Herbal Medicinal Products from Passiflora for Anxiety: an Unexploited Potential
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Hindawi e Scientific World Journal Volume 2020, Article ID 6598434, 18 pages https://doi.org/10.1155/2020/6598434 Review Article Herbal Medicinal Products from Passiflora for Anxiety: An Unexploited Potential Lyca R. da Fonseca,1,2 Rafaele de A. Rodrigues,1,2 Aline de S. Ramos ,1 Jefferson D. da Cruz,1,3 Jose´ Luiz P. Ferreira,1,4 Jefferson Rocha de A. Silva ,5 and Ana Claudia F. Amaral 1 1Laboratory of Medicinal Plants and Derivatives, Department of Chemistry of Natural Products, Farmanguinhos, Fiocruz, Rio de Janeiro 21041-250, Brazil 2Professional Postgraduate Program in Management, Research and Development in Pharmaceutical Industry, Farmanguinhos, Fiocruz, Rio de Janeiro 21041-250, Brazil 3Academic Postgraduate Program in Translational Research in Drugs and Medicines, Farmanguinhos, Fiocruz, Rio de Janeiro 21041-250, Brazil 4Faculty of Pharmacy, Fluminense Federal University, Niter´oi 24241-002, Brazil 5Laboratory of Chromatography, Department of Chemistry, Federal University of Amazonas, Manaus 69077-000, Brazil Correspondence should be addressed to Aline de S. Ramos; [email protected] and Ana Claudia F. Amaral; [email protected] Received 11 February 2020; Revised 12 June 2020; Accepted 27 June 2020; Published 20 July 2020 Academic Editor: Abdu Adem Copyright © 2020 Lyca R. da Fonseca et al. 'is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Herbal medicines containing Passiflora species have been widely used to treat anxiety since ancient times. 'e species Passiflora incarnata L. is included in many Pharmacopoeias, and it is the most used species in food, cosmetic, and pharmaceutical industries. However, there are around 600 species of the genus Passiflora and probably other species that can be used safely. 'us, this article was based on a search into the uses of the main species of the genus Passiflora with anxiolytic activity and its main secondary metabolites and some pharmacological studies, patents, and registered products containing Passiflora. Furthermore, the Brazilian Regulatory Health Agency Datavisa, Medicines and Healthcare Products Regulatory Agency of the United Kingdom, and the European Medicines Agency websites were consulted. 'e results showed that Passiflora species have health benefits but clinical trials are still scarce. 'e complexity of Passiflora extracts creates challenges for the development of herbal medicines. P. incarnata is the most studied species of the genus and the most used in natural anxiolytic herbal medicine formulations. However, there are hundreds of Passiflora species potentially useful for medicinal and nutraceutical purposes that are still little explored. 1. Introduction Passiflora species, have been growing among doctors and patients [1]. In vitro and in vivo studies are needed to establish 'e contemporaneous tense lifestyle is responsible for the the bioequivalence of herbal formulations. In the case of wide use of anxiolytic substances, mainly those of the ben- Passiflora formulations, the standardization can be based on zodiazepine group. 'is class of synthetic drugs is one of the the potency in animal models, such as the open arm plus- most prescribed antianxiety drugs in the world to treat stress maze using rats or mice. After the isolation of the substances and anxiety. However, many risks are associated to their use, responsible for the anxiolytic activity, the pharmaceutical such as dependence, abstinence syndrome, and the reduction equivalence can be applied [2]. of motor reflexes. 'erefore, the use and acceptance of herbal Many countries have laws regulating herbal medicinal medicines and nutraceuticals for these purposes, including products. Germany, that is considered the world’s largest 2 'e Scientific World Journal market for these products [3], defines herbal medicinal absorption, solubility that affect their bioavailability. Ad- products as “medicinal products that exclusively contain, as ditionally, there are the possible unknown toxic effects, active substances, one or more herbal substances, one or potential harmful interactions of herbal medicinal products more herbal preparations, or one or more such herbal and the lack of pharmacokinetic parameters such as gas- substances in combination with one or more such herbal trointestinal absorption, protein binding, and plasma preparations, according to the German Drug Law [4].” clearance by the liver and kidneys, which are all important Estimates suggest that Germany spends more than 2 billion challenges to overcome to be able to produce new medicines dollars on herbal medicinal products each year [3]. from medicinal plants. 