Elsevier

Pharmacological Research

Volume 112, October 2016, Pages 4-29
Pharmacological Research

Review
Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives

https://doi.org/10.1016/j.phrs.2016.01.021Get rights and content

Abstract

This review article focuses on pre-clinical and clinical studies with some selected Brazilian medicinal plants in different areas of interest, conducted by research groups in Brazil and abroad. It also highlights the Brazilian market of herbal products and the efforts of Brazilian scientists to develop new phytomedicines. This review is divided into three sections. The section I describes the Brazilian large biodiversity and some attempts of Brazilian scientists to assess the pharmacological profile of most plant extracts or isolated active principles. Of note, Brazilian scientists have made a great effort to study the Brazilian biodiversity, especially among the higher plants. In fact, more than 10,000 papers were published on plants in international scientific journals between 2011 and 2013. This first part also discussed the main efforts to develop new medicines from plants, highlighting the Brazilian phytomedicines market. Despite the large Brazilian biodiversity, notably with the higher plants, which comprise over 45,000 species (20–22% of the total worldwide), and the substantial number of scientific publications on medicinal plants, only one phytomedicine is found in the top 20 market products. Indeed, this market is still only worth about 261 million American dollars. This represents less than 5% of the global Brazilian medicine market. The section II of this review focus on the use of Brazilian plant extract and/or active principles for some selected diseases, namely: central nervous systems disorders, pain, immune response and inflammation, respiratory diseases, gastrointestinal tract and metabolic diseases. Finally, section III discusses in more details some selected Brazilian medicinal plants including: Cordia verbenacea, Euphorbia tirucalli, Mandevilla velutina, Phyllanthus spp., Euterpe oleracea, Vitis labrusca, Hypericum caprifoliatum and Hypericum polyanthemum, Maytenus ilicifolia, Protium kleinii and Protium heptaphylium and Trichilia catigua. Most of these publications are preliminary and only report the effects of crude extracts, both in vitro and in vivo studies. Only very few studies have been dedicated to investigate the mechanisms of action of isolated compounds. Likewise, studies on safety (toxicology), pharmacokinetic, and especially on well-conducted clinical trials are rare. In conclusion, in spite of the abundant Brazilian biodiversity and the thousands of academic publications on plants in international peer-reviewed scientific journals, few patents and medicines have been derived from such studies. Undoubtedly, great efforts must be made to improve the development of plant-derived medicine market in Brazil, especially by involving the partnership between academia and pharmaceutical companies.

Introduction

The use of medicinal plants by the population, as an alternative therapy to treat many diseases, has been a common practice since thousands of years before Christ. For example, the use of poppy (Papaver somnniferum) and marijuana (Cannabis sativa) has been described for as long as 4000 years. However, the search for the active constituents present in medicinal plants only began in the nineteenth century, thus leading to the conception of the first drug with the characteristics that we know today. Friedrich Serturner, in 1806, was a pioneer when he isolated the alkaloid morphine from poppy: an event that prompted a continuous search for other plant-derived medicines. In 1824, Pierre-Jean Robiquet isolated codeine, an antitussive agent also from poppy, and in 1848, George Merck Fraz isolated the anti-spasmodic alkaloid papaverine from this same plant. Other important examples of active constituents isolated from medicinal plants comprise atropine (muscarinic antagonist) isolated from Atropa belladonna by Mein in 1831; caffeine obtained by Runge in 1820 from Coffea arabica; digoxin (digitalis) isolated by Claude-Adolphe Nativelle in 1869 from Digitalis lanata; and curare (muscle relaxant) isolated by Winstersteiner and Dutcher in 1943 from Chondrodendron tomentosum, among many other examples.

The historical landmark in the global pharmaceutical industry development was the discovery of salicin (analgesic and antipyretic) by Rafaele Piria, in 1832, from Salix alba. In 1839, the first structural modification from salicin was performed, yielding salicylic acid to be used in the treatment of rheumatoid arthritis. From the salicylic acid, Felix Hoffman synthesized aspirin (acetylsalicylic acid) in 1897. Thus, the famous and powerful pharmaceutical industry Bayer in Germany was born, as well as the first patent in the area of drugs.

