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Pharmaceuticals
  • Feature Paper
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11 November 2021

Pharmacology and Phytochemistry of Ecuadorian Medicinal Plants: An Update and Perspectives

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1
Departamento de Química, Universidad Técnica Particular de Loja, Loja 1101608, Ecuador
2
Medical Analysis Department, Faculty of Science, Tishk International University, Erbil 44001, Iraq
3
Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1040, Venezuela
*
Authors to whom correspondence should be addressed.
This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest 2022

Abstract

The use of plants as therapeutic agents is part of the traditional medicine that is practiced by many indigenous communities in Ecuador. The aim of this study was to update a review published in 2016 by including the studies that were carried out in the period 2016–July 2021 on about 120 Ecuadorian medicinal plants. Relevant data on raw extracts and isolated secondary metabolites were retrieved from different databases, resulting in 104 references. They included phytochemical and pharmacological studies on several non-volatile compounds, as well as the chemical composition of essential oils (EOs). The tested biological activities are also reported. The potential of Ecuadorian plants as sources of products for practical applications in different fields, as well the perspectives of future investigations, are discussed in the last part of the review.

1. Introduction

The geographic location of Ecuador, together with its geological features, makes the country’s biodiversity one of the richest in the world. Ecuador is, indeed, considered among the 17 megadiverse countries, accounting for about 10% of the entire world plant species, and every year new plants are discovered and added to the long list of the species already known. This fact makes Ecuador an invaluable source of potentially new natural products of biological and pharmaceutical interest, such as carnosol, tiliroside [1], and dehydroleucodine (DL) [2]. Moreover, most plants are considered to be medicinal, where they are a fundamental part of the health systems of several Ecuadorian ethnic groups [3]. The knowledge of traditional healer practitioners has been maintained over hundreds or even thousands of years [4]. Therefore, herbal remedies have gained acceptance thanks to the apparent efficacy and safety of plants over the centuries [5]. As a result, several doctors, especially in government intercultural health districts, practice integrated forms of modern and traditional medicine nowadays.
Scientific evidence of the therapeutic efficacy and absence of toxicity in Ecuadorian medicinal plants and their products has started to be collected only in the last few decades by the researchers of several groups in different Ecuadorian Universities. This scientific activity has increased dramatically in recent years, thanks to the support of the Ecuadorian people and government authorities, who consider the sustainable use of biodiversity resources a possible source of economic wealth.
This review gives a comprehensive analysis of recent phytochemical and biologically oriented studies that were carried out on Ecuadorian medicinal plants and is focused on the potential relationships between traditional uses and pharmacological effects, assessing the therapeutic potential of natural remedies. This review completes the information that was provided by our group in 2016 [3]. Since then, more than 100 scientific articles have been published concerning phytochemical and pharmacological studies of more than 120 plants belonging to 42 different botanical families. In addition, a few naturally derived products have been patented [6]. Moreover, traditional natural preparations, such as Colada morada, which is consumed on the Day of the Dead (Día de los Muertos) [7], and Horchata lojana, which is a typical beverage that is made of a mixture of medicinal and aromatic plants consumed by the people of southern Ecuador [8,9,10], have received great attention. Other typical preparations are an infusion of guaviduca from Piper carpunya Ruiz & Pav. [11], which is a traditional drink of the Amazonian people, and the infusion of Ilex guayusa Loes., which is an emblematic tree of the Amazon Region of Ecuador that is widely used in folk medicine, ritual ceremonies, and for making industrial beverages [12,13].
Many of the scientific articles mentioned in this review refer to studies that were carried out on plants and traditional preparations from southern Ecuador, especially from the province of Loja (Figure 1), which has a long tradition in exporting medicinal plants of great importance for human health, such as quina (Cinchona spp.) and condurango (Marsdenia condurango Rchb.f.).
Figure 1. Provinces of Ecuador.
Possible future research directions are also discussed in this review. In addition, the therapeutic potential of some herbal products for the development of new drugs was indicated.

2. Literature Search Strategies and Sources

Relevant data on medicinal plants from Ecuador were retrieved using the keywords “medicinal plants from Ecuador,” “pharmacology,” “toxicity,” “phytochemistry,” and “biological studies” in different databases, including Pubmed, SciFinder, Springer, Elsevier, Wiley, Web of Science, and Google Scholar. The search range was 2016–July 2021. The plant names and authorities were checked with the database WFO (2021): World Flora Online, published on the Internet at http://www.worldfloraonline.org (accessed on 25 September 2021). Data contained in Doctorate and Master’s theses were not considered. Articles on specific studies of Andean or Amazonian foods and fruits were not analyzed.

