Anthelmintic Plants across the Globe: Comparison
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Please note this is a comparison between Version 2 by Rita Xu and Version 1 by Sami Simsek.

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. These parasitic worms are categorized into two major groups: roundworms (phylum Nematoda) and flatworms (phylum Platyhelminthes). Among these parasites, gastrointestinal parasites pose a serious threat to livestock production.

  • ethnomedicine
  • anthelmintic
  • medicinal plant
  • helminth

1. Introduction

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][1]. Recently, some anthelmintics have demonstrated loss of efficacy owing to anthelmintic resistance [4][2]; 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][3].
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][4]
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][5]
Echinococcus granulosus (protoscolex) In vitro Anacardiaceae Pistacia atlantica Fruits and leaves Hydroalcoholic extracts 100%; killed protoscoleces (50 mg/mL in 10 min) [3][1]
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][6]
In vitro Lamiaceae Salvia officinalis Aerial parts Ethanolic extract 100% (6–8 days) [10][7]
Fabaceae Prosopis farcta Leaves Ethanolic extract

Crude alkaloids		 25% scolicidal activity with a 500 mg/mL dose after 24 h [11][8]
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][9]
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][10]
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][11]
Euphorbiaceae Mallotus philippinensis Fruits Methanolic extracts 99% scolicidal activity with a 20 mg/mL dose after

60 min		 [15][12]
Echinococcus granulosus protoscolex In vitro Meliaceae Azadirachta indica Whole plant Ethanolic extracts Up to 97% mortality with 30 min of incubation [16][13]
Echinostoma caproni In vitro Rosaceae Hagenia abyssinica Female flowers Crude extract 51 h (100 µg/mL) [8][5]
Fasciola hepatica In vitro Fabaceae Acacia farnesiana Leaves Hexane, ethyl acetate, and methanolic extracts 0% (500 mg/L) [17][14]
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][15]
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][16]
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][17]
Fasciola hepatica In vitro Rosaceae Hagenia abyssinica Female flowers Crude extract 1 h (100 µg/mL) [8][5]
Fasciolopsis buski In vitro Zingiberaceae Alpinia nigra Shoot Crude alcoholic extract 3.94 ± 0.06 h death time (20 mg/mL concentration) [21][18]
Gastrothylax crumenifer In vitro Fabaceae Sesbania sesban var. bicolor Fresh leaves Methanolic extracts of dried plants Better than praziquantel [22][19]
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][20]
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][21]
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][22]
Paramphistomum gracile In vitro Fabaceae Senna alata, S. alexandrina, and S. occidentalis Leaf extract Ethanolic extracts Dose-dependent effects on motility and mortality [26][23]
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][24]
Raillietina echinobothrida In vitro Asteraceae Acmella oleracea Leaves Methanolic extract 18.42 ± 0.95 h survival time (20 mg/mL concentration) [28][25]
Raillietina spiralis In vitro Malvaceae Thespesia lampas Roots Aqueous extracts 51 ± 0.33 min death time (20 mg/mL concentration) [29][26]
Raillietina spiralis In vitro Meliaceae Azadirachta Indica Leaves Aqueous extract 46 ± 0.53 min death time (20 mg/mL concentration) [30][27]
Raillietina spiralis In vitro Scrophulariaceae Verbascum Thapsus Fresh Leaves Methanolic extract 86 ± 5 min death time (20 mg/mL concentration) [31][28]
Raillietina spiralis In vitro Asteraceae Achillea wilhelmsii Fresh Leaves Methanolic extract 40 min death time (20 mg/mL concentration) [32][29]
Raillietina spiralis In vitro Lauraceae Cinnamomum camphora Leaves Aqueous extracts 47 ± 0.54 min death time (20 mg/mL concentration) [33][30]
Raillietina spiralis In vitro Verbenaceae Clerodendron inerme Leaves Aqueous extracts 45 ± 0.52 min death time (20 mg/mL concentration) [34][31]
Raillietina tetragona In vitro Poaceae Imperata cylindrica Underground parts (rhizomes and roots) Chloroform (medium polar solvent) Dose-dependent anthelmintic activity [35][32]
Schistosoma mansoni In vitro Apocynaceae Rauwolfia vomitoria Stem bark and roots Ethanolic extract High activity against cercariae and adult worms [36][33]
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][21]
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][22]
Schistosoma mansoni In vivo Asteraceae Baccharis trimera Leaves Crude dichloromethane extract (DE) and aqueous fraction (AF) 98% (AF) 97% (DE) [37][34]
Tanacetum vulgare Aerial parts Crude extract and Essential oil 100% [38][35]
Schistosoma mansoni In vitro Rosaceae Hagenia abyssinica Female flowers Crude extract 3 h (100 µg/mL) [8][5]
Schistosoma mansoni In vitro Euphorbiaceae Euphorbia conspicua Leaves Leaf extract 100%

(100 µg/mL)		 [39][36]
Piperaceae Piper chaba Fruits Methylene chloride extract Strongest activity [40][37]
Taenia solium In vitro Asclepiadaceae Pergularia daemia Leaves Ethanolic extract 210.00 ± 0.52 min death time (25 mg/mL concentration) [41][38]
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][39]

2. 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][40]. 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][41]. 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][42][43][44][45]. 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][42][44][46]. In general, many plant secondary metabolites including chalcones, coumarins, terpenoids, tannins, alkaloids, antioxidants, and flavonoids [132,133][47][48] possess anthelmintic and neurotoxic properties [134][49] and inhibit mitochondrial oxidative phosphorylation [135,136][50][51]. These plant-based compounds typically show higher biological activity than synthetic compounds [137][52]. In many parts of the world, plants have been used for many generations and are still being used to treat parasitic diseases [138][53]. 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][54], 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.

3. 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][35]. 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][21]. 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][39]. 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][55]. 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][56]. 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][57]. 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][58]. 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][58]. Terpenes block the tyramine receptors of parasites, whereas alkaloids create unfavorable conditions in the host intestine by generating nitrated and free sugars [97,124][59][60]. However, it is important to conduct more studies on the underlying molecular mechanisms and adverse effects on the host to improve drug development.

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