Next Article in Journal
Applications and Trends of Machine Learning in Genomics and Phenomics for Next-Generation Breeding
Previous Article in Journal
Evolutionary Analysis of Calcium-Dependent Protein Kinase in Five Asteraceae Species
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Plants
Volume 9
Issue 1
10.3390/plants9010033
plants-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Promising Potential of Lonchocarpus utilis against South American Myasis

by
Carmen X. Luzuriaga-Quichimbo
1,
José Blanco-Salas
2,*,
Carlos E. Cerón-Martínez
3,
Juan Carlos Alías-Gallego
4 and
Trinidad Ruiz-Téllez
2
1
Faculty of Health Sciences Eugenio Espejo, University UTE, Quito 170147, Ecuador
2
Área de Botánica, Facultad de Ciencias, Universidad de Extremadura, Avda. Elvas s/n, 06071 Badajoz, Spain
3
Herbarium Alfredo Paredes, QAP, Ecuador Central University UCE, Quito 170521, Ecuador
4
Área de Ecología, Facultad de Ciencias, Universidad de Extremadura, Avda. Elvas s/n, 06071 Badajoz, Spain
*
Author to whom correspondence should be addressed.
Plants 2020, 9(1), 33; https://doi.org/10.3390/plants9010033
Submission received: 2 December 2019 / Revised: 13 December 2019 / Accepted: 17 December 2019 / Published: 25 December 2019
Browse Figures
Review Reports Versions Notes

Abstract

:
Traditional medicine is especially important in the treatment of neglected tropical diseases because it is the way the majority of populations of affected countries manage primary healthcare. We present a case study that can serve as an example that can be replicated by others in the same situation. It is about the validation of a local remedy for myasis in Amazonian Ecuador, which is contrasted by bibliographic chemical reviews and in silico activity tests. We look for scientific arguments to demonstrate the reason for using extracts of Lonchocarpus utilis against south American myasis (tupe). We provide a summary of the isoflavonoids, prenylated flavonoids, chalcones, and stilbenes that justify the action. We make modeling predictions on the affinity of eight chemical components and enzyme targets using Swiss Target Prediction software. We conclude that the effects of this extract can be reasonably attributed to an effect of the parasite that causes the disease, similar to the one produced by synthetic drugs used by conventional medicine (e.g., Ivermectine).

Graphical Abstract

1. Introduction

The World Health Organization (WHO) has estimated that more than 80% of the world’s population routinely uses traditional medicine to meet their primary healthcare needs [1], and many traditional treatments involve the use of plant extracts or their active ingredients [2]. This is especially important in the treatment of neglected tropical diseases (NTD) [1]. The WHO has recognized twenty NTD: buruli ulcer, chagas disease, dengue and chikungunya, dracunculiasis (guinea-worm disease), echinococcosis, foodborne trematodiases, human african trypanosomiasis (sleeping sickness), leishmaniasis, leprosy (Hansen’s disease), lymphatic filariasis, mycetoma, chromoblastomycosis and other deep mycoses, onchocerciasis (river blindness), rabies, scabies and other ectoparasites, schistosomiasis, soil-transmitted helminthiases, snakebite envenoming, taeniasis/cysticercosis, trachoma and yaws (endemic treponematoses). These diseases represent an important cause of morbidity, disability, and mortality in the poorest people living in developing countries. They are so named because of the lack of financial investment in the development of new drugs by high-income countries to treat them [3]. In this context, the Amazonian countries have large sectors of the population that use plants from the tropical forests where they live daily as a legacy of their ancestors. This represents knowledge that can be articulated with the Western scientist [4,5]. and may produce advances in the field of health. We present a case study that can serve as an example for future replicate studies in this direction.
We investigate the plant known in Spanish as barbasco or poison rope, Lonchocarpus utilis A.C. Ye. (Lonchocarpus nicou, Lonchocarpus nicou var. languidus, Lonchocarpus nicou var. urucu, Deguelia utilis, Fabaceae). This is a wild bush plant found in the rainforests of Brazil, Colombia, Guyana, Guyana, Peru, Surinam, Venezuela, and Ecuador, which is sometimes cultivated in indigenous communities for its use [6]. It has different common names according to the original language of the population (e.g., shili bun (tsafi’ki), anku hanpi, auka hanpi, hanpi, lumu hanpi, shikitu hanpi, timun hanpi, tullu hanpi, waska hanpi (kichwa), avu signo’mba, macoroje’cho indica’mba, seña’mba (a’ingae), airo eó, eó, eopo eó, jo’ya eó (pai coca), kompago, kompagon, konpago, meneko (wao tededo), timiu (shuar chicham)).
In Ecuador, several indigenous nationalities have used it both in traditional medicine and ancestral fishing procedures (Table A1). During a study carried out by one of the authors [7] in the Bobonaza river province of Pastaza, some uses (Table A2) that had rarely been mentioned in the area were observed [8,9,10,11]. These provide good examples of the use of natural resources due to the degree of isolation of the communities.
In this case, the plant was employed to treat a very significant illness locally named the “tupe”. This is a myiasis involving the infestation of dipterous larvae favored by the tropical hot and humid climate. More than 170 million people are at risk of contracting this neglected tropical disease [12]. In South America, the largest number of cases are produced by Dermatobia hominis, an autochthonous species that acts as a parasite of living tissues [13,14,15]. When the female is willing to lay eggs, she catches a blood-sucking arthropod, a fly or mosquito (mainly of the genus Psorophoro), that acts as an intermediate host and deposits eggs (15 to 30) on her abdomen, which are fixed with a kind of adhesive. The intermediary distributes the eggs when looking for animal or human blood to feed on and these will hatch, releasing young larvae that penetrate the skin over a time period that varies from 5 to 10 min in the location of the bite or through the hair follicles [16]. The preferred places in humans are the trunk, thighs, buttocks, and back [17]. Initially, they are skin lesions of little relevance. Infections are unlikely because the larva itself secretes antibiotics as an adaptive strategy to have food in good condition [18]. Infection is much more likely following scratching, handling without conditions of asepsis, or if the larvae are only partially extracted because remains are left under the skin [19]. In this case, it can turn into erythematous papules that increase in size, becoming pustular. If the larvae penetrate further, they form subcutaneous nodules of 1–2 cm, which can form painful abscesses. There may be regional lymphadenopathy, lymphangitis, and eosinophilia. This can affect the skin, mucous membranes, intestine, genitourinary system, lungs, and brain (migration of larvae by fontanelles) [20]. Others, such as those produced by Sarcopiiaga tiaemorriioidaiis, S. iambens, Cynomyopsis cadaverina, C. vicina, Phaenicia sericata, and P. cuprina are also common if there are predisposing factors such as poor hygiene, advanced age, or poor peripheral vascular circulation [21]. More rare are Musa domestica, Stomoxys caicitrans, and Fannia spp., which lay eggs on open lesions [22,23,24]. A great number of cases of myasis are associated with vulnerable people living in rural areas and poverty or underdevelopment [12]. Given the importance of this neglected pathology, the present bibliographical study was designed.
In addition to this, molecular docking studies have been revealed as a useful tool to predict activity [25,26,27,28,29] and to orientate pharmacological research, saving time, and economic resources. Arguments and hypotheses can be reinforced or confirmed using in silico tests. These approaches are becoming more frequent. As was recently written in Nature [30], “bioinformatics can boost basic science in countries with limited resources”. This can be especially useful for NTD.
Based on the above, our research objective is to find experimental evidence of chemical composition and activity, aimed at a scientific validation of myasis treatment employed by the Kichwa people from Amazonian Ecuador.

