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Pathogens logoLink to Pathogens
. 2023 Jan 13;12(1):131. doi: 10.3390/pathogens12010131

An Inventory of Anthelmintic Plants across the Globe

Haroon Ahmed 1, Seyma Gunyakti Kilinc 2, Figen Celik 3, Harun Kaya Kesik 2, Sami Simsek 3,*, Khawaja Shafique Ahmad 4, Muhammad Sohail Afzal 5, Sumaira Farrakh 1, Waseem Safdar 6, Fahad Pervaiz 1, Sadia Liaqat 1, Jing Zhang 7, Jianping Cao 7,8,9,10,*
Editors: Timothy G Geary, Valentina Virginia Ebani
PMCID: PMC9866317  PMID: 36678480

Abstract

A wide range of novelties and significant developments in the field of veterinary science to treat helminth parasites by using natural plant products have been assessed in recent years. To the best of our knowledge, to date, there has not been such a comprehensive review of 19 years of articles on the anthelmintic potential of plants against various types of helminths in different parts of the world. Therefore, the present study reviews the available information on a large number of medicinal plants and their pharmacological effects, which may facilitate the development of an effective management strategy against helminth parasites. An electronic search in four major databases (PubMed, Scopus, Web of Science, and Google Scholar) was performed for articles published between January 2003 and April 2022. Information about plant species, local name, family, distribution, plant tissue used, and target parasite species was tabulated. All relevant studies meeting the inclusion criteria were assessed, and 118 research articles were included. In total, 259 plant species were reviewed as a potential source of anthelmintic drugs. These plants can be used as a source of natural drugs to treat helminth infections in animals, and their use would potentially reduce economic losses and improve livestock production.

Keywords: ethnomedicine, anthelmintic, medicinal plant, helminth, global distribution

1. Introduction

Livestock production plays a key role in the economic development of a country. Helminthiasis caused by a helminth infection is a major constraint in global livestock production. The mortality and morbidity in animal populations owing to infections caused by parasitic helminths are rapidly increasing worldwide [1]. These parasitic worms are categorized into two major groups: roundworms (phylum Nematoda) and flatworms (phylum Platyhelminthes) [2]. Among these parasites, gastrointestinal parasites pose a serious threat to livestock production. In recent decades, continuous and intensive use of synthetic anthelmintics has been the only method to control gastrointestinal nematodes. However, resistance to all available anthelmintic drug classes has been reported in livestock species. Resistance to an anthelmintic drug is often observed within a few years of introduction of the drug, indicating a remarkably high rate of resistance development, which likely results from a combination of large, genetically diverse parasite populations, and strong selection pressure for resistance. Plants are an ideal source of naturally occurring compounds that can be used as alternative dewormers in livestock [3]. Recently, some anthelmintics have demonstrated loss of efficacy owing to anthelmintic resistance [4]; as a result, parasitic load progressively increases, leading to high mortality and morbidity. Traditional use of medicinal plants for controlling helminth infections is more acceptable owing to the eco-friendly nature and sustainable supply of medicinal plants [5].

The present review is a comprehensive approach to show a geographical distribution of medicinal plants in a given time period and their anthelmintic potential, which would facilitate their use as an effective management strategy against helminth parasites. An electronic search in four major databases (PubMed, Scopus, Web of Science, and Google Scholar) was performed for data published between January 2003 and April 2022. Using database-specific strings, different combinations of the following keywords were used: “anthelmintic activity of plants”, “gastrointestinal nematodes”, “Platyhelminthes”, “roundworms”. The studies were required to include information about plant species, local name, plant family, distribution, plant tissue used, and target parasite species. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement [6] was used as a guide. Prespecified outcome-specific quality criteria were used to judge the admission of each qualitative and quantitative outcome into the appropriate analysis. Two investigators independently reviewed each eligible study and extracted the information and data necessary to carry out the qualitative analysis and the meta-analysis. Disagreements were resolved by consensus among all authors. All relevant studies meeting the criteria were assessed. In some references, multiple lines were used to show them because the authors were working on multiple plant species in the same article. In total, 2202 articles were obtained. However, since not all of them could be included in the current review, it was reduced to 118 articles by sampling (by paying attention to different countries and different plant species and parasites) and used in this review (Figure 1). Finally, 259 plant species from 36 countries worldwide were reviewed as a potential source of anthelmintic drugs. The distribution of the articles used in this review by country is shown in Figure 1.

Figure 1.

Figure 1

The PRISMA chart showing the summary of the literature search and query results.

The details of anthelmintic plants and their extracts potentially effective against Platyhelminthes and Nematoda are presented in Table 1 and Table 2, respectively.

Table 1.

List of anthelmintic plants and their extracts effective against flatworms (Platyhelminthes).

