Anthelmintics in the future: current trends in the discovery and development of new drugs against gastrointestinal nematodes

Zajíčková, Markéta; Nguyen, Linh Thuy; Skálová, Lenka; Stuchlíková, Lucie Raisová; Matoušková, Petra

doi:10.1016/j.drudis.2019.12.007

Cited by 68 publications

(50 citation statements)

References 96 publications

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“…Anthelmintic strategies for controlling gastrointestinal nematode (GIN) parasites in small ruminants mostly use the repeated application of synthetic drugs that can lead to the development of anthelmintic resistance [ 1 , 2 ]. The current global trend is to develop new anthelmintics that are effective mainly against resistant species of nematodes [ 3 ]. Well-known anthelmintic effects of herbal medicines against the GIN Haemonchus contortus are associated with bioactive compounds, mainly tannins, saponins, and flavonoids, with two possible general mechanisms of action: direct effects on the parasite, or indirect effects by interaction with the host immune system [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Medicinal Plants and Organic Selenium against Ovine Haemonchosis

Komáromyová

Mravčáková

Petrič

et al. 2021

Animals

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The objective of this study was to determine the effect of traditional medicinal plants typical to Central Europe as well as organic selenium on increasing the resistance of lambs to gastrointestinal nematode (GIN) infection with Haemonchus contortus. 21 female lambs were infected with third-stage larvae of H. contortus on the day (D) 0 and re-infected on D49 and D77. The animals were divided into three groups based on a treatment diet: a basal diet (control), a diet enriched with dry plants (Herbmix), and a diet enriched with selenized yeast (Selplex). The number of eggs per gram (EPG) of feces was quantified on D21, D28, D35, D42, D49, D56, D63, D70, D77, D84, D91, D98, D105, D112, and D119. The mean reductions in EPG on D28 were 43.4 and 28.6% for Selplex and Herbmix, respectively. The reduction in egg output was nearly uniform throughout the experiment for Selplex. However, for Herbmix the mean reduction was only 19.8% up to D91 and 46.1% after D91. Glutathione peroxidase activity in the blood from D35 to D98 was two to three-fold higher for Selplex than the other groups. Both supplements slowed the dynamics of GIN infection and gradually increased the resistance of lambs against ovine haemonchosis.

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Section: Introductionmentioning

confidence: 99%

Effects of Medicinal Plants and Organic Selenium against Ovine Haemonchosis

Komáromyová

Mravčáková

Petrič

et al. 2021

Animals

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“…Their excessive use, however, has led to the development of anthelmintic resistance in GIN populations [2] and has increased the level of chemical residues in animal products [3]. The expansion of anthelmintic resistance and consumer demand for chemical free animal products has created an urgent need for a more sustainable alternative control of GINs [4,5], such as nutritional supplementation with medicinal plants [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Effect of Artemisia absinthium and Malva sylvestris on Antioxidant Parameters and Abomasal Histopathology in Lambs Experimentally Infected with Haemonchus contortus

Mravčáková

Sobczak-Filipiak

Váradyová

et al. 2021

Animals

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This study evaluated the effect of Artemisia absinthium and Malva sylvestris on antioxidant response and histopathological changes in the abomasa of the Haemonchus contortus infected lambs. Twenty-four lambs were divided into four groups: unsupplemented lambs (UNS), lambs supplemented with A. absinthium (ART), lambs supplemented with M. sylvestris (MAL), and lambs supplemented with both plants (ARTMAL). Lambs were infected orally with approximately 5000 third-stage (L3) larvae of H. contortus. The experiment was conducted for 75 d (days), all animals were then slaughtered; and the abomasal tissues were examined for antioxidant parameters and histopathology. The concentration of malondialdehyde in the abomasal mucosa was lower in ARTMAL (p < 0.05), and the total antioxidant capacity was higher in MAL (p < 0.05), than in UNS. Increased mucus production was observed in the ARTMAL. The number of mast cells in UNS and ART was significantly higher than the number in MAL (p < 0.01 and p < 0.05). Plasma cell numbers were higher in ARTMAL than the number in MAL (p < 0.05). Abomasal tissue regenerated more frequently in ARTMAL. These results represent the first report of the impact of A. absinthium and M. sylvestris on antioxidant parameters and local immune responses of abomasal mucosa of lambs infected with a GIN parasite.

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“…Currently, the control of H. contortus and related nematodes relies on the use of a limited number of anti-parasitic drugs and their excessive and often uncontrolled use has led to widespread resistance in these worms against these drugs (within as few as two years) [7,8], even to those most-recently introduced into the commercial market (e.g., monepantel) [9][10][11]. The relatively rapid emergence (within 5-10 years) of resistance in gastrointestinal nematode populations [7] means that there is a continued need for the discovery of new compounds with modes/mechanisms of action which are distinct from those presently available on the commercial market [12,13].…”

Section: Introductionmentioning

confidence: 99%

Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus

et al. 2020

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Eight secondary metabolites (1 to 8) were isolated from a marine sponge, a marine alga and three terrestrial plants collected in Australia and subsequently chemically characterised. Here, these natural product-derived compounds were screened for in vitro-anthelmintic activity against the larvae and adult stages of Haemonchus contortus (barber’s pole worm)—a highly pathogenic parasitic nematode of ruminants. Using an optimised, whole-organism screening system, compounds were tested on exsheathed third-stage larvae (xL3s) and fourth-stage larvae (L4s). Anthelmintic activity was initially evaluated on these stages based on the inhibition of motility, development and/or changes in morphology (phenotype). We identified two compounds, 6-undecylsalicylic acid (3) and 6-tridecylsalicylic acid (4) isolated from the marine brown alga, Caulocystis cephalornithos, with inhibitory effects on xL3 and L4 motility and larval development, and the induction of a “skinny-straight” phenotype. Subsequent testing showed that these two compounds had an acute nematocidal effect (within 1–12 h) on adult males and females of H. contortus. Ultrastructural analysis of adult worms treated with compound 4 revealed significant damage to subcuticular musculature and associated tissues and cellular organelles including mitochondria. In conclusion, the present study has discovered two algal compounds possessing acute anthelmintic effects and with potential for hit-to-lead progression. Future work should focus on undertaking a structure-activity relationship study and on elucidating the mode(s) of action of optimised compounds.

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Anthelmintics in the future: current trends in the discovery and development of new drugs against gastrointestinal nematodes

Cited by 68 publications

References 96 publications

Effects of Medicinal Plants and Organic Selenium against Ovine Haemonchosis

Effects of Medicinal Plants and Organic Selenium against Ovine Haemonchosis

Effect of Artemisia absinthium and Malva sylvestris on Antioxidant Parameters and Abomasal Histopathology in Lambs Experimentally Infected with Haemonchus contortus

Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus

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