2. Results

The phytochemical composition of L. utilis has been widely studied [31,32,33,34,35,36,37,38]. The most important compounds found in the leaves, stems, and roots are rotenone (44%), rotenolone (6.7%), deguelin (22%), and thephrosin (4.3%) [39], which are rotenoids—isoflavones with additional pyrane/furane rings. Other significant components are prenylated flavanols (prenyl-urucuol A, prenyl-isotirumalin and prenylutilinol), prenylated flavones (3′-methoxylupinifolin), prenylated flavanones (2S)-6-(γ,γ-dimethylallyl)-5,4′-dihydroxy-3′-methoxy-6″, 6″-dimethylpyran [2″,3″:7,8] flavanone, and prenylutiline, chalcones (4-hydroxylonchocarpin), and stilbenes (lonchocarpene, methoxylonchocarpene, 3,5-dimethoxy-4-O-prenyl-cis-stilbene and 3,5-dimethoxy-4-hydroxy-3-prenyl-trans-stilbene). The structures are organized [40] and summarized in Figure 1.
The biological activity of these components, experimentally tested by different authors, is summarized in Table 1.
Figure A1, Figure A2, Figure A3, Figure A4, Figure A5, Figure A6 and Figure A7 (Appendix A) belong to the Swiss Target prediction report files obtained using the corresponding cited structures as query molecules: Figure A1—rotenone; Figure A2—rotenolone; Figure A3—deguelin; Figure A4—tephrosin; Figure A5—3′metoxylupinifolin; Figure A6—4-hydroxylonchocarpin; Figure A7—lonchocarpene.
As it can be observed in the probability graphics of these figures, rotenoids have shown the most affinity for ornithine decarboxylase (ODC), tyrosyl-DNA phosphodiesterase 1, arginine decarboxylase, NADH ubiquinone oxidoreductase chai-4, and the microtubule-associated protein tau (the latter especially for rotenone and rotenolone). Rotenone has shown the best relations with the cytochrome P450 group of enzymes.
Chalcones (4-hydroxylonchocarpin) have shown the most affinity with ODC, tyrosyl-DNA phosphodiesterase 1, arginine decarboxylase, and have a probability of more than 50% with different protein kinases.
The prenylated flavone that was tested in our in silico experiments (3′-methoxylupinifolin) showed affinity with ornithine decarboxylase (ODC), tyrosyl-DNA phosphodiesterase 1, and arginine decarboxylase. Lonchocarpene (stilbene) showed affinity with ornithine decarboxylase (ODC), tyrosyl-DNA phosphodiesterase 1, and arginine decarboxylase.
Another stilbene that has been tested (3,5-dimetoxy-4-hydroxy-3 prenyl-trans-stilbene) has not shown any reliable affinity nor activity.

