Anthelmintic Plants across the Globe

Anthelmintic Plants across the Globe: Comparison

Please note this is a comparison between Version 1 by Sami Simsek and Version 2 by Rita Xu.

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 ^[1][3]. Recently, some anthelmintics have demonstrated loss of efficacy owing to anthelmintic resistance ^[2][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 ^[3][5].

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	^[4]	[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)	^[5]	[8]
Echinococcus granulosus (protoscolex)	In vitro	Anacardiaceae	Pistacia atlantica	Fruits and leaves	Hydroalcoholic extracts	100%; killed protoscoleces (50 mg/mL in 10 min)	^[1]	[3]
	In vitro	Anacardiaceae	Pistacia atlantica	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	^[6]	[9]
	In vitro	Lamiaceae	Salvia officinalis	Aerial parts	Ethanolic extract	100% (6–8 days)	^[7]	[10]
		Fabaceae	Prosopis farcta	Leaves	Ethanolic extract Crude alkaloids	25% scolicidal activity with a 500 mg/mL dose after 24 h	^[8]	[11]
		Fabaceae	Prosopis farcta	Leaves	Ethanolic extract Crude alkaloids	57% scolicidal activity with a 500 mg/mL dose after 24 h	^[8]	[11]
		Ranunculaceae	Nigella sativa	Seeds	Essential oil (Thymoquinone)	100% scolicidal activity with a 1 mg/mL dose after 10 min	^[9]	[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)	^[10]	[13]
		Euphorbiaceae	Jatropha unicostata	Leaves	Aqueous and methanolic extracts	100% scolicidal activity with a 1000 μg/mL dose after 288 h (both extracts)	^[10]	[13]
		Berberidaceae	Berberis vulgaris	Fruits	Aqueous extracts	98.7% scolicidal activity with a 2 mg/mL dose after 30 min	^[11]	[14]
		Euphorbiaceae	Mallotus philippinensis	Fruits	Methanolic extracts	99% scolicidal activity with a 20 mg/mL dose after 60 min	^[12]	[15]
Echinococcus granulosus protoscolex	In vitro	Meliaceae	Azadirachta indica	Whole plant	Ethanolic extracts	Up to 97% mortality with 30 min of incubation	^[13]	[16]
Echinostoma caproni	In vitro	Rosaceae	Hagenia abyssinica	Female flowers	Crude extract	51 h (100 µg/mL)	^[5]	[8]
Fasciola hepatica	In vitro	Fabaceae	Acacia farnesiana	Leaves	Hexane, ethyl acetate, and methanolic extracts	0% (500 mg/L)	^[14]	[17]
		Asteraceae	Artemisia absinthium			0% (500 mg/L)
		Asteraceae	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)
		Lamiaceae	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	^[15]	[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%	^[16]	[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	^[17]	[20]
Fasciola hepatica	In vitro	Rosaceae	Hagenia abyssinica	Female flowers	Crude extract	1 h (100 µg/mL)	^[5]	[8]
Fasciolopsis buski	In vitro	Zingiberaceae	Alpinia nigra	Shoot	Crude alcoholic extract	3.94 ± 0.06 h death time (20 mg/mL concentration)	^[18]	[21]
Gastrothylax crumenifer	In vitro	Fabaceae	Sesbania sesban var. bicolor	Fresh leaves	Methanolic extracts of dried plants	Better than praziquantel	^[19]	[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)	^[20]	[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)	^[21]	[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)	^[22]	[25]
Paramphistomum gracile	In vitro	Fabaceae	Senna alata	,	S. alexandrina	, and	S. occidentalis	Leaf extract	Ethanolic extracts	Dose-dependent effects on motility and mortality	^[23]	[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	^[24]	[27]
Raillietina echinobothrida	In vitro	Asteraceae	Acmella oleracea	Leaves	Methanolic extract	18.42 ± 0.95 h survival time (20 mg/mL concentration)	^[25]	[28]
Raillietina spiralis	In vitro	Malvaceae	Thespesia lampas	Roots	Aqueous extracts	51 ± 0.33 min death time (20 mg/mL concentration)	^[26]	[29]
