Immunomodulatory, Trypanocide, and Antioxidant Properties of Essential Oil Fractions of Lippia Alba (Verbenaceae)

Abstract

Background: Parasite persistence, exacerbated and sustained immune response, and continuous oxidative stress have been described to contribute to the development of the cardiac manifestations in chronic Chagas disease. Nevertheless, there are no efficient therapies to resolve the Trypanosoma cruzi infection and prevent the disease progression. Interestingly, trypanocide, antioxidant, and immunodulatory properties have been reported separately for some major terpenes (citral, limonene, and caryophyllene oxide) presents in essential oils extracted from two chemotypes (Citral and Carvone) of Lippia alba. The aim of this study was to obtain L. alba essential oil fractions enriched with the aforementioned bioactive terpenes and to evaluate the impact of these therapies on trypanocide, oxidative stress, mitochondrial bioenergetics, genotoxicity, and inflammatory markers on T. cruzi-infected macrophages.Methods: T. cruzi-infected J774A.1 macrophage were treated with limonene-enriched (ACT1) and citral/caryophyllene oxide-enriched (ACT2) essential oil fractions derived from Carvone and Citral-L. alba chemotypes, respectively.Results: ACT1 and ACT2 exhibit similar trypanocidal effects to Benznidazole (BZN), against amastigotes. Synergistic antiparasitic activity was observed when ACT1 was combined with BZN or ACT2. This compound also decreased the oxidative stress, mitochondrial metabolism, and genotoxicity of the therapies. The experimental treatments (ACT1+ACT2 and ACT1+BZN) reduced the pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α), while increased the anti-inflammatories (IL-4 and IL-10).Conclusion: Due to its highly trypanocidal and immunomodulatory properties, ACT1 (whether alone or in combination with BZN or ACT2) represents a promising compound for further studies in drug development towards the Chagas disease control.

Essential Oils from Different Myrtaceae Species from Brazilian Atlantic Forest Biome – Chemical Dereplication and Evaluation of Antitrypanosomal Activity

“…It is known that improvements in the trypanocidal activity can be achieved with the association between different compounds. The association between caryophyllene oxide and/or citral, limonene and benznidazole improved the trypanocidal activity, suggesting a possible synergistic interaction [26,27] . The synergistic effect between caryophyllene oxide and limonene in the trypanocidal activity was also described by Moreno and collaborators (2018) [27] …”

“…The association between caryophyllene oxide and/or citral, limonene and benznidazole improved the trypanocidal activity, suggesting a possible synergistic interaction. [26,27] The synergistic effect between caryophyllene oxide and limonene in the trypanocidal activity was also described by Moreno and collaborators (2018). [27] (E)-caryophyllene was one of the major compounds in the species considered promising active, corroborating with previous anti-T. cruzi activitites studies involving (E)-caryophyllene rich EOs such as Cordia verbenaceae (18.77 %), Eugenia brejoensis (9.77 %), Hyptis pectinata (30.91 %), Annona pickelii (27.8 %), Protium ovatum (14 %), and Vernonia brasiliana (10.4 %).…”

“…[26,27] The synergistic effect between caryophyllene oxide and limonene in the trypanocidal activity was also described by Moreno and collaborators (2018). [27] (E)-caryophyllene was one of the major compounds in the species considered promising active, corroborating with previous anti-T. cruzi activitites studies involving (E)-caryophyllene rich EOs such as Cordia verbenaceae (18.77 %), Eugenia brejoensis (9.77 %), Hyptis pectinata (30.91 %), Annona pickelii (27.8 %), Protium ovatum (14 %), and Vernonia brasiliana (10.4 %). [21][22][23][24][25] Although (E)-caryophyllene is pointed out as being one the most important compounds responsible for the observed biological activity, its presence does not guarantee a good anti-parasitic activity.…”

“…It is interesting to observe that among the identified compounds in E. florida EOs, a significant trypanocidal activity can be attributed to the presence of α‐pinene and ( E )‐caryophyllene, since both compounds displayed anti‐ T. cruzi activity in previous studies [17,21–25] . There are also reports of improved anti‐ T. cruzi activity achieved by the combination of limonene and caryophyllene oxide [26,27] …”

“…[17,[21][22][23][24][25] There are also reports of improved anti-T. cruzi activity achieved by the combination of limonene and caryophyllene oxide. [26,27] For C. brasilienses, the second most promising species against T. cruzi, there are no previous reports describing the chemical composition of its essential oil, while for E. acutata the only published report concerning its EO chemical composition points out βcaryophyllene as the main compound. [28] Previous studies on C. xantocarpa EOs also reported the occurrence of β-caryophyllene as the main compound, besides ledol.…”