3. Discussion

The hospital treatment of tupe is surgical: the application of local anaesthetics and removal of the larvae through the entrance orifice. For oral medical treatments, the drugs that might be employed are thiabendazole imidazols and macrocyclic lactones. Thiabendazole inhibits fumarate reductase, an enzyme specific for helminths. It is absorbed rapidly in the gastrointestinal tract, is metabolized in the liver, and it is eliminated by the kidney. However, it has many side effects. Ivermectin [58,59] has more selective activity with few systemic effects on mammals. It acts by binding to the anionic glutamate channels of gamma amino butyric acid (GABA) on the nerves and muscle cells of invertebrates, causing pharyngeal paralysis and death of the parasite by asphyxia and starvation. Our results for the Swiss Target prediction reports of isoflavonic rotenoids such as rotenone and rotenolone revealed strong interactions with many cytochrome P450 isozymes, NADH-ubiquinone oxidoreductase, and the microtubule-associated protein tau. Another rotenoid, deguelin, is especially akin to ornithine and arginine decarboxylases, and tephrosin shows affinity to tyrosyl-DNA phosphodiesterase, due to the probability levels shown in the Appendix A predictions. These results obtained by our in silico tests explain the activities of L. utilis. We also found a strong relation to the former decarboxylases and other groups of molecules of the extract: stilbenes (as lonchocarpene), chalcones (as 4-hydroxylonchocarpin), and prenylated flavones (such as 3′methoxylupinifolin). Rotenoids have the capacity to act against multiplication or growth, as summarized in the experimental results of Table 1. They cause a lack of energy, respiratory depression, respiratory arrest, and death. They lead to failure in the electron transport chain, which, at the mitochondrial level, translates into a blockade of the passage from ADP to ATP. Their inhibitory effect on NADHU-ubiquinone oxidoreductase has been demonstrated in the laboratory and as a consequence of the (ODC) phorbol ester-induced ornithine decarboxylase [60]. Rotenone is specifically classified as an insecticide type II with low toxicity to humans and warm-blooded animals [61]. The selective toxicity of rotenone in insects and fish versus mammals is related to its poor absorption from the gastrointestinal tract of the latter as well as the overall metabolic differences. Rotenone is converted into highly toxic metabolites in insects and fish. On the contrary, it is converted into non-toxic metabolites in mammals. In the motor system, 5-hydroxytriptamine (5HT) can depress GABA-mediated transmission and structures controlling movement [62]. Rotenone and rotenolone showed a great affinity for the membrane receptors of 5HT in our Swiss Target in silico tests, which is indirect evidence of the capacity of these molecules to behave similarly to Ivermectine when it causes helminth muscle paralysis.

4. Conclusions

In Latin America, myasis, as a disease, remains somewhat misunderstood. It is excluded from basic epidemiological research and hospital treatments are often lacking [63]. In this framework, traditional ethnomedicine is revealed as a powerful ally to improve the state of health, especially considering cases such as this case study. It can serve as an example that can be replicated by others in the same situation. We have looked for scientific arguments to demonstrate the reason for using extracts of Lonchocarpus utilis against south American myasis (tupe). We have provided a summary of the isoflavonoids, prenylated flavonoids, chalcones, and stilbenes that justify the action. We have performed modeling predictions on the affinity of eight chemical components and enzyme targets using Swiss Target prediction software.
We have concluded that the effects of this extract can be reasonably attributed to an effect of the parasite that causes the disease. Once again, the importance of the plant world in the drug discovery processes must be considered, and a call is made for plant conservation to be used as a source of obtaining added value bioproducts.

5. Materials and Methods

5.1. Ethnobotanical Study

All the information regarding the study where the data came from is available in Appendix B. It contains references to the voucher specimens of herbarium material collected, the permits and authorizations obtained, and the procedures applied. Table A1 and Table A2 (in Appendix B) summarize the traditional uses given to the species.

5.2. Bibliographic Review

A bibliographic study was performed following the Prisma 2009 flow diagram methodology [64]. The databases accessed were Academic Search Complete, Agricola, Agris, Biosis, CABS, Cochrane, Cybertesis, Dialnet, Directory of Open Access Journals, Embase, Espacenet, Google Patents, Google Academics, Medline, PubMed, Science Direct, Scopus, Theseus, and ISI Web of Science. The aim was to find publications on chemical composition and/or activity. The abovementioned ones and the Latin names of the species and synonyms were used as keywords. The selected citations were summarized. Critical reading of this literature allowed us to elaborate on the discussion of the results and main statements.

5.3. In Silico Activity Test

Swiss Target prediction software [65,66] was eventually used to investigate the activity in silico to reinforce the principal arguments. Prediction reports were made with the following query molecules:
  • Rotenone;
  • Rotenolone;
  • Deguelin;
  • Tephrosin;
  • 3′metoxylupinifolin;
  • 4 hydroxylonchocarpin;
  • Lonchocarpene.

Author Contributions

Methodology, T.R.-T., C.E.C.-M. and C.X.L.-Q.; Validation J.B.-S.; Formal Analysis, J.C.A.-G.; Investigation, C.X.L.-Q.; Data Curation, C.E.C.-M. and C.X.L.-Q.; Writing—Original Draft Preparation, T.R.-T.; Writing—Review & Editing, J.B.-S. and J.C.A.-G.; Visualization, J.C.A.-G.; Supervision, C.X.L.-Q.; Project Administration, T.R.-T.; Funding Acquisition, C.X.L.-Q. and T.R.-T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was partially funded by the Government of Extremadura (Spain) and the European Union through the action “Apoyos a los Planes de Actuación de los Grupos de Investigación Catalogados de la Junta de Extremadura: FEDER GR18169”.

Acknowledgments

We are very grateful to the People’s Assembly of Pakayaku, the President, Luzmila Gayas, and the collaborating community. F. Centeno Velázquez (Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura) helped us with the in silico docking.

Conflicts of Interest

The authors declare no conflict of interest.

Appendix A

Plants 09 00033 g0a1 550
Figure A1. Swiss Target prediction Report Files obtained using Rotenone as query molecule.
Figure A1. Swiss Target prediction Report Files obtained using Rotenone as query molecule.
Plants 09 00033 g0a1
Plants 09 00033 g0a2 550
Figure A2. Swiss Target prediction Report Files obtained using Rotenolone as query molecule.
Figure A2. Swiss Target prediction Report Files obtained using Rotenolone as query molecule.
Plants 09 00033 g0a2
Plants 09 00033 g0a3 550
Figure A3. Swiss Target prediction Report Files obtained using Deguelin as query molecule.
Figure A3. Swiss Target prediction Report Files obtained using Deguelin as query molecule.
Plants 09 00033 g0a3
Plants 09 00033 g0a4 550
Figure A4. Swiss Target prediction Report Files obtained using Thephrosin as query molecule.
Figure A4. Swiss Target prediction Report Files obtained using Thephrosin as query molecule.
Plants 09 00033 g0a4
Plants 09 00033 g0a5 550
Figure A5. Swiss Target prediction Report Files obtained using 3′ metoxylupinifolin as query molecule.
Figure A5. Swiss Target prediction Report Files obtained using 3′ metoxylupinifolin as query molecule.
Plants 09 00033 g0a5
Plants 09 00033 g0a6 550
Figure A6. Swiss Target prediction Report Files obtained using 4-hydroxylonchocarpin as query molecule.
Figure A6. Swiss Target prediction Report Files obtained using 4-hydroxylonchocarpin as query molecule.
Plants 09 00033 g0a6
Plants 09 00033 g0a7 550
Figure A7. Swiss Target prediction Report Files obtained using Lonchocarpene as query molecule.
Figure A7. Swiss Target prediction Report Files obtained using Lonchocarpene as query molecule.
Plants 09 00033 g0a7

