In Vitro Anti-Trypanosoma cruzi Activity of Halophytes from Southern Portugal Reloaded: A Special Focus on Sea Fennel (Crithmum maritimum L.)

Marine halophytes are an outstanding reservoir of natural products and several species have anti-infectious traditional uses. However, reports about their potential use against neglected tropical ailments, such as Chagas disease, are scarce. This work evaluated for the first time the in vitro anti-Trypanosoma cruzi activity of extracts from the aromatic and medicinal species Helichrysum italicum subsp. picardii (Boiss. & Reut.) Franco (Asteraceae, everlasting) and Crithmum maritimum L. (Apiaceae, sea fennel). For that purpose, decoctions, tinctures, and essential oils from everlasting’s flowers and sea fennel’s stems, leaves, and flowers were tested against intracellular amastigotes of two T. cruzi strains. The extract from the sea fennel flower decoction displayed significant anti-trypanosomal activity and no toxicity towards the host cell (EC50 = 17.7 µg/mL, selectivity index > 5.65). Subsequent fractionation of this extract afforded 5 fractions that were re-tested in the same model of anti-parasitic activity. Fraction 1 was the most active and selective (EC50 = 0.47 μg/mL, selectivity index = 59.6) and was submitted to preparative thin-layer chromatography. One major compound was identified, falcarindiol, which was likely the one responsible for the observed anti-trypanosomal activity. This was confirmed using a commercially sourced molecule. Target-fishing studies showed falcarindiol as a ligand of T. cruzi spermidine synthase, pointing to a potential enzyme-inhibiting anti-trypanosomal mechanism of action. Overall, this work shows that sea fennel can provide effective anti-parasitic molecule(s) with potential pharmacological applications in the treatment of CD.

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In Vitro Anti-Trypanosoma Cruzi Activity of Halophytes From Southern Portugal Reloaded: A Special Focus on Sea Fennel (Crithmum Maritimum L.)

10.21203/rs.3.rs-129046/v1 ◽

2020 ◽

Author(s):

Catarina Pereira ◽

Carolina Moraes ◽

Caio Franco ◽

Raphaël Grougnet ◽

Euzébio Barbosa ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Preparative Thin Layer Chromatography ◽

Selectivity Index ◽

Special Focus ◽

Medicinal Species ◽

Southern Portugal ◽

Parasitic Activity ◽

First Time ◽

Layer Chromatography

Abstract Marine halophytes are an outstanding reservoir of natural products and several species have anti-infectious traditional uses. However, little is known about their potential against neglected tropical ailments, such as Chagas disease. This work evaluated for the first time the in vitro anti-Trypanosoma cruzi activity of extracts from the aromatic and medicinal species Helichrysum italicum subsp. picardii (Boiss. & Reut.) Franco (Asteraceae, everlasting) and Crithmum maritimum L. (Apiaceae, sea fennel). For that purpose, decoctions, tinctures and essential oils from everlasting’s flowers and sea fennel’s stems, leaves and flowers were tested against intracellular amastigotes of two T. cruzi strains. Sea fennel’s flowers decoction displayed significant anti-trypanosomal activity and no toxicity towards the host cell (EC50 = 17.7 µg/mL, selectivity index > 5.65). This extract was partitioned using liquid-liquid extraction affording 5 fractions that were re-tested in the same model of anti-parasitic activity. Fraction 1 was the most active and selective (EC50 = 0.47 μg/mL, selectivity index = 59.6) and was submitted to preparative thin layer chromatography. The major compound present, likely responsible for the observed anti-trypanosomal activity, was identified as falcarindiol. Target fishing studies showed falcarindiol as a ligand of T. cruzi spermidine synthase, pointing to a potential enzyme-inhibiting anti-trypanosomal mechanism of action.

