Eugenia piauhiensis Vellaff. essential oil and γ-elemene its major constituent exhibit antileishmanial activity, promoting cell membrane damage and in vitro immunomodulation

• Published in: Chemico-biological interactions Vol. 339; p. 109429
• Main Authors: Nunes, Thaís Amanda de Lima, Costa, Lellis Henrique, De Sousa, Julyanne Maria Saraiva, De Souza, Vanessa Maria Rodrigues, Rodrigues, Raiza Raianne Luz, Val, Maria da Conceição Albuquerque, Pereira, Anna Carolina Toledo da Cunha, Ferreira, Gustavo Portela, Da Silva, Marcos Vinícius, Da Costa, João Marcos Antônio Rodrigues, Véras, Leiz Maria Costa, Diniz, Roseane Costa, Rodrigues, Klinger Antonio da Franca
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 25.04.2021
• Subjects: Animals; Antileishmanial activity; Antiprotozoal Agents - pharmacology; Cell Line; Cell Membrane - drug effects; Eugenia - chemistry; Eugenia piauhiensis; Immunomodulation - drug effects; Leishmania amazonensis; Leishmania mexicana - drug effects; Leishmaniasis - drug therapy; Leishmaniasis - parasitology; Macrophages - parasitology; Mice; Oils, Volatile - pharmacology; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - pharmacology; Sesquiterpenes - pharmacology; γ-Elemene; PBS; NO; IL; γ-Elemene; CL; Eugenia piauhiensis; H2DCFDA; MTT; TNF; EpEO; FBS; VL; ROS; Antileishmanial activity; Leishmania amazonensis; ML
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2021.109429

Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. The search for new therapeutic agents from natural sources has been a constant for the treatment of diseases such as leishmaniasis. The objective of this study was to evaluate the biological activity of Eugenia piauhiensis Vellaff. essential oil (EpEO) and its major constituent γ-elemene on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis, its cytotoxicity, and possible mechanisms of action. EpEO was more active (IC50 6.43 ± 0.18 μg/mL) against promastigotes than γ-elemene [9.82 ± 0.15 μg/mL (48.05 ± 0.73 μM)] and the reference drug miltefosine [IC50 17.25 ± 0.26 μg/mL (42.32 ± 0.64 μM)]. EpEO and γ-elemene exhibited low cytotoxicity against J774.A1 macrophages, with CC50 225.8 ± 3.57 μg/mL and 213.21 ± 3.3 μg/mL (1043 ± 16.15 μM), respectively. Additionally, EpEO and γ-elemene present direct activity against the parasite, decreasing plasma membrane integrity. EpEO and γ-elemene also proved to be even more active against intracellular amastigotes of the parasite [IC50 4.59 ± 0.07 μg/mL and 8.06 ± 0.12 μg/mL (39.44 ± 0.59 μM)], respectively), presenting indirect effects through macrophage activity modulation. Anti-amastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels. In conclusion, our results suggest EpEO and γ-elemene as promising candidates for new drug development against leishmaniasis. •EpEO and γ-elemene showed antileishmanial activity in vitro to L. amazonensis.•EpEO and γ-elemene exhibited selectivity indexes (SI) greater than reference drugs.•EpEO and γ-elemene decreased plasma membrane integrity. .•EpEO and γ-elemene reduced the infection index of macrophages by L. amazonensis.•EpEO and γ-elemene stimulated TNF-α, IL-12, ROS and NO production in macrophages infected.