Appendix B

The Kichwa community of Pakayaku lies in a fairly isolated Amazonic region of the Bobonaza River in Pastaza, Ecuador. One of us (C.X.L.-Q.) was based at the Biological Station Pindo Mirador in the northern river basin (S1°27′09″–W 78°04′51″), and plant collection permissions were granted by the Ministry of the Environment: Reference MAE-DPAP-2016-2243. Plant vouchers were deposited at the QAP Herbarium José Alfredo Paredes, Universidad Central de Ecuador, Quito with the following code numbers: QAP 92494, QAP 92519, QAP 92523, QAP 92623, QAP 92838, QAP 92920, QAP 93783, QAP 93785; QAP 93789, QAP 93794.
To perform the ethnobotanical survey under the Nagoya Protocol rules, collective written research consent was granted by the community president of the Assembly, Mrs. Luzmila Gayas. Prior individual consents had been obtained from the persons taking part in our survey. The survey consisted of a series of planned residential visits accompanied by Kichwa interpreters. Semi-structured interviews were recorded. Four knowledgeable elders of the Pakayaku community acted as informants and agreed to reveal their knowledge on the barbasku tree. The informants answered freely on several topics, including the common name of Kichwa, the part of the plant used, a description of its usage, the harvest season, storage (if any), preparation of concoctions, and the target of the treatment. After the fieldwork, the data were included in an spreadsheet Excel 2016 (Microsoft, Redmon, WA, USA). The existing ethnobotanical literature from Ecuador included in Table A1 was compared with the recorded uses that are summarized in Table A2.
Table
Table A1. Synthesis of the ethnobotanical knowledge of Lonchocarpus utilis A.C.Sm. from the indigenous communities of Ecuador based on [67] and the bibliographic revision of [7]. R, root; L, leaves; S, stem.
Table A1. Synthesis of the ethnobotanical knowledge of Lonchocarpus utilis A.C.Sm. from the indigenous communities of Ecuador based on [67] and the bibliographic revision of [7]. R, root; L, leaves; S, stem.
Use CategoryPart PreparationTraditional KnowledgeNative CommunityProvince of Ecuador
Medicinal
Digestive systemRPlasterStomach pain and diarrheaKichwa of Eastern Napo
Unidentified ethnicityPastaza
Skin and subcutaneous cellular tissueRPlasterChupos treatment: abscesses with pusKichwa of Eastern Napo
Unidentified ethnicityPastaza
Other infectious and parasitic diseasesRCrushedMycosis treatmentKichwa of Eastern Orellana
Symptoms of undefined originLMilledChronic pain caused by witchcraftKichwa of Eastern Pastaza
Toxic usesR, L, SCrushed and spread in the riverCatch fishSecoyaSucumbíos
Poison,
Insecticide
Pesticide		SionaSucumbíos
Unidentified ethnicityOrellana
Napo
Zamora Chinchipe
Tsa’chiPichincha
CofánSucumbíos
Amazon
Kichwa of Eastern Sucumbíos
Napo
Orellana
Pastaza
Zamora Chinchipe
WaoNapo
Orellana
ShuarOrellana
Pastaza
Morona Santiago
Social, symbolic, and ritual usesLLeaves, alone or with ají leaves burnedDrives away evil spirits when you sleep in the forestUnidentified ethnicityNapo
Protection rituals
Other handling Collection and sale (rotenone content)CofánAmazon
CommercializationR
Table
Table A2. Specific ethnobotanical uses of Lonchocarpus utilis reported in the fieldwork (Pakayaku, Pastaza, Ecuador). Local names: intillama shilu, barbasku. Vouchers: QAP Herbarium.
Table A2. Specific ethnobotanical uses of Lonchocarpus utilis reported in the fieldwork (Pakayaku, Pastaza, Ecuador). Local names: intillama shilu, barbasku. Vouchers: QAP Herbarium.
Use CategoriesPartPreparationMethod of Usage/Purpose of Use
Human Medicine
Used against myiasis: “to kill the tupe” (human bot fly)RExtraction of “milk” by pressureThe “milk” is deposited on a piece of paper and placed where tupe has stung
Hits and body achesRCrush rootsCrushed root is placed directly on the skin
Veterinary
External antiparasiticRExtraction of “milk” by pressureThe “milk” is deposited on a piece of paper and placed where tupe has stung
Toxic
Catch fishRCrushed roots to be used as soon as possible (in 1–2 days)The “milk” obtained is spread in the water of rivers and ravines

