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Revista Brasileira de Parasitologia... 2017Thymol is a monoterpene and acetylation form of this compound can reduce the toxicity and enhance its biological effects. The objective of this study was to evaluate the...
Thymol is a monoterpene and acetylation form of this compound can reduce the toxicity and enhance its biological effects. The objective of this study was to evaluate the effect of thymol and thymol acetate (TA) on egg, larva and adult Haemonchus contortus and the cuticular changes, acute toxicity in mice and the efficacy on sheep gastrointestinal nematodes. In vitro tests results were analyzed by analysis of variance (ANOVA) and followed by comparison with Tukey test or Bonferroni. The efficacy of in vivo test was calculated by the BootStreet program. In the egg hatch test (EHT), thymol (0.5 mg/mL) and TA (4 mg/mL) inhibited larval hatching by 98% and 67.1%, respectively. Thymol and TA (8 mg/mL) inhibited 100% of larval development. Thymol and TA (800 µg/mL) reduced the motility of adult worms, by 100% and 83.4%, respectively. Thymol caused cuticular changes in adult worm teguments. In the acute toxicity test, the LD50 of thymol and TA were 1,350.9 mg/kg and 4,144.4 mg/kg, respectively. Thymol and TA reduced sheep egg count per gram of faeces (epg) by 59.8% and 76.2%, respectively. In in vitro tests thymol presented better anthelmintic activity than TA. However TA was less toxic and in in vivo test efficacy was similar.
Topics: Acetates; Acetylation; Animals; Anthelmintics; Female; Haemonchus; Mice; Nematoda; Nematode Infections; Sheep; Sheep Diseases; Thymol
PubMed: 28977246
DOI: 10.1590/S1984-29612017056 -
Chemical & Pharmaceutical Bulletin 2012Naturally occurring avermectins (AVMs) and its derivatives are potent endectocide compounds, well-known for their novel mode of action against a broad range of nematode... (Review)
Review
Naturally occurring avermectins (AVMs) and its derivatives are potent endectocide compounds, well-known for their novel mode of action against a broad range of nematode and anthropod animal parasites. In this review, chemical and pharmaceutical aspects of AVM derivatives are described including stability, synthetic and purification processes, impurities and degradation pathways, and subsequent suggestions are made to improve the chemical stability. It has been found out that unique structure of AVM molecules and presence of labile groups facilitated the derivatization of AVM into various compounds showing strong anthelmintic activity. However, the same unique structure is also responsible for labile nature related to sensitive stability profile of molecules. AVMs are found to be unstable in acidic and alkaline conditions. In addition, these compounds are sensitive to strong light, and subsequently presence of photo-isomer in animals treated topically with AVM product is well known. The pharmacoepial recommendations for addition of antioxidant into drug substance, as well as its products, arises from the fact that AVM are very sensitive to oxidation. Formations of solvates, salts, epoxides, reduction of double bonds and developing liquid formulation around pH 6.2, were some chemical approaches used to retard the degradation in AVM. This coherent review will contribute towards the better understanding of the correlation of chemical processes, stability profile and biological activity; therefore, it will help to design the shelf-life stable formulations containing AVMs.
Topics: Animals; Anthelmintics; Drug Stability; Hydrogen-Ion Concentration; Ivermectin; Molecular Structure; Oxidation-Reduction
PubMed: 22863694
DOI: 10.1248/cpb.c12-00258 -
Molecules (Basel, Switzerland) May 2019() Ridsdale (Leeaceae) is found in tropical and subtropical countries and has historically been used as a traditional medicine in local healthcare systems. Although...