Parasite Study Model Plant Family Plant Name Plant Tissue Extract Effective Concentration and Mortality Rate (%) Reference
Carmyerius spatiosus In vitro Leguminosae Cassia siamea Leaves and heartwood Ethyl acetate extracts Highest anthelminthic effect [7]
Plumbaginaceae Plumbago zeylanica Roots n-butanol extract
Plumbaginaceae Plumbago indica Roots hexane, ethyl acetate, and n-butanol extract
Combretaceae Terminalia catappa Leaves n-butanol and water extract
Clonorchis sinensis In vitro Rosaceae Hagenia abyssinica Female flowers Crude extract 5 h (100 µg/mL) [8]
Echinococcus granulosus (protoscolex) In vitro Anacardiaceae Pistacia atlantica Fruits and leaves Hydroalcoholic extracts 100%; killed protoscoleces (50 mg/mL in 10 min) [3]
Leaves and fruits Hydroalcoholic extracts 0.1% concentration of fresh fruit extract (99.09 ± 1.27 mg/mL) and leaf extract (89.25 ± 18.42 mg/mL) had strong scolicidal effects in 360 min [9]
In vitro Lamiaceae Salvia officinalis Aerial parts Ethanolic extract 100% (6–8 days) [10]
Fabaceae Prosopis farcta Leaves Ethanolic extract
Crude alkaloids
25% scolicidal activity with a 500 mg/mL dose after 24 h [11]
57% scolicidal activity with a 500 mg/mL dose after 24 h
Ranunculaceae Nigella sativa Seeds Essential oil (Thymoquinone) 100% scolicidal activity with a 1 mg/mL dose after 10 min [12]
Cucurbitaceae Dendrosicyos socotrana Leaves Aqueous and methanolic extracts 100% scolicidal activity with a 5000 μg/mL dose after
360 h (methanolic extract)
and 408 h (aqueous extract)
[13]
Euphorbiaceae Jatropha unicostata Aqueous and methanolic extracts 100% scolicidal activity with a 1000 μg/mL dose after
288 h (both extracts)
Berberidaceae Berberis vulgaris Fruits Aqueous extracts 98.7% scolicidal activity with a 2 mg/mL dose after
30 min
[14]
Euphorbiaceae Mallotus philippinensis Fruits Methanolic extracts 99% scolicidal activity with a 20 mg/mL dose after
60 min
[15]
Echinococcus granulosus protoscolex In vitro Meliaceae Azadirachta indica Whole plant Ethanolic extracts Up to 97% mortality with 30 min of incubation [16]
Echinostoma caproni In vitro Rosaceae Hagenia abyssinica Female flowers Crude extract 51 h (100 µg/mL) [8]
Fasciola hepatica In vitro Fabaceae Acacia farnesiana Leaves Hexane, ethyl acetate, and methanolic extracts 0% (500 mg/L) [17]
Asteraceae Artemisia absinthium 0% (500 mg/L)
Artemisia mexicana 100% (500 mg/L)
Papaveraceae Bocconia frutescens 100% (500 mg/L)
Fabaceae Cajanus cajan 100% (500 mg/L)
Boraginaceae Cordia spp. 0% (500 mg/L)
Malvaceae Hibiscus rosa sinensis 0% (500 mg/L)
Verbenaceae Lantana camara 100% (500 mg/L)
Fabaceae Leucaena diversifolia 0% (500 mg/L)
Meliaceae Melia azedarach 13% (500 mg/L)
Lamiaceae Mentha sp. 0% (500 mg/L)
Ocimum basilicum 0% (500 mg/L)
Piperaceae Piper auritum 100% (500 mg/L)
Dysphania Teloxys ambrosioides 0% (500 mg/L)
Fasciola larvae (sporocyst, redia, and cercaria) In vitro Rosaceae Potentilla fulgens Dried root powder Ether, chloroform, methanolic, acetone, and ethanolic extracts 8 h LC50 was 54.20 mg/L for sporocysts, 49.37 mg/L for redia, and 38.13 mg/L for cercaria [18]
Fasciola gigantica larvae (sporocysts, redia, and cerceria) In vivo Asparagaceae Asparagus racemosus Dried root powder Ether, chloroform, methanolic, acetone, and ethanolic extracts 2 h LC50 was 79.93% [19]
Fasciola gigantica and Taenia solium In vitro Euphorbiaceae Acalypha wilkesiana Extracts Methanolic extracts of leaves, stems, and roots All extracts exhibited anthelmintic activity in vitro [20]
Fasciola hepatica In vitro Rosaceae Hagenia abyssinica Female flowers Crude extract 1 h (100 µg/mL) [8]
Fasciolopsis buski In vitro Zingiberaceae Alpinia nigra Shoot Crude alcoholic extract 3.94 ± 0.06 h death time (20 mg/mL concentration) [21]
Gastrothylax crumenifer In vitro Fabaceae Sesbania sesban var. bicolor Fresh leaves Methanolic extracts of dried plants Better than praziquantel [22]
Cyperaceae Cyperus compressus Roots
Asparagaceae Asparagus racemosus Roots
Hymenolepis diminuta and Syphacia obvelata In vitro
In vivo
Asparagaceae Asparagus racemosus Roots Methanolic extract 53.88% and 24% reduction in EPG * and worm counts, respectively (30 mg/mL concentration) [23]
Hymenolepis diminuta In vitro Cyperaceae Cyperus compressus Roots Methanolic extract 61.74% reduction in the EPG and 24% reduction in worm counts (30 mg/mL concentration) [24]
Hymenolepis diminuta In vitro Fabaceae Sesbania sesban Fresh Leaves Methanolic extract 65.10%
reduction in EPG counts, 56% reduction in worm counts (30 mg/mL concentration)
[25]
Paramphistomum gracile In vitro Fabaceae Senna alata, S. alexandrina, and S. occidentalis Leaf extract Ethanolic extracts Dose-dependent effects on motility and mortality [26]
Paramphistomum microbothrium In vitro Zygophyllaceae Balanites aegyptiaca Fruits Methanolic extract 200 µg/ml, at which distinct
damage to the whole body surface of the trematodes
[27]
Raillietina echinobothrida In vitro Asteraceae Acmella oleracea Leaves Methanolic extract 18.42 ± 0.95 h survival time (20 mg/mL concentration) [28]
Raillietina spiralis In vitro Malvaceae Thespesia lampas Roots Aqueous extracts 51 ± 0.33 min death time (20 mg/mL concentration) [29]
Raillietina spiralis In vitro Meliaceae Azadirachta Indica Leaves Aqueous extract 46 ± 0.53 min death time (20 mg/mL concentration) [30]
Raillietina spiralis In vitro Scrophulariaceae Verbascum Thapsus Fresh Leaves Methanolic extract 86 ± 5 min death time (20 mg/mL concentration) [31]
Raillietina spiralis In vitro Asteraceae Achillea wilhelmsii Fresh Leaves Methanolic extract 40 min death time (20 mg/mL concentration) [32]
Raillietina spiralis In vitro Lauraceae Cinnamomum camphora Leaves Aqueous extracts 47 ± 0.54 min death time (20 mg/mL concentration) [33]
Raillietina spiralis In vitro Verbenaceae Clerodendron inerme Leaves Aqueous extracts 45 ± 0.52 min death time (20 mg/mL concentration) [34]
Raillietina tetragona In vitro Poaceae Imperata cylindrica Underground parts (rhizomes and roots) Chloroform (medium polar solvent) Dose-dependent anthelmintic activity [35]
Schistosoma mansoni In vitro Apocynaceae Rauwolfia vomitoria Stem bark and roots Ethanolic extract High activity against cercariae and adult worms [36]
Syphacia obvelata In vitro Cyperaceae Cyperus compressus Roots Methanolic extract 28.92% reduction in the EPG and 33.85% reduction in worm counts (30 mg/mL concentration) [24]
Syphacia obvelata In vitro Fabaceae Sesbania sesban Fresh leaves Methanolic extract EPG
and worm counts reduced by 34.32% and 47.08%,
respectively (30 mg/mL concentration)
[25]
Schistosoma mansoni In vivo Asteraceae Baccharis trimera Leaves Crude dichloromethane extract (DE) and aqueous fraction (AF) 98% (AF) 97% (DE) [37]
Tanacetum vulgare Aerial parts Crude extract and Essential oil 100% [38]
Schistosoma mansoni In vitro Rosaceae Hagenia abyssinica Female flowers Crude extract 3 h (100 µg/mL) [8]
Schistosoma mansoni In vitro Euphorbiaceae Euphorbia conspicua Leaves Leaf extract 100%
(100 µg/mL)
[39]
Piperaceae Piper chaba Fruits Methylene chloride extract Strongest activity [40]
Taenia solium In vitro Asclepiadaceae Pergularia daemia Leaves Ethanolic extract 210.00 ± 0.52 min death time (25 mg/mL concentration) [41]
Aqueous extract 221.12 ± 0.61
Taenia tetragona In vitro Asteraceae Acmella oleracea Leaves Hexane extract The lethal concentration (LC50) of the plant extract was 5128.61 ppm on T. tetragona and 8921.50 ppm on A. perspicillum [42]