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Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo

Parasitology ◽

10.1017/s0031182019001276 ◽

2019 ◽

Vol 147 (1) ◽

pp. 108-119 ◽

Cited By ~ 4

Author(s):

Matheus Marques Milagre ◽

Renata Tupinambá Branquinho ◽

Maira Fonseca Gonçalves ◽

GMP de Assis ◽

Maykon Tavares de Oliveira ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Sesquiterpene Lactone ◽

Selectivity Index ◽

H9c2 Cells ◽

Therapeutic Activity ◽

Control Groups ◽

Disease Treatment ◽

And Control

AbstractBackground:The current drugs for Chagas disease treatment present several limitationsMethods:The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.Results:The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.Conclusion:GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.

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Unlocking the in vitro anti-Trypanosoma cruzi activity of halophyte plants from the southern Portugal

Asian Pacific Journal of Tropical Medicine ◽

10.1016/j.apjtm.2016.06.015 ◽

2016 ◽

Vol 9 (8) ◽

pp. 735-741 ◽

Cited By ~ 2

Author(s):

Marta Oliveira ◽

Policarpo Ademar Sales Junior ◽

Maria João Rodrigues ◽

Marina DellaGreca ◽

Luísa Barreira ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Southern Portugal

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In vitro anti-parasitic activity of Cyclosporin A analogs on Trypanosoma cruzi

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2004.07.003 ◽

2004 ◽

Vol 14 (18) ◽

pp. 4633-4637 ◽

Cited By ~ 23

Author(s):

Jacqueline Búa ◽

Andrés M. Ruiz ◽

Mariana Potenza ◽

Laura E. Fichera

Keyword(s):

Trypanosoma Cruzi ◽

Cyclosporin A ◽

Parasitic Activity

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Tambjamines and Prodiginines: Biocidal Activity against Trypanosoma cruzi

Pharmaceutics ◽

10.3390/pharmaceutics13050705 ◽

2021 ◽

Vol 13 (5) ◽

pp. 705

Author(s):

Rocío Herráez ◽

Roberto Quesada ◽

Norma Dahdah ◽

Miguel Viñas ◽

Teresa Vinuesa

Keyword(s):

Oxygen Consumption ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Selectivity Index ◽

Biocidal Activity ◽

Potent Effect ◽

Ic50 Values ◽

Vitro Analysis ◽

In Vitro Analysis

The aim of this work was to explore new therapeutic options against Chagas disease by the in vitro analysis of the biocidal activities of several tambjamine and prodiginine derivatives, against the Trypanosoma cruzi CLB strain (DTU TcVI). The compounds were initially screened against epimastigotes. The five more active compounds were assayed in intracellular forms. The tambjamine MM3 and both synthetic and natural prodigiosins displayed the highest trypanocidal profiles, with IC50 values of 4.52, 0.46, and 0.54 µM for epimastigotes and 1.9, 0.57, and 0.1 µM for trypomastigotes/amastigotes, respectively. Moreover, the combination treatment of these molecules with benznidazole showed no synergism. Finally, oxygen consumption inhibition determinations performed using high-resolution respirometry, revealed a potent effect of prodigiosin on parasite respiration (73% of inhibition at ½ IC50), suggesting that its mode of action involves the mitochondria. Moreover, its promising selectivity index (50) pointed out an interesting trypanocidal potential and highlighted the value of prodigiosin as a new candidate to fight Chagas disease.

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Limonoids from the Endemic Brazilian Species Raulinoa echinata

Zeitschrift für Naturforschung C ◽

10.1515/znc-2001-7-815 ◽

2001 ◽

Vol 56 (7-8) ◽

pp. 570-574 ◽

Cited By ~ 15

Author(s):

Maique W. Biavatti ◽

Paulo C. Vieira ◽

M. Fatima G. F. da Silva ◽

João B. Fernandes ◽

Sérgio Albuquerque

Keyword(s):

Trypanosoma Cruzi ◽

Acid Derivative ◽

Inhibitory Activity ◽

Structure Elucidation ◽

The South ◽

Brazilian Species ◽

Stems And Leaves ◽

First Time

Phytochemical survey of stems and leaves of the South Brazilian endemic Raulinoa echinata Cowan, Rutaceae led to the isolation of five limonoid derivatives: the widespread limonin, limonexic acid, kihadalactone B, a methoxylated limonexic acid derivative and a degraded limonoid structurally related to fraxinellone. The two latter compounds have been isolated for the first time. These compounds displayed weak inhibitory activity when assayed in vitro against trypomastigote forms of Trypanosoma cruzi. In this paper, the isolation, structure elucidation and bioactivity of these compounds are reported