References

  1. World Health Organization (WHO) Neglected Tropical Diseases. Available online: https://web.archive.org/web/20140227152033/; http://www.who.int/neglected_diseases/en/ (accessed on 13 December 2019).
  2. Katewa, S.S.; Chaudhary, B.L.; Jain, A. Folk herbal medicines from tribal area of Rajasthan, India. J. Ethnopharmacol. 2004, 92, 41–46. [Google Scholar] [CrossRef] [PubMed]
  3. Carreño-Hidalgo, P.C. La etnobotánica y su importancia como herramienta para la articulación entre conocimientos ancestrales y científicos. In Trabajo de Grado para Optar a Título de Licenciado; Universidad Distrital Francisco José de Caldas: Bogotá, Colombia, 2016. [Google Scholar]
  4. Hotez, P.J.; Alvarado, M.; Basáñez, M.-G.; Bolliger, I.; Bourne, R.; Boussinesq, M.; Brooker, S.J.; Brown, A.S.; Buckle, G.; Budke, C.M. The global burden of disease study 2010: Interpretation and implications for the neglected tropical diseases. PLoS Negl. Trop. Dis. 2014, 8, e2865. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  5. Nemoga Soto, R. Globalizacion y transformacion de las formas juridicas: Apropiacion de material genetico. Pensam. Jurídico 1:138-148. ISSN 2357-6170. 2013. Available online: https://revistas.unal.edu.co/index.php/peju/article/view/38893 (accessed on 17 December 2019).
  6. Torres Morocho, D.M.; Orea Igarza, U.; Brito Vallina, M.L.; Cordero Machado, E. Estudio de la extracción del follaje de Barbasco (Lonchocarpus nicou) como fuente biocida (en condiciones de la Amazonía en Ecuador). Rev. Cienc. Técnicas Agropecu. 2013, 22, 41–49. [Google Scholar]
  7. Luzuriaga-Quichimbo, C.X. Estudio Etnobotánico en Comunidades Kichwas Amazónicas de Pastaza, Ecuador. Ph.D. Thesis, Universidad de Extremadura, Badajoz, España, 2017. [Google Scholar]
  8. Borgtoft, H.; Skov, F.; Fjeldsa, J.; Øllgaard, B. People and Biodiversity. Two case studies from the Andean foothills of Ecuador. Centre for research on cultural and biological diversity of Andean rainforests. Diva Tech. Rep. 1998, 3, 1–190. [Google Scholar]
  9. Álvarez, C. Historias desde el Aula; Abya-Yala: Quito, Ecuador, 2006. [Google Scholar]
  10. GADP-Pastaza. Estudio del Impacto Ambiental del Proyecto de Construcción del Afirmado Camino Vecinal Latasas-Umupi, Parroquia Canelos, Provincia Pastaza; Gobierno Autónomo Descentralizado de Pastaza: Puyo, Ecuador, 2013.
  11. GADP-Pastaza. Plan de Desarrollo y Ordenamiento Territorial del Cantón Pastaza, 2015–2020; Gobierno autónomo Descentralizado de Pastaza: Puyo, Ecuador, 2015.
  12. Widdowson, M.-A.; Iuliano, A.D.; Dawood, F.S. Challenges to global pandemic mortality estimation. Lancet Infect. Dis. 2014. [Google Scholar] [CrossRef]
  13. Zúñiga Carrasco, I.R. Miasis: Un problema de salud poco estudiado en México. Rev. Enferm. Infecc. Pediatr. 2009, 22, 121–125. [Google Scholar]
  14. Tamir, J.; Haik, J.; Orenstein, A.; Schwartz, E. Dermatobia hominis myiasis among travelers returning from South America. J. Am. Acad. Derm. 2003, 48, 630–632. [Google Scholar] [CrossRef]
  15. Mathieu, M.E.; Wilson, B.B. Myiasis, 5th ed.; Co, C.L., Ed.; Churchill Livingstone Co: Philadelphia, PA, USA, 2000. [Google Scholar]
  16. Martinez-Estrada, V.; Aguilera, V.; Jurado, F. Miasis furunculoide. Comun. Caso. Dermatol. Rev. Mex 2002, 46, 280–284. [Google Scholar]
  17. Mengarelli, R.H.; Cevallos, M.V. Manejo de las miasis en heridas agudas y crónicas: Presentación de casos y revisión de la bibliografía. Rev. Argent. Dermatol. Ciudad Autónoma Buenos Aires 2012, 93, 1–8. [Google Scholar]
  18. Ginarte, M.; García Doval, I.; Peteiro, C.; Toribio, J. Miasis cutánea por Dermatobia hominis. Actas Dermosifiliogr. 1996, 87, 340–342. [Google Scholar]
  19. de Hollanda Ramírez, A.M.; Silva Rodríguez, A.R.; Zaracho, G. Invermectina in the treatment of Human Miasis. La Fac. Cienc. Médicas 2005, 38, 62–71. [Google Scholar]
  20. Manrique, A.; Manrique, D.; Catacora, J. Miasis cutánea: Reporte de un caso y revisión de la literatura. Folia Derm. Peru 2009, 20, 23–26. [Google Scholar]
  21. Rubio, C.; de Guevara, C.L.; Martín, M.A.; Campos, L.; Quesada, A.; Casado, M. Miasis cutáneas sobre lesiones tumorales: Presentación de tres casos. Actas Dermosifiliogr. 2006, 97, 39–42. [Google Scholar] [CrossRef]
  22. Izquierdo, M.J.; Pastor, M.A.; Carrasco, L.; Fariña, M.C.; Martín, L.; Requena, L.; Fernández, R.; Gadea, I. Miasis forunculoide: Descripción de dos casos con estudio histológico de las diferentes larvas. Actas Dermosifiliogr. 2001, 92, 456–460. [Google Scholar] [CrossRef]
  23. Chan, J.C.M.; Lee, J.S.W.; Dai, D.L.K.; Woo, J. Unusual cases of human myiasis due to Old World screwworm fly acquired indoors in Hong Kong. Trans. R. Soc. Trop. Med. Hyg. 2005, 99, 914–918. [Google Scholar] [CrossRef]
  24. Moya, J.; Spelta, G.; Gavazza, S.; Barbarulo, A.M.; Fontana, M.I.; Barerra, M.; Jurjo, L.L.; Azcune, R. Miasis cutánea Revisión sobre el tema y presentación de un caso de miasis forunculoide. Arch. Argent. Derm. 2007, 57, 217–222. [Google Scholar]
  25. Lima, T.C.; Santos, A.D.C.; Costa, D.T.M.; Souza, R.J.; Barison, A.; Steindel, M.; Biavatti, M.W. Chromenes from leaves of Calea pinnatifida and evaluation of their leishmanicidal activity. Rev. Bras. Farm. 2015, 25, 7–10. [Google Scholar] [CrossRef] [Green Version]
  26. Mishra, T.; Shukla, S.; Meena, S.; Singh, R.; Pal, M.; Upreti, D.K.; Datta, D. Isolation and identification of cytotoxic compounds from a fruticose lichen Roccella montagnei, and it’s in silico docking study against CDK-10. Rev. Bras. Farm. 2017, 27, 724–728. [Google Scholar] [CrossRef]