* EPG: Egg per gram.

Table 2.

List of anthelmintic plants and their extracts effective against roundworms (Nematoda).

Parasite Study Model Plant Family Plant Name Plant Part Used Extract/Compound LC50 * References
Allolobophora caliginosa In vitro Fabaceae Indigofera oblongifolia Leaves Leaf extracts 15 ± 2 and 8.6 ± 1 h survival time with leaf extracts at 200 mg/mL and 300 mg/mL, respectively [43]
Ancylostoma caninum, Haemonchus placei, andCyathostomins In vivo Ebenaceae Diospyros anisandra Leaves and bark Extracts and active compounds Wide-spectrum anthelmintic activity [44]
Ascardia galli In vitro Malvaceae Thespesia lampas Roots Aqueous extracts 43 ± 0.86 min death time (20 mg/mL concentration) [29]
Ascardia galli In vitro Mimosaceae Acacia oxyphylla Fresh stems Ethanolic extracts 55.17  h  ±  1.04 h death time (0. 5 mg/ mL concentration) [45]
Ascardia galli In vitro Meliaceae Azadirachta Indica Leaves Aqueous extract 46 ± 0.26 min death time (20 mg/mL concentration) [30]
Ascardia galli In vitro Scrophulariaceae Verbascum Thapsus Fresh Leaves Methanolic extract 81 ± 4 min death time (20 mg/mL concentration) [31]
Ascardia galli In vitro Asteraceae Achillea wilhelmsii Fresh Leaves Methanolic extract 40 min death time (20 mg/mL concentration) [32]
Ascardia galli In vitro Lauraceae Cinnamomum camphora Leaves Aqueous extracts 52 ± 0.43 min death time (20 mg/mL concentration) [33]
Ascardia galli In vitro Verbenaceae Clerodendron inerme Leaves Aqueous extracts 50 ± 0.31 min death time (20 mg/mL concentration) [34]
Ascardia galli and Pheretima posthuma In vitro Malvaceae Malvastrum coromandelianum Leaves Methanolic and ethyl acetate extracts Significant anthelmintic activity [46]
Ascaris lumbricoides In vitro Musaceae Musa paradisiaca, M. sapientum, and M. nana Roots Methanol root extracts Death time 151.39 ± 0.1 min at 200 mg/mL [47]
Ascaris lumbricoides In vitro Asclepiadaceae Pergularia daemia Leaves Ethanolic Extract 98.42 ± 0.57 min death time (25 mg/mL concentration) [41]
Aqueous Extract 109.91 ± 0.49 min death time (25 mg/mL concentration)
Ascaris suum L3 larvae In vitro Lythraceae Punica granatum Fruit Peel Ethanolic extracts EC50 values 164% [48]
Rutaceae Zanthoxylum zanthoxyloides Roots EC50 values 97%
Rutaceae Clausena anisata Roots EC50 values 74%
Ascaris suum L3 larvae In vitro Acetone/water extracts Ascaris suum L3 migratory inhibition activity EC50 ** values [49]
Pinaceae Pinus sylvestris Bark 48.2%
Fabaceae Onobrychis viciifolia Whole plant 41.9%
Fabaceae Trifolium repens Flowers 98.4%
Grossulariaceae Ribes nigrum Leaves 91.8%
Ribes rubrum Leaves 86%
Brugia malayi In vivo Piperaceae Piper betle Leaves Methanolic extracts Moderate activity [50]
Brugia malayi In vitro/
In vivo
Apiaceae Trachyspermum ammi Dried fruits Methanolic extracts 58.93% [51]
Brugia malayi In vivo Caesalpiniaceae Caesalpinia bonducella Seed kernels Ethanolic extracts 96.0% microfilaricidal
and 100% sterilization in females
[52]
Butanolic extracts
Aqueous fraction
Brugia malayi In vivo/
In vitro
Verbenaceae Lantana camara Stem Ethanolic extracts 43.05% adulticidal activity; sterilization of 76% of surviving
females
[53]
Brugia pahangi In vitro Asteraceae Neurolaena lobata Leaves Ethanolic extracts Completely immotile after 24 h incubation at 500 μg/mL concentration [54]
Caenorhabditis elegans In vitro Laminaceae Tetradenia riparia Leaves Ethyl acetate extracts Most effective minimum lethal concentration value was 0.004 mg/mL [55]
Caenorhabditis elegans In vitro Combretaceae Anogeissus leiocarpus Stem bark Ethanolic extracts 72 h LC50 was between 0.38 and 4.00 mg/mL [56]
Meliaceae Khaya senegalensis Leaves
Euphorbiaceae Euphorbia hirta
Annonaceae Annona senegalensis Aqueous extracts
Apocynaceae Parquetina nigrescens
Caenorhabditis elegans In vitro Sapindaceae Acer rubrum Leaves Ethanolic extracts Killed 50% (LC50) or 90% (LC90) of the nematodes in 24 h [57]
Fagaceae Quercus alba
Rosaceae Rosa multiflora
Anarcardiaceae Rhus typhina
Fabaceae Robinia pseudoacacia
Lespedeza cuneata Leaves and stems
Caenorhabditis elegans In vitro Meliaceae Khaya senegalensis Stem bark Ethanolic and aqueous extracts 72 h LC50 was between 0.38 and 4.00 mg/mL [56]
Combretaceae Anogeissus leiocarpus Leaves
Euphorbiaceae Euphorbia hirta
Annonaceae Annona senegalensis
Apocynaceae Parquetina nigrescens
Fabaceae Senna petersiana