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Anti-Hepatocellular Carcinoma (HepG2) Activities of Monoterpene Hydroxy Lactones Isolated from the Marine Microalga Tisochrysis Lutea

Marine Drugs ◽

10.3390/md18110567 ◽

2020 ◽

Vol 18 (11) ◽

pp. 567

Author(s):

Katkam N. Gangadhar ◽

Maria João Rodrigues ◽

Hugo Pereira ◽

Helena Gaspar ◽

F. Xavier Malcata ◽

...

Keyword(s):

Hepg2 Cells ◽

Preparative Thin Layer Chromatography ◽

Omega 3 ◽

Nmr Analysis ◽

Tisochrysis Lutea ◽

Marine Microalga ◽

Bioassay Guided Fractionation ◽

First Time ◽

Layer Chromatography

Tisochrysis lutea is a marine haptophyte rich in omega-3 polyunsaturated fatty acids (e.g., docosahexaenoic acid (DHA)) and carotenoids (e.g., fucoxanthin). Because of the nutraceutical applications of these compounds, this microalga is being used in aquaculture to feed oyster and shrimp larvae. In our earlier report, T. lutea organic crude extracts exhibited in vitro cytotoxic activity against human hepatocarcinoma (HepG2) cells. However, so far, the compound(s) accountable for the observed bioactivity have not been identified. Therefore, the aim of this study was to isolate and identify the chemical component(s) responsible for the bioactivity observed. Bioassay-guided fractionation through a combination of silica-gel column chromatography, followed by preparative thin layer chromatography (PTLC), led to the isolation of two diastereomers of a monoterpenoid lactone, namely, loliolide (1) and epi-loliolide (2), isolated for the first time in this species. The structural elucidation of both compounds was carried out by GC-MS and 1D (1H and 13C APT) and 2D (COSY, HMBC, HSQC-ed, and NOESY) NMR analysis. Both compounds significantly reduced the viability of HepG2 cells and were considerably less toxic towards a non-tumoral murine stromal (S17) cell line, although epi-loliolide was found to be more active than loliolide.

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Terpenoids from the Oleo-Gum-Resin of Boswellia serrata and Their Antiplasmodial Effects In Vitro

Planta Medica ◽

10.1055/s-0043-116943 ◽

2017 ◽

Vol 83 (14/15) ◽

pp. 1214-1226 ◽

Cited By ~ 9

Author(s):

Hippolyt Greve ◽

Marcel Kaiser ◽

Reto Brun ◽

Thomas Schmidt

Keyword(s):

Mass Spectrometry ◽

Natural Products ◽

Selectivity Index ◽

In Vitro Activity ◽

Boswellic Acid ◽

Boswellia Serrata ◽

Skeletal Myoblasts ◽

Ic50 Values ◽

First Time

AbstractIn the course of our ongoing search for new natural products as leads against protozoal diseases, the dichloromethane extract of Indian frankincense, the oleo-gum-resin obtained from Boswellia serrata, showed in vitro activity against Plasmodium falciparum. Bioactivity-guided fractionation led to the isolation of eight diterpenes: (1S,3E,7E,11R)-verticilla-3,7,12(18)-triene (1), cembrene A (2), serratol (3), 1S,3E,7R,8R,11E-7,8-epoxy-cembra-3,11-dien-1-ol (4), incensole oxide (5), rel (1S,3R,7E,11S,12R)-1,12-epoxy-4-methylenecembr-7-ene-3, 11-diol (6), isoincensole oxide (7), and isodecaryiol (8). Furthermore, 10 triterpenes, namely, oleanolic acid (9), 11-keto-β-boswellic acid (10), 3-epi-neoilexonol (11), uvaol (12), β-boswellic aldehyde (13), 5α-tirucalla-8,24-dien-3α-ol (14), isoflindissone lactone (15), isoflindissol lactone (16), rel (8R,9S,20R)-tirucall-24-ene-3β,20-diol (17), and rel (3α,8R, 9S,20R,24S)-20,24-epoxytirucalla-3,25-diol (18) as well as the sesquiterpene β-bourbonene (19), the monoterpene carvacrol (20) and the phenyl propanoids methyleugenol (21), and p-methoxycinnamaldehyde (22) were isolated. All compounds were identified by mass spectrometry and nuclear magnetic resonance spectroscopic measurements. Compounds 6, 11, and 16–18 are described for the first time. Compounds 13 – 15 are isolated as natural products for the first time, compound 8 for the first time from a plant. Antiplasmodial IC50 values and cytotoxicity against L6 rat skeletal myoblasts were determined. Isoflindissone lactone (15) was the most active compound with an IC50 of 2.2 µM against P. falciparum and a selectivity index of 18.