3. Phytochemical and Biological Activity Data

The literature information is summarized in Table 1, where the plants, in alphabetical order, were grouped in their corresponding botanical family. For each species, the vernacular name and some botanical information, when available, are indicated, together with the traditional use and the phytochemical and the biological activity data when available. The structures of some characteristic compounds are reported in Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12 and Figure 13.
Table 1. Literature on Ecuadorian medicinal plants in the period 2016–July 2021.
Figure 2. Structures of compounds 1 from Pseudodranassa spp., 2 and 3 from Baccharis obtusifolia, 4 and 5 from Gynoxis verrucosa, 6 from Hedyosmum racemosum, and 7 from Clusia latipes.
Figure 3. Structures of compounds 812 from Bejaria resinosa and 1316 from Croton ferrugineus.
Figure 4. Structures of compounds 1723 from Croton thurifer.
Figure 5. Structures of compounds 2427 from Otholobium mexicanum.
Figure 6. Structures of compounds 28 and 29 from Lepechinia heteromorpha; 3033 from L. mutica; 2830 and 34 from L. paniculata; and 33, 35, and 36 from L. radula.
Figure 7. Structures of compounds 3739 from Grias neubertii and 4045 from Gaiadendron punctatum.
Figure 8. Structures of compounds 4650 from Huperzia compacta, H. columnaris, and H. tetragona; 51 and 52 from H. brevifolia and H. espinosana; and 5356 from H. crassa.
Figure 9. Structures of compounds 5760 from Piper barbatum; 61 and 62 from P. coruscans; 62 and 63 from P. ecuadorense; 6466 from Piper lanceifolium; and 61, 62, 67 and 68 from P. pubinervulum.
Figure 10. Structures of compounds 6973 from Piper subscutatum.
Figure 11. Structures of compounds 7480 from Muehlenbeckia tamnifolia.
Figure 12. Structures of compounds 8184 from Oreocallis grandiflora and 8587 from Roupala montana.
Figure 13. Structures of compounds 88110 from Arcytophyllum thymifolium and 111 from Siparuna echinata.

