Antigiardial Activity of Podophyllotoxin-Type Lignans from Bursera fagaroides var. fagaroides (original) (raw)
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PLOS Neglected Tropical Diseases, 2017
Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.
Plants and chemical constituents with giardicidal activity
Revista Brasileira de Farmacognosia, 2006
RESUMO: "Plantas e constituintes químicos com atividade giardicida". Infecção intestinal causada por Giardia lamblia representa grave problema de saúde pública, com elevadas taxas de prevalência em diversos países. O aumento de resistência do parasita e os efeitos colaterais dos fármacos de referência empregados no tratamento da giardíase, tornam necessário a busca de novos agentes terapêuticos. Produtos naturais, especialmente de origem vegetal, representam excelentes fontes de pesquisas. Este trabalho tem como objetivo revisar a literatura de extratos de plantas, frações e compostos químicos com estudos in vitro de avaliação da atividade giardicida. A revisão refere 153 (cento e cinqüenta e três) espécies vegetais de 69 (sessenta e nove) famílias que foram submetidas à avaliação da atividade giardicida. Descreve a distribuição geográfi ca das espécies vegetais, parte usada, preparação, cepa de Giardia lamblia testada e resultados por autores. Apresenta 101 (cento e um) compostos isolados de espécies vegetais classifi cados por classes químicas. Discute aspectos recentes da pesquisa de produtos naturais de origem vegetal empregados no tratamento da giardíase.
BioMed Research International, 2014
Human Giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts of Yucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with 5×10 6 Giardia trophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified. Yucca extracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts of Y. baccata may represent an effective and natural therapeutic alternative for human giardiosis.
Piqueria trinervia as a source of metabolites against Giardia intestinalis
Pharmaceutical Biology
Context: Piqueria trinervia Cav. (Asteraceae) is a plant species with a long history in traditional medicine to cure diarrhoea and other digestive disorders. Objective: The study investigates the antigiardial activity of piquerol, trinervinol, red oil and two fractions (F1 and F2) from P. trinervia. Materials and methods: P. trinervia was collected in the Ajusco in Mexico City. Aerial parts were ground and mixed with water to obtain the extract, which was treated with dichloromethane to isolate piquerol and trinervinol (P & T). Remnants were the red oil, fractions 1 and 2 (RO, F1 & F2). Trophozoites of Giardia intestinalis were treated with P, T, RO, F1 and F2 at different concentrations (0.78-200 lg/mL) for 48 h. Antigiardial activity was measured using the methylene blue reduction, and the cytotoxicity assayed on human fibroblasts and Vero cells by reduction of tetrazolium salts. Results: Trinervinol and piquerol showed antigiardial activity with an IC 50 ¼ 2.03 and 2.42 lg/mL, and IC 90 ¼ 13.03 and 8.74 lg/mL, respectively. The concentrations of trinervinol (CC 50 ¼ 590 lg/mL) and piquerol (CC 50 ¼ 501 lg/mL) were not cytotoxic to human fibroblasts. Conclusions: Compounds from P. trinervia showed antigiardial activity; to enhance this activity, piquerol and trinervinol can be chemically modified.
Cytotoxic Podophyllotoxin Type-Lignans from the Steam Bark of Bursera fagaroides var. fagaroides
Molecules, 2012
The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides displayed potent cytotoxic activity against four cancer cell lines, namely KB (ED 50 = 9.6 × 10 −2 μg/mL), PC-3 (ED 50 = 2.5 × 10 −1 μg/mL), MCF-7 (ED 50 = 6.6 μg/mL), and HF-6 (ED 50 = 7.1 × 10 −3 μg/mL). This extract also showed anti-tumour activity when assayed on mice inoculated with L5178Y lymphoma cells. Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin-type lignans identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5′-desmethoxy-β-peltatin-A-methylether (3), desmethoxyyatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D and 2DNMR and FAB-MS analyses, and comparison with reported values. All the isolated compounds showed potent cytotoxic activity in the cell lines tested, especially compound 3, which exhibited greater activity than camptothecin and podophyllotoxin against
Parasitology …, 2006
In the world, giardiosis is still a very important parasitic disease; only in Asia, Africa and America, there are more than 200 million of infected people in a year. The usual treatments are drugs that produce undesirable secondary effects, perhaps favouring the resistant strain selection. One alternative is to research compounds from plants used as antidiarrhoeic or antiparasitic in the traditional medicine. In a previous work, we found that Lippia beriandieri (Oregano) revealed to be more potent than tinidazole, a common antigiardiasic drug. In this current work, we tested the cell viability by re-culture and reduction of MTT-tetrazolium salts to MTT-formazan, and we showed the effect of oregano ethanolic extracts against Giardia intestinalis (synonyms: Giardia duodenalis, Giardia lamblia) trophozoites at concentrations ranging form 58 to 588 μg. We demonstrated the ultrastructural injury produced by oregano extracts in this parasite. Trophozoites lost their size and shape and showed damage in nucleus structure, perhaps by breaking the pattern of nucleoskeleton proteins.