The interest in medicinal products derived from higher plants [also known as herbal remedies or herbal medicines (phytomedicines)] has increased significantly worldwide. This interest is especially seen in developed countries, mainly in some European countries and in the United States. It is estimated that the global market for this class of drugs has reached 20 billion dollars annually [1]. Notably, the plant-derived compounds are currently employed in modern therapy, in addition to playing an important role for the synthesis of some more complex molecules. It has been estimated that about 30% of the available therapeutic medications are derived from natural sources, notably from plants and microorganisms. In some therapeutic areas, such as oncology, the amount of plant-derived medicines achieves 60% [1], [2], [3], [4].

Many classes of active principles have been isolated from Brazilian medicinal plants [5]. In fact, Brazil has the highest total of biodiversity in the world, comprising over 45,000 species of higher plants (20–22% of the total existing on the planet), 4680 algae, 32,715 angiosperms, 1519 of bryophytes, 5652 fungi, 30 gymnosperms and ferns, and 1239 lycophytes. Additionally, there are over 7000 species of known vertebrates, with 692 species of mammals, 1026 species of amphibians, 744 species of reptiles, 1901 species of birds, in addition to 3000 species of fishes. There is known to be 96,660 to 129,840 species of invertebrates. Beetles and butterflies are particularly abundant—each group with about 26,000 species (http://www.sibbr.gov.br/areas/?area=biodiversidade).

The Brazilian population has a long tradition in the use of medicinal plants for the treatment of different acute and chronic diseases. This has called the attention of Brazilian researchers and some Brazilian pharmaceutical companies to study native medicinal plants and their active principles. More recently, the use of new technologies, such as proteomic and genomic approaches, has led to a recurring interest in natural products both from academia and from pharmaceutical companies [6], [7].

Keeping in mind the above data, this review article will focus on recent studies conducted to evaluate the pharmacological properties of extracts and active principles isolated from Brazilian medicinal plants. Special attention will be given to those medicinal plants that were the subject of pharmacological studies published in international peer-review journals, with attempts to discuss the mechanisms of action of the active constituents.

Section snippets

Brazilian market of herbal drugs (Phytotherapeutic agents)

In view of Brazil’s large biodiversity and because of the great ethical influence of early colonization, Brazilians have a great interest in the use of herbal drugs to treat different illnesses [1]. It was in 1994 that the Brazilian Ministry of Health established the first directive to evaluate the safety, quality and efficacy of marketed herbal drugs. This proposed regulation was based mainly in the World Health Organization (WHO) guidelines and in the German and French directives that

Medicinal plants and central nervous systems disorders

The central nervous system (CNS) is a complex and refined system that regulates and coordinates the body's main activities. It is vulnerable to a range of disorders, including: (i) vascular disorders (stroke and hemorrhage); (ii) infections (meningitis and encephalitis); (iii) structural disorders (brain or spinal cord injury, peripheral neuropathy and Guillain–Barré syndrome); (iv) functional disorders (headache and epilepsy); (v) neuromuscular diseases (motor neuron disease); (vi)

Cordia verbenacea

C. verbenacea (Borraginaceae), popularly known as “erva-baleeira” or “maria-milagrosa”, is a perennial bush that grows throughout the Brazilian coast, within the Atlantic Forest. In folk medicine, their leaves have been used for their anti-inflammatory and cicatrizing effects. During the last 20 years, a few groups have investigated the potential effects of this plant and the related compounds, especially concerning its promising actions against inflammatory conditions. Accordingly, a Brazilian

Concluding remarks

In this review article, we highlighted the recent efforts made by Brazilian researchers to study, in pre-clinical and clinical aspects, some medicinal plants widely used in folk medicine. Brazil has the greatest amount of biodiversity in the world, representing approximately 20–22% of all known plant species. Certainly, the area of ​​plants is one of the most relevant fields of investigation in Brazil, as echoed by the great number of scientific articles published in peer-reviewed scientific

Conflict of interest

The authors declare that there are no conflict of interest.