'e quality of herbal products from a 'e Directive 2001/83/EC [5] and Directive 2004/24/EC technological point of view is ensured for the intermediate [6] of the European Parliament of the Council of the Eu- and finished products, using adequate production planning, ropean Union are codes for medicinal products and tradi- appropriate production processes, and strict control of the tional herbal medicinal products for human use. 'e code raw materials from the plant species used. All of these cares defines herbal medicinal products as any medicinal product must ultimately result in products with constant quality, exclusively containing, as active ingredients, one or more efficacy, and security. herbal substances (whole or fragmented plants) or herbal 'is article was based on a literature search into the preparations (tinctures, extracts, essential oils, etc). In the widespread use of the main species of the genus Passiflora same code, traditional herbal medicinal products have sim- and their main secondary metabolites to treat anxiety. 'e plified registration, because they can be used without pre- search covered pharmacological studies, patents, and reg- scription or monitoring treatment and the products are not istered products that were focused on the promising Bra- harmful when used according to the instructions of the zilian market. 'is report about Passiflora herbal medicinal manufacture. 'ey may be administered orally, topically, or products comprises eight sections: Passiflora genus (Passi- by inhalation. 'e pharmacological effects or efficacy are floraceae); chemical constituents; mechanism of anxiolytic based on long experience (at least 30 years, including at least action; Passiflora extract: standardization and chemical 15 years within the European Community) but the safety of marker; pharmacology, pharmacokinetics and safety; pat- the product must be ensured, and the quality must be verified ents and intellectual property in Brazil; registered medicines according to the European Pharmacopoeia monographs, or containing Passiflora in Brazil; and patents and registered those in the Pharmacopoeia of a Member State [7]. products containing Passiflora outside Brazil. 'e regulatory requirements for the registration of herbal medicines in Brazil are similar to those in Europe. In 2. Methods Brazil, these preparations are classified as herbal medicines if they are obtained only from active raw vegetal material, of Empirical searches were conducted via the databases which the efficacy and safety have been validated through Scopus (http://www.scopus.com) [11], Scirus (http://www. ethnopharmacological surveys, scientific and technical scirus.com)® [12], SciFinder (http://scifinder.cas.org/) [13], documentation, or clinical evidence [8]. 'ese products may Google Scholar (https://scholar.google.com.br/)® [14], as well be registered and marketed as traditional herbal medicine, if as periodicals using the following three keywords: ‘Passiflora evidence of their safe and effective use has been published in incarnata’, ‘Passiflora edulis’, and ‘Passiflora alata’. Other scientific and technical literature, and there is evidence of keywords used with the genus Passiflora were extraction, continuous safe use for a minimum period of thirty years. pharmacophores, ADMET, flavonoids, and formulation. A Furthermore, they may not be used for any serious diseases; search for clinical trials using the keywords ‘anxiety’ and they may not contain materials in toxic concentrations; and ‘Passiflora’ were performed in the database ClinicalTrials. they should not be administered by the ophthalmic or in- gov (https://clinicaltrials.gov), of the National Institutes of travenous routes. 'e safety and efficacy of herbal medicines Health (NIH), an agency of the U.S. Department of Health are based on clinical evidence, and they are characterized by and Human Services [15]. All of the information about the consistent quality [9]. Any registrations or marketing au- plants, their past and present therapeutic uses, and data thorizations in other countries, and the reasons for refusal of about marketing of herbal medicines in Brazil and outside registration or marketing authorization must be stated [3]. Brazil, including species of Passiflora in combination with Traditional herbal medicinal products are designed for use other active ingredients, were taken directly from selected without the supervision of a physician in terms of diagnosis, papers and searched in the following websites: the National prescription, or monitoring. Institute of Industrial Property (Instituto Nacional de Arifin and coworkers [10] list and discuss several Propriedade Industrial, INPI), https://gru.inpi.gov.br/pePI/ challenges that impact the development of a herbal me- servlet/PatenteServletController [16]; National Health dicinal