Chemical composition and potential antileishmanial and cytotoxic activity of Duguetia stelechantha (Diels) R.E.Fr. essential oil

https://doi.org/10.1016/j.indcrop.2023.116978Get rights and content

Highlights

  • In the chemical characterization of Duguetia stelechantha monoterpenes predominate.

  • The essential oil and microemulsion has β-pinene its major compound.

  • The essential oil of D. stelechantha has moderate effect against L. (L.) amazonensis.

  • D. stelechantha microemulsion is active against L. (L.) amazonensis promastigotes.

  • D. stelechantha essential oil is cytotoxic for RAW 264.7 macrophages.

Abstract

Duguetia stelechantha (Diels) R.E.Fr., popularly known as “ata brava” in Brazil, belongs to the Annonaceae family. Biologically active monoterpenes and sesquiterpenes identified in this genus and family, comprising a source of new drugs against several conditions, including leishmaniasis. In this context, the aim of the present study was to extract and chemically characterize the essential oil (EO-DU) obtained from D. stelechantha for the first time. The potential antileishmanial activity and in vitro cytotoxicity of an EO microemulsion (EO-ME) formulated with Tween 80 and Transcutol P surfactants were also evaluated. Duguetia stelechantha leaves were submitted to a hydrodistillation process and their chemical composition was determined by GC/MS. The major identified EO components were β-pinene (46.17 %), α-pinene (20.2 %), and spathulenol (6.68 %). A headspace characterization indicated major EO-DU compounds present in the prepared ME, confirming incorporation. The extracted EO was moderately active against Leishmania (L.) amazonensis promastigotes (IC50 =138.3 µg/mL), while the EO-ME was determined as active, inhibiting these parasites at a lower concentration (IC50 =4.47 µg/mL) compared to the EO-DU, indicating high selectivity against L. (L) amazonensis promastigotes. The major compound α-pinene was also tested, and presented IC50 = 64.78 µg/mL, considering it active against the tested parasites. Considering that D. stelechantha is an abundant species in the Brazilian Legal Amazon and that the antileishmanial potential of the extracted EO was enhanced by EM incorporation, this assessment provides relevant perspectives for future studies focused on the bioeconomy.

Introduction

Leishmaniasis affects 1 million of people worldwide every year (Jesus et al., 2021, WHO, 2023). American tegumentary leishmaniasis is a non-contagious infectious disease transmitted to humans through the bite of sandfly females (Phlebotomus and Lutzomya genus) infected by protozoa belonging to the Leishmania genus. Leishmania amazonensis is associated with American tegumentary leishmaniasis, causing skin and mucous membrane ulcers in humans (Lima et al., 2020).

The current arsenal used to treatment leishmaniasis comprises pentavalent antimonials, amphotericin B and its liposomal formulation AmBisome, miltefosine, paromomycin, and pentamidine. However, high toxicity to humans and cases of parasite resistance have led to limitations regarding these therapeutic resources (Neto et al., 2019, Ponte-Sucre et al., 2017), resulting in an urgent search for effective control methods. In this regard, aromatic compounds and terpenes are excellent candidates for antileishmanial drug production. Furthermore, the effects of these compounds can be enhanced when incorporated into certain formulations, such as microemulsions (ME), which are thermodynamically stable and increase the bioavailability of active principles, optimizing biological activity while at the same time reducing compound toxicity.

Duguetia stelechantha (Diels) R.E.Fr. (synonym Aberemoa stelechantha), popularly known as “ata brava”, “envira amarela” and “envirataia” in Brazil, belongs to the Annonaceae family Duguetia genus (SiBBr, 2022). The Duguetia genus, in particular, is very abundant in Brazil, with about 100 species identified to date in the country (Monteiro et al., 2022; Lobão, 2023). D. stelechantha is geographically distributed throughout in the states of Amazonas, Pará, and Rondônia, although it is also non-endemic to Brazil, and found in Colombia and Bolivia (Lobão, 2023; GBIF.org, 2022).

Chemical and biological studies on this species are scarce. In this regard, we postulate that D. stelechantha contains secondary metabolites, such as terpenes, with biotechnological potential, i.e., biological activities that may be employed as a source of new drugs. Furthermore, the effects of these compounds can be enhanced when incorporated into certain formulations, such as microemulsions (ME), which are thermodynamically stable and increase the bioavailability of active principles, optimizing biological activity while at the same time reducing compound toxicity.

In this context, the aim of the present study was to chemically characterize the essential oil (EO-DU) obtained from D. stelechantha for the first time and assess potential antileishmanial action against L. (Leishmania) amazonensis promastigotes and cytotoxicity against RAW 264.7 macrophages of a EO D. stelechantha microemulsion (EO-ME).

Section snippets

Collection of plant material

The plant material of D. stelechantha was collected in São Bento, Maranhão, Brazil, in the Grajaú district (02°43'56.8 "S; 044°51'27.9 "W). The botanical identification of the plant is catalogued at Herbário Rosa Mochel, São Luís, Maranhão, Brazil, under the registration number SLUI005612. This species was collected and registered of according to the National System for the Management of Genetic Heritage and Associated Traditional Knowledge (SisGen) under number AA3D4EE.

