In Vitro antileishmania activity of sesquiterpene-rich essential oils from Nectandra species

Abstract

Context: New antileishmanias are needed because of toxicity, high cost and resistance problems associated with available drugs. Nectandra (Lauraceae) produces several classes of compounds but its essential oil has not previously been reported to have antileishmania activity.Objective: We evaluated the cytotoxicity and antileishmania activity of essential oils from Nectandra amazonum Nees, N. gardneri Meisn., N. hihua (Ruiz & Pav.) Rohwer and N. megapotamica (Spreng.) Mez.Materials and methods:Nectandra oils were extracted from stem bark/leaves by hydrodistillation and compounds were identified by GC-MS. Oils were tested against Leishmania infantum and L. amazonensis intracellular amastigotes and nitric oxide production was evaluated. Cytotoxicity was achieved on NIH/3T3 and J774.A1 cells for the selectivity index (SI).Results and discussion:Nectandra gardneri was active against L. infantum and L. amazonensis (IC50 = 2.7 ± 1.3/2.1 ± 1.06 μg/mL) and contained 85.4% sesquiterpenes, of which 58.2% was intermediol. Besides low cytotoxicity (SI >11.3), N. gardneri induced a significant increase in NO production by L. infantum-infected macrophages. Nectandra hihua had the best activity on L. infantum amastigotes (IC50 = 0.2 ± 1.1 μg/mL). This oil was 89.0% sesquiterpenes, with 28.1% bicyclogermacrene. The two specimens of N. megapotamica had different activities on amastigotes. The one richer in sesquiterpenes (49.9%) was active against both species (IC50 = 12.5 ± 1.4/21.3 ± 1.2) and had phenylpropanoid E-asarone as the main compound (42.4%). Nectandra amazonum showed moderate activity on both the species (IC50 = 31.9 ± 2.0/22.1 ± 1.3 μg/mL) and low selectivity (0.9 < SI >2.6), probably due to the major presence of β-caryophyllene (28.5%).Conclusions: Our data identify compounds that can now be isolated and used for the development of new antileishmanias.

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

“…Mahanine inhibits JAK1 and Src which subsequently promotes the degradation of STAT3, an important transcription factor in macrophages that causes upregulation of IL-10 expression and suppression of Th1 responses ( Biswas et al, 2011 ; Lee et al, 2011 ; Das et al, 2014 ). While mahanine possesses its own unique immunomodulatory effects, several other natural compounds stimulate ROS and NO production in vitro including but not limited to, lupeol from Sterculia villosa , dehydroabietic acid from Pinus elliottii , and oil extracts from Nectandra species ( da Costa-Silva et al, 2015 ; Bosquiroli et al, 2017 ; Das et al, 2017 ; Goncalves et al, 2018 ). For example, Punica granatum , commonly known as pomegranate, has been shown to have antiparasitic and antioxidant properties ( Kaur et al, 2006 ).…”

Chemical Diversity and Biological Activities of Essential Oils from Licaria, Nectrandra and Ocotea Species (Lauraceae) with Occurrence in Brazilian Biomes

“…The EO of Nectandra amazonum Nees collected in Cáceres (MS, Brazil) showed high amounts of sesquiterpene hydrocarbons (68.4%) with β-caryophyllene (28.5%) and germacrene D (14.8%) the most representative [ 28 ]. The content of sesquiterpene hydrocarbons in the EO of N. barbellata Coe-Teixeira was 37.64%, and δ-cadiene (11.42%) and β-caryophyllene (9.79%) were the major compounds [ 3 ].…”

“…collected in Maracaju (MS, Brazil), displayed an oil dominated by bicyclogermacrene (28.1%), germacrene D (13.8%) and β-caryophyllene (9.0%). The total amount of sesquiterpene hydrocarbons was of 68.0% [ 28 ]. Sesquiterpene hydrocarbons displayed contents of 64.6% and 79.6% in specimens of N. lanceolata collected in Novo Mundo (MS, Brasil) and Barracão (RS, Brasil), respectively.…”

“…The main compounds in the oil of specimens collected from a wet site were elemicin (41.7%), ( E )-asarone (19.7%), and α-pinene (8.5%) (profile I). However, the plant collected in a dry site showed ( E )-asarone (42.4%), α-cadinol (14.4%), and τ-cadinol (8.1%) (profile II) as the main constituents [ 28 ].…”

“…In contrast, the stem bark of N. megapotamica (sample 2) was dominated by ( E )-asarone (42.40%), α-cadinol (14.40%) and δ-cadinene (5.80%). Fibroblast cells lines NIH/3T3 indicated IC 50 252.60 µg/mL, and J774A.1 sarcoma cells showed IC 50 415.60 µg/mL [ 28 ].…”