  27. dos Santos Passos, C.; Klein-Júnior, L.C.; de Mello Andrade, J.M.; Matté, C.; Henriques, A.T. The catechol-O-methyltransferase inhibitory potential of Z-vallesiachotamine by in silico and in vitro approaches. Rev. Bras. Farm. 2015, 25, 382–386. [Google Scholar] [CrossRef] [Green Version]
  28. Moraga-Nicolás, F.; Jara, C.; Godoy, R.; Iturriaga-Vásquez, P.; Venthur, H.; Quiroz, A.; Becerra, J.; Mutis, A.; Hormazábal, E. Rhodolirium andicola: A new renewable source of alkaloids with acetylcholinesterase inhibitory activity, a study from nature to molecular docking. Rev. Bras. Farm. 2018, 28, 34–43. [Google Scholar] [CrossRef]
  29. Moradi-Afrapoli, F.; Shokrzadeh, M.; Barzegar, F.; Gorji-Bahri, G.; Zadali, R.; Nejad Ebrahimi, S. Cytotoxic activity of abietane diterpenoids from roots of Salvia sahendica by HPLC-based activity profiling. Rev. Bras. Farm. 2018, 28, 27–33. [Google Scholar] [CrossRef]
  30. Mangul, S.; Martin, L.S.; Langmead, B.; Sanchez-Galan, J.E.; Toma, I.; Hormozdiari, F.; Pevzner, P.; Eskin, E. How bioinformatics and open data can boost basic science in countries and universities with limited resources. Nat. Biotechnol. 2019, 37, 324–326. [Google Scholar] [CrossRef] [PubMed]
  31. Fang, N.B.; Casida, J.E. Cube resin insecticide: Identification and biological activity of 29 rotenoid constituents. J. Agric. Food Chem. 1999, 47, 2130–2136. [Google Scholar] [CrossRef] [PubMed]
  32. de Oliveira, D.G.; de Almeida, C.M.C.; Silva, C.; Arruda, M.S.P.; Arruda, A.C.; Lopes, D.C.F.; Yamada, E.S.; da Costa, E.T.; da Silva, M.N. Flavonoids from the Leaves of Deguelia utilis (Leguminosae): Structural Elucidation and Neuroprotective Properties. J. Braz. Chem. Soc. 2012, 23, 1933–1939. [Google Scholar] [CrossRef] [Green Version]
  33. Lawson, M.A.; Kaouadji, M.; Allais, D.P.; Champavier, Y.; Chulia, A.J. Substituted tubaic acids, new oxidative rotenoid metabolites from Lonchocarpus nicou. Tetrahedron Lett. 2006, 47, 451–454. [Google Scholar] [CrossRef]
  34. Lawson, M.A.; Kaouadji, M.; Chulia, A.J. A single chalcone and additional rotenoids from Lonchocarpus nicou. Tetrahedron Lett. 2010, 51, 6116–6119. [Google Scholar] [CrossRef]
  35. Lawson, A.M.N.V. O-Benzoquinone and Ester-Linked Hydroxyfatatty Acid as Additional compounds from Lonchocarpus nicou. Open J. Plant Sci. 2016, 1, 1–4. [Google Scholar] [CrossRef] [Green Version]
  36. Fang, N.B.; Casida, J.E. New bioactive flavonoids and stilbenes in cube resin insecticide. J. Nat. Prod. 2000, 63, 293. [Google Scholar] [CrossRef]
  37. Lawson, M.A.; Kaouadji, M.; Chulia, A.J. Nor-dehydrodeguelin and nor-dehydrorotenone, C(22) coumaronochromones from Lonchocarpus nicou. Tetrahedron Lett. 2008, 49, 2407–2409. [Google Scholar] [CrossRef]
  38. Kaouadji, M.; Agban, A.; Mariotte, A.M. Lonchocarpene, a stilbene, and lonchocarpusone, an isoflavone—2 new pyronopolyphenols from Lonchocarpus nicou roots. J. Nat. Prod. 1986, 49, 281–285. [Google Scholar] [CrossRef]
  39. Fang, N.B.; Casida, J.E. Anticancer action of cube insecticide: Correlation for rotenoid constituents between inhibition of NADH: Ubiquinone oxidoreductase and induced ornithine decarboxylase activities. Proc. Natl. Acad. Sci. USA 1998, 95, 3380–3384. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  40. Muhaisen, H.M.H. Introduction and Interpretation of Flavonoids. Adv. Sci. Eng. Med. 2014, 6, 1–16. [Google Scholar] [CrossRef]
  41. Caboni, P.; Sherer, T.B.; Zhang, N.J.; Taylor, G.; Na, H.M.; Greenamyre, J.T.; Casida, J.E. Rotenone, deguelin, their metabolites, and the rat model of Parkinson’s disease. Chem. Res. Toxicol. 2004, 17, 1540–1548. [Google Scholar] [CrossRef]
  42. Fuchino, H.; Kiuchi, F.; Yamanaka, A.; Obu, A.; Wada, H.; Mori-Yasumoto, K.; Kawahara, N.; Flores, D.; Palacios, O.; Sekita, S.; et al. New Leishmanicidal Stilbenes from a Peruvian Folk Medicine, Lonchocarpus nicou. Chem. Pharm. Bull. (Tokyo) 2013, 61, 979–982. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Ibrahim, B.; M’Batchi, B.; Mounzeo, H.; Bourobou, H.P.B.; Posso, P. Effect of Tephrosia vogelii and Justicia extensa on Tilapia nilotica in vivo. J. Ethnopharmacol. 2000, 69, 99–104. [Google Scholar] [CrossRef]
  44. Sarwar, M. The killer chemicals for control of agriculture insect pests: The botanical insecticides. Int. J. Chem. Biomol. Sci. 2015, 1, 123–128. [Google Scholar]
  45. Fuchino, H.; Sekita, S.; Mori, K.; Kawahara, N.; Satake, M.; Kiuchi, F. A New Leishmanicidal Saponin from Brunfelsia grandiflora. Chem. Pharm. Bull. (Tokyo) 2008, 56, 93–96. [Google Scholar] [CrossRef] [Green Version]
  46. Preston, S.; Korhonen, P.K.; Mouchiroud, L.; Cornaglia, M.; McGee, S.L.; Young, N.D.; Davis, R.A.; Crawford, S.; Nowell, C.; Ansell, B.R.E.; et al. Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain. FASEB J. 2017, 31, 4515–4532. [Google Scholar] [CrossRef] [Green Version]
  47. Kim, W.Y.; Chang, D.J.; Hennessy, B.; Seo, S.Y. A Novel Derivative of the Natural Agent Deguelin for Cancer Chemoprevention and Therapy. Cancer Prev. Res. 2009, 2, 186. [Google Scholar] [CrossRef] [Green Version]
  48. Lee, S.-G.; Kim, M.-M. Anti-inflammatory Effect of Scopoletin in RAW264.7 Macrophages. J. Life Sci. 2015, 25, 1377–1383. [Google Scholar] [CrossRef] [Green Version]
  49. Murillo, G.; Salti, G.I.; Kosmeder, J.W.; Pezzuto, J.M.; Mehta, R.G. Deguelin inhibits the growth of colon cancer cells through the induction of apoptosis and cell cycle arrest. Eur. J. Cancer 2002, 38, 2446–2454. [Google Scholar] [CrossRef]
  50. Lee, H.Y.; Oh, S.H.; Woo, J.K.; Kim, W.Y.; Van Pelt, C.S.; Price, R.E.; Cody, D.; Tran, H.; Pezzuto, J.M.; Moriarty, R.M.; et al. Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis. J. Natl. Cancer Inst. 2005, 97, 1695–1699. [Google Scholar] [CrossRef] [PubMed]
