Dysidenin from the Marine Sponge Citronia sp. Affects the Motility and Morphology of Haemonchus contortus Larvae In Vitro

High-throughput screening of the NatureBank marine extract library (n = 7616) using a phenotypic assay for the parasitic nematode Haemonchus contortus identified an active extract derived from the Australian marine sponge Citronia sp. Bioassay-guided fractionation of the CH2Cl2/MeOH extract from Citronia sp. resulted in the purification of two known hexachlorinated peptides, dysidenin (1) and dysideathiazole (2). Compound 1 inhibited the growth/development of H. contortus larvae and induced multiple phenotypic changes, including a lethal evisceration (Evi) phenotype and/or somatic cell and tissue destruction. This is the first report of anthelmintic activity for these rare and unique polychlorinated peptides.

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

Pathogens ◽

10.3390/pathogens9070550 ◽

2020 ◽

Vol 9 (7) ◽

pp. 550

Author(s):

Aya C. Taki ◽

Robert Brkljača ◽

Tao Wang ◽

Anson V. Koehler ◽

Guangxu Ma ◽

...

Keyword(s):

Haemonchus Contortus ◽

Brown Alga ◽

Parasitic Nematode ◽

Anthelmintic Activity ◽

Adult Males ◽

Terrestrial Plants ◽

Third Stage ◽

Future Work ◽

Marine Brown Alga

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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Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against Haemonchus contortus

Marine Drugs ◽

10.3390/md17110598 ◽

2019 ◽

Vol 17 (11) ◽

pp. 598 ◽

Cited By ~ 3

Author(s):

H. Herath ◽

Sarah Preston ◽

Abdul Jabbar ◽

Jose Garcia-Bustos ◽

Aya Taki ◽

...

Keyword(s):

Haemonchus Contortus ◽

Marine Invertebrates ◽

Anthelmintic Activity ◽

Marine Sponges ◽

Parasitic Nematodes ◽

Natural Ecosystems ◽

Bioassay Guided Fractionation ◽

Guanidine Alkaloids ◽

Nematocidal Activity

There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus — a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 ± 0.74 µM) and L4 motility (IC50 = 39.4 ± 4.83 µM), although it had a relatively low potency at inhibiting of xL3 motility (IC50 ≥ 100 µM). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.

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Chemical characterization and in vitro anthelmintic activity of Citrus bergamia Risso and Citrus X paradisii Macfad essential oil against Haemonchus contortus Kirby isolate

Acta Tropica ◽

10.1016/j.actatropica.2021.105869 ◽

2021 ◽

Vol 217 ◽

pp. 105869

Author(s):

Vivien Patricia Garbin ◽

Beatriz Munguía ◽

Jenny Carolina Saldaña ◽

Cícero Deschamps ◽

Roger Raupp Cipriano ◽

...

Keyword(s):

Essential Oil ◽

Haemonchus Contortus ◽

Chemical Characterization ◽

Anthelmintic Activity ◽

Citrus Bergamia

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In vitro anthelmintic activity of Dennettia tripetala G. Baker (Annonaceae) Fruits against Haemonchus contortus

Journal of Parasitic Diseases ◽

10.1007/s12639-021-01438-2 ◽

2021 ◽

Author(s):

Rachel A. Nwosu ◽

Mohammed M. Suleiman ◽

Hussaina J. Makun ◽

Matthew P. Ameh ◽

Manji A. Shetshak ◽

...

Keyword(s):

Haemonchus Contortus ◽

Anthelmintic Activity ◽

Dennettia Tripetala

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In Vitro Nematocidal Effect and Anthelmintic Activity of Artemisia cina Against Haemonchus contortus in Gerbils and Relative Expression of Hc29 Gene in Transitional Larvae (L3–L4)

Acta Parasitologica ◽

10.1007/s11686-021-00364-w ◽

2021 ◽

Author(s):

Rosa Isabel Higuera-Piedrahita ◽

Mariana Dolores-Hernández ◽

Luis Gerardo Jiménez-Pérez ◽

Brígida C. Camacho-Enríquez ◽

Alejandro Zamilpa ◽

...

