemistry 105, 25–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Scholey, A., Bauer, I., Neale, C., Savage, K., Camfield, D., White, D., Maggini, S., Pipingas, A., Stough, C., Hughes, M., 2013. Acute effects of different multivitamin mineral preparations with and without guarana on mood, cognitive performance and functional brain activation. Nutrients 5, 3589–3604.

    PubMed  PubMed Central  Google Scholar 

  181. Scholey, A., Haskell, C., 2008. Neurocognitive effects of guarana plant extract. Drugs Fut. 33, 869.

    Google Scholar 

  182. Sharpe, P.A., Granner, M.L., Conway, J.M., 2006. Availability of weight-loss supplements: results of an audit of retail outlets in a southeastern city. J. Am. Diet. Assoc. 106, 2045–2051.

    PubMed  PubMed Central  Google Scholar 

  183. Silva, F.D., Liotti, R.G., Boleti, A.P.D., Reis, E.D., Passos, M.B.S., dos Santos, E.L., Sampaio, O.M., Januario, A.H., Branco, C.L.B., da Silva, G.F., de Mendonca, E.A.F., Soares, M.A., 2018. Diversity of cultivable fungal endophytes in Paullinia cupana (Mart.) Ducke and bioactivity of their secondary metabolites. PLoS ONE 13, https://doi.org/10.1371/journal.pone.0195874.

  184. Silva, M., Polonio, J.C., Quecine, M.C., de Almeida, T.T., Bogas, A.C., Pamphile, J.A., Pereira, J.O., Astolfi, S., Azevedo, J.L., 2016. Endophytic cultivable bacterial community obtained from the Paullinia cupana seed in Amazonas and Bahia regions and its antagonistic effects against Colletotrichum gloeosporioides. Microb. Pathog. 98, 16–22.

    PubMed  PubMed Central  Google Scholar 

  185. Silvestrini, G.I., Marino, F., Cosentino, M., 2013. Effects of a commercial product containing guarana on psychological well-being, anxiety and mood: a singleblind, placebo-controlled study in healthy subjects. J. Negat. Results Biomed. 12, https://doi.org/10.1186/1477-5751-12-9.

  186. Smith, N., Atroch, A.L., 2007. Guarana’s journey from regional tonic to aphrodisiac and global energy drink. J. Evid. Based Complement. Altern. Med. 7, 279–282.

    Google Scholar 

  187. Sombra, L.L., Gómez, M.R., Olsina, R., Luis, D., Martínez, L.D., Silva, M.F., 2005. Comparative study between capillary electrophoresis and high performance liquid chromatography in ‘guarana’ based phytopharmaceuticals. J. Pharm. Biomed. Anal. 36, 989–994.

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Sousa, S.A., Alves, S.F., Paula, J.A.M.d., Fiuza, T.S., Paula, J.R., Bara, M.T.F., 2010. Determination of tannins and methylxanthines in powdered guarana (Paullinia cupana Kunth, Sapindaceae) by high performance liquid chromatography. Rev. Bras. Farmacogn. 20, 866–870.

    CAS  Google Scholar 

  189. Sousa, S.A., Pascoa, H., Conceição, E.C., Alves, S.F., Diniz, D.G.A., Paula, J.R., Bara, M.T.F., 2011. Dissolution test of herbal medicines containing Paullinia cupana: validation of methods for quantifcation and assessment of dissolution. Braz. J. Pharm. Sci. 47, 269–277.

    Google Scholar 

  190. Spinella, M., 2001. Herbal medicines and epilepsy: the potential for benefit and adverse effects. Epilepsy Behav. 2, 524–532.

    PubMed  PubMed Central  Google Scholar 

  191. Spoladore, D.S., Boaventura, M.A.M., Sáes, L.A., 1987. Teor de cafeína em sementes matrizes do guaranazeiro. Bragantia 46, 425–429.

    CAS  Google Scholar 

  192. Suframa, 2003. Potencialidades estudo de viabilidade econômica: guarana. Super-intendência da zona franca de Manaus - Suframa. Instituto superior de administração eeconomia ISAE/Fundação Getúlio Vargas (FGV), Manaus, Brazil, pp. 1–34.

    Google Scholar 

  193. Tfouni, S.A.V., Camargo, M.C.R., Vitorino, S.H.P., Menegário, T.F., Toledo, M.C.F., 2007. Contribution of guarana powder (Paullinia cupana) as a source of caffeine in the diet. Rev. Nutrição 20, 63–68.

    CAS  Google Scholar 

  194. The Plant List, 2013. in: http://www.tropicos.org/Name/28600664 (Ed.), Paullinia cupana Kunth Published on the Internet; http://www.theplantlist.org/.

