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1.
J Ethnopharmacol ; 331: 118269, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697409

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria, caused by Plasmodium parasites, remains a significant global health challenge, particularly in tropical and subtropical regions. At the same time, the prevalence of toxoplasmosis has been reported to be 30% worldwide. Traditional medicines have long played a vital role in discovering and developing novel drugs, and this approach is essential in the face of increasing resistance to current antimalarial and anti-Toxoplasma drugs. In Indonesian traditional medicine, various plants are used for their therapeutic properties. This study focuses on eleven medicinal plants from which nineteen extracts were obtained and screened for their potential medicinal benefits against malaria and toxoplasmosis. AIMS OF THE STUDY: The aim of this study was to evaluate the efficacy of extracts from Indonesian medicinal plants to inhibit Plasmodium falciparum, a parasite responsible for malaria, and Toxoplasma gondii, an opportunistic parasite responsible for toxoplasmosis. METHODS: Nineteen extracts from eleven plants were subjected to in vitro screening against P. falciparum 3D7 (a chloroquine-sensitive strain) and the T. gondii RH strain. In vitro treatments were conducted on P. falciparum 3D7 and K1 (multidrug-resistant strains) using the potent extracts, and in vivo assessments were carried out with mice infected with P. yoelii 17XNL. LCMS analysis was also conducted to identify the main components of the most effective extract. RESULTS: Seven extracts showed significant antiplasmodial activity (>80% inhibition) at a concentration of 100 µg/ml. These extracts were obtained from Dysoxylum parasiticum (Osbeck) Kosterm., Elaeocarpus glaber (Bl.) Bijdr., Eleutherine americana Merr., Kleinhovia hospita L., Peronema canescens Jack, and Plectranthus scutellarioides (L.) R.Br. Notably, the D. parasiticum ethyl acetate extract exhibited high selectivity and efficacy both in vitro and in vivo. Herein, the key active compounds oleamide and erucamide were identified, which had IC50 values (P. falciparum 3D7/K1) of 17.49/23.63 µM and 32.49/51.59 µM, respectively. CONCLUSIONS: The results of this study highlight the antimalarial potential of plant extracts collected from Indonesia. Particularly, extracts from D. parasiticum EtOH and EtOAc stood out for their low toxicity and strong antiplasmodial properties, with the EtOAc extract emerging as a notably promising antimalarial candidate. Key compounds identified within this extract demonstrate the complexity of extracts' action against malaria, potentially targeting both the parasite and the host. This suggests a promising approach for developing new antimalarial strategies that tackle the multifaceted challenges of drug resistance and disease management. Future investigations are necessary to unlock the full therapeutic potential of these extracts.


Assuntos
Antimaláricos , Extratos Vegetais , Plantas Medicinais , Plasmodium falciparum , Toxoplasma , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Animais , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Indonésia , Toxoplasma/efeitos dos fármacos , Antimaláricos/farmacologia , Antimaláricos/isolamento & purificação , Camundongos , Feminino , Malária/tratamento farmacológico , Malária/parasitologia
2.
Pharmaceutics ; 14(3)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35335918

RESUMO

The emerging spread of drug-resistant malaria parasites highlights the need for new antimalarial agents. This study evaluated the growth-inhibitory effects of sparsomycin (Sm), a peptidyl transferase inhibitor, against Plasmodium falciparum 3D7 (chloroquine-sensitive strain), P. falciparum K1 (resistant to multiple drugs, including chloroquine), P. yoelii 17XNL (cause of uncomplicated rodent malaria) and P. berghei ANKA (cause of complicated rodent malaria). Using a fluorescence-based assay, we found that Sm exhibited half-maximal inhibitory concentrations (IC50) of 12.07 and 25.43 nM against P. falciparum 3D7 and K1, respectively. In vitro treatment of P. falciparum 3D7 with Sm at 10 or 50 nM induced morphological alteration, blocked parasites in the ring state and prevented erythrocyte reinvasion, even after removal of the compound. In mice infected with P. yoelii 17XNL, the administration of 100 µg/kg Sm for 7 days did not affect parasitemia. Meanwhile, treatment with 300 µg/kg Sm resulted in a significantly lower parasitemia peak (18.85%) than that observed in the control group (40.13%). In mice infected with P. berghei ANKA, both four and seven doses of Sm (300 µg/kg) prolonged survival by 33.33%. Our results indicate that Sm has potential antiplasmodial activities in vitro and in vivo, warranting its further development as an alternative treatment for malaria.

3.
Fitoterapia ; 151: 104859, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33610746

RESUMO

Six new triterpenoid saponins, named senegalosides A-F (1-6) were isolated from the seedpods and roots of Acacia senegal (Mimosaceae). Their structures were elucidated using 1D and 2D-NMR spectroscopic analysis and mass spectrometry. Compound 1 possesses an unusual sapogenin, 3ß-hydroxy-21-oxo-olean-12-en-28-oic acid (machaeric acid), and was reported here in its natural form for the first time within the genus Acacia. Senegaloside A is the first example of a machaeric-type triterpenoid glycoside in the plant kingdom. The cytotoxic effect of isolated saponins was evaluated on the H4IIE rat hepatoma cell line. As a result, compounds 1, 3-6 were not significantly cytotoxic to H4IIE cells even at 200 µM. Compound 2 was suppressed cell viability at 50-200 µM.


