An Inventory of Anthelmintic Plants across the Globe

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.

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.

The details of anthelmintic plants and their extracts potentially effective against Platyhelminthes and Nematoda are presented in

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.

and

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	Plumbagozeylanica	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.

, respectively.

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. 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.