Acute oral toxicity in BALB/c mice of Tridax procumbens and Allium sativum extracts and (3S)-16,17-didehydrofalcarinol.

ETHNOPHARMACOLOGICAL RELEVANCE: Approximately 80% of people in developing countries depend on medicinal plants for their health care. Tridax procumbens (T. procumbens) and Allium sativum (A. sativum) have beneficial effects against parasitic and bacterial diseases. On the other side, the biological activity of the oxylipin (3S)-16,17-didehydrofalcarinol isolated from T. procumbens against the parasite Leishmania mexicana has been verified. AIM OF THE STUDY: To evaluate the acute oral toxicity of the methanolic extract of T. procumbens, the aqueous extract of A. sativum, their mixture, and pure oxylipin (3S)-16,17-didehydrofalcarinol in BALB/c mice. MATERIALS AND METHODS: Doses of 2000 and 5000 mg/kg of the methanolic extract of T. procumbens, the aqueous extract of A. sativum, and their mixture (1:1), and doses of 300 and 500 mg/kg of pure oxylipin were administered orally to female mice of the strain BALB/c, which were observed for 72 h in search of signs of toxicity. After 14 days, the animals were euthanized, blood was extracted for the measurement of transaminases, and the livers were recovered and stained with hematoxylin/eosin for histopathological analysis. RESULTS: No clinical signs of toxicity were observed in any of the animals dosed with T. procumbens and A. sativum extracts, while the majority of the animals dosed with pure oxylipin showed signs of toxicity and died. There was no difference in the weight index in most of the animals, except for the animals treated with T. procumbens at doses of 2000 mg/kg who presented an increase in the weight index, nor was there a correlation between the dose of A. sativum and the mixture and food consumption; however, a direct proportional correlation was observed between T. procumbens dose and food consumption. In none of the animals dosed with T. procumbens, A. sativum, and the mixture there was a difference in the levels of transaminases. In the histopathology study, slight lesions were observed in the hepatocytes of the mice treated with T. procumbens, A. sativum, and their mixture at doses of 2000 and 5000 mg/kg. On the other side, moderate injuries were observed in animals treated with pure oxylipin and it was considered as toxic due to almost all the animals died. CONCLUSION: The extracts of T. procumbens and A. sativum evaluated and applied orally did not cause signs of acute toxicity or severe liver damage, suggesting to evaluate their chronic toxicity including other biochemical parameters in the future. However, pure oxylipin caused signs of acute toxicity and death so it is recommended to work with lower doses.

Lupane Triterpene Derivatives Improve Antiproliferative Effect on Leukemia Cells through Apoptosis Induction.

Leukemia is one of the most frequent types of cancer. No effective treatment currently exists, driving a search for new compounds. Simple structural modifications were made to novel triterpenes isolated from Phoradendron wattii. Of the three resulting derivatives, 3α-methoxy-24-hydroxylup-20(29)-en-28-oic acid (T1m) caused a decrease in the median inhibitory concentration (IC50) on the K562 cell line. Its mode of action was apparently apoptosis, ROS generation, and loss of mitochondrial membrane potential (MMP). Molecular docking analysis showed T1m to produce lower binding energies than its precursor for the Bcl-2 and EGFR proteins. Small, simple, and viable modifications to triterpenes can improve their activity against leukemia cell lines. T1m is a potentially promising element for future research. Clarifying the targets in its mode of action will improve its applicability.

Secundiflorol G isolated from Aeschynomene fascicularis, a Mayan medicinal plant, induces apoptosis in cervical cancer cells.

Secundiflorol G (SG) is an isoflavan isolated from the root bark of Aeschynomene fascicularis, a Mayan medicinal plant used to treat cancer-like symptoms. SG has been shown to have cytotoxic effects on cervical cancer cells (HeLa). Assays were done to identify the mechanisms of SG's cytotoxic effect.HeLa cells treated with SG exhibited early and late apoptosis, and caspase-9, -8 and -3 activities. It also induces generation of reactive oxygen species and disrupted mitochondrial membrane potential.SG isolated from A. fascicularis induces apoptosis through extrinsic and intrinsic pathways on HeLa cells. SG could be a candidate for in vivo studies and a promising natural compound in cervical cancer treatment.

Quantitative seasonal variation of the falcarinol-type polyacetylene (3S)-16,17-didehydrofalcarinol and its spatial tissue distribution in Tridax procumbens.