Caenorhabditis elegans In vitro Plumbaginaceae Plumbago indica Root Methylene chloride Strongest activity [40]
Cooperia spp. In vitro Fabaceae Leucaena leucocephala Fresh leaves Aqueous extract 52.02 ± 12.39 of egg hatching within 48 h of exposure [58]
Eudrilus eugeniae In vitro Lamiaceae Ocimum basilicum Fruits Ethanol and hexane extracts 213.39 ± 1.05 and 362.98 ± 1.54 death time of ethanolic extract and hexane extract, respectively, at 250 μg/mL concentration [59]
Gastrointestinal nematodes In vitro/
In vivo
Lamiaceae Prunella vulgaris
Whole plant Phenolic compounds Highest nematode motility (100%) with higher concentrations of methanolic extracts (50 mg/ mL) [60]
Gastrointestinal nematodes
In vivo
Lythraceae Punica granatum Fruit peel
Pomegranate peel extract
7 days after the first and second doses, 85–97% decrease in fecal egg count (FEC) [61]
Gastrointestinal nematodes In vitro Moringaceae Moringa oleifera lectin Seeds Distilled water homogenization 40.4% of eggs unhatched at 250 μg/mL dose [62]
Gastrointestinal nematodes In vitro Phyllanthaceae Bridelia ferruginea Leaves Methanolic and
acetone extracts
The number of eggs that hatched was reduced in a concentration-dependent manner (p  <  0.01) upon treatment [63]
Combretaceae Combretum glutinosum
Rubiaceae Mitragyna inermis
Gastrointestinal nematodes of goats In vitro Vitaceae Cissus quadrangularis Aerial parts Aqueous (cold and boiled) and methanolic extracts Statistically significant effect [64]
Asphodelaceae Aloe marlothii Leaves
Mimosoideae Albizia anthelmintica Bark
Vitaceae Cissus rotundifolia Bark
Anacardiaceae Sclerocarya birrea Bark
Fabaceae Vachellia xanthophloea Bark
Gastrointestinal nematodes of sheep In vivo Punicaceae Punica granatum Fruit (seeds and peel) Boiled extracts 8–40% (21st day) [65]
Asteraceae Artemisia campestris Whole plant 3–36% (21st day)
Salicaceae Salix caprea Bark and leaves 7–40% (21st day)
Gastrointestinal nematodes of sheep In vitro Myrtaceae Psidium cattleianum Fruits Hydroalcoholic extract 80% in the inhibition of larval migration [66]
Gastrointestinal nematodes of sheep In vitro Punicaceae Aqueous Pomegranate Fruit pulp Methanolic and gallic acid extracts Significant inhibition of egg hatching within 48 h of exposure, highlighting a high (>82%) efficacy in vitro at all tested doses [67]
Gastrothylax crumenifer In vitro Menispermaceae Tinospora cordifolia Plant stems Alcoholic and aqueous extracts mortality rate of 100% at concentration of 100 mg/mL [68]
Haemonchus contortus In vitro Asteraceae Artemisia maritima Whole plants Methanolic extracts 84.5% [69]
Artemisia vestita 87.2%
Haemonchus contortus In vitro Ericaceae Arctostaphylos uva-ursi Leaves Methanolic extracts 95.8 ± 0.5% inhibition in DMSO [70]
Anacardiaceae Rhus glabra 90.2 ± 0.9%
inhibition in DMSO
Asteraceae Balsamorhiza sagittata 88.1 ± 1.2% inhibition in DMSO
Ranunculaceae Caltha palustris 86.5 ± 1.2% inhibition in DMSO
Boraginaceae Cynoglossum officinale 84.7 ± 1.0% inhibition in DMSO
Asteraceae Solidago mollis 82.8 ± 1.4%
inhibition in DMSO
Asteraceae Centaurea stoebe 78.1 ± 1.5% inhibition in DMSO
Fabaceae Glycyrrhiza lepidota 77.6 ± 2.3% inhibition in DMSO
Anacardiaceae Rhus aromatica 100% inhibition in DMSO
Asteraceae Ericameria nauseosa 100% inhibition in DMSO
Apiaceae Perideridia gairdneri 100% inhibition in DMSO
Geraniaceae Geranium viscosissimum 100% inhibition in DMSO
Asteraceae Chrysothamnus viscidiflora 100% inhibition in DMSO
Asteraceae Liatris punctata Roots 100% inhibition in DMSO
Fabaceae Melilotus alba Leaves 100% inhibition in DMSO
Fabaceae Melilotus officinalis 100% inhibition in DMSO
Papaveraceae Sanguinaria canadensis Roots 98.5 ± 0.3%
inhibition in DMSO
Orobanchaceae Pedicularis racemosa Leaves 74.2 ± 0.9% inhibition in DMSO
Lamiaceae Stachys palustris 72.9 ± 1.8% inhibition in DMSO
Lamiaceae Agastache foeniculum 70.05 ± 0.7% inhibition in DMSO
Lamiaceae Monarda fistulosa 69.5 ± 1.5% inhibition in DMSO
Fabaceae Pediomelum argophyllum 69.7 ± 1.8% inhibition in DMSO
Lamiaceae Lycopus americanus 76.0 ± 2.3% inhibition in DMSO
Ranunculaceae Clematis ligusticifolia 68.7 ± 2.0% inhibition in DMSO
Amaryllidaceae Allium cernuum 68.4 ± 1.3% inhibition in DMSO
Asteraceae Conyza canadensis 76.8 ± 2.1% Inhibition in MOPS
Cornaceae Cornus sericea 57.4 ± 3.1% inhibition in DMSO
Rosaceae Rubus idaeus 51.9 ± 1.6% inhibition in DMSO