  51. Boreddy, S.R.; Srivastava, S.K. Deguelin suppresses pancreatic tumor growth and metastasis by inhibiting epithelial-to-mesenchymal transition in an orthotopic model. Oncogene 2013, 32, 3980–3991. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  52. Thamilselvan, V.; Menon, M.; Thamilselvan, S. Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 beta/beta-catenin pathway. Int. J. Cancer 2011, 129, 2916–2927. [Google Scholar] [CrossRef]
  53. Wang, A.M.; Wang, W.N.; Chen, Y.Q.; Ma, F.Q.; Wei, X.M.; Bi, Y.Y. Deguelin induces PUMA-mediated apoptosis and promotes sensitivity of lung cancer cells (LCCs) to doxorubicin (Dox). Mol. Cell. Biochem. 2018, 442, 177–186. [Google Scholar] [CrossRef]
  54. Bortul, R.; Tazzari, P.L.; Billi, A.M.; Tabellini, G.; Mantovani, I.; Cappellini, A.; Grafone, T.; Martinelli, G.; Conte, R.; Martelli, A.M.; et al. PI3K/AKT inhibitor, enhances chemosensitivity of leukaemia cells with an active PI3K/AKT pathway. Br. J. Haematol. 2005, 129, 677–686. [Google Scholar] [CrossRef]
  55. Ackerman, J.L.; Bellwood, D.R. Reef fish assemblages: A re-evaluation using enclosed rotenone stations. Mar. Ecol. Prog. Ser. 2000, 206, 227–237. [Google Scholar] [CrossRef]
  56. Aladdin, N.-A.; Jamal, J.A.; Talip, N.; Hamsani, N.A.M.; Rahman, M.R.A.; Sabandar, C.W.; Muhammad, K.; Husain, K.; Jalil, J.; Lima, N.M.; et al. Antifungal activity of extracts and phenolic compounds from Deguelia duckeana. Rev. Bras. Farm. 2018, 28, 697–702. [Google Scholar] [CrossRef] [Green Version]
  57. Lobo, L.T.; da Silva, G.A.; de Freitas, M.C.C.; Souza, A.P.S.; da Silva, M.N.; Arruda, A.C.; Guilhon, G.; Santos, L.S.; Santos, A.S.; Arruda, M.S.P. Stilbenes from Deguelia rufescens var. urucu (Ducke) A. M. G. Azevedo Leaves: Effects on Seed Germination and Plant Growth. J. Braz. Chem. Soc. 2010, 21, 1838–1844. [Google Scholar] [CrossRef] [Green Version]
  58. Omura, S. Ivermectin: 25 years and still going strong. Int. J. Antimicrob. Agents 2008, 31, 91–98. [Google Scholar] [CrossRef]
  59. Õmura, S.; Crump, A. The life and times of ivermectin—a success story. Nat. Rev. Microbiol. 2004, 2, 984. [Google Scholar] [CrossRef] [PubMed]
  60. Silva, G.; Lagunes, A.; Rodriguez, J.C.; Rodriguez, D. Insecticidas vegetales; una vieja y nueva alternativa en el manejo de insectos. Rev. Manejo Integr. Plagas Agroecol. 2002, 66, 4–12. [Google Scholar]
  61. Gupta, R.C. Biomarkers in Toxicology; Academic Press: Cambridge, MT, USA, 2014; ISBN 9780124046306. [Google Scholar]
  62. McGarry, J.W. Tropical myiases: Neglected and well travelled. Lancet Infect. Dis. 2014, 14, 672–674. [Google Scholar] [CrossRef]
  63. World Health Organization (WHO), International Programme on Chemical Safety. The WHO Recommended Classification of Pesticides by Hazard. Guidelines to Classification; World Health Organization: Geneve, Switzerland, 2009; ISBN 9789241547963. [Google Scholar]
  64. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Int. J. Surg. 2010. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Gfeller, D.; Michielin, O.; Zoete, V. Shaping the interaction landscape of bioactive molecules. Bioinformatics 2013, 29, 3073–3079. [Google Scholar] [CrossRef]
  66. Gfeller, D.; Grosdidier, A.; Wirth, M.; Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res. 2014, 42, 32–38. [Google Scholar] [CrossRef]
  67. De la Torre, L.; Navarrete, H.; Muriel, P.; Maciá, J.; Balslev, H. Enciclopedia de las plantas Útiles en Ecuador; Escuela de Ciencias Biológicas de la Pontífica Universidad Católica del Ecuador & Herbario AAU del Departamento de Ciencias Biológicas de la Universidad de Aarhus: Quito, Ecuador; Aahrus, Dinamarca, 2008; ISBN 978-9978-77-135-8. [Google Scholar]
Plants 09 00033 g001 550
Figure 1. Chemical structures of the main components of Lonchocarpus utilis.
Figure 1. Chemical structures of the main components of Lonchocarpus utilis.
Plants 09 00033 g001
Table
Table 1. Biological activity and applications of some chemical compounds present in Lonchocarpus utilis.
Table 1. Biological activity and applications of some chemical compounds present in Lonchocarpus utilis.
MoleculeTested inActivityReferences
RotenoneRatInhibition of mitochondrial activity (diminished NADH: ubiquinone oxidoreductase activity) [41]
CellInhibition of growth [31]
LehismaniaAntilehismaniasic[42]
CellAntiproliferative[39]
FishToxic for fish[41,43]
InsectInsecticide and pesticide[44]
Rotenolone RatInhibition of mitochondrial activity (diminished NADH: ubiquinone oxidoreductase activity) (25% less active than rotenone).[41]
CellInhibition of growth[31]
Deguelin Inhibition of mitochondrial activity (diminished NADH: ubiquinone oxidoreductase activity) (50% less active than rotenone).[41]
CellInhibition of growth[31,45]
CellAntiproliferative [39]
NematodeNematocide[46]
Anti-inflammatory in transplants[46,47]
CellPotent apoptotic and antiangiogenic [48,49]
CellInhibition of progression of tumors such as lung, stomach, prostate, colon, ovary, and pancreas.[49,50,51,52,53]
CellInhibition of tumor cell growth and metastasis.[51,52]
Cell Chemical adjuvant against leukemia[54]
Tephrosin RatInhibition of mitochondrial activity (diminished NADH: ubiquinone oxidoreductase activity)[41]
CellInhibition of growth[43]
Prenyl-urucuol ACellCytoprotective activity of neurons in rats (Complete fraction)[55]
Prenyl-isotirumalin
Prenylutilinol
3′-methoxylupinifolin
Prenylutiline
(2S)-6-(γ,γ-dimethylallyl)-5,4′-dihydroxy-3′-methoxy-6″,6″-dimethylpyran [2 ″,3″:7,8] flavanoneCellInhibition of growth[36]
4-hydroxylonchocarpin Antifungal[56]
Lonchocarpene SeedlingInhibition of growth/development[57]
4-methoxylonchocarpene Seedling
3,5-dimethoxy-4-hydroxy-3-prenyl-trans-stilbeneSeedling

