Ramón Scull

Activity of the essential oil from Chenopodium ambrosioides grown in Cuba against Leishmania amazonensis.

Background and Methods: Current therapy against leishmaniasis is unsatisfactory. Efficacious and safe new drugs are needed.In this study, we show the leishmanicidal effect of an essential oil from Chenopodiumambrosioides against Leishmania amazonensis. Results: The tested product had a potent inhibitory action against promastigote and amastigote forms, with 50% effective dose values of 3.7 and 4.6 µg/ml, respectively. The essential oil showed a moderate toxicity on macrophages from BALB/c mice. An optimal dose of 30 mg/kg/day was effective when administered during 15 days by intraperitoneal route to BALB/c mice infected experimentally. Conclusion: These studies revealed a potential source for the discovery of novel drugs to combat the leishmaniasis based on the traditional medicine.

Essential oil from Chenopodium ambrosioides and main components: activity against Leishmania, their mitochondria and other microorganisms.

Chenopodium ambrosioides is an aromatic herb used by native people to treat parasitic diseases. The aim of this work is to compare the in vitro anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide) and study their mechanism of action and activity against a panel of microorganism. Antileishmanial activity and cytotoxicity of the EO and major components was study. In addition, experiments to elucidate the mechanism of action were perform and activities against other microorganisms (bacteria, fungi and protozoa) were evaluate. All products were active against promastigote and amastigote forms of Leishmania. Ascaridole exhibited the better antileishmanial activity and the EO the highest selectivity index. The exploration of the mechanism suggests that the products cause a breakdown of mitochondrial membrane potential and a modification of redox indexes. Only EO showed antiprotozoal effect against Plasmodium falciparum and Trypanosoma brucei; while no activity against bacteria and fungi was observed. Our results demonstrate the potentialities of EO in cellular and molecular system, which could be consider in future studies to develop new antileishmanial drugs with a wide anti-parasitic spectrum.

Chemistry, cytotoxicity and antileishmanial activity of the essential oil from Piper auritum

Leishmaniasis is one of the most important parasitic infections, but current treatments are unsatisfactory due to their toxicity, cost and resistance. Therefore, the development of new antileishmanial compounds is imperative. Many people who live in endemic areas use plants as an alternative to treat the disease. In this paper, we characterised the essential oil from Piper auritum, evaluated its cytotoxicity and determined its antileishmanial activity. The chromatogram obtained by gas chromatography revealed 60 peaks and we found that safrole was the most abundant compound, composing 87% of the oil. The oil was active against the promastigotes of Leishmania major, Leishmania mexicana, Leishmania braziliensis and Leishmania donovani with a favourable selectivity index against peritoneal macrophages from BALB/c mice. The Piper-oil inhibited the growing of intracellular amastigotes of L. donovani with an IC50 value of 22.3 +/- 1.8 microg/mL. This study demonstrates the usefulness of the essential oils as a promising alternative to treat leishmaniasis.

Screening of medicinal plants against Leishmania amazonensis.

Context: Leishmaniasis is a widespread tropical infection caused by different species of Leishmania protozoa. There is no immunoprophylaxis (vaccination) available for Leishmania infections and conventional treatments are unsatisfactory; therefore antileishmanial drugs are urgently needed. Natural products are attractive due to their structural diversity. Objective: The present work investigated the antileishmanial action of 21 species of plants. Materials and methods: Plants were collected and their hydroalcoholic extracts were screened against promastigotes and amastigotes of L. amazonensis. Their toxicity was also assayed against peritoneal macrophages from BALB/c mice. Results: Five extracts showed significant growth inhibitory activity against promastigote form. Only the extracts from Bidens pilosa L. (Asteraceae) and Punica granatum L. (Punicaceae) inhibited the growth of intracellular amastigotes, with IC50 values of 42.6 and 69.6 µg/mL, respectively. In addition, a low toxicity on macrophage from BALB/c mice was observed. Discussion: The antiparasitic activities of B. pilosa and P. granatum have been reported against other parasitic agents and their actions can be the results of flavonoids present in the extracts. Conclusion: This study supports the importance of natural products as potential sources in the search for new antileishmanial drugs.

Activity of Cuban Plants Extracts against Leishmania amazonensis

Natural products have long been providing important drug leads for infectious diseases. Leishmaniasis is a major health problem worldwide that affects millions of people especially in the developing nations. There is no immunoprophylaxis (vaccination) available for Leishmania infections, and conventional treatments are unsatisfactory; therefore, antileishmanial drugs are urgently needed. In this work, 48 alcoholic extracts from 46 Cuban plants were evaluated by an in vitro bioassay against Leishmania amazonensis. Furthermore, their toxicity was assayed against murine macrophage. The three most potent extracts against the amastigote stage of Leishmania amazonensis were from Hura crepitans, Bambusa vulgaris, and Simarouba glauca.