Ranunculaceae Actaea rubra 45.2 ± 1.5% Inhibition in DMSO
Caprifoliaceae Symphoricarpos occidentalis 43.1 ± 3.3% Inhibition in DMSO
Asteraceae Artemisia ludoviciana 40.8 ± 2.0% inhibition in DMSO
Asteraceae Artemisia frigida 36.2 ± 1.65% inhibition in DMSO
Asteraceae Tanacetum vulgare 33.5 ± 2.0% inhibition in DMSO
Cleomaceae Cleome serrulata 23.9 ± 1.7% Inhibition in DMSO
Onagraceae Epilobium angustifolium 23.2 ± 3.5% inhibition in DMSO
Fagaceae Quercus macrocarpa 18.3 ± 2.2% Inhibition in DMSO
Salicaceae Salix exigua 5.9 ± 0.7%
Inhibition in DMSO
Haemonchus contortus In vitro Asteraceae Artemisia absinthium Leaves Crude aqueous and ethanolic extracts Aqueous extracts exhibited greater anthelmintic activity [71]
Haemonchus contortus In vitro Rutaceae Citrus aurantifolia Essential oils from fruit peel Oil extracts Oil has limonene (56.37%), β-pinene (11.86%) and γ-terpinene (11.42%) [72]
Annonaceae Annona muricata Leaves Aqueous extracts Aqueous extract of A. muricata leaves at serial dilutions of 50%, 25%, 12.5% and 6.25% inhibited the motility of L3 by 83.29%, 89.08%, 74.62% and 30.47% respectively
Haemonchus contortus In vitro Anacardiaceae Myracrodruon urundeuva Seeds Ethanolic and hexane extracts Inhibition of larval development (LC50 = 0.29 mg mL−1) [73]
Haemonchus contortus In vitro Liliaceae Allium sativum Bulbs Ethanolic extracts 84.0 ± 4.3 [74]
Asphodelaceae Aloe ferox Leaves 86.9 ± 2.9
Bromeliaceae Ananas comosus 100 ± 1.0
Caricaceae Carica papaya 76.0 ± 5.1
Moraceae Ficus benjamina 78.1 ± 3.5
Moraceae Ficus ingens 78.1 ± 5.7
Moraceae Ficus carica (brown) 56.3 ± 2.8
Moraceae Ficus carica (white) 74.1 ± 7.9
Moraceae Ficus indica 44.5 ± 7.0
Moraceae Ficus lutea 60.0 ± 6.3
Moraceae Ficus elastica 77.8 ± 6.6
Moraceae Ficus natalensis 68.8 ± 7.2
Moraceae Ficus sur 81.3 ± 5.6
Moraceae Ficus sycomorus 6.3 ± 4.3
Moraceae Ficus ornamental thai 60.0 ± 1.7
Lamiaceae Leonotis leonurus 56.5 ± 6.1
Moraceae Melia azedarach 66.7 ± 4.4
Fabaceae Peltophorum africanum 65.2 ± 4.0
Amaryllidaceae Scadoxus puniceus 59.4 ± 8.2
Fabaceae Lespedeza cuneata 100 ± 1.6
Leguminosae Tephrosia inandensis 64.0 ± 7.8
Canellaceae Warburgia ugandensis 81.5 ± 3.5
Canellaceae Warburgia salutaris 80.8 ± 3.4
Cucurbitaceae Cucumis myriocarpus 60.0 ± 5.7
Zingiberaceae Zingiber officinale Rhizomes 72.0 ± 2.5
Haemonchus contortus In vitro Asteraceae Vernonia amygdalina Leaves Hot water extracts Ineffective [75]
Annonaceae Annona senegalensis Stem barks 88.5%
Haemonchus contortus In vivo Fabaceae Acacia nilotica Leaves Without extraction 10% reduction in worm [76]
Acacia karroo 34% reduction in worm
Haemonchus contortus In vitro and
In vivo
Amaranthaceae Chenopodium ambrosioides Leaves and stems Organic maceration 96.3% (invitro), 45.8% (in vivo) at 40 mg/mL dose [77]
Simaroubaceae Castela tortuosa 78.9% (in vitro) 27.1% (in vivo) at 20 mg/mL dose
Haemonchus contortus In vivo and
In vitro
Lamiaceae Mentha pulegium Aerial parts Hydroethanolic extract 91.58% inhibition in the egg hatch assay at 8 mg/mL after 48 h. 65.2% inhibition at 8 mg/mL after 8 h in adult worm motility [78]
Haemonchus contortus In vitro Apocynaceae Tylophora Indica Leaves Methanolic extract 100% mortality after 6 h exposure at 50 mg/mL of concentration [79]
Haemonchus contortus In vitro Passifloraceae Turnera ulmifolia Leaves and roots Hydroacetonic and hydroalcoholic extracts The highest egg hatching inhibition with the lowest LC50 value of 430 μg/mL (95%, CI 400–460 μg/mL) [80]
Fabaceae Parkia platycephala Leaves and seeds LC50 1340, 95% CI 1170-1550 μg/mL
Fabaceae Dimorphandra gardneriana Leaves and bark Ineffective
Haemonchus contortus In vitro Lauraceae Persea americana Dried seeds Hot water extracts 76.9 ± 7.2% effective in 500 μg/mL dose [81]
Haemonchus contortus In vitro and
In vivo
Asteraceae Artemisia absinthium Whole plant Crude methanolic extracts Strong anthelmintic effect [82]
Malvaceae Malva sylvestris
Haemonchus contortus In vitro Asteraceae Artemisia herba-alba Stems and leaves Crude methanolic extracts 98.67% inhibition of egg hatching at 1 mg/mL concentration [83]
Punicaceae Punica granatum Peel and roots Eggs unhatched at the end of the observation period
Haemonchus contortus In vitro Asteraceae Artemisia vulgaris Leaves Aqueous and ethanolic extracts %100 [84]