Piqueria trinervia as a source of metabolites against Giardia intestinalis
2017
Context: Piqueria trinervia Cav. (Asteraceae) is a plant species with a long history in traditional medicine to cure diarrhoea and other digestive disorders. Objective: The study investigates the antigiardial activity of piquerol, trinervinol, red oil and two fractions (F1 and F2) from P. trinervia. Materials and methods: P. trinervia was collected in the Ajusco in Mexico City. Aerial parts were ground and mixed with water to obtain the extract, which was treated with dichloromethane to isolate piquerol and trinervinol (P & T). Remnants were the red oil, fractions 1 and 2 (RO, F1 & F2). Trophozoites of Giardia intestinalis were treated with P, T, RO, F1 and F2 at different concentrations (0.78-200 lg/mL) for 48 h. Antigiardial activity was measured using the methylene blue reduction, and the cytotoxicity assayed on human fibroblasts and Vero cells by reduction of tetrazolium salts. Results: Trinervinol and piquerol showed antigiardial activity with an IC 50 ¼ 2.03 and 2.42 lg/mL, and IC 90 ¼ 13.03 and 8.74 lg/mL, respectively. The concentrations of trinervinol (CC 50 ¼ 590 lg/mL) and piquerol (CC 50 ¼ 501 lg/mL) were not cytotoxic to human fibroblasts. Conclusions: Compounds from P. trinervia showed antigiardial activity; to enhance this activity, piquerol and trinervinol can be chemically modified.
Research Paper, 2019
Key words: C.citratus, P. undulata, MTZ, anti-giardiasis, medicinal plants Background: Metronidazole (MTZ) is the drug of choice for treatment of giardiasis, but it has many drawbacks and there is a need to find out medicinal plants having anti-giardiasis efficacy to be alternative to MTZ. Objectives: This work aimed to study the in vitro and in vivo anti-giardial effectiveness of the aqueous extracts of two plants; Cymbopogon(C.)citratus and Pulicaria (P.)undulata in comparison with MTZ. Methodology: For in vitro study, one mL from different concentrations of plant extracts and MTZ were added to one mL of Giardia cysts suspension for 5, 15, 30 and 60 min. The viability was distinguished by 0.1 % eosin. Also, morphological alterations of Giardia cysts were examined by scanning electron microscope (SEM). For in vivo study, 50 male Albino mice were divided into: Group I: non-infected control; Group II: infected-untreated (IU); Group III: infected-treated with 15 mg/kg of MTZ; Group IV: infected treated with 500 mg/kg of C. citratus extract and Group V: infected-treated with 200 mg/kg of P. undulata extract. The effectiveness of the extracts was evaluated by cyst count per gram of feces, histopathological and transmission electron microscopic (TEM) examination of the small intestine. Results: in vitro mortality percentages of Giardia cysts showed a significant dose and time dependent effect regarding each extract. The aqueous extract of C. citratus extract at 500 ug/mL revealed the highest significant mortality percentages. P.undulata at 400ug/mL, MTZ and C. citratus at 250 µg/mL showed high mortality percentages with significant differences on comparison with C. citratus at 500 µg/mL. The ultrastructure morphological alternations of G. lamblia cysts were observed mainly with C.citratus. In the in vivo study, C. citratus revealed significant early complete absence of the parasite from fecal samples at 5 th days post treatment, while P. undulata and MTZ achieved complete cure at 10 th days post treatment. Progressive improvement of intestinal mucosa pathological changes and the mucosal ultrastructure were observed in the treated mice. Conclusion: C.citratus and P. undulata aqueous extracts were effective against G. lamblia both in vitro and in vivo and they could be natural therapeutic alternative agents to MTZ.
African Journal of Traditional, Complementary and Alternative Medicines, 2015
Background: Giardia lamblia is a parasite that causes giardiasis in humans and other mammals. The common treatment includes different drugs, which were described to produce unpleasant side effects. Citrus aurantifolia, popularly known as "lima", is a plant used in traditional medicine to treat gastrointestinal symptoms. The aim of the present study was to evaluate the anti-Giardia activity of 10 pure compounds obtained from a hexanic extract of Mexican lime on the basis of trophozoite growth inhibition. Materials and Methods: A hexanic extract obtained from fresh fruit peels of Citrus aurantifolia was tested on G. lamblia strain 0989:IMSS trophozoites cultured in TYI-S-33 medium. The concentration of all standard drugs, analyzed by gas chromatography, was adjusted at 10 mg/mL. Metronidazole was used as a positive control. Growth inhibition was determined by counting the number of trophozoites using a Neubauer chamber. The 50% inhibitory concentration (IC 50) of each drug was calculated by probit analysis and 95% confidence limits were calculated. Results: 4-hexen-3-one, citral and geraniol showed IC 50 values of 34.2, 64.5 and 229.49 µg/ml in axenic cultures after 24 hr of incubation, respectively. When these results were compared with a positive control of metronidazole; 4-hexen-3-one was 66 times; citral was 112 and geraniol was 441 times less active respectively. The other tested compounds did not inhibit the growth of cultured G. lamblia trophozoites. Conclusion: The obtained results lead us to propose that these tested compounds from C. aurantifolia have potential for use as therapeutic agents against giardiasis.