Extraction of the essential oil

The leaves of the

Oil composition analysis

The oil yield was 1.37 % and volatile composition of the essential oil (EO) extracted from D. stelechantha are displayed in Table 1. Forty-one volatile EO compounds were identified by GC-MS, comprising about 96.4 % of the total oil composition (Table 1 and Fig. 1S).

A high oil content (1.37 %) was observed in D. stelechantha compared to previous studies conducted with the leaves of other Duguetia species also found in Brazil, such as D. furfuracea (A. St. Hil.) Saff. (0.8 %), D. lanceolata St.

Conclusion

The incorporation of natural products, such as the EO extracted from the leaves of Duguetia stelechantha, in microemulsions optimizes the bioavailability of bioactive principles, improving the potential of biological activities, such as the antileishmania action. The major compounds detected in the EO, α-pinene, β-pinene and spathulenol, showed a moderate effect against Leishmania (L.) amazonensis promastigotes, while the ME, with these more bioavailable compounds, was considered active against

Funding sources

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001, PROCAD-AM [88887.472618/2019-00 (CQR)] and FAPEMA (Proc.: INFRA-02263/21).

CRediT authorship contribution statement

Auxiliadora C.C. Barata Lope: Methodology, Validation, Investigation, Formal analysis, Writing – original draft. Marcos B.P. Camara: Methodology, Validation, Investigation. Aldilene S. Lima: Conceptualization, Investigation, Writing – review & editing. Matheus Oliveira do Nascimento: Methodology, Validation, Investigation. Júlia Karla A. M. Xavier: Methodology, Validation, Investigation, Formal analysis, Writing – original draft. Caroline M. de Jesus: Methodology, Validation, Investigation.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (55)

  • J.L. Bezerra et al.

    Avaliação da atividade leishmanicida in vitro de plantas medicinais

    Rev. Bras. De. Farmacogn.

    (2006)
  • A.Á. Brustolin et al.

    In vitro activity of cinnamaldehyde on Leishmania (Leishmania) amazonensis

    Exp. Parasitol.

    (2022)
  • S.L. Ciríaco et al.

    Development of microemulsion of tamsulosin and dutasteride for benign prostatic hyperplasia therapy

    Colloids Surf. B: Biointerfaces

    (2020)
  • E.V.; Costa et al.

    Duguetia pycnastera Sandwith (Annonaceae) Leaf Essential Oil Inhibits HepG2 cell growth in vitro and in vivo

    Molecules

    (2022)
  • Fabrowski, F.J., 2022. Eucalyptus smiîhii R. T. Baker (Myrtaceae) gomo espécie produtora de óleo essencial no sul do...
  • T. Fronza et al.

    Nanoemulsões como Sistemas de Liberação para Fármacos Oftálmicos

    Acta Farm. Bonaer.

    (2004)
  • GBIF.org, 2022. Duguetia stelechantha (Diels) R. E. Fr.....
  • M.A. Hellmann et al.

    Leishmaniose e plantas medicinais: uma revisão

    Arq. De. Ciências Da Saúde Da UNIPAR

    (2018)
  • A.J. Jesus et al.

    Leishmanicidal activity and ultrastructural changes of maslinic acid isolated from Hyptidendron canum

    Evid. Based Complement. Altern. Med.

    (2021)
  • P. Kumar et al.

    Análise de Viabilidade Celular pelo Ensaio MTT

    Cold Spring Harb. Protoc.

    (2018)
  • Leite, M.F. , 2009. Desenvolvimento e caracterização de microemulsões contendo extrato e óleo essencial de Baccharis...
  • Lias, S.G., Mikaia, A.I., Sparkman, O.D., Stein, S.E., & Zaikin, G. , 2022, December 3. The NIST/EPA/NIH Mass Spectral...
  • A. Lima et al.

    Use of encapsulated carvacrol with yeast cell walls to control resistant strains of Rhipicephalus microplus (Acari: Ixodidae

    Ind. Crops Prod.

    (2017)
  • A.S. Lima et al.

    Anthelmintic evaluation and essential oils composition of Hyptis dilatata Benth. and Mesosphaerum suaveolens Kuntze from the Brazilian Amazon

    Acta Trop.

    (2022)
  • B.S.S. Lima et al.

    Study of the differentially abundant proteins among Leishmania amazonensis, L. braziliensis, and L. infantum

    PLoS One

    (2020)
  • Lobão, A.Q., & Bazante, M.L. , 2023. Duguetia in Flora e Funga do Brasil....
  • Lyra, L.P.S., 2019. Desenvolvimento de Nanoemulsão de geraniol e óleo essencial da palmarosa (Cymbopogon martinii) e...
  • 1

    ORCID: 0000-0002-3578-1869.

    View full text