Haemonchus contortus In vitro Fagaceae Castanea sativa Stems and leaves Ethanolic extracts All plants showed some anthelmintic activity on both L3 larvae and adult worms) [85]
Fabaceae Sarothamnus scoparius Stems and leaves
Pinaceae Pinus sylvestris Stems and leaves
Fagaceae Quercus robur Leaves
Oleaceae Fraxinus excelsior Leaves
Betulaceae Corylus avellana Leaves
Ericaceae Erica erigena Stems and leaves
Fabaceae Acacia holosericea
Acacia salicina
Cupressaceae Callitris endlicheri
Casuarina cunninghamiana
Lauraceae Neolitsea dealbata
Haemonchus contortus In vivo Asteraceae Artemisia absinthium Whole plant Aqueous and methanolic extracts 4.3–67.2%
reduction in EPG
[86]
Haemonchus contortus In vitro Asteraceae Artemisia absinthium Aerial parts Crude aqueous extracts Worm motility inhibition was 73.6% [87]
Crude ethanolic extracts Worm motility inhibition was 94.7%
Haemonchus contortus In vivo Anacardiaceae Pistacia lentiscus Leaves Acetone extracts Significant decreases in egg excretion [88]
Fagaceae Quercus coccifera
Onobrychis viciifolia
Ceratonia siliqua
Medicago sativa
Haemonchus contortus eggs In vitro Combretaceae Terminalia glaucescens Leaves Methanolic extracts 87.55% inhibition of egg hatching at the 100 µg/mL dose [89]
Haemonchus contortus eggs In vitro Lamiaceae Leucas martinicensis Stems and bark Crude aqueous and hydroalcoholic extracts Complete inhibition of egg hatching at the 1 mg/mL dose [90]
Leonotis ocymifolia Aerial parts
Fabaceae Senna occidentalis Leaves
Polygonaceae Rumex abyssinicus Stems and bark
Leguminosae Albizia schimperiana
Haemonchus contortus eggs and larvae In vitro Fabaceae Acacia farnesiana Dried pods Hydroalcoholic extracts 100% ovicidal and 75.2% larvicidal activity at the 50 mg/mL dose [91]
Haemonchus contortus eggs and larvae In vitro Fabaceae Senegalia gaumeri Leaves Methanolic extracts Ovicidal effect in the morula stage [92]
Haemonchus spp. In vitro Casuarinaceae Allocasuarina torulosa Fresh leaves Methanolic extracts 64.14–89.83% exposure at the 30 mg/mL concentration [93]
Fabaceae Acacia holosericea
Acacia salicina
Cupressaceae Callitris endlicheri
Casuarinaceae Casuarina cunninghamiana
Lauraceae Neolitsea dealbata
Onchocerca gutturosa In vitro Annonaceae Polyalthia suaveolens Bark Hexane extracts Significant inhibitory effect on the vitality of adult male worms [94]
Euphorbiaceae Discoglypremna caloneura
Onchocerca ochengi In vitro Salicaceae Homalium africanum Leaves Hexane methylene chloride extracts Significant effect [95]
Parascaris equorum In vitro Asteraceae Artemisia dracunculus Leaves Methanolic extracts 90% inhibition of egg hatching and high larvicidal effect at concentrations ≥100 mg/mL [96]
Myrtaceae Eucalyptus camadulensis Leaves
Lamiaceae Mentha pulegium Aerial parts
Lamiaceae Zataria multiflora Aerial parts
Liliaceae Allium sativum Bulbs
Pheretima posthuma In vitro Nyctaginaceae Bougainvillea spectabilis Crude extract of flowers Ethanolic and
aqueous extracts
39 min (time of death) at a concentration of 50 mg/mL [97]
Pheretima posthuma In vitro Acanthaceae Barleria buxifolia Leaves Ethanolic extract 89.00 ± 1.82 min for death time at a concentration of 100 mg/mL [98]
Pheretima posthuma In vitro Plumbaginaceae Plumbago zeylanica Leaves Methanolic Extract 81 ± 1.5 min death time (concentration of 20 mg/mL) [99]
Water Extract 228 ± 1.2 min death time (concentration of 20 mg/mL
Strongyloides venezuelensis In vitro Siparunaceae Siparuna guianensis Leaves Hexane extracts Significant inhibitory effect on the vitality of adult male worms [100]
Toxocara vitulorum In vitro Zygophyllaceae Balanites aegyptiaca Fruits Methanolic extract 120 μg/ml after 24 h complete disruption of the muscle cells [101]
Teladorsagia circumcincta L1 larvae In vivo Fabaceae Phaseolus vulgaris Seeds Lectin purification Worm burden
4416 ± 878 (control)
3475 ± 792 (treated)
[102]
Trichostrongylus colubriformis L1 larvae Worm burden
6708 ± 414 (control)
6500 ± 295.5 (treated)
Trichostrongylus colubriformis In vivo Moraceae Artocarpus integrifolia Whole plant Ethanolic extracts Reduced concentration of nematode eggs (2.3 mg semi-purified PHA lectin/kg LW/day) [102]
Fabaceae Canavalia ensiformis
Fabaceae Phaseolus vulgaris
Fabaceae Maackia murensis
Fabaceae Robinia pseudoacacia
Moraceae Maclura pomifera
Fabaceae Dolichos biflorus
Poaceae Triticum vulgare
Amaryllidaceae Galanthus nivalis
Rosaceae Rosa multiflora