Raillietina spiralis	In vitro	Meliaceae	Azadirachta Indica	Leaves	Aqueous extract	46 ± 0.53 min death time (20 mg/mL concentration)	^[27]	[30]
Raillietina spiralis	In vitro	Scrophulariaceae	Verbascum Thapsus	Fresh Leaves	Methanolic extract	86 ± 5 min death time (20 mg/mL concentration)	^[28]	[31]
Raillietina spiralis	In vitro	Asteraceae	Achillea wilhelmsii	Fresh Leaves	Methanolic extract	40 min death time (20 mg/mL concentration)	^[29]	[32]
Raillietina spiralis	In vitro	Lauraceae	Cinnamomum camphora	Leaves	Aqueous extracts	47 ± 0.54 min death time (20 mg/mL concentration)	^[30]	[33]
Raillietina spiralis	In vitro	Verbenaceae	Clerodendron inerme	Leaves	Aqueous extracts	45 ± 0.52 min death time (20 mg/mL concentration)	^[31]	[34]
Raillietina tetragona	In vitro	Poaceae	Imperata cylindrica	Underground parts (rhizomes and roots)	Chloroform (medium polar solvent)	Dose-dependent anthelmintic activity	^[32]	[35]
Schistosoma mansoni	In vitro	Apocynaceae	Rauwolfia vomitoria	Stem bark and roots	Ethanolic extract	High activity against cercariae and adult worms	^[33]	[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)	^[21]	[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)	^[22]	[25]
Schistosoma mansoni	In vivo	Asteraceae	Baccharis trimera	Leaves	Crude dichloromethane extract (DE) and aqueous fraction (AF)	98% (AF) 97% (DE)	^[34]	[37]
Schistosoma mansoni	In vivo	Asteraceae	Tanacetum vulgare	Aerial parts	Crude extract and Essential oil	100%	^[35]	[38]
Schistosoma mansoni	In vitro	Rosaceae	Hagenia abyssinica	Female flowers	Crude extract	3 h (100 µg/mL)	^[5]	[8]
Schistosoma mansoni	In vitro	Euphorbiaceae	Euphorbia conspicua	Leaves	Leaf extract	100% (100 µg/mL)	^[36]	[39]
Schistosoma mansoni	In vitro	Piperaceae	Piper chaba	Fruits	Methylene chloride extract	Strongest activity	^[37]	[40]
Taenia solium	In vitro	Asclepiadaceae	Pergularia daemia	Leaves	Ethanolic extract	210.00 ± 0.52 min death time (25 mg/mL concentration)	^[38]	[41]
Taenia solium	In vitro	Asclepiadaceae	Pergularia daemia	Leaves	Aqueous extract	221.12 ± 0.61	^[38]	[41]
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	^[39]	[42]

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 ^[40][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 ^[41][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 ^{[42][43][44][45]}[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 ^[42][44][46][127,129,131]. In general, many plant secondary metabolites including chalcones, coumarins, terpenoids, tannins, alkaloids, antioxidants, and flavonoids ^[47][48][132,133] possess anthelmintic and neurotoxic properties ^[49][134] and inhibit mitochondrial oxidative phosphorylation ^[50][51][135,136]. These plant-based compounds typically show higher biological activity than synthetic compounds ^[52][137]. In many parts of the world, plants have been used for many generations and are still being used to treat parasitic diseases ^[53][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 ^[54][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.

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 ^[35][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 ^[21][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 ^[39][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 ^[55][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 ^[56][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 ^[57][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 ^[58][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 ^[58][73]. Terpenes block the tyramine receptors of parasites, whereas alkaloids create unfavorable conditions in the host intestine by generating nitrated and free sugars ^[59][60][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.