Acknowledgements

This review article and cited papers from our group were supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), all from Brazil.

References (379)

  • M.S. Antunes et al.

    Protective effect of hesperidin in a model of parkinson's disease induced by 6-hydroxydopamine in aged mice

    Nutrition

    (2014)
  • M. Figueiro et al.

    The amazonian herbal marapuama attenuates cognitive impairment and neuroglial degeneration in a mouse alzheimer model

    Phytomedicine

    (2011)
  • T.B. Alberti et al.

    Essential oil from pterodon emarginatus seeds ameliorates experimental autoimmune encephalomyelitis by modulating th1/treg cell balance

    J. Ethnopharmacol.

    (2014)
  • G.L. Mendes et al.

    Anti-hyperalgesic properties of the extract and of the main sesquiterpene polygodial isolated from the barks of Drymis winteri (winteraceae)

    Life Sci.

    (1998)
  • A. Malheiros et al.

    A sesquiterpene drimane with antinociceptive activity from drimys winteri bark

    Phytochemistry

    (2001)
  • C. Scheidt et al.

    Evidence for the involvement of glutamatergic receptors in the antinociception caused in mice by the sesquiterpene drimanial

    Neuropharmacology

    (2002)
  • E. Andre et al.

    Pharmacological characterisation of the plant sesquiterpenes polygodial and drimanial as vanilloid receptor agonists

    Biochem. Pharmacol.

    (2006)
  • E. Andre et al.

    Evidence for the involvement of vanilloid receptor in the antinociception produced by the dialdeydes unsaturated sesquiterpenes polygodial and drimanial in rats

    Neuropharmacology

    (2004)
  • I.D. Duarte et al.

    Possible participation of endogenous opioid peptides on the mechanism involved in analgesia induced by vouacapan

    Life Sci.

    (1992)
  • I.D. Duarte et al.

    Evidence of the involvement of biogenic amines in the antinociceptive effect of a vouacapan extracted from Pterodon polygalaeflorus Benth

    J. Ethnopharmacol.

    (1996)
  • L.P. Coelho et al.

    Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds

    J. Ethnopharmacol.

    (2005)
  • H.M. Spindola et al.

    Geranylgeraniol and 6alpha,7beta-dihydroxyvouacapan-17beta-oate methyl ester isolated from Pterodon pubescens Benth.: further investigation on the antinociceptive mechanisms of action

    Eur. J. Pharmacol.

    (2011)
  • C. Nucci et al.

    Oleaginous extract from the fruits Pterodon pubescens Benth induces antinociception in animal models of acute and chronic pain

    J. Ethnopharmacol.

    (2012)
  • G. Negri et al.

    Antinociceptive activity of the HPLC- and MS-standardized hydroethanolic extract of Pterodon emarginatus vogel leaves

    Phytomedicine

    (2014)
  • K.C. Sabino et al.

    In vitro and in vivo toxicological study of the Pterodon pubescens seed oil

    Toxicol. Lett.

    (1999)
  • R.O. de Campos et al.

    Antinociceptive properties of the hydroalcoholic extract and preliminary study of a xanthone isolated from Polygala cyparissias (polygalaceae)

    Life Sci.

    (1997)
  • A.L. Rodrigues et al.

    Involvement of monoaminergic system in the antidepressant-like effect of the hydroalcoholic extract of Siphocampylus verticillatus

    Life Sci.

    (2002)
  • E. Colpo et al.

    Brazilian nut consumption by healthy volunteers improves inflammatory parameters

    Nutrition

    (2014)
  • P.R. Viecili et al.