() Ridsdale (Leeaceae) is found in tropical and subtropical countries and has historically been used as a traditional medicine in local healthcare systems. Although extracts have been found to possess anthelmintic and antioxidant-related nephroprotective and hepatoprotective effects, little attention has been paid toward the investigation of phytochemical constituents of this plant. In the current study, phytochemical analysis of isolates from led to the identification of 24 compounds, including a novel phenolic glucoside, seven triterpenoids, eight flavonoids, two phenolic glycosides, four diglycosidic compounds, and two miscellaneous compounds. The phytochemical structures of the isolates from were elucidated using spectroscopic analyses including 1D- and 2D-NMR and ESI-Q-TOF-MS. The presence of triterpenoids and flavonoids supports the evidence for anthelmintic and antioxidative effects of
Topics: Anthelmintics; Antioxidants; Flavonoids; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medicine, Traditional; Molecular Structure; Phytochemicals; Plant Components, Aerial; Triterpenes; Vitaceae
PubMed: 31060200
DOI: 10.3390/molecules24091733 -
BMC Complementary Medicine and Therapies Nov 2020Imperata cylindrica is considered as an agricultural weed, but it is a valuable plant in the traditional medicines of Southeast Asia. In the Mizo traditional medicine of...
BACKGROUND
Imperata cylindrica is considered as an agricultural weed, but it is a valuable plant in the traditional medicines of Southeast Asia. In the Mizo traditional medicine of India and Myanmar, the rhizomes and roots are used as a remedy for bacterial, fungal and intestinal helminth infections.
METHODS
An extract of the whole underground parts was prepared in Soxhlet apparatus using chloroform as a solvent. After concentrating in a vacuum rotary evaporator, the extract was analysed using gas chromatography-mass spectrometry. Anthelmintic activity was tested in vitro against the tapeworm Raillietina tetragona and the roundworm Ascaridia galli. Scanning electron microscopy was used to examine the structural changes on the helminths after treatment with the plant extract.
RESULTS
Twenty-two compounds were identified from the plant extract out of which fatty acids were the predominant compounds. Palmitic acid was the most abundant. Bioactive phytosterols such as campesterol and stigmasterol were also detected. The plant extract was significantly effective on both the helminths and showed dose-dependent anthelmintic activity as that of albendazole. The tapeworm treated with the plant extract showed deformities on the suckers, clumping of the spines, tegumental folds and erosion of microtriches. Extensive damage was also seen on the roundworm including cuticular shrinkage, collapse of the lips, and formation of warty surface throughout the body.
CONCLUSION
I. cylindrica extract effectively killed and caused detrimental effects on parasitic tapeworm and roundworm. The study therefore validates the traditional usage among the Mizo people, and guarantees further investigation on the exact compound(s) and mechanism of action.
Topics: Animals; Anthelmintics; Ascaridia; Cestoda; Humans; In Vitro Techniques; India; Phytochemicals; Plant Extracts; Plant Roots; Poaceae
PubMed: 33158437
DOI: 10.1186/s12906-020-03125-w -
Scientific Reports Jul 2022The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of...
The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants.
Topics: Animals; Anthelmintics; Benzimidazoles; Gerbillinae; Haemonchiasis; Haemonchus; Mice; Nematoda; Sheep; Sheep Diseases
PubMed: 35906366
DOI: 10.1038/s41598-022-17112-3 -
Acta Crystallographica. Section C,... Sep 2021A chemical study of the hydro-ethanol extract of the leaves of Combretum glutinosum resulted in the isolation of nine compounds, including 5-demethylsinensetin (1),...
A chemical study of the hydro-ethanol extract of the leaves of Combretum glutinosum resulted in the isolation of nine compounds, including 5-demethylsinensetin (1), umuhengerin (2), (20S,24R)-ocotillone (3), lupeol (4), β-sitosterol (5), oleanolic acid (6), betulinic acid (7), corymbosin (8) and β-sitosterol glucoside (9). Four compounds have been isolated for the first time from the genus Combretum [viz. (1), (2), (3) and (8)]. The crystal structures of flavonoid (2), CHO, Z' = 2, and triterpene (3), CHO, Z' = 1, have been determined for the first time; the latter confirmed the absolute configuration of native (20S,24R)-ocotillone previously derived from the crystal structures of related derivatives. The molecules of (3) are linked into supramolecular chains by intermolecular O-H...O hydrogen bonds. The crude extracts obtained by aqueous decoction and hydro-ethanolic maceration, as well as the nine isolated compounds, were tested for their anthelmintic activity on the larvae and adult worms of Haemonchus contortus, a hematophage that causes parasitic disorders in small ruminants. The evaluated anthelmintic activity showed that the extracts at different doses, as well as all the compounds tested at 150 µg ml, inhibited the migration of the larvae and the motility of the adult worms of the parasite compared with the phosphate buffer solution negative reference control. The best activity was obtained with flavonoids (1), (2) and (8) on both stages of the parasite. The flavones that showed good activity can be used for the further development of other derivatives, which could increase the anthelmintic efficacy.