Keyword(s):

Haemonchus Contortus ◽

Anthelmintic Activity ◽

Relative Expression

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Anthelmintic activity in vitro of Citrus sinensis and Melaleuca quinquenervia essential oil from Cuba on Haemonchus contortus

Industrial Crops and Products ◽

10.1016/j.indcrop.2015.07.056 ◽

2015 ◽

Vol 76 ◽

pp. 647-652 ◽

Cited By ~ 7

Author(s):

Yousmel Aleman Gaínza ◽

Luciana Ferreira Domingues ◽

Oriela Pino Perez ◽

Márcio Dias Rabelo ◽

Eugenio Roque López ◽

...

Keyword(s):

Essential Oil ◽

Haemonchus Contortus ◽

Citrus Sinensis ◽

Anthelmintic Activity ◽

Melaleuca Quinquenervia

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The effects of flubendazole and its metabolites on the larval development of Haemonchus contortus (Nematoda: Trichostrongylidae): an in vitro study

Helminthologia ◽

10.2478/s11687-010-0042-7 ◽

2010 ◽

Vol 47 (4) ◽

pp. 269-272 ◽

Cited By ~ 6

Author(s):

H. Bártíková ◽

L. Skálová ◽

J. Lamka ◽

B. Szotáková ◽

M. Várady

Keyword(s):

Larval Development ◽

Haemonchus Contortus ◽

Anthelmintic Activity ◽

In Vitro Study ◽

Lethal Concentration ◽

Resistant Isolate ◽

Susceptible Isolate ◽

Marked Resistance ◽

Larval Development Test

AbstractThe anthelmintic effects of flubendazole (FLU), its two main metabolites reduced flubendazole (FLU-R) and hydrolyzed flubendazole (FLU-H), and thiabendazole (TBZ) were compared using an in vitro larval development test in two isolates of Haemonchus contortus, a fully susceptible isolate (HCS) and a multi-resistant isolate (HCR). Results were quantified as 50 % lethal concentration (LC50), 99 % lethal concentration (LC99), efficacy factor (EF), and resistance factor (RF). For HCS, both LC50 and LC99 of FLU were lower than those of the reference TBZ. The anthelmintic activity of FLU-R in HCS and HCR was 13 and 6 times lower than the activity of FLU, respectively. The anthelmintic activity of FLU-H was negligible (approximately 363–853 times lower) compared to that of FLU. Although a marked resistance of the HCR isolate to TBZ was confirmed, only a low tolerance to FLU-R and slightly higher tolerance to FLU were found.

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In Vitro Anthelmintic Activity of Crude Extracts of Artemisia herba-alba and Punica granatum against Haemonchus contortus

Journal of Parasitology Research ◽

10.1155/2020/4950196 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Aliyi Hassen Ahmed ◽

Mebrat Ejo ◽

Teka Feyera ◽

Dereje Regassa ◽

Bahar Mummed ◽

...

Keyword(s):

