In vivo and in vitro antiplasmodial activities of some plants traditionally used in Guatemala against malaria.

We present an evaluation of the antiplasmodial and cytotoxic effects of four plants commonly used in Guatemalan folk medicine against malaria. Methanol extracts of Simarouba glauca D. C., Sansevieria guineensis Willd, Croton guatemalensis Lotsy, and Neurolaena lobata (L.)R.Br. significantly reduced parasitemias in Plasmodium berghei-infected mice. Dichloromethane fractions were screened for their cytotoxicities on Artemia salina (brine shrimp) larvae, and 50% inhibitory concentrations were determined for Plasmodium falciparum in in vitro cultures. Both chloroquine-susceptible and -resistant strains of P. falciparum were significantly inhibited by these extracts. Of all dichloromethane extracts, only the S. glauca cortex extract was considered to be toxic to nauplii of A. salina in the brine shrimp test.

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Silver Nanoparticles and Their Antibacterial Applications

International Journal of Molecular Sciences ◽

10.3390/ijms22137202 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7202

Author(s):

Tamara Bruna ◽

Francisca Maldonado-Bravo ◽

Paul Jara ◽

Nelson Caro

Keyword(s):

Silver Nanoparticles ◽

Antibacterial Agents ◽

Multidrug Resistant ◽

Secondary Effects ◽

Cytotoxic Effects ◽

Factors Affecting ◽

Gram Positive Bacteria ◽

Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

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Anti-plasmodial Effects of Zanthoxylum zanthoxyloides

Planta Medica ◽

10.1055/a-0973-0067 ◽

2019 ◽

Vol 85 (13) ◽

pp. 1073-1079 ◽

Cited By ~ 1

Author(s):

Christopher Dean Goodman ◽

An Thuy Hoang ◽

Drissa Diallo ◽

Karl Egil Malterud ◽

Geoffrey I. McFadden ◽

...

Keyword(s):

Brine Shrimp ◽

Methanol Extract ◽

Stem Bark ◽

Artemia Salina ◽

Root Bark ◽

Ic50 Values ◽

Zanthoxylum Zanthoxyloides ◽

Parasitic Activity ◽

Resistant Strains

Abstract Zanthoxylum zanthoxyloides, syn. Fagara zanthoxyloides, is a tree growing in West Africa and is used in traditional medicine against a variety of diseases, including malaria. In the work reported here, root bark and stem bark extracts of this tree, as well as compounds isolated from the extracts, have been investigated for activity in vitro against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, toxicity against nauplii of the brine shrimp Artemia salina has been studied. Dichloromethane extracts of the root bark and stem bark, and a methanol extract of the stem bark, showed anti-parasitic activity towards chloroquine-sensitive as well as chloroquine-resistant P. falciparum, with IC50 values between 1 and 10 µg/mL. Among the isolated compounds, bis-dihydrochelerythrinyl ether, buesgenine, chelerythrine, γ-fagarine, skimmianine, and pellitorine were the most active, with IC50 values of less than 5 µg/mL. The dichloromethane extracts were toxic to brine shrimp nauplii, with LC50 values of less than 1 µg/mL. Methanol extracts were much less toxic (LC50 between 50 and 100 µg/mL). Among the isolated substances, bis-dihydrochelethrinyl ether was the most toxic (LC50 ca. 2 µg/mL).

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Novel 4-Aminoquinoline Analogs Highly Active against the Blood and Sexual Stages of PlasmodiumIn VivoandIn Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01061-12 ◽

2012 ◽

Vol 56 (9) ◽

pp. 4685-4692 ◽

Cited By ~ 22

Author(s):

Fabián E. Sáenz ◽

Tina Mutka ◽

Kenneth Udenze ◽

Ayoade M. J. Oduola ◽

Dennis E. Kyle

Keyword(s):

Plasmodium Berghei ◽

Multidrug Resistant ◽

New Drugs ◽

Content Type ◽

Highly Active ◽

Resistant Strains ◽

Sexual Stages ◽

The 1960S

ABSTRACTNew drugs to treat malaria must act rapidly and be highly potent against asexual blood stages, well tolerated, and affordable to residents of regions of endemicity. This was the case with chloroquine (CQ), a 4-aminoquinoline drug used for the prevention and treatment of malaria. However, since the 1960s,Plasmodium falciparumresistance to this drug has spread globally, and more recently, emerging resistance to CQ byPlasmodium vivaxthreatens the health of 70 to 320 million people annually. Despite the emergence of CQ resistance, synthetic quinoline derivatives remain validated leads for new drug discovery, especially if they are effective against CQ-resistant strains of malaria. In this study, we investigated the activities of two novel 4-aminoquinoline derivatives, TDR 58845,N1-(7-chloro-quinolin-4-yl)-2-methyl-propane-1,2-diamine, and TDR 58846,N1-(7-chloro-quinolin-4-yl)-2,N2,N2-trimethylpropane-1,2-diamine and found them to be active againstP. falciparumin vitroandPlasmodium bergheiin vivo. TheP. falciparumclones and isolates tested were susceptible to TDR 58845 and TDR 58846 (50% inhibitory concentrations [IC50s] ranging from 5.52 to 89.8 nM), including the CQ-resistant reference clone W2 and two multidrug-resistant parasites recently isolated from Thailand and Cambodia. Moreover, these 4-aminoquinolines were active against early and lateP. falciparumgametocyte stages and cured BALB/c mice infected withP. berghei. TDR 58845 and TDR 58846 at 40 mg/kg were sufficient to cure mice, and total doses of 480 mg/kg of body weight were well tolerated. Our findings suggest these novel 4-aminoquinolines should be considered for development as potent antimalarials that can be used in combination to treat multidrug-resistantP. falciparumandP. vivax.

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Cytotoxic Metabolites Produced by Alternaria No.28, an Endophytic Fungus Isolated from Ginkgo biloba

Natural Product Communications ◽

10.1177/1934578x0900401106 ◽

2009 ◽

Vol 4 (11) ◽

pp. 1934578X0900401 ◽

Cited By ~ 3

Author(s):

Jian-Chun Qin ◽

Ya-Mei Zhang ◽

Ling Hu ◽

Ya-Tuan Ma ◽

Jin-Ming Gao

Keyword(s):

Ginkgo Biloba ◽

Endophytic Fungus ◽

Brine Shrimp ◽

Culture Media ◽

Monomethyl Ether ◽

Artemia Salina ◽

Fungal Endophyte ◽

Alternariol Monomethyl Ether ◽

Cytotoxic Effects

From the medicinal plant Ginkgo biloba the fungal endophyte Alternaria no.28 was isolated. Extract of the fungus grown in liquid culture media exhibited marked cytotoxic activity when tested in vitro against brine shrimp (Artemia salina). Eight compounds were isolated from the extract of cultures of this endophytic fungus and were elucidated as alterperylenol (1), altertoxin I (2), alternariol (3), alternariol monomethyl ether (4), tenuazonic acid (5) and its derivative (6), together with ergosterol and ergosta-4, 6, 8, 22-tetraen-3-one by means of spectroscopic analysis. Among them, both 5 and 6 showed significant cytotoxic effects in the brine shrimp bioassy, with mortality rates of 73.6% and 68.9%, respectively, at a concentration of 10 μg.mL−1, and they were first isolated from endophytic fungi.

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Naphthoquinones and derivatives for chemotherapy: perspectives and limitations of their anti-trypanosomatids activities

Current Pharmaceutical Design ◽

10.2174/1381612826666201109111802 ◽

2020 ◽

Vol 26 ◽

Author(s):

Luíza Dantas-Pereira ◽

Edézio F. Cunha-Junior ◽

Valter V. Andrade-Neto ◽

John F. Bower ◽

Guilherme A. M. Jardim ◽

...

Keyword(s):

Large Scale ◽

Neglected Tropical Diseases ◽

Folk Medicine ◽

Leishmania Species ◽

Parasitic Infections ◽

Mechanistic Analysis ◽

Leishmania Spp ◽

Nanomolar Range

: Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo are essential for the development of a novel, specific and safe derivative, minimizing adverse effects.

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The Toxic Effects of Two Dental Materials on Human Buccal Epithelium In Vitro and Monkey Buccal Epithelium In Vivo

Alternatives to Laboratory Animals ◽

10.1177/026119298701400313 ◽

1987 ◽

Vol 14 (3) ◽

pp. 166-167

Author(s):

D. Arenholt-Bindslev ◽

P. Hørsted-Bindslev ◽

H.P. Philipsen

Keyword(s):

Dental Materials ◽

Microscopical Examination ◽

Buccal Epithelium ◽

Cytotoxic Effects ◽

Buccal Epithelial Cells ◽

Toxicity In Vitro ◽

Toxic Reactions ◽

Light Microscopical Examination

The aim of the present study was to compare the toxicity in vitro with the toxicity in vivo of two commercial chemicals marketed for use in the oral cavity (GLUMA BondR and 3M Etching LiquidR). Confluent cultures of human buccal epithelial cells were exposed to graded concentrations of GLUMA Bond or 3M Etching Liquid for 5 minutes. The cytotoxic effects induced by this treatment were observed (cytomorphology, proliferation rate). In vivo, monkey buccal epithelium was exposed to GLUMA Bond or 3M Etching Liquid for 5 minutes. Biopsies were taken after 24 hours, and the buccal epithelium processed for light microscopical examination. In both models, the toxic reactions to GLUMA Bond were far more extensive than those caused by 3M Etching Liquid.

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Satureja subspicata and S. horvatii Extracts Induce Overexpression of the BCl-2 Family of Anti-apoptotic Genes and Reduce Micronuclei Frequency in Mice

Natural Product Communications ◽

10.1177/1934578x1801300617 ◽

2018 ◽

Vol 13 (6) ◽

pp. 1934578X1801300

Author(s):

Jasmina Čakar ◽

Naida Kadrić Lojo ◽

Anja Haverić ◽

Maida Hadžić ◽

Lejla Lasić ◽

...

Keyword(s):

Human Lymphocyte ◽

Micronucleus Assay ◽

Balkan Peninsula ◽

Lymphocyte Culture ◽

Cytotoxic Activities ◽

Cytotoxic Effects ◽

Apoptotic Genes ◽

Apoptotic Activity

Satureja subspicata and S. horvatii are endemic species of the Balkan Peninsula and often used in traditional medicine in Bosnia and Herzegovina to treat different health conditions. We aimed to analyze the unevaluated apoptotic, genotoxic and cytotoxic effects of two Satureja species, as well as their content of phenolics that are mainly responsible for the plant's biological activity. Apoptotic and geno/cytotoxic activities of S. subspicata and S. horvatii were investigated in vitro in human lymphocyte culture and in vivo in mice. The content of the main phenolics in plant extracts was determined by ultra-high pressure liquid chromatography-MS-MS (UHPLC–MS/MS). Genotoxic and cytotoxic activities of Satureja extracts were evaluated in vitro by applying a cytokinesis-block micronucleus cytome assay in human lymphocyte culture and in vivo applying a mice reticulocytes micronucleus assay. SALSA RT-MLPA R011-C1 apoptosis assay was used for measuring the relative expression of 44 genes associated with the regulation of the apoptotic pathways in human lymphocyte cultures treated with different concentrations of two Satureja extracts. The first analysis of phenolic compounds in S. horvatii and S. subspicata determined by an UHPLC-MS/MS method revealed high levels of rosmarinic and caffeic acids. Minor genotoxic potential was determined in relation to the tested concentrations while no cytostatic and cytotoxic effects were revealed in vitro. However, when applied in concentrations of 200 mg/kg per os, aqueous extracts of two Satureja species significantly decreased frequency of reticulocytes micronuclei in treated mice against controls. Extracts of S. subspicata and S. horvatii in concentrations of 0.2 mg/mL, regardless of solvent used, downregulated pro-apoptotic and upregulated anti-apoptotic genes, showing anti-apoptotic activity. Our results indicate that the registered anti-genotoxic and anti-apoptotic activity is most likely related to the high level of phenolic acids (particularly rosmarinic and caffeic) in the tested extracts.

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Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus

Pathogens ◽

10.3390/pathogens10050532 ◽

2021 ◽

Vol 10 (5) ◽

pp. 532

Author(s):

Hae-Soo Yun ◽

Sylvatrie-Danne Dinzouna-Boutamba ◽

Sanghyun Lee ◽

Zin Moon ◽

Dongmi Kwak ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Hematological Parameters ◽

Significant Inhibition ◽

Ic50 Values ◽

The Republic

In traditional Chinese medicine, Ranunculus japonicus has been used to treat various diseases, including malaria, and the young stem of R. japonicus is consumed as a food in the Republic of Korea. However, experimental evidence of the antimalarial effect of R. japonicus has not been evaluated. Therefore, the antimalarial activity of the extract of the young stem of R. japonicus was evaluated in vitro using both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains; in vivo activity was evaluated in Plasmodium berghei-infected mice via oral administration followed by a four-day suppressive test focused on biochemical and hematological parameters. Exposure to extracts of R. japonicus resulted in significant inhibition of both chloroquine-sensitive (3D7) and resistant (Dd2) strains of P. falciparum, with IC50 values of 6.29 ± 2.78 and 5.36 ± 4.93 μg/mL, respectively. Administration of R. japonicus also resulted in potent antimalarial activity against P. berghei in infected mice with no associated toxicity; treatment also resulted in improved hepatic, renal, and hematologic parameters. These results demonstrate the antimalarial effects of R. japonicus both in vitro and in vivo with no apparent toxicity.

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EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

Neuro-Oncology ◽

10.1093/neuonc/noz175.400 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi97-vi97

Author(s):

Satoshi Suehiro ◽

Takanori Ohnishi ◽

Akihiro Inoue ◽

Daisuke Yamashita ◽

Masahiro Nishikawa ◽

...

Keyword(s):

Tumor Cells ◽

Malignant Gliomas ◽

Glioma Cells ◽

High Intensity Focused Ultrasound ◽

Control Group ◽

Normal Brain ◽

Sonodynamic Therapy ◽

Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

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Papaya shoot tip associated endophytic bacteria isolated from in vitro cultures and host–endophyte interaction in vitro and in vivo

Canadian Journal of Microbiology ◽

10.1139/w06-141 ◽

2007 ◽

Vol 53 (3) ◽

pp. 380-390 ◽

Cited By ~ 36

Author(s):

Pious Thomas ◽

Sima Kumari ◽

Ganiga K. Swarna ◽

T.K.S. Gowda

Keyword(s):

Culture Medium ◽

Carica Papaya ◽

In Vitro Cultures ◽

Dependent Manner ◽

16S Rdna Sequence ◽

16S Rdna Sequence Analysis ◽

Single Organism ◽

Dose Dependent

Fourteen distinct bacterial clones were isolated from surface-sterilized shoot tips (~1 cm) of papaya (Carica papaya L. ‘Surya’) planted on Murashige and Skoog (MS)-based papaya culture medium (23/50 nos.) during the 2–4 week period following in vitro culturing. These isolates were ascribed to six Gram-negative genera, namely Pantoea ( P. ananatis ), Enterobacter ( E. cloacae ), Brevundimonas ( B. aurantiaca ), Sphingomonas , Methylobacterium ( M. rhodesianum ), and Agrobacterium ( A. tumefaciens ) or two Gram-positive genera, Microbacterium ( M. esteraromaticum ) and Bacillus ( B. benzoevorans ) based on 16S rDNA sequence analysis. Pantoea ananatis was the most frequently isolated organism (70% of the cultures) followed by B. benzoevorans (13%), while others were isolated from single stocks. Bacteria-harboring in vitro cultures often showed a single organism. Pantoea, Enterobacter, and Agrobacterium spp. grew actively on MS-based normal papaya medium, while Microbacterium, Brevundimonas, Bacillus, Sphingomonas, and Methylobacterium spp. failed to grow in the absence of host tissue. Supplying MS medium with tissue extract enhanced the growth of all the organisms in a dose-dependent manner, indicating reliance of the endophyte on its host. Inoculation of papaya seeds with the endophytes (20 h at OD550 = 0.5) led to delayed germination or slow seedling growth initially. However, the inhibition was overcome by 3 months and the seedlings inoculated with Pantoea, Microbacterium, or Sphingomonas spp. displayed significantly better root and shoot growths.

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