Topics: Animals; Anthelmintics; Anti-Infective Agents; Combretaceae; Combretum; Crystallography, X-Ray; Flavones; Flavonoids; Haemonchus; Hydrogen Bonding; Larva; Plant Leaves
PubMed: 34482293
DOI: 10.1107/S2053229621007841 -
PLoS Pathogens Apr 2023Treatment of parasitic nematode infections in humans and livestock relies on a limited arsenal of anthelmintic drugs that have historically reduced parasite burdens....
Treatment of parasitic nematode infections in humans and livestock relies on a limited arsenal of anthelmintic drugs that have historically reduced parasite burdens. However, anthelmintic resistance (AR) is increasing, and little is known about the molecular and genetic causes of resistance for most drugs. The free-living roundworm Caenorhabditis elegans has proven to be a tractable model to understand AR, where studies have led to the identification of molecular targets of all major anthelmintic drug classes. Here, we used genetically diverse C. elegans strains to perform dose-response analyses across 26 anthelmintic drugs that represent the three major anthelmintic drug classes (benzimidazoles, macrocyclic lactones, and nicotinic acetylcholine receptor agonists) in addition to seven other anthelmintic classes. First, we found that C. elegans strains displayed similar anthelmintic responses within drug classes and significant variation across drug classes. Next, we compared the effective concentration estimates to induce a 10% maximal response (EC10) and slope estimates of each dose-response curve of each strain to the laboratory reference strain, which enabled the identification of anthelmintics with population-wide differences to understand how genetics contribute to AR. Because genetically diverse strains displayed differential susceptibilities within and across anthelmintics, we show that C. elegans is a useful model for screening potential nematicides before applications to helminths. Third, we quantified the levels of anthelmintic response variation caused by genetic differences among individuals (heritability) to each drug and observed a significant correlation between exposure closest to the EC10 and the exposure that exhibited the most heritable responses. These results suggest drugs to prioritize in genome-wide association studies, which will enable the identification of AR genes.
Topics: Humans; Animals; Caenorhabditis elegans; Genome-Wide Association Study; Anthelmintics; Nematoda; Antinematodal Agents; Nematode Infections; Drug Resistance
PubMed: 37011090
DOI: 10.1371/journal.ppat.1011285 -
Veterinary Research 2002The control of ruminant gastrointestinal nematodes and ectoparasites, one of the major production health problems, are heavily reliant on the systematic and sometimes... (Review)
Review
The control of ruminant gastrointestinal nematodes and ectoparasites, one of the major production health problems, are heavily reliant on the systematic and sometimes abusive use of anthelmintic drugs. Endectocides are the most frequently used drugs, having high potency against arthropods and nematodes. Their dung pat residues enhance the risk of adverse effects on non-target invertebrates and on the general grazing cattle ecosystem. In this scenario, our objective is to review current knowledge of the agro-environmental and biodiversity impact and risks of endectocides in South America. The effects of faecal drug residues of ivermectin and doramectin on dung colonising invertebrates and dung degradation have been reported in studies carried out in the temperate centre of Argentina and in the subtropical region of Brazil. The results from Argentina showed a depression in invertebrate colonisation and degradation of dung recovered from endectocide treated cattle during the autumn. Comparisons have shown that ivermectin and doramectin have similar adverse effects. A decrease of Coleoptera larvae, Diptera larvae, Staphylinidae, Collembola, Acari and dung specific nematodes was noted in pats from both endectocides. The results from Brazil showed that dipterous larvae, Polyphaga coleopteran larvae and adults and mites were significantly reduced in the ivermectin treated group. The disturbances that macrocyclic lactones can produce on non-targeted invertebrates and on their associated participation in dung degradation and soil element recycling, are unpredictable and can negatively influence biodiversity and the agricultural ecosystem sustainability.
