Antileishmanial and cytotoxic activities of four Andean plant extracts from Colombia.

BACKGROUND AND AIM: Licania salicifolia (L.S) Cuatrec., Persea ferruginea (P.F) Kunth, Oreopanax floribundus (O.F), and Psychotria buchtienii (P.B) belong to the families Chrysobalanaceae, Lauraceae, Araliaceae, and Rubiaceae, respectively, which have been used as medicines by communities in the Andes. This study evaluated the leishmanicidal and cytotoxic activities of alcohol and non-alcohol extracts from four Andean plant extracts (L.S, O.F, P.F, and P.B). MATERIALS AND METHODS: Extracts were obtained by percolation with solvents of different polarities - hexane, dichloromethane, ethyl acetate, and ethanol. Phytochemical screening was conducted based on reported methods. All products were evaluated in vitro to determine the leishmanicidal activity against amastigotes of Leishmania panamensis and cytotoxicity against U937 cells. RESULTS: Flavonoids, triterpenes, and tannins were the main secondary metabolites found. From the results, dichloromethane extracts from O.F and P.B, ethanol extract from P.B, and ethyl acetate extracts of all plants were active, with EC50 <30 µg/mL. Ethyl acetate was the most active extract, which showed EC50 values of 9.8, 14.1, 23.7, and 25.5 µg/mL, for L.S, P.B, O.F, and P.F, respectively. Hexane extracts from P.B and O.F exhibited moderate activity with EC50 values of 84.8 and 87.4 µg/mL, respectively. Hexane and ethanol extracts from O.F, ethyl acetate, and ethanol extracts from L.S, and all extracts from P.F were not toxic. Alternatively, hexane and dichloromethane extracts from L.S and P.B as well as dichloromethane and ethyl acetate extracts from O.F displayed high toxicity. CONCLUSION: Based on the activity we observed, ethyl acetate extract can continue in its usage in the search for new antileishmanial drugs, mainly ethyl acetate extract from L.S showed activity comparable to meglumine antimoniate and was not cytotoxic.

Alkaloids of Amaryllidaceae as Inhibitors of Cholinesterases (AChEs and BChEs): An Integrated Bioguided Study.

INTRODUCTION: Enzymatic inhibition of acetylcholinesterase (AChE) is an essential therapeutic target for the treatment of Alzheimer's disease (AD) and AChE inhibitors are the first-line drugs for it treatment. However, butyrylcholinesterase (BChE), contributes critically to cholinergic dysfunction associated with AD. Thus, the development of novel therapeutics may involve the inhibition of both cholinesterase enzymes. OBJECTIVE: To evaluate, in an integrated bioguided study, cholinesterases alkaloidal inhibitors of Amaryllidaceae species. METHODOLOGY: The proposed method combines high-performance thin-layer chromatography (HPTLC) with data analysis by densitometry, enzymatic bioautography with different AChEs and BChEs, the detection of bioactive molecules through gas chromatography mass spectrometry (GC-MS) analysis of spots of interest, and theoretical in silico studies. RESULTS: To evaluate the bioguided method, the AChE and BChE inhibitory activities of seven Amaryllidaceae plant extracts were evaluated. The alkaloid extracts of Eucharis bonplandii exhibited a high level of inhibitory activity (IC50  = 0.72 ± 0.05 µg/mL) against human recombinant AChE (hAChE). Regarding human serum BChE (hBChE), the bulb and leaf extracts of Crinum jagus had the highest activity (IC50  = 8.51 ± 0.56 µg/mL and 11.04 ± 1.21 µg/mL, respectively). In the HPTLC spots with high inhibitory activity, several alkaloids were detected using GC-MS, and some of these alkaloids were identified. Galanthamine, galanthamine N-oxide and powelline should be the most prominent inhibitors of substrate accommodation in the active site of the Torpedo californica AChE (TcAChE), hAChE and hBChE enzymes. CONCLUSIONS: These results are evidence of the chemical relevance of the Colombian's Amaryllidaceae species for the inhibition of cholinesterases and as potent sources for the palliative treatment of AD. Copyright © 2017 John Wiley & Sons, Ltd.