INTRODUCTION: (3S)-16,17-Didehydrofalcarinol (1) has been isolated from Tridax procumbens and has proved to have notorious bioactivity against Leishmania mexicana. In this study, hexane fractions obtained from the methanol extract of each plant part (roots, stems, leaves, flowers, and fruits) of T. procumbens collected monthly during a year were analysed in order to determine the quantity of 1 associated with biotic variables. OBJECTIVE: The aim of this study was to find the season of the year in which the bioactive metabolite 1 is at the highest concentration and to correlate it with temperature, length of day light, and rainfall. METHODS: Hexane fractions were obtained by liquid-liquid extraction and an accurate quantitation of 1 was performed using gas chromatography with a flame ionisation detector (GC-FID) employing pelargonic acid vanillyl amide (2) as internal standard. Partial validation was based on linearity and precision. RESULTS: Our results indicated that the total content of 1 has significant variation (P ≤ 0.05) during the different collecting months. The total content of the metabolite reached its highest level in the roots of the plant during June in the rainfall season (0.0358 ± 0.001 mg/g), and its lowest values in February and March during the drought season (0.0015 ± 0.000 and 0.0008 ± 0.000 mg/g, respectively). CONCLUSION: Our study provided evidence that the content of 1 in roots is strongly influenced by the variables of the harvesting season, also indicating that the biosynthesis of the active metabolite is enhanced during the warm and rainy months.

Neuroprotective effect of Mayan medicinal plant extracts against glutamate-induced toxicity.

Neurological disorders are a public health problem worldwide for which there is currently no direct treatment of the cause of the disorder. The goal of this study was to investigate the potential in vitro neuroprotective property of plants used in Mayan traditional medicine. Plant ethanolic extracts were prepared and tested on models in which neuronal damage was induced by glutamate, i.e., a human neuroblastoma cell line (SH-SY5Y) and rat cortical neurons. HPLC profiles from active extracts were also obtained. A total of 51 plant species were identified in the literature as plant species used in Mayan traditional medicine for the treatment of symptoms suggestive of neurological disorders, and we studied 34 of these in our analysis. Six extracts had a neuroprotective effect on SH-SY5Y cells, with the most active extract being that from Schwenckia americana roots (half maximal effective concentration [EC50] 11.3 ± 2.9 µg/mL), and three extracts exhibited a neuroprotective effect in the rat neuron cortical model, with the most active extract being that from Elytraria imbricata aerial parts (EC50 6.8 ± 3.1 µg/mL). These results suggest that the active extracts from such plants have the potential to be a great resource. Future studies should be performed that are more extensive and which isolate the active constituents.

Lupane-Type Triterpenes of Phoradendron vernicosum.

Three new lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (1), 3α,23-dihydroxy-30-oxolup-20(29)-en-28-oic acid (2), and 3α,23-O-isopropylidenyl-3α,23-dihydroxylup-20(29)-en-28-oic acid (3), together with eight known compounds (4-11) were isolated from a methanol extract of Phoradendron vernicosum aerial parts. The chemical structures of 1-3 were determined on the basis of spectroscopic data interpretation. The isolated compounds were tested against seven human cancer cell lines and two normal cell lines.

Bio-guided Isolation of a New Sesterterpene from Serjania goniocarpa.

Serjania goniocarpa is a plant used in Mayan traditional medicine as a remedy for the treatment of cancer-like symptoms. Bio-guided fractionation of the methanol extract of the leaves led to the isolation of an α- and ß-amyrin mixture, palmitic acid, phytol and the new sesterterpene goniocarpic acid whose structure was elucidated by IR, GC-MS, and NMR spectroscopic analyses. Goniocarpic acid exhibited cytotoxic and antiproliferative activity against several cancer cell lines.

Isolation and Identification of Cytotoxic Compounds from Aeschynomene fascicularis, a Mayan Medicinal Plant.

The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a crude extract. The methanol extract was partitioned successively with solvents with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic fraction. These fractions were tested for their cytotoxic activities using an MTT assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4). Their structures were identified based on spectroscopic evidence and chemical properties. All compounds were subjected to cytotoxicity and antiproliferative assays against a panel of seven cell lines, including one normal-type cell line. Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and antiproliferative activity against the KB cell line. Secundiflorol G (4) showed strong cytotoxic activity towards KB and Hep-2 cell lines. In addition, isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The active Compounds 2, 3 and 4 are potential therapeutic entities against cancer.

Pterocarpans from the root bark of Aeschynomene fascicularis.

A new pterocarpan, aeschynocarpin (1), and the known pterocarpan 2-methoxymedicarpin (2) were isolated for the first time from Aeschynomene fascicularis (Fabaceae) and their structures elucidated by means of spectroscopic {UV/Vis, IR, and NMR (1H, 13C, COSY, HMQC,and HMBC)} andmass spectrometric (EI-MS and HRCIMS) techniques. Both compounds were tested in vitro for their cytotoxic and antiproliferative activities against a panel of cancer cell lines. This is the first report on the presence of pterocarpans in the genus Aeschynomene.

Isolation of a p-hydroxyphenyl anhydride from the leaves of Diphysa carthagenensisw.

Diphysidione (1), a new p-hydroxyphenyl anhydride, and vitexin (2) were isolated from the leaves of Diphysa carthagenensis. The structure of the new metabolite was characterised as 4-(4-hydroxy-phenyl)-3H-pyran-2,6-dione using 1D and 2D NMR spectroscopy.

Screening of plants used in Mayan traditional medicine to treat cancer-like symptoms.

AIM OF THE STUDY: To investigate the potential of plants used in Mayan traditional medicine to treat cancer-like symptoms using the Mayan ethnobotany literature, and evaluate their organic extracts for in vitro cytotoxic activity on cancer cell lines. MATERIALS AND METHODS: The selection of the plants studied in this investigation was based on the Mayan ethnobotanical information provided by different literature sources. Extracts were obtained by maceration with methanol for 72 h of each plant part used and evaporated in vacuo to give the corresponding dried extract. Each methanol extract was tested for its cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay performed in 96-well tissue plates on seven cancer cell lines, lung carcinoma (A549), cervix adenocarcinoma (HeLa), laryngeal carcinoma (Hep-2), nasopharynx carcinoma (KB), breast adenocarcinoma (MCF-7), prostate adenocarcinoma (PC-3), and cervix squamous carcinoma cells (SiHa), as well as normal human embryonic kidney cell line (HEK-293). Cell proliferation/viability was spectrophotometrically assessed at 540 nm after addition of MTT. RESULTS: 51 plants were found in the literature to be used for the treatment of symptoms suggestive of cancer, 21 were chosen to evaluate the cytotoxic activity. Aeschynomene fascicularis root bark extract showed a pronounced cytotoxic activity on Hela and KB cell lines and Bonellia macrocarpa stem and root bark extracts showed similar prominent activities on KB cells. CONCLUSION: 21 plants were selected according to their use in the treatment of cancer-like symptoms recorded in the ethnobotanical literature. Plant extracts prepared from Aeschynomene fascicularis root bark and Bonellia macrocarpa stem and root bark have been selected for extensive studies leading to the isolation of the active constituents.

The leishmanicidal effect of (3S)-16,17-didehydrofalcarinol, an oxylipin isolated from Tridax procumbens, is independent of NO production.

The in vitro leishmanicidal effect of (3S)-16,17-didehydrofalcarinol (1) isolated from Tridax procumbens whole plant against Leishmania mexicana, the causative agent of cutaneous leishmaniasis (chiclero's ulcer) in the New World, was investigated. This oxylipin showed significant in vitro activity against promastigotes and intracellular amastigotes of L. mexicana. Its inhibitory effect on amastigotes was not due to activation of NO in recombinant gamma-interferon-stimulated macrophages, since the production of NO was decreased in presence of the oxylipin. This is the first report on the leishmanicidal activity against the intracellular stage (amastigote) of the oxylipin (3S)-16,17-didehydrofalcarinol.

In vitro activity of Tridax procumbens against promastigotes of Leishmania mexicana.

ETHNOPHARMACOLOGICAL RELEVANCE: Tridax procumbens is an active herb against leishmaniasis. AIM OF THE STUDY: Leishmaniasis is a group of diseases caused by Leishmania protozoa. We investigated the antileishmanial activity of Tridax procumbens extracts and a pure compound against promastigotes of Leishmania mexicana, the causative agent of cutaneous leishmaniasis in the New World. MATERIALS AND METHODS: Extracts and (3S)-16,17-didehydrofalcarinol (1) were obtained by chromatographic methods from Tridax procumbens, and the latter identified by spectroscopic analysis. The effect of these extracts and 1 on the growth inhibition of promastigotes of Leishmania mexicana was evaluated. In order to test the safety of extracts and 1, mammalian cells were treated with them, and cell viability was assessed using trypan blue and MTT. RESULTS: We demonstrated that extracts of Tridax procumbens and 1 showed a pronounced activity against Leishmania mexicana. The methanol extract inhibited promastigotes growth of Leishmania mexicana with a 50% inhibitory concentration (IC(50)) of 3 microg/ml, while oxylipin 1 exhibited the highest inhibition at IC(50)=0.478 microg/ml. CONCLUSIONS: In this study we report the biological activity of extracts and (3S)-16,17-didehydrofalcarinol (1), obtained from Tridax procumbens, on the promastigote form of Leishmania mexicana, with no effect upon mammalian cells.