    Effects of Campomanesia xanthocarpa on inflammatory processes, oxidative stress, endothelial dysfunction and lipid biomarkers in hypercholesterolemic individuals

    Atherosclerosis

    (2014)
  • L.A. Luna et al.

    Immune responses induced by Pelargonium sidoides extract in serum and nasal mucosa of athletes after exhaustive exercise: modulation of secretory IgA, IL-6 and IL-15

    Phytomedicine

    (2011)
  • G.G. Brusselle et al.

    Inflammasomes in respiratory disease: from bench to bedside

    Chest

    (2014)
  • B. Ballabh et al.

    Traditional medicinal plants of cold desert ladakh—used in treatment of cold, cough and fever

    J. Ethnopharmacol.

    (2007)
  • H. Kim et al.

    Traditional plant-based therapies for respiratory diseases found in north jeolla province, korea

    J. Altern. Complement. Med.

    (2012)
  • M. Rigat et al.

    Traditional and alternative natural therapeutic products used in the treatment of respiratory tract infectious diseases in the eastern catalan pyrenees (iberian peninsula)

    J. Ethnopharmacol.

    (2013)
  • R.Y. Cavero et al.

    Medicinal plants used for respiratory affections in navarra and their pharmacological validation

    J. Ethnopharmacol.

    (2014)
  • S. Kayani et al.

    Ethnobotanical uses of medicinal plants for respiratory disorders among the inhabitants of gallies—Abbottabad, northern Pakistan

    J. Ethnopharmacol.

    (2014)
  • I.M. Fierro et al.

    Studies on the anti-allergic activity of mikania glomerata

    J. Ethnopharmacol.

    (1999)
  • M.A. Antonio et al.

    Oral anti-inflammatory and anti-ulcerogenic activities of a hydroalcoholic extract and partitioned fractions of Turnera ulmifolia (turneraceae)

    J. Ethnopharmacol.

    (1998)
  • J.B. Calixto

    Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents)

    Braz. J. Med. Biol. Res.

    (2000)
  • D.J. Newman et al.

    Natural products as sources of new drugs over the 30 years from 1981 to 2010

    J. Nat. Prod.

    (2012)
  • M. Valli et al.

    Development of a natural products database from the biodiversity of Brazil

    J. Nat. Prod.

    (2013)
  • A.L. Harvey et al.

    The re-emergence of natural products for drug discovery in the genomics era

    Nat. Rev. Drug Discov.

    (2015)
  • C. Sheridan

    Recasting natural product research

    Nat. Biotechnol.

    (2012)
  • R.C. Dale et al.

    Biomarkers of inflammatory and auto-immune central nervous system disorders

    Curr. Opin. Pediatr.

    (2010)
  • J.E. Sherin et al.

    Post-traumatic stress disorder: the neurobiological impact of psychological trauma

    Dialogues Clin. Neurosci.

    (2011)
  • W.M. Pardridge

    Drug transport across the blood-brain barrier

    J. Cereb. Blood Flow Metab.

    (2012)
  • K.C. de Lima et al.

    The ginkgo biloba extract, EGb 761, fails to reduce brain infarct size in rats after transient, middle cerebral artery occlusion in conditions of unprevented, ischemia-induced fever

    Phytother. Res.

    (2006)
  • V.C. Barreiros et al.

    Morphological and morphometric analyses of crushed sciatic nerves after application of a purified protein from natural latex and hyaluronic acid hydrogel

    Growth Factors

    (2014)
  • M. Perez et al.

    Neuroprotection and reduction of glial reaction by cannabidiol treatment after sciatic nerve transection in neonatal rats

    Eur. J. Neurosci.

    (2013)
  • L.C. Klein-Junior et al.

    Antihyperalgesic activity of the methanol extract and some constituents obtained from polygala cyparissias (polygalaceae)

    Basic Clin. Pharmacol. Toxicol.

    (2012)
  • Cited by (256)

    View all citing articles on Scopus
    View full text