Share and Cite

MDPI and ACS Style

Luzuriaga-Quichimbo, C.X.; Blanco-Salas, J.; Cerón-Martínez, C.E.; Alías-Gallego, J.C.; Ruiz-Téllez, T. Promising Potential of Lonchocarpus utilis against South American Myasis. Plants 2020, 9, 33. https://doi.org/10.3390/plants9010033

AMA Style

Luzuriaga-Quichimbo CX, Blanco-Salas J, Cerón-Martínez CE, Alías-Gallego JC, Ruiz-Téllez T. Promising Potential of Lonchocarpus utilis against South American Myasis. Plants. 2020; 9(1):33. https://doi.org/10.3390/plants9010033

Chicago/Turabian Style

Luzuriaga-Quichimbo, Carmen X., José Blanco-Salas, Carlos E. Cerón-Martínez, Juan Carlos Alías-Gallego, and Trinidad Ruiz-Téllez. 2020. "Promising Potential of Lonchocarpus utilis against South American Myasis" Plants 9, no. 1: 33. https://doi.org/10.3390/plants9010033

APA Style

Luzuriaga-Quichimbo, C. X., Blanco-Salas, J., Cerón-Martínez, C. E., Alías-Gallego, J. C., & Ruiz-Téllez, T. (2020). Promising Potential of Lonchocarpus utilis against South American Myasis. Plants, 9(1), 33. https://doi.org/10.3390/plants9010033

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop