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Scientific Reports May 2023Over the past few decades, the green synthesis of nanoparticles has gained importance for their therapeutic efficacy and eco-friendly nature. Integrating green chemistry...
Over the past few decades, the green synthesis of nanoparticles has gained importance for their therapeutic efficacy and eco-friendly nature. Integrating green chemistry principles into multidisciplinary nanoscience research has paved the way for developing environmentally benign and sustainable methods for synthesizing gold and silver nanoparticles. In the present study, the flowers obtained from Clerodendrum infortunatum (L.), belonging to the family Verbenaceae, have been used for biosynthesizing silver nanoparticles (AgNPs) to evaluate the anthelmintic potential. UV-Vis spectroscopy, XRD, FTIR, SEM and TEM analyses were performed to ascertain the formation of AgNPs. Clerodendrum-derived AgNP (CLE-AgNP) has significantly affected the normal physiological functions of the poultry parasite Raillietina spp., a menace to the livestock industry. Our study manifests that CLE-AgNPs cause considerable distortion of the surface tegument of this cestode parasite leading to changes in the host-parasite interface. The histochemical localization studies of the tegument-associated enzymes viz. AcPase, AlkPase, ATPase and 5'-Nu, exposed to the drug, showed a substantial activity decline, thus establishing the anthelmintic potential of the CLE-AgNPs.
Topics: Metal Nanoparticles; Silver; Clerodendrum; Anti-Infective Agents; Anthelmintics; Spectroscopy, Fourier Transform Infrared; Plant Extracts; Anti-Bacterial Agents; Green Chemistry Technology
PubMed: 37150767
DOI: 10.1038/s41598-023-34221-9 -
Parasites & Vectors Jul 2023Helminth infections are an important public health problem in humans and have an even greater impact on domestic animal and livestock welfare. Current readouts for...
BACKGROUND
Helminth infections are an important public health problem in humans and have an even greater impact on domestic animal and livestock welfare. Current readouts for anthelmintic drug screening assays are stage development, migration, or motility that can be subjective, laborious, and low in throughput. The aim of this study was to apply and optimize a fluorometric technique using resazurin for evaluating changes in the metabolic activity of Ascaris suum third-stage larvae (L3), a parasite of high economic relevance in swine.
METHODS
Ascaris suum L3 were mechanically hatched from 6- to 8-week embryonated and sucrose-gradient-enriched eggs. Resazurin dye and A. suum L3 were titrated in 96-well microtiter plates, and resazurin reduction activity was assessed by fluorometry after 24 h of incubation. Fluorescence microscopy was used to localize the resazurin reduction site within the larvae. Finally, we exposed A. suum L3 to various stress conditions including heat, methanol, and anthelmintics, and investigated their impact on larval metabolism through resazurin reduction activity.
RESULTS
We show that the non-fluorescent dye resazurin is reduced inside vital A. suum L3 to fluorescent resorufin and released into the culture media. Optimal assay parameters are 100-1000 L3 per well, a resazurin concentration of 7.5 µg/ml, and incubation at 37 °C/5% CO for 24 h. An intact L2 sheath around the L3 of A. suum completely prevents the uptake of resazurin, while in unsheathed L3, the most intense fluorescence signal is observed along the larval midgut. L3 exposed to methanol or heat show a gradually decreased resazurin reduction activity. In addition, 24 h exposure to ivermectin at 0.625 µM, mebendazole at 5 µM, and thiabendazole from 10 to 100 µM significantly decreased larval metabolic activity by 55%, 73%, and 70% to 89%, respectively.
CONCLUSIONS
Together, our results show that both metabolic stressors and anthelmintic drugs significantly and reproducibly reduce the resazurin reduction activity of A. suum L3, making the proposed assay a sensitive and easy-to-use method to evaluate metabolic activity of A. suum L3 in vitro.
Topics: Humans; Animals; Swine; Ascaris suum; Methanol; Anthelmintics; Xanthenes; Ascariasis; Larva
PubMed: 37468906
DOI: 10.1186/s13071-023-05871-5 -
International Journal For Parasitology.... Dec 2020Control of helminth parasites is a key challenge for human and veterinary medicine. In the absence of effective vaccines and adequate sanitation, prophylaxis and...
Control of helminth parasites is a key challenge for human and veterinary medicine. In the absence of effective vaccines and adequate sanitation, prophylaxis and treatment commonly rely upon anthelmintics. There are concerns about the development of drug resistance, side-effects, lack of efficacy and cost-effectiveness that drive the need for new classes of anthelmintics. Despite this need, only three new drug classes have reached the animal market since 2000 and no new classes of anthelmintic have been approved for human use. So where are all the anthelmintics? What are the barriers to anthelmintic discovery, and what emerging opportunities can be used to address this? This was a discussion group focus at the 2019 8th Consortium for Anthelmintic Resistance and Susceptibility (CARS) in Wisconsin, USA. Here we report the findings of the group in the broader context of the human and veterinary anthelmintic discovery pipeline, highlighting challenges unique to antiparasitic drug discovery. We comment on why the development of novel anthelmintics has been so rare. Further, we discuss potential opportunities for drug development moving into the 21st Century.
Topics: Animals; Anthelmintics; Drug Discovery; Drug Resistance; Helminths; Humans
PubMed: 32814269
DOI: 10.1016/j.ijpddr.2020.07.001 -
International Journal of Pharmaceutics Sep 2023In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely...
In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely praziquantel (PZQ) and niclosamide (NCM) in a 1:3 molar ratio, and it can be obtained through a sustainable one-step mechanochemical process in the presence of micromolar amounts of methanol. The novel solid phase crystallizes in the monoclinic space group of P2/c, showing one PZQ and three NCM molecules linked through homo- and heteromolecular hydrogen bonds in the asymmetric unit, as also attested by SSNMR and FT-IR results. A plate-like habitus is evident from scanning electron microscopy analysis with a melting point of 202.89 °C, which is intermediate to those of the parent compounds. The supramolecular interactions confer favorable properties to the cocrystal, preventing NCM transformation into the insoluble monohydrate both in the solid state and in aqueous solution. Remarkably, the PZQ - NCM cocrystal exhibits higher anthelmintic activity against in vitro S. mansoni models than corresponding physical mixture of the APIs. Finally, due to in vitro promising results, in vivo preliminary tests on mice were also performed through the administration of minicapsules size M.
Topics: Animals; Mice; Praziquantel; Niclosamide; Antiparasitic Agents; Pharmaceutical Preparations; Spectroscopy, Fourier Transform Infrared; Anthelmintics; Schistosoma mansoni
PubMed: 37579827
DOI: 10.1016/j.ijpharm.2023.123315 -
Molecules (Basel, Switzerland) Mar 2022Helminth infections continue to be a neglected global threat in tropical regions, and there have been growing cases of anthelmintic resistance reported towards the...
Helminth infections continue to be a neglected global threat in tropical regions, and there have been growing cases of anthelmintic resistance reported towards the existing anthelmintic drugs. Thus, the search for a novel anthelmintic agent has been increasing, especially those derived from plants. (LL) is a leguminous plant that is known to have several pharmacological activities, including anthelmintic activity. It is widely known to contain a toxic compound called mimosine, which we believed could be a potential lead candidate that could exert a potent anthelmintic effect. Hence, this study aimed to validate the presence of mimosine in LL extract and to investigate the anthelmintic effect of LL extract and mimosine on head thrashing, egg-laying, and pharyngeal pumping activities using the animal model Mimosine content in LL extract was confirmed through an HPLC analysis of spiking LL extract with different mimosine concentrations, whereby an increasing trend in peak heights was observed at a retention time of 0.9 min. LL extract and mimosine caused a significant dose-dependent increase in the percentage of worm mortality, which produced LC50s of 73 mg/mL and 6.39 mg/mL, respectively. Exposure of to different concentrations of LL extract and mimosine significantly decreased the head thrashing, egg-laying, and mean pump amplitude of pharyngeal pumping activity. We speculated that these behavioral changes are due to the inhibitory effect of LL extract and mimosine on an L-type calcium channel called EGL-19. Our findings provide evidential support for the potential of LL extract and its active compound, mimosine, as novel anthelmintic candidates. However, the underlying mechanism of the anthelmintic action has yet to be elucidated.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Fabaceae; Mimosine; Plant Extracts
PubMed: 35335240
DOI: 10.3390/molecules27061875 -
BMC Complementary Medicine and Therapies Jul 2020Traditional medicines are the main source of treatment of helminthiasis in endemic areas of Togo. The present study aimed to investigate the plants used by Traditional...
BACKGROUND
Traditional medicines are the main source of treatment of helminthiasis in endemic areas of Togo. The present study aimed to investigate the plants used by Traditional healers (THs) to treat helminth infections in endemic communities within the Central and Kara regions of Togo and to evaluate the anthelmintic activity of the three most cited plants.
METHODS
An ethnobotanical survey was conducted from 19 to 24 June 2017 among traditional healers in the Central and Kara regions of Togo. The anthelmintic activity of the most cited plants namely Aframomum melegueta K. Schum, Khaya senegalensis A. Juss and Xylopia aethiopica A. Rich, was evaluated using microfilariae (Mf) of Litomosoides sigmodontis. The plants were evaluated for cytotoxicity according to the recommendation of NF EN ISO 10993-5 standard using the propidium iodide (PI) dye by flow cytometry on human peripheral blood mononuclear cells.
RESULTS
A total of 197 THs were interviewed and 41 plant species were recorded. Leguminosae (14.6%) and Annonaceae (9.7%) families constitute the highest number of species cited for treatment of helminth infections. Afromomum melegueta was the most cited by the THs for the treatment of onchocerciasis (UV = 0.036) while X. aethiopica was associated with the treatment of schistosomiasis (UV = 0.061) and lymphatic filariasis (UV = 0.061). There was a great agreement among the THs regarding ethnomedicinal uses of plants to treat helminthiasis with ICF values ranging from 0.57 to 0.67. The anthelmintic assay yielded lethal doses values of 233 μg/mL, 265 μg/mL and 550 μg/mL, respectively for X. aethiopica, A. melegueta and K. senegalensis. Afromomum melegueta and X. aethiopica presented no cytotoxicity, less than 20% death, whereas K. senegalensis induced moderate toxicity, 24 ± 8% death.
CONCLUSION
This study demonstrated the scientific rationale for the use of plants to treat helminthiasis in the Togolese traditional medicine. However, the use of K. senegalensis requires more caution since the plant is fairly toxic.
TRIAL REGISTRATION
NA.
Topics: Adult; Anthelmintics; Ethnobotany; Female; Helminthiasis; Humans; Male; Medicine, African Traditional; Meliaceae; Surveys and Questionnaires; Togo; Xylopia; Zingiberaceae
PubMed: 32635909
DOI: 10.1186/s12906-020-03008-0 -
International Journal For Parasitology.... Dec 2018The third scientific meeting in the series "Anthelmintics: From Discovery to Resistance" was held in Indian Rocks Beach, Florida, at the end of January 2018. The meeting...
The third scientific meeting in the series "Anthelmintics: From Discovery to Resistance" was held in Indian Rocks Beach, Florida, at the end of January 2018. The meeting focused on a variety of topics related to the title, including the identification of novel targets and new leads, the mechanism of action of existing drugs and the genetic basis of resistance against them. Throughout there was an emphasis on the exploitation of new technologies and methods to further these aims. The presentations, oral and poster, covered basic, veterinary and medical science with strong participation by both academic and commercial researchers. This special issue contains selected papers from the meeting.
Topics: Animals; Anthelmintics; Congresses as Topic; Drug Delivery Systems; Drug Discovery; Humans; Ion Channels
PubMed: 30429103
DOI: 10.1016/j.ijpddr.2018.11.002 -
International Journal of Molecular... Jul 2020Tumors of the digestive system, when combined together, account for more new cases and deaths per year than tumors arising in any other system of the body and their... (Review)
Review
Tumors of the digestive system, when combined together, account for more new cases and deaths per year than tumors arising in any other system of the body and their incidence continues to increase. Despite major efforts aimed at discovering and validating novel and effective drugs against these malignancies, the process of developing such drugs remains lengthy and costly, with high attrition rates. Drug repositioning (also known as drug repurposing), that is, the process of finding new uses for approved drugs, has been gaining popularity in oncological drug development as it provides the opportunity to expedite promising anti-cancer agents into clinical trials. Among the drugs considered for repurposing in oncology, compounds belonging to some classes of anthelmintics-a group of agents acting against infections caused by parasitic worms (helminths) that colonize the mammalian intestine-have shown pronounced anti-tumor activities and attracted particular attention due to their ability to target key oncogenic signal transduction pathways. In this review, we summarize and discuss the available experimental and clinical evidence about the use of anthelmintic drugs for the treatment of cancers of the digestive system.
Topics: Anthelmintics; Antineoplastic Agents; Benzimidazoles; Clinical Trials as Topic; Digestive System Neoplasms; Drug Discovery; Drug Repositioning; Drug Screening Assays, Antitumor; Humans; Salicylanilides; Signal Transduction
PubMed: 32668817
DOI: 10.3390/ijms21144957 -
BMC Complementary and Alternative... Oct 2016It has been recently recognized that oxidative stress, helminth and microbial infections are the cause of much illness found in the underdeveloped, developing and...
BACKGROUND
It has been recently recognized that oxidative stress, helminth and microbial infections are the cause of much illness found in the underdeveloped, developing and developed countries. The present study was undertaken to identify the chemical composition, and to assess anthelmintic, antimicrobial and antioxidant effects of Thymus bovei essential oil.
METHODS
The chemical composition of the essential oil was analyzed using gas chromatography mass spectrometry (GC-MS). Antimicrobial activity was tested against the selected strains from American Type Culture Collection (ATCC) and clinical isolates such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Methicillin Resistant Staphylococcus aureus, Candida albicans using MIC assay. The anthelmintic assay was carried out on adult earthworm (Pheretima posthuma), while antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method.
RESULTS
Trans-geraniol (35.38 %), α-citral (20.37 %) and β-citral (14.76 %) were the major compounds comprising 70.51 % of the essential oil. Our results showed that T. bovei essential oil exhibited strong anthelmintic activity, even higher than piperazine citrate, the used reference standard, with potential antioxidant activity almost equal to the Trolox standard. Furthermore, T. bovei essential oil had powerful antibacterial and antifungal activities against the studied pathogens.
CONCLUSION
Essential oil of T. bovei exerted excellent antioxidant, antimicrobial, and anthelmintic activities. Moreover, this study found that T. bovei volatile oil contains active substances that could potentially be used as natural preservatives in food and pharmaceutical industries, these substances could also be employed for developing new anthelmintic, antimicrobial and antioxidant agents.
Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Antioxidants; Bacteria; Biphenyl Compounds; Oils, Volatile; Oligochaeta; Picrates; Plant Oils; Thymus Plant
PubMed: 27782845
DOI: 10.1186/s12906-016-1408-2 -
Molecules (Basel, Switzerland) Apr 2021The objective of this study is to develop a comprehensive and simple method for the simultaneous determination of anthelmintic and antiprotozoal drug residues in fish....
The objective of this study is to develop a comprehensive and simple method for the simultaneous determination of anthelmintic and antiprotozoal drug residues in fish. For sample preparation, we used the "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) method with a simple modification. The sample was extracted with water and 1% formic acid in acetonitrile/methanol (MeCN/MeOH) (95:5, /), followed by phase separation (salting out) with MgSO and NaCl (4:1, /). After centrifugation, an aliquot of the extract was purified by dispersive solid-phase extraction (d-SPE) prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The method was validated at three concentration levels for all matrices, in accordance with the Codex guidelines (CAC/GL-71). Quantitative analysis was performed using the method of matrix-matched calibration. The recoveries were between 60.6% and 119.9%, with coefficients of variation (CV) <30% for all matrices. The limit of quantitation (LOQ) of the method ranged from 0.02 μg kg to 4.8 μg kg for all matrices. This comprehensive method can be used for the investigation of both anthelmintic and antiprotozoal drugs belonging to different chemical families in fishery products.
Topics: Animals; Anthelmintics; Antiparasitic Agents; Chromatography, Liquid; Drug Residues; Fishes; Food Analysis; Tandem Mass Spectrometry
PubMed: 33925124
DOI: 10.3390/molecules26092575