* LC50: Lethal concentration. ** EC50: Effective concentration.

2. Chemical Compounds

The literature review revealed that active chemical compounds present in plants were determined using plant volatile essential oils or extracts in ethanol, butanol, methylene chloride, methanol, hydroalcoholic solvents, dichloromethane, chloroform, petroleum ether, or n-hexane. The following active compounds and secondary metabolites were reported: glycosides, tetrahydroharmine, tannins, gallocatechin, epigallocatechin monomers, jacalin, phytohemagglutinin E2L2, phytohemagglutinin L4, phytohemagglutinin E3L, kidney bean albumin, Maclura pomifera agglutinin, Robinia pseudoacacia agglutinin, wheat germ agglutinin, cysteine proteinases, ursolic acid, galactolipid 2 and 3, aporphines, hexylresorcinol, Dolichos biflorus agglutinin, Galanthus nivalis agglutinin, polycarpol, 3-O-acetyl aleuritolic acid, jacalin (jackfruit agglutinin), concanavalin A (jack bean lectin), Maackia amurensis lectin, dichloromethane, and plumbagin (Table 3).

Table 3.

Candidate natural substances with anthelmintic effects.

Compound Parasite Species Study Model Reported Mortality Reference
A penta-substituted pyridine alkaloid Schistosoma mansoni In vitro 100% [103]
Essential oil Echinococcus granulosus (protoscolex) In vitro 79.22% scolicidal activity with the 20 mg/mL dose during 60 min [104]
Essential oil (Thymoquinone) Echinococcus granulosus (protoscolex) In vitro 100% scolicidal activity with the 1 mg/mL dose after 10 min [12]
Essential oil Haemonchus contortus In vitro and in vivo 33.3% and 87.5% inhibition motility for flower essential oil [105]
29.1% and 75% for leaf
essential oil
87.2%
Lectin purification Teladorsagia circumcincta (L1) In vivo Worm burden
4416 ± 878 (control)
3475 ± 792 (treated)
[102]
Trichostrongylus colubriformis (L1) Worm burden
6708 ± 414 (control)
6500 ± 295.5 (treated)
Tannin Cooperia spp. In vivo Higher activity [106]
Cysteine proteinases (CP) Hymenolepis diminuta In vitro CP extracts exhibited anthelmintic activity in vitro [107]
Pristimerin Anticestodal Invitro
In vivo
EPG by 94 ± 5%, 8 ± 4%, 6 ± 3%, and 97 ± 4%, respectively [60]
Ursolic acid Brugia malayi Invitro
In vivo
86% inhibition [108]
Withaferin A Brugia malayi In vivo 4.3% reduced parasite load using 8 μg/mL within 24 h [109,110]
Galactolipid-1
Galactolipid-2 Galactolipid-3
Galactolipid-4
Brugia malayi In vitro
In vivo
Fraction F1: 80%; Fraction F2: 30%; Fraction F3: 40%;
Fraction F4: 100%
(31.25 μg/mL)
[111]
Curcumin Schistosoma mansoni In vitro 100% mortality in male and female [112]
Aporphine Anisakis simplex and
Hymenolepis nana
In vitro No cestocidal and nematocidal effects against H. nana and A. simplex [113]
Derived saponins Donkey Gastrointestinal Nematodes In vitro Significant (p < 0.05) inhibition of nematode egg hatching (>80%) [114]
Maclura pomifera agglutinin Teladorsagia circumcincta In vivo Direct anthelmintic effect on nematode fecundity and an indirect effect by enhancing local immune responses in the host [102]
Tannins Teladorsagia circumcincta, Haemonchus contortus, and Trichostrongylus colubriformis In vitro Larval migration inhibition assay on third-stage larvae (L3) and adult worm
motility inhibition assay
[85]
Essential oil Gastrointestinal nematodes In vitro 33.30% inhibition motility [105]
87.50% inhibition motility
Saponins Gastrointestinal nematodes In vitro Strong anthelmintic activity [115]
Donkey strongyles In vitro Strong anthelmintic activity [116]
Tannins Trichostrongylus colubriformis In vitro Larval migration inhibition assay on third-stage larvae (L3) and adult worms [85]
Condensed and hydrolyzable tannins Caenorhabditis elegans In vitro Killed 50% (LC50) or 90% (LC90) of nematodes in 24 h [57]
Tannins Trichostrongylus colubriformis In vitro Larval migration inhibition assay on third-stage larvae (L3) and adult worms [85]
Flavonoids, condensed tannins, and gallotannin Caenorhabditis elegans In vitro Minimum lethal concentration was 0.13–0.52 mg/mL [117]
Methylene chloride Caenorhabditis elegans In vitro Strongest effect [40]
Tannins, phenolic compounds, and steroids Haemonchus contortus In vitro,
In vivo
100% inhibition of egg hatching, highest activity for adult motility, and larvicidal assay [118]
Antimicrobial agents, alkaloids, flavonoids, tannins, and phenols Haemonchus contortus In vitro High activity for adulticidal and egg hatching inhibition [119]
Polyphenols Caenorhabditis elegans In vitro and in vivo Inhibition of larval migration [120]
Phenolic compounds Gastrointestinal nematodes In vitro
In vivo
Highest nematode motility (100%) in the higher concentrations of methanolic extract (50 mg/mL) [60]
Presence of saponin, alkaloids, flavonoids, and tannins Haemonchus contortus In vitro High mortality rate [121]
Presence of eugenol and asarone Moniezia expansa In vitro 100 mg/mL concentration and the time taken for the paralysis of the parasite amounts to 66.3 ± 0.03 min and death was recorded after 93.2 ± 0.09 min [122]
Proanthocyanidins and flavonoids Haemonchus contortus In vitro Larval migration inhibition and adult worms’ motility inhibition [123]
Essential oils Neoechinorhynchus buttnerae, endoparasite of Colossoma macropomum In vitro All essential oils showed 100% anthelmintic efficacy within 24 h [124]
100% mortality was observed in the group treated with 100 mg/mL of herbal complex Haemonchus contortus In vitro Anthelmintic potential [125]

3. Effect of Plant Extracts in Drug-Resistant Helminths

Medicinal plant extracts have long been used against helminth parasites in humans and livestock; however, scientific support for their application and research on the characterization of active composites remains limited [123]. Numerous studies have investigated anthelmintic resistance, especially in small ruminants. Most studies have used the fecal egg count reduction test (FECRT), which is based on field management practices. Nevertheless, in vivo experiments on drug efficacy have been conducted in areas with high economic importance. Notably, sheep have been studied more extensively than other livestock species, and a broad spectrum of therapeutics have already been developed for sheep [126].