Assuntos
Acacia/química , Antineoplásicos Fitogênicos/farmacologia , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Camarões , Linhagem Celular Tumoral , Sobrevivência Celular , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Ratos , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação
4.
Fitoterapia ; 132: 75-81, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30496810

RESUMO

Five polyketides, paralactonic acids A-E (1-5) were isolated from Paraconiothyrium sp. SW-B-1, an endophytic fungus isolated from the seaweed, Chondrus ocellatus Holmes. Their structures were determined by various spectroscopic methods, predominantly by 2D NMR spectroscopic analyses. The absolute configurations of compounds 1-5 were determined by comparison of the experimental and calculated ECD spectra. Compound 5 showed moderate antibacterial activity and restored the growth of a mutant yeast strain inhibited by hyperactivated Ca2+-signaling.


Assuntos
Antibacterianos/química , Ascomicetos/química , Chondrus/microbiologia , Policetídeos/química , Antibacterianos/isolamento & purificação , Japão , Estrutura Molecular , Policetídeos/isolamento & purificação , Alga Marinha/microbiologia
5.
Fitoterapia ; 127: 356-361, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29621598

RESUMO

Four new compounds, namely, nectriapyrones A (2) and B (3), nectriaquinone B (5), and zythiostromic acid C (8), were isolated from the brown rice culture of Nectria pseudotrichia 120-1NP together with four known compounds (1, 4, 6, and 7). To the best of our knowledge, this is the first report of 4 from a natural source. Their structures were determined on the basis of 1D/2D-NMR spectroscopy and HRESITOFMS data. In addition, the absolute configuration of secondary alcohols in 8 were determined using modified Mosher's ester method. All isolated compounds were evaluated for their antimicrobials activity, phytotoxicity, and cytotoxicity.


Assuntos
Diterpenos/isolamento & purificação , Isocumarinas/isolamento & purificação , Naftoquinonas/isolamento & purificação , Nectria/química , Células HL-60 , Humanos , Lactuca/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular
6.
J Antibiot (Tokyo) ; 70(12): 1129-1132, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29066795

RESUMO

A new eremophilane sesquiterpene, 13,13-dimethoxyintegric acid (1), together with known compound integric acid (2) have been isolated from a fungus, Xylaria sp. V-27, obtained from a dead branch. The structure of 1 was established by means of spectroscopic analyses. 1 and 2 promoted growth restoring activity against the mutant yeast strain (Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ)) and inhibited degranulation of rat basophilic leukemia RBL-2H3 cells stimulated by immnunoglobulin G + 2,4-dinitrophenylated-bovine serum albumin (IgE+DNP-BSA), thapsigargin and A23187.


Assuntos
Ácidos Carboxílicos/farmacologia , Degranulação Celular/efeitos dos fármacos , Naftalenos/farmacologia , Saccharomyces cerevisiae/crescimento & desenvolvimento , Sesquiterpenos/farmacologia , Animais , Ácidos Carboxílicos/isolamento & purificação , Linhagem Celular Tumoral , Naftalenos/isolamento & purificação , Sesquiterpenos Policíclicos , Ratos , Saccharomyces cerevisiae/genética , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Xylariales/metabolismo
7.
J Antibiot (Tokyo) ; 70(12): 1133-1137, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29066796

RESUMO

The novel compound, 11-O-methylpetasitol (1), was isolated from Penicillium sp. N-175-1, and two new compounds, cosmochlorins D (5) and E (6), were isolated from Phomopsis sp. N-125. In addition, three known eremophilane sesquiterpenes, sporogen-AO1 (2), petasol (3) and 6-dehydropetasol (4), were isolated from Penicillium sp. N-175-1. The structures of 1, 5 and 6 were elucidated by a combination of extensive spectroscopic analyses, including 2D NMR, high-resolution electrospray ionization time-of-flight mass spectrometry (HRESITOFMS) and chemical reactions. Compounds 2, 3, 5 and 6 exhibited cytotoxicity to HL60 and 2 and 3 to HeLa cells. Furthermore, 2 and 3 showed robust growth-restoring activity of a Saccharomyces cerevisiae (cdc2-1 rad9Δ) mutant strain, whereas 5 and 6 exhibited minor growth-restoring activity in this strain. Thus, these compounds may inhibit the growth of HL60 and HeLa cells by blocking the cell cycle, and they may be utilized as new lead compounds that act as inhibitors of survival signal transduction pathways.


Assuntos
Ascomicetos/metabolismo , Endófitos/metabolismo , Ficus/microbiologia , Penicillium/metabolismo , Resorcinóis/química , Sesquiterpenos/farmacologia , Ciclo Celular/efeitos dos fármacos , Descoberta de Drogas , Células HL-60 , Células HeLa , Humanos , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação
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