Topics: Animal Husbandry; Animals; Anthelmintics; Drug Residues; Drug Resistance; Ecosystem; Ectoparasitic Infestations; Feces; Invertebrates; Nematode Infections; Ruminants; South America
PubMed: 12387490
DOI: 10.1051/vetres:2002039 -
International Journal For Parasitology.... Dec 2016The second scientific meeting in the series: "Anthelmintics: From Discovery to Resistance" was held in San Diego in February, 2016. The focus topics of the meeting,...
The second scientific meeting in the series: "Anthelmintics: From Discovery to Resistance" was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand. The papers were a great representation of the field, and included the use of C. elegans for lead discovery, mechanisms of anthelmintic resistance, nematode neuropeptides, proteases, B. thuringiensis crystal protein, nicotinic receptors, emodepside, benzimidazoles, P-glycoproteins, natural products, microfluidic techniques and bioinformatics approaches. The NIH also presented NIAID-specific parasite genomic priorities and initiatives. From these papers we introduce below selected papers with a focus on anthelmintic drug screening and development.
Topics: Animals; Anthelmintics; Drug Discovery; Drug Resistance; Helminthiasis; Humans
PubMed: 27814986
DOI: 10.1016/j.ijpddr.2016.09.002 -
Parasitology Oct 2022This work aimed to evaluate the anthelmintic effect of carvone nanoemulsions on . Three R-carvone nanoemulsions were prepared: uncoated R-carvone nanoemulsions...
This work aimed to evaluate the anthelmintic effect of carvone nanoemulsions on . Three R-carvone nanoemulsions were prepared: uncoated R-carvone nanoemulsions homogenized in a sonicator (UNAlg-son) and homogenized in an ultrahomogenizer (UNAlg-ultra) and sodium alginate-coated R-carvone (CNAlg-ultra). The physicochemical characterizations of the nanoemulsions were carried out. The anthelmintic activity was evaluated using egg hatch test (EHT), larval development test (LDT) and adult worm motility test (AWMT). Changes in cuticle induced in adult were evaluated by scanning electron microscopy (SEM). The results were subjected to analysis of variance and compared using the Tukey test ( < 0.05). The effective concentration to inhibit 50% (EC) of egg hatching and larval development was calculated. The particle sizes were 281.1 nm (UNAlg-son), 152.7 nm (UNAlg-ultra) and 557.8 nm (CNAlg-ultra), and the zeta potentials were −15 mV (UNAlg-son), −10.8 mV (UNAlg-ultra) and −24.2 mV (CNAlg-ultra). The encapsulation efficiency was 99.84 ± 0.01%. SEM of the nanoemulsions showed an increase in size. In EHT, the EC values of UNAlg-son, UNAlg-ultra and CNAlg-ultra were 0.19, 0.02 and 0.17 mg mL, respectively. In LDT, they were 0.29, 0.31 and 0.95 mg mL for UNAlg-son, UNAlg-ultra and CNAlg-ultra, respectively. The adult motility inhibition was 100% after 12 h of exposure to UNAlg-ultra and CNAlg-ultra, while for UNAlg-son, it was 79.16%. SEM showed changes in the buccal capsule and cuticular damage. It was concluded that R-carvone nanoemulsions showed antiparasitic action demonstrating promise for the control of infections caused by gastrointestinal nematodes in small ruminants.
Topics: Animals; Haemonchus; Haemonchiasis; Anthelmintics; Cyclohexane Monoterpenes; Larva; Plant Extracts
PubMed: 36052509
DOI: 10.1017/S0031182022001135