    Google Scholar 

  195. Trevisan, M.T.S., Macedo, F.V.V., 2003. Screening for acetylcholinesterase inhibitors from plants to treat Alzheimer’s disease. Quim. Nova 26, 301–304.

    Google Scholar 

  196. Ushirobira, T.M.A., Yamaguti, E., Uemura, L.M., Audi, E.A., Mello, J.C.P., 2004. Avaliação físico-química de sementes de guarana secas por diferentes métodos. Rev. Bras. Farmacogn. 14, 15–20.

    Google Scholar 

  197. Ushirobira, T.M.A., Yamaguti, E., Uemura, L.M., Nakamura, C.V., Dias Filho, B.P., Mello, J.C.P., 2007. Chemical and microbiological study of extract from seeds of guarana (Paullinia cupana var. sorbilis). Acta Farm. Bonaer. 26, 5–9.

    Google Scholar 

  198. Veasey, R.C., Haskell-Ramsay, C.F., Kennedy, D.O., Wishart, K., Maggini, S., Fuchs, C.J., Stevenson, E.J., 2015. The effects of supplementation withavitamin and mineral complex with guarana prior to fasted exercise on affect, exertion, cognitive performance, and substrate metabolism: a randomized Controlled Trial. Nutrients 7, 6109–6127.

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Veiga, L.L.A., Amorim, H., Moraes, J., Silva, M.C., Raices, R.S.L., Quiterio, S.L., 2014. Quantificationofpolycyclic aromatichydrocarbonsintoastedguarana (Paullinia cupana) byhigh-performanceliquid chromatographywithafluorescence detector. Food Chem. 152, 612–618.

    CAS  PubMed  PubMed Central  Google Scholar 

  200. Wanczinski, B.J., Felipe, D.F., Cardoso, M.L.C., Cavalcanti, O.A., 2002. Development of AAS 500mg tablets influenced by direct compression (CD) process. Acta Sci. 24, 649–655.

    CAS  Google Scholar 

  201. Weckerle, C.S., Stutz, M.A., Baumann, T.W., 2003. Purine alkaloids in Paullinia. Phy-tochemistry 64, 735–742.

    CAS  Google Scholar 

  202. White, D.J., Camfield, D.A., Maggini, S., Pipingas, A., Silberstein, R., Stough, C., Scholey, A., 2017. The effect of a single dose of multivitamin and mineral combinations with and without guarana on functional brain activity during a continuous performance task. Nutr. Neurosci. 20, 8–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  203. WHO, 1998. Quality Control Methods for Medicinal Plant Materials. World Health Organization, Geneva.

    Google Scholar 

  204. Yamaguti-Sasaki, E., Ito, L.A., Canteli, V.C.D., Ushirobira, T.M.A., Ueda-Nakamura, T., Dias Filho, B.P., Nakamura, C.V., Mello, J.C.P., 2007. Antioxidant capacity and invitro preventionofdentalplaqueformationbyextractsandcondensed tannins of Paullinia cupana. Molecules 12, 1950–1963.

    CAS  PubMed  PubMed Central  Google Scholar 

  205. Yonekura, L., Martins, C.A., Sampaio, G.R., Monteiro, M.P., Cesar, L.A.M., Mioto, B.M., Mori, C.S., Mendes, T.M.N., Ribeiro, M.L., Arcari, D.P., Torres, E., 2016. Bioavail-ability of catechins from guarana (Paullinia cupana) and its effect on antioxidant enzymes and other oxidative stress markers in healthy human subjects. Food Funct. 7, 2970–2978.

    CAS  PubMed  PubMed Central  Google Scholar 

  206. Youdim, K.A., Shukitt-Hale, B., Joseph, J.A., 2004. Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic. Biol. Med. 37, 1683–1693.

    CAS  PubMed  PubMed Central  Google Scholar 

  207. Zeidan-Chulia, F., Gelain, D.P., Kolling, E.A., Rybarczyk-Filho, J.L., Ambrosi, P., Terra, S.R., Pires, A.S., da Rocha, J.B., Behr, G.A., Moreira, J.C.F., 2013. Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production. Oxid. Med. Cell Longev, https://doi.org/10.1155/2013/791795.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to João Carlos Palazzo de Mello.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Marques, L.L.M., Ferreira, E.D.F., de Paula, M.N. et al. Paullinia cupana: a multipurpose plant — a review. Rev. Bras. Farmacogn. 29, 77–110 (2019). https://doi.org/10.1016/j.bjp.2018.08.007

Download citation

Keywords

  • Guarana
  • Pharmacological properties
  • Quality control
  • Standardization
  • Toxicology