Combinations of ascaridole, carvacrol, and caryophyllene oxide against Leishmania

To date there are no vaccines against Leishmania and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs currently used for leishmaniasis therapy are significantly toxic, expensive, and result in a growing frequency of refractory infections. In this study, we evaluated the effect of combinations of the main components of essential oil from Chenopodium ambrosioides (ascaridole, carvacrol, and caryophyllene oxide) against Leishmaniaamazonensis. Anti-leishmanial effects of combinations of pure compounds were evaluated in vitro and the fractional inhibitory concentration (FIC) indices were calculated. BALB/c mice infected with L. amazonensis were treated with different concentrations of ascaridole-carvacrol combinations by intralesional doses every 4 days. Disease progression and parasite burden in infected tissues were determined. In vitro experiments showed a synergistic effect of the combination of ascaridole-carvacrol against promastigotes of Leishmania with a FIC index of 0.171, while indifferent activities were observed for ascaridole-caryophyllene oxide (FIC index=3.613) and carvacrol-caryophyllene oxide (FIC index=2.356) combinations. The fixed ratio method showed that a 1:4 ascaridole-carvacrol ratio produced a better anti-protozoal activity on promastigotes, lower cytotoxicity, and synergistic activity on intracellular amastigotes (FIC index=0.416). Significant differences (p<0.05) in lesion size and parasite burden were demonstrated in BALB/c mice experimentally infected and treated with the ascaridole-carvacrol combinations compared with control animals. Carvacrol showed significant higher anti-radical activity in the DPPH assay compared with caryophyllene oxide. Electron spin resonance spectroscopy in combination with spin trapping suggested the presence of carbon-centered radicals after activation of ascaridole by Fe(2+). The intensity of the signals is preferably decreased upon addition of carvacrol. The ascaridole-carvacrol combination could represent a future alternative to monotherapeutic anti-leishmanial agents.

Antileishmanial activity of essential oil from Chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in BALB/c mice.

UNLABELLED Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases. AIMS OF THE STUDY To compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide). MATERIALS AND METHODS Anti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined. RESULTS EO prevented lesion development compared (p<0.05) with untreated animals and treated with vehicle. In addition, the efficacy of EO was also statistically superior (p<0.05) compared with the glucantime-treated animals. No potential effects were observed with pure components treatment. Mix of pure compounds cause death of animals after 3 days of treatment. CONCLUSIONS Our results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis.

Combined effect of the essential oil from Chenopodium ambrosioides and antileishmanial drugs on promastigotes of Leishmania amazonensis

To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against promastigotes of Leishmania amazonensis. However, an indifferent effect has been found for combinations of meglumine antimoniate or amphotericin B and the essential oil.

Antileishmanial Activity of the Essential Oil from Bixa orellana

Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa. There is currently no vaccine against leishmaniasis, and chemotherapy remains the only effective control. However, conventional drugs are toxic, expensive, and require long periods of treatment, and resistance to clinical chemotherapeutic agents is emerging. Recent research on plants has shown a successful approach to obtain new antileishmanial alternatives. Herein, the in vitro and in vivo effects of the essential oil from Bixa orellana seeds against Leishmania amazonensis were evaluated. A total of 73 compounds were detected by gas chromatography–mass spectrometry analysis, of which ishwarane (18.6%) and geranylgeraniol (9.1%) were the major components. The oil showed activity against intracellular amastigote form (IC50 = 8.5 µg/mL), while the cytotoxic concentration was sevenfold higher for the host cells. The ability of Bixa oil to control disease progression of established cutaneous leishmaniasis in BALB/c mice was demonstrated, after a treatment with 30 mg/kg by intraperitoneal administration over 14 days. The present study reports for the first time the antileishmanial potentialities of the essential oil from B. orellana. Copyright

Antileishmanial assessment of leaf extracts from Pluchea carolinensis, Pluchea odorata and Pluchea rosea

OBJECTIVE To evaluate the antileishmanial activity of different extracts from three Cuban Pluchea species. METHODS In in vitro assays the IC(50) was calculated in the promastigotes and amastigotes forms as cytotoxicity in murine macrophages. In leishmaniasis cutanea experiment, mortality, weight loss, lesion size and burden parasite were measured. RESULTS Extracts evaluated showed inhibitive effect on growing of promastigote form; however, active extracts caused a high toxicity. Ethanol and n-hexane extracts demonstrated specific antileishmanial activity. Ethanol and n-hexane extracts from Pluchea carolinensis (P. carolinensis) caused similar inhibition against amastigote form. The intraperitoneal administration of the ethanol extract of P. carolinensis at 100 mg/kg prevented lesion development compared with control groups. CONCLUSIONS The antileishmanial experiment suggests that ethanol extracts from P. carolinensis is the most promising. Further studies are still needed to evaluate the potential of this plant as a source of new antileishmanial agents.