Neuropharmacological effects of the ethanolic extract of Sida acuta

ABSTRACT Sida acuta Burm. f., Malvaceae, is regarded as astringent, tonic and useful in treating urinary diseases and blood disorders, bile, liver and as treatment for nervous diseases. Different methods were developed: sodium pentobarbital-induced sleeping time, anxiolytic activity, test for muscle-effects, pentylenetetrazole (PTZ)-induced seizures, effect on normal body temperature. All experiments were performed in an isolated room with 12/12 h light/dark cycles at 22 ± 1 ºC. The effects described in this work for Sida acuta are according to what is known in traditional medicine, where is used as sedative agent. At the higher doses used in this work (500 and 1000 mg/kg), the Sida acuta extract reduced the latency time (T1) and increased the sleeping time (T2) induced by pentobarbital, indicating a sedative and hypnotic effect of the plant's extract. The extract of Sida acuta shows an increase in open arm exploration (anxiolytic activity). Results obtained in the rota-rod test showed that only the elevated dose (750 mg/kg) of Sida acuta extract, acutely administered, promotes significant changes, at 60 and 120 min post-administration, in the time of permanence in the rod. The ethanolic extract from the leaves and stems of Sida acuta, causes effects on the central nervous system in experimental animals.

Antileishmanial Effect of 5,3'-Hydroxy-7,4'-dimethoxyflavanone of Picramnia gracilis Tul. (Picramniaceae) Fruit: In Vitro and In Vivo Studies.

Species of Picramnia genus are used in folk medicine to treat or prevent skin disorders, but only few species have been studied for biological activity and chemical composition. P. gracilis Tul. is a native species from Central and South America and although its fruits are edible, phytochemical analysis or medicinal uses of this species are not known. In the search of candidates to antileishmanial drugs, this work aimed to evaluate the antileishmanial activity of P. gracilis Tul. in in vitro and in vivo studies. Only ethanolic extract of fruits showed leishmanicidal activity. The majoritarian metabolite was 5,3'-hydroxy-7,4'-dimethoxyflavanone ether that exhibited high activity against L. (V.) panamensis (EC50 17.0 + 2.8 mg/mL, 53.7 µM) and low toxicity on mammalian U-937 cells, with an index of selectivity >11.8. In vivo studies showed that the flavanone administered in solution (2 mg/kg/day) or cream (2%) induces clinical improvement and no toxicity in hamsters with CL. In conclusion, this is the first report about isolation of 5,3'-hydroxy-7,4'-dimethoxyflavanone of P. gracilis Tul. The leishmanicidal activity attributed to this flavanone is also reported for the first time. Finally, the in vitro and in vivo leishmanicidal activity reported here for 5,3'-hydroxy-7,4'-dimethoxyflavanone offers a greater prospect towards antileishmanial drug discovery and development.

Neuroprotective activity and acetylcholinesterase inhibition of five Amaryllidaceae species: a comparative study.

AIMS: Amaryllidaceae alkaloids exhibit a wide range of physiological effects, of which the acetylcholinesterase (AChE) inhibitory activity is the most relevant. However, scientific evidence related to their neuroprotective effectiveness against glutamate-induced toxicity has been lacking. Thus, the purpose of this study was to conduct a comparative study of the neuroprotective activity and the AChE inhibitory activity of species of Amaryllidaceae. MAIN METHODS: The neuroprotective activity against glutamate-induced toxicity was measured in rat cortical neurons and the Ellman method was employed for the quantification of acetylcholinesterase inhibitory activity of alkaloidal extracts of five species of Amaryllidaceae (Crinum jagus, Crinum bulbispermum, Hippeastrum barbatum, Hippeastrum puniceum and Zephyranthes carinata). The alkaloid Amaryllidaceae patterns based on GC/MS analyses were also investigated. KEY FINDINGS: The results showed that the alkaloidal extract from C. jagus presented a high neuroprotective activity in both pre- and post-treatments against a glutamate excitotoxic stimulus. Furthermore, the alkaloid extracts from C. jagus and Z. carinata revealed an inhibitory activity of AChE from the electric eel with IC50 values of 18.28±0.29 and 17.96±1.22µg/mL, respectively. In addition, 46 alkaloids were detected by GC/MS, and 20 of them were identified based on their mass spectra and retention index. The results suggest that the neuroprotective effects might be associated with lycorine and crinine-type alkaloids, whereas the acetylcholinesterase enzyme inhibitory activity could be related to galanthamine and lycorine-type alkaloids, although not based on synergistic processes. SIGNIFICANCE: In summary, Amaryllidaceae species are sources of alkaloids with potential use for Alzheimer's disease.