4. Conclusions and Perspectives

The criteria for investigating most of the 120 species cited in this review appeared to be based mainly on an ethnobotanical and ethnopharmacological approach. Indeed, scientific evidence has often confirmed traditional uses; however, not rarely, tested biological activities were not strictly related to the traditional uses. On the other hand, plants were not collected with the aim of including extracts or products in high throughput screening programs. This strategy should, instead, be involved in future research projects since it is the only investigational system that is available for discovery programs that addresses the effects of natural products on selected enzymes and receptor targets emanating from molecular biology.
Essential oils (EOs) were the most frequently investigated products. In general, oil compositions were fully determined using GC/MS and GC/FID analyses; in addition, the oil enantiomer composition and odorant characteristics were often established. As regards the biological activities of the EOs, the activity of Renealmia thyrsoidea EO against Escherichia coli and Pseudomonas aeruginosa [102], as well as the antifungal activity of Lepechinia radula [63], Ocimum campechianum [65], Piper ecuadorense [88], and Piper pubinervulum [90] EOs against Candida and Trichophyton strains, which are common causes of severe forms of candidiasis and dermatophytosis, are of great interest. Moreover, it is important to underline the strong acaricidal activity of a mixture of Bursera graveolens and Schinus molle EOs [44], the repellent effects of Dacryodes peruviana EO against mosquitoes [45], and the anti-termite properties of Ocotea quixos EO [70].
Thus, many EOs have the potential to be used not only as components of new perfumes due to the pleasing organoleptic properties but also as ingredients in the formulations of phytocosmetics, as well as antiseptic and insect repellent products. Moreover, essential oils should be screened in the future against clinically important bacteria and strains that are resistant to common antibiotics.
Alzheimer’s disease is the most common cause of dementia affecting elderly people and it is associated with a loss of cholinergic neurons in parts of the brain. Cholinesterase inhibitors (ChEIs) delay the breakdown of acylcholine that is released into synaptic clefts and so enhance cholinergic neurotransmission; thanks to these effects, ChEIs are considered efficacious at treating mild-to-moderate AD. In this context, the study of EO cholinesterase inhibitory activity is a relatively new area of research; in particular, the oil mechanisms of action have been poorly investigated so far. It is, therefore, of great interest that several EOs described in this review exhibited such inhibitory effects; in particular, the highly selective BuChE inhibitory activity exhibited by Clinopodium brownei [58], Coreopsis triloba [35], Myrcianthes myrsinoides [77], and Salvia leucantha [66] EOs is worthy of further studies. Equally interesting is the ChEI activity that was found for the flavonoid tiliroside, the diterpene carnosol (30) [1], and the alkaloids found in a few Phaedranassa species [17,18].
Concerning the non-volatile fractions and isolated compounds, the studies were less systematic and the compounds that are responsible for many plants’ activities are still unknown. Isolated compounds belonged to different biosynthetic families, including new ones, such as the high-molecular-weight alkaloids occurring in some Huperzia species, whose complete structures are, however, still unknown [4]. Extracts and isolated metabolites were subjected, almost routinely, to antiradical, e.g., DPPH, ABTS, and antioxidant (e.g., β-CLAMS and FRAP) assays. These tests are expected and, therefore, of little scientific significance for extracts containing phenolic compounds, unless high antioxidant products may be developed as phytotherapeutic agents or food supplements with health-promoting activities through the in vivo reduction of the oxidative stress. In this context, the high antioxidant activities of Baccharis obtusifolia [20], Oreocallis grandiflora [94], and Zingiber officinale [103] are worthy of note.
Oxidative stress induces the activation of pro-inflammatory cytokines and subsequent inflammation; therefore, the in vitro antioxidant activity of a product is often considered good evidence of its anti-inflammatory property. However, a more scientifically sound approach should require the study of the molecular mechanisms that underline anti-inflammatory activities. In this context, the expression of mitogen-activated protein kinases (MAPKs) or the release of numerous pro-inflammatory mediators, such as COX-2, the inducible nitric oxide synthase (iNOS), and interleukins IL-1β and IL-6, play a major role in the pathogenesis of various inflammatory disorders and, thus, serve as significant biomarkers for the assessment of the inflammatory process. The investigation of the anti-inflammatory effects of Salvia sagittata ethanolic extract [68] is a significant example of such an approach.
Several extracts and isolated compounds that were discussed in this review showed interesting inhibitory activity of the enzymes α-glucosidase and/or α-amylase. Indeed, pancreatic and intestinal glucosidases are the key enzymes of dietary carbohydrate digestion, and inhibitors of these enzymes may be effective in slowing glucose absorption to suppress postprandial hyperglycemia. In this context, it is significant to mention that the extracts and phenolic or flavonoid contents of Gaiadendron punctatum [73], Muehlenbeckia tamnifolia [93], Oreocallis grandiflora [19], and Otholobium mexicanum [56], as well as trans-tiliroside (22) [53], prenyloxy eriodictyol (92), and rhamnetin (101) [96], showed enzymatic inhibitory activity that was comparable or superior to acarbose, which is a drug that is currently used in the treatment of diabetes mellitus. Therefore, these results should promote studies on determining whether these hypoglycemic products can become sources of new antidiabetic drugs.
It is very well known that some of the most used drugs in cancer chemotherapy derive from natural products. In this context, the high antiproliferative effects shown by the extracts of some plants, such as Annona montana [15] and Grias neuberthii [72], against several human tumor cell lines are of great interest. Isolated compounds with potent in vitro cytotoxic properties include the flavonoid tricin (52) from Huperzia spp. [74], the triterpene ursolic acid (11) from Bejaria resinosa [51], and the sesquiterpene lactones onoseriolide (6) from Hedyosmum racemosus [48] and dehydroleucodine (5) from Gynoxis verrucosa [2]. The antileukemic properties of dehydroleucodine (5) and some derivatives were the objects of patents [6]. These findings should stimulate more systematic screening of the cytotoxic effects of Ecuadorian plants’ metabolites and the investigation of the mechanisms of the cell antiproliferative effects.
Considering the overall research activities that has been carried out so far in Ecuador on natural products, it can be concluded that little or scarce attention has been dedicated to the semi-synthesis of derivatives of isolated bioactive compounds with the aims to increase their activity, to study the structure–bioactivity relationships, and to explore the mechanisms of action and the signaling pathways that are involved in the biological activities. Even fewer efforts have been put into the synthesis of new chemical entities using computational approaches (in silico) to model the structures of natural products or to design completely new molecules. Indeed, research activities on these themes should be encouraged because they were demonstrated to be highly successful in the discovery of new bioactive compounds.
Finally, further studies, including those in vivo, are required to understand the relevance and selectivity of biological effects that have only been demonstrated in vitro so far. It is also important for practical applications to know potential acute and chronic toxicities, risks, and side effects of the plant-derived products. In fact, even raw extracts can be used as food additives and therapeutic remedies once the absence of toxicity has been demonstrated, the contents have been standardized, and the efficacy has been scientifically shown.
In conclusion, this review has clearly demonstrated the great potential of Ecuadorian plants as sources of products for different purposes and applications. Moreover, some guidelines for future research programs concerning possible sustainable uses of local therapeutic resources were indicated.
Ultimately, an important purpose of this paper is to stimulate more extensive studies on the rich medicinal flora of Ecuador.

Author Contributions

Conceptualization, C.A., A.I.S. and J.R.; writing—original draft preparation, J.R., A.I.S., M.S. and C.A.; literature retrieval, A.I.S., M.S., J.R. and C.A.; review supervision and editing, G.V. All authors have read and agreed to the published version of the manuscript.

Funding

This research is funding by Universidad Técnica Particular de Loja.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

We are grateful to the Universidad Técnica Particular de Loja (UTPL) for open access publication.

Conflicts of Interest

The authors declare no conflict of interest.

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