Haemonchus Contortus ◽

Anthelmintic Activity ◽

Punica Granatum ◽

Limiting Factor ◽

Egg Hatching ◽

Traditional Use ◽

Egg Hatch ◽

Inhibition Effect ◽

Crude Extracts

Gastrointestinal nematodes (GINs) are the major limiting factor for the successfulness of livestock production throughout the world. Emergence of resistance strains as well as scarcity and high cost of the currently available drugs has led to the evaluation of other alternative helminth control options, mainly from plants. The current study is aimed at investigating the in vitro anthelmintic efficacy of crude methanolic extracts of two traditionally important medicinal plants, Artemisia herba-alba and Punica granatum, against Haemonchus contortus using adult motility assay (AMA) and egg hatch inhibition assay (EHIA). Four graded concentrations of the extracts were tested for both the AMA (10, 5, 2.5, and 1.25 mg/mg) and EHIA (0.1, 0.25, 0.5, and 1 mg/mL) in replicates. Albendazole and phosphate-buffered saline (AMA) or distilled water (EHIA) were used as the positive and negative controls, respectively. The crude extracts of A. herba-alba and P. granatum exhibited a potential anthelmintic activity at all dose levels in a concentration- and time-dependent fashion. The highest concentration (10 mg/mL) of all the extracts caused a significantly (p<0.05) superior nematocidal activity compared to the negative control. Moreover, significant and concentration-dependent egg hatching inhibition effect was observed from both plant extracts. Maximal (98.67%) egg hatching inhibition effect was exhibited by the flower extract of A. herba-alba at 1 mg/mL concentration. The relative egg hatch inhibition efficacy indicated that both plants caused a significantly (p<0.05) greater egg hatch inhibition within 48 hr of exposure. The current study validated the traditional use of both plants as a natural anthelmintic against H. contortus justifying a need to undertake detail pharmacological and toxicological investigation on both plants.

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In Vitro Anthelmintic Activity of Three Tropical Plant Extracts on Haemonchus contortus

Acta Parasitologica ◽

10.2478/s11686-019-00116-x ◽

2019 ◽

Vol 65 (1) ◽

pp. 11-18 ◽

Cited By ~ 2

Author(s):

Tulasi Davuluri ◽

Sreedevi Chennuru ◽

Malakondaiah Pathipati ◽

Sudhakar Krovvidi ◽

G. S. Rao

Keyword(s):

Plant Extracts ◽

Haemonchus Contortus ◽

Anthelmintic Activity ◽

Tropical Plant

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Isorhamnetin: A Nematocidal Flavonoid from Prosopis laevigata Leaves Against Haemonchus contortus Eggs and Larvae

Biomolecules ◽

10.3390/biom10050773 ◽

2020 ◽

Vol 10 (5) ◽

pp. 773

Author(s):

Edgar Jesús Delgado-Núñez ◽

Alejandro Zamilpa ◽

Manasés González-Cortazar ◽

Agustín Olmedo-Juárez ◽

Alexandre Cardoso-Taketa ◽

...

Keyword(s):

Haemonchus Contortus ◽

Laser Scanning ◽

Larval Mortality ◽

Small Ruminants ◽

Environmental Scanning Electron Microscopy ◽

Anthelmintic Activity ◽

Ethyl Acetate Fraction ◽

Confocal Laser ◽

Eggs And Larvae

Haemonchus contortus affect small ruminants all over the world. Anthelmintics cause resistance, contamination, and a risk of public health. Prosopis laevigata is a plant used as a home remedy against many diseases in Mexico. This study arose from a preliminary study where a P. laevigata hydroalcoholic extract (Pl-hae) showed anthelmintic activity (aa) against H. contortus. Searching for bioactive compounds (bac) with high aa, the Pl-hae was fractioned obtaining an aqueous (Aq-F) and an ethyl acetate fraction (EtAc-F), and a flavonoid with aa identified as isorhamnetin was obtained from EtAc-F. Both fractions were in vitro assessed by the egg hatch test (eht) and larval mortality (lm) assays. The bac obtained from EtAc-F were characterised by NMR analysis. The highest aa were recorded with EtAc-F, resulting in 100% eht and 80.45% lm at 0.75 and 30 mg/mL, respectively. Alterations in eggs and larvae attributed to isorhamnetin were recorded by environmental scanning electron microscopy, confocal laser scanning and by high-resolution digital-coupled camera. This flavonoid caused 100% eht at 0.07 mg/mL after 48 h and 100% lm at 7.5 mg/mL after 72 h exposure. Isorhamnetin has promising potential as an anthelmintic against sheep haemonchosis.

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