Alkaloid metabolite profiles by GC/MS and acetylcholinesterase inhibitory activities with binding-mode predictions of five Amaryllidaceae plants.

Acetylcholinesterase (AChE) enzymatic inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the mainstay drugs for its treatment. In order to discover new sources of potent AChE inhibitors, a combined strategy is presented based on AChE-inhibitory activity and chemical profiles by GC/MS, together with in silico studies. The combined strategy was applied on alkaloid extracts of five Amaryllidaceae species that grow in Colombia. Fifty-seven alkaloids were detected using GC/MS, and 21 of them were identified by comparing their mass-spectral fragmentation patterns with standard reference spectra in commercial and private library databases. The alkaloid extracts of Zephyranthes carinata exhibited a high level of inhibitory activity (IC50 = 5.97 ± 0.24 µg/mL). Molecular modeling, which was performed using the structures of some of the alkaloids present in this extract and the three-dimensional crystal structures of AChE derived from Torpedo californica, disclosed their binding configuration in the active site of this AChE. The results suggested that the alkaloids 3-epimacronine and lycoramine might be of interest for AChE inhibition. Although the galanthamine group is known for its potential utility in treating AD, the tazettine-type alkaloids should be evaluated to find more selective compounds of potential benefit for AD.

Pentacyclic triterpenes from Cecropia telenitida with immunomodulatory activity on dendritic cells

Pentacyclic triterpene Natural product Cytokine modulation Anti-inflammatory activity Dendritic cells Pentacyclic triterpenes are a large family of plant metabolites that exhibit a wide array of biological activities. The genus Cecropia, which encompasses many plant species, has been used as traditional medicine for the treatment of inflammatory diseases and is known to produce many active pentacyclic triterpenes. In this study we investigated the chemical composition of a pentacyclic triterpene fraction from the roots of Cecropia telenitida Cuatrec., Urticaceae. A novel compound, which we termed yarumic acid, and four known molecules (serjanic acid, spergulagenic acid A, 20-hydroxy-ursolic acid and goreishic acid I) were isolated and characterised. In a dendritic cell (DC)based assay, we demonstrated that non-toxic doses of these pentacyclic triterpenes inhibited the secretion of at least one of the proinflammatory cytokines tested (IL-1β, IL-12p40, IL-12p70, TNF-α). Spergulagenic acid A also inhibited nitric oxide production in lipopolysaccharide-stimulated dendritic cell. Serjanic acid and spergulagenic acid A, which were the most potent abundant compounds in the pentacyclic triterpene fraction, showed the most activity in the dendritic cell-based assay. These results show that all pentacyclic triterpenes might contribute to the anti-inflammatory activities of C. telenitida. Moreover, yarumic acid as well as the four known pentacyclic triterpenes, can be exploited as potential immunomodulatory/anti-inflammatory agents.

Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae.

Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25 microg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=10 and 16, respectively). The extracts from Desmopsis panamensis, Pseudomalmea boyacana, Rollinia exsucca and Rollinia pittieri showed good antiplasmodial activity (IC50 < 10 microg/ml). No correlation between antiplasmodial activity and inhibition of beta-hematin production was found. The present study gives specific and useful information about antiprotozoal and cytotoxic activities of some Annonaceae extracts. Results presented here also demonstrate which plants and/or plant parts could be useful in the treatment of leishmaniasis, Chagas' disease and malaria.