Molecular methods are promising strategies for in vivo and in vitro diagnosis of many infections and may prove to be effective in the detection of parasitic nematodes and anthelmintic resistance [127,128,129,130]. Gaining knowledge about the mechanisms of resistance will ultimately help to reduce anthelmintic drug resistance in parasites. The diagnosis of drug resistance associated with genomic changes using molecular techniques would help in avoiding unnecessary treatments and thus reduce health complications. However, the use of natural plant compounds has the potential to be a complementary control option that can reduce dependence on drug therapy and delay the development of resistance [127,129,131].

In general, many plant secondary metabolites including chalcones, coumarins, terpenoids, tannins, alkaloids, antioxidants, and flavonoids [132,133] possess anthelmintic and neurotoxic properties [134] and inhibit mitochondrial oxidative phosphorylation [135,136]. These plant-based compounds typically show higher biological activity than synthetic compounds [137]. In many parts of the world, plants have been used for many generations and are still being used to treat parasitic diseases [138]. The identification of novel compounds from plants as anthelmintics is an emerging field of research. According to a study, between 2000 and 2019, 40 patents were granted for natural-product-based nematicides divided into seven structural classes [139], but none of them have yet been commercialized. However, difficulties in determining the mechanism of action of the main active ingredients in plant extracts are among the main barriers for researchers.

4. Advantages and Disadvantages of Using Plants for Helminth Parasite Control

Limited information is available on gastrointestinal helminth infections in livestock, which remain a major constraint to livestock production worldwide. Nevertheless, a recent study suggests that anthelmintic plants can be used as a potential resource to improve livestock production [38]. The use of plants as anthelmintics has certain benefits over contemporary veterinary treatments, including affordability, lack of adverse effects, and easy accessibility.

Although most of the information available about the antiparasitic properties of medicinal plants is oral and lacked scientific validity until recently, there is now a growing number of controlled laboratory experiments aiming to confirm and quantify anthelmintic plant activity [24]. Plants can be used in the following two manners: 1. plant parts can be used to cure infected animals naturally or 2. plant extracts and concoctions can be tested both in vitro and in vivo for their anthelmintic potential. The advantages of using antiparasitic plants include effectiveness against species resistant to synthetic anthelmintic drugs, limited or no risk of resistance development, and environmentally friendly procedure [42]. A major drawback is that, to date, only a small number of anthelmintic compounds such as macrocyclic lactones, cyclic octadepsipeptides, benzimidazoles, and imidazothiazoles have been identified in plants after decades of research [65]. Another drawback is the inconsistency between in vitro and in vivo studies on the use of plants as anthelmintics, raising questions regarding their validity and reliability [67]. Additionally, neurological effects associated with the dosage and bioavailability of some medicinal plants need to be elucidated before their use. The choice of an appropriate host–parasite system is tricky in in vivo studies because caring for the animal models adequately is expensive, time-consuming, and labor-intensive [100]. Other drawbacks include uncertainty about plant efficacy, nonspecific responses, irreproducible preparations, and potential negative consequences. An alternative strategy is to use plant secondary metabolites with anthelmintic activity [73]. Secondary metabolites exhibit various modes of action for anthelmintic activity. For example, tannins hinder the feeding process of parasites through forming complexes with parasite proteins or deactivating key enzymes [73]. Terpenes block the tyramine receptors of parasites, whereas alkaloids create unfavorable conditions in the host intestine by generating nitrated and free sugars [97,124]. However, it is important to conduct more studies on the underlying molecular mechanisms and adverse effects on the host to improve drug development.

5. Recommendations

An ideal anthelmintic agent should have a broad spectrum of action, a high treatment rate with a single therapeutic dose, low toxicity to the host, and cost-effectiveness. Most currently used synthetic drugs do not meet these requirements. Commonly used drugs have side effects such as nausea, drowsiness, and intestinal disorders. The development of resistance to existing drugs in parasites and the high cost of drugs have led researchers to explore novel anthelmintic effective agents. Ethnobotanical drugs are the source of easily available and effective anthelmintic agents for humans, especially in tropical and developing countries. Thus, people use various herbs or products derived from plants to treat helminth infections. Plants produce secondary metabolites with various ecophysiological functions, such as defense against pathogen attacks and protection against abiotic stresses. These metabolites have potential medicinal effects in humans and animals.

6. Conclusions and Future Perspectives

It is estimated that more than 2.5 billion people are affected with helminth parasites at some stage in their lives. Parasitic diseases remain the major reason of substantial economic loss owing to their impact on livestock health and unexpected deworming costs. According to the literature review, potential anthelmintic plants exhibit great diversity in terms of species and compounds. Nevertheless, initially, all anthelmintics are tested in livestock before being used for human therapy; thus, developments in veterinary anthelmintics could also lead to advancements in human therapy. In addition, studies on nutritional support and vaccination are also required to develop livestock with low parasite susceptibility.

Author Contributions

Conceptualization and design, S.S., J.C. and H.A.; analysis and interpretation of data, H.K.K., H.A., F.C., S.G.K. and K.S.A.; writing—original draft preparation, H.A., M.S.A. and W.S.; statistical analysis, S.F.; supervision, S.S. and J.C.; writing—review and editing, H.A., M.S.A., K.S.A., S.F., S.S., J.Z., F.P., S.L. and J.C. All authors approved the final version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Funding Statement

This study was supported by the National Natural Science Foundation of China (Nos. 81971969, 82272369, and 81772225 to JC) and the Three-Year Public Health Action Plan (2020–2022) of Shanghai (No. GWV-10.1-XK13 to JC). The funders had no role in the study design, the data collection, and analysis, the decision to publish, or the preparation of the manuscript.

Footnotes

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