Chemical Composition and In Vitro and In Silico Antileishmanial Evaluation of the Essential Oil from Croton linearis Jacq. Stems.

Croton linearis Jacq. is an aromatic shrub that has been utilized in traditional medicine in the Bahamas, Jamaica, and Cuba. Recent studies have revealed the antiprotozoal potential of its leaves. The present work is aimed to identify the volatile constituents of essential oil from the stems of C. linearis (CLS-EO) and evaluate its in vitro antileishmanial activity. In addition, an in silico study of the molecular interactions was performed using molecular docking. A gas chromatographic-mass spectrometric analysis of CLS-EO identified 1,8-cineole (27.8%), α-pinene (11.1%), cis-sabinene (8.1%), p-cymene (5.7%), α-terpineol (4.4%), epi-γ-eudesmol (4.2%), linalool (3.9%), and terpinen-4-ol (2.6%) as major constituents. The evaluation of antileishmanial activity showed that CLS-EO has good activity on both parasite forms (IC50Promastigote = 21.4 ± 0.1 µg/mL; IC50Amastigote = 18.9 ± 0.3 µg/mL), with a CC50 of 49.0 ± 5.0 µg/mL on peritoneal macrophages from BALB/c mice (selectivity index = 2 and 3 using the promastigote and amastigote results). Molecular docking showed good binding of epi-γ-eudesmol with different target enzymes of Leishmania. This study is the first report of the chemical composition and anti-Leishmania evaluation of CLS-EO. These findings provide support for further studies of the antileishmanial effect of this product.

Antiplasmodial activity of alkaloids from Croton linearis leaves.

Croton linearis is a shrub that grows in Caribbean regions, which is rich in metabolites such as alkaloids. The main aim of this study was to evaluate the antiplasmodial effect of alkaloids from this species. Three isoquinoline alkaloids, i.e. reticuline (1), laudanidine (2) and 8,14-dihydrosalutaridine (3), were isolated from the leaves of C. linearis by flash chromatography and semi-preparative HPLC-DAD-MS. Their structures were elucidated by spectroscopic techniques. Antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and cytotoxicity against MRC-5 cells (human fetal lung fibroblast cells) were assessed in vitro. Reticuline, laudanidine and 8,14-dihydrosalutaridine showed moderate antiplasmodial activity with IC50 values of 46.8 ± 0.6, 17.7 ± 0.6 and 16.0 ± 0.5 µM, respectively, but no cytotoxicity was observed in a concentration up to 64.0 µM. This is the first report on the antiplasmodial activity of laudanidine and 8,14-dihydrosalutaridine.

Novel flavonol-3-O-methylethers from Zanthoxylum pistaciifolium Griseb. (Rutaceae).

Zanthoxylum pistaciifolium Griseb. is a tree endemic to Cuba, occasionally used in herbal medicine. Previously, the antitrypanosomal activity of a n-hexane-2-butanone extract of Z. pistaciifolium leaves and of its constituent skimmianine were published. In the current study a more thorough examination of the respective extract is performed, which led to the isolation and identification of three flavonoids, more specifically, the flavonol-3-O-methylethers kaempferol-3-O-methylether (1) and novel compounds kaempferol-3-O-methylether-5-O-ß-D-glucoside (2) and kaempferol-8-hydroxy-3,7-O-dimethylether-5-O-ß-D-glucoside (3). All compounds were screened for their antimicrobial and antiprotozoal activity and cytotoxicity towards MRC-5 SV2 cells. Compound 1 showed a moderate to weak activity against Trypanosoma cruzi (IC50 30.8 µM), T. brucei (IC50 15.4 µM) and Plasmodium falciparum (IC50 53.8 µM), but also showed cytotoxicity (CC50 19.0 µM). Compounds 2 and 3 did not display activity in any of the assays (IC50 and CC50 > 64 µM).[Formula: see text].