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Micropropagation of Plantago asiatica L. through culture of shoot-tips

Acta Societatis Botanicorum Poloniae ◽

10.5586/asbp.2003.025 ◽

2011 ◽

Vol 72 (3) ◽

pp. 191-194 ◽

Cited By ~ 4

Author(s):

Joanna Makowczyńska ◽

Emilia Andrzejewska-Golec

Keyword(s):

Shoot Tips ◽

Shoot Tip ◽

Ms Medium ◽

Medicinal Species ◽

Ground Field ◽

Plantago Asiatica ◽

Field Culture ◽

First Time ◽

Shoot Tip Multiplication

Shoot-tip multiplication of the medicinal species - Plantago asiatica was carried on MS medium with IAA and BAP or kinetin. Best results in micropropagation were achieved by adding 0.1 mg/dm3 IAA and 1 mg/dm3 BAP. After 6 weeks shoots were transferred to MS medium for rooting. The resulting plantlets were transferred after 8 weeks into pots and after a period of adaptation into the ground (field culture).The species Plantago asiatica was propagated in vitro by shoot-tip multiplication for the first time.

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Critical Contribution of CD28-CD80/CD86 Costimulatory Pathway to Protection from Trypanosoma cruzi Infection

Infection and Immunity ◽

10.1128/iai.71.6.3131-3137.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3131-3137 ◽

Cited By ~ 24

Author(s):

Yasushi Miyahira ◽

Masaharu Katae ◽

Seiki Kobayashi ◽

Tsutomu Takeuchi ◽

Yoshinosuke Fukuchi ◽

...

Keyword(s):

T Cell ◽

Trypanosoma Cruzi ◽

Protective Immunity ◽

Wild Type ◽

Natural Protection ◽

Blocking Antibodies ◽

First Time ◽

Deficient Mice ◽

Costimulatory Pathway

ABSTRACT The CD28-CD80/CD86-mediated T-cell costimulatory pathway has been variably implicated in infectious immunity. In this study, we investigated the role of this costimulatory pathway in resistance to Trypanosoma cruzi infection by using CD28-deficient mice and blocking antibodies against CD80 and CD86. CD28-deficient mice exhibited markedly exacerbated T. cruzi infection, as evidenced by unrelenting parasitemia and 100% mortality after infection with doses that are nonlethal in wild-type mice. The blockade of both CD80 and CD86 by administering specific monoclonal antibodies also exacerbated T. cruzi infection in wild-type mice. Splenocytes from T. cruzi-infected, CD28-deficient mice exhibited greatly impaired gamma interferon production in response to T. cruzi antigen stimulation in vitro compared to those from infected wild-type mice. The induction of T. cruzi antigen-specific CD8+ T cells was also impaired in T. cruzi-infected, CD28-deficient mice. In addition to these defects in natural protection against T. cruzi infection, CD28-deficient mice were also defective in the induction of CD8+-T-cell-mediated protective immunity against T. cruzi infection by DNA vaccination. These results demonstrate, for the first time, a critical contribution of the CD28-CD80/CD86 costimulatory pathway not only to natural protection against primary T. cruzi infection but also to DNA vaccine-induced protective immunity to Chagas' disease.

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