Antimicrobial activity of leaf extracts and isolated constituents of Croton linearis.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Croton linearis, known as "rosemary", are widely used in folk medicine in Caribbean countries to treat fever and colds (associated to infections). AIM OF THE STUDY: To evaluate the in vitro antimicrobial activity of extracts and fractions derived from C. linearis leaves. MATERIALS AND METHODS: Bioassay-guided fractionation and isolation of compounds from an ethanolic extract of C. linearis, using flash chromatography and semi-preparative HPLC-DAD-MS (High Performance Liquid Chromatography - Diode Array Detection - Mass Spectrometry). Isolated compounds were characterized by MS, 1D- and 2D-NMR (Nuclear Magnetic Resonance) spectroscopy. The microdilution method with resazurin, as well as direct counting with an optical microscope, were used to determine the in vitro antimicrobial activity against bacteria, fungi and parasites. Moreover, the cytotoxicity on human fetal lung fibroblasts (MRC-5) was evaluated. RESULTS: The total extract and chloroform fraction (ClF) showed high activity against protozoa with IC50 values ranging from 1 to 26 µg/mL, but also cytotoxicity on MRC-5 and PMM (Peritoneal Murine Macrophages). Seven compounds were isolated and characterized for first time in this species: the alkaloids laudanidine, laudanosine, reticuline, corydine, glaucine and cularine and the flavonoid glycoside isorhamnetin-3-O-(6″O-p-trans-coumaroyl)-ß-glucopyranoside. Reticuline showed a weak activity against L. infantum (IC50 148.0 ±â€¯1.2 µM), while the flavonoid was active against T. cruzi (IC50 35.6 ±â€¯2.3 µM). CONCLUSIONS: The results show the antiprotozoal potential of the extract and some isolated constituents, which supports the use of this species in Caribbean folk medicine.

An ethnobotanical survey of medicinal plants used by inhabitants of Holguín, Eastern Region, Cuba / Estudio etnobotánico de las plantas medicinales usadas por los habitantes de Holguín, Región Oriental, Cuba

The present study was aimed to archive the etnhnomedicinal knowledge of plants used by inhabitants of seven villages of Holguín, Eastern region, Cuba. The ethnomedicinal information was collected through interviews. The collected data were analyzed through use value (UV), informant consensus factor (Fic) and fidelity level (FL). A total of 195 species of plants distributed in 166 genera belonging to 70 families were identified for the treatment of 17 ailment categories. The most treated conditions were digestive and liver disorders. The most important species according to their use value were Lippia alba (Mill.) N.E. Br. ex Britton & P. Wilson (0.236) and Annona muricata L. (0.194). Cancer and tumors had the Fic value of 0.94. A total of 19 species has a highest FL of 100 percent. This was the first ethnobotanical survey conducted in Holguín region, which will contribute to preserve valuable information of medicinal plants that may otherwise be lost to future generations.

El presente estudio tuvo como objetivo registrar el conocimiento etnomedicinal de las plantas usadas por los pobladores en 7 comunidades de Holguín, Región Oriental, Cuba. La información fue recogida a través de entrevistas y analizada cuantitativamente mediante indicadores etnobotánicos: valor de uso (UV), factor del consenso de los informantes (Fic) e índice de fidelidad (FL). Fueron reportadas un total de 195 especies de plantas, distribuidas en 166 géneros y 70 familias, para el tratamiento de 17 categorías de usos. Las indicaciones más frecuentes fueron los problemas digestivos y del hígado. Las especies medicinales con mayor UV fueron Lippia alba (Mill.) N.E. Br. ex Britton & P. Wilson (0.236) y Annona muricata L. (0.194). Cáncer y tumores tuvieron el valor más alto de Fic (0.94). Solo 19 especies presentaron un valor de FL de 100 %. Este primer estudio contribuirá a preservar la información de las plantas medicinales y que esta no se pierda en las futuras generaciones.