Emerging Anthelmintic Resistance in Poultry: Can Ethnopharmacological Approaches Offer a Solution?

Abstract

Limited pharmacological studies have been conducted on plant species used against poultry helminths. The objective of this study was to provide a basis for plant based anthelmintics as possible alternatives against poultry anthelmintic resistance. The study justified the need for alternative anthelmintics. The study places emphasis on the increasing anthelmintic resistance, mechanism of resistance, and preparational protocols for plant anthelmintics and their associated mechanism of action. Pharmaceutical studies on plants as alternative therapies for the control of helminth parasites have not been fully explored especially in several developing countries. Plants from a broad range of species produce a wide variety of compounds that are potential anthelmintics candidates. Important phenolic acids have been found in Brassica rapa L. and Terminalia avicenniodes Guill. and Perri that affect the cell signaling pathways and gene expression. Benzo (c) phenanthridine and isoquinoline alkaloids are neurotoxic to helminths. Steroidal saponins (polyphyllin D and dioscin) interact with helminthic mitochondrial activity, alter cell membrane permeability, vacuolation and membrane damage. Benzyl isothiocyanate glucosinolates interfere with DNA replication and protein expression, while isoflavones from Acacia oxyphylla cause helminth flaccid paralysis, inhibit energy generation, and affect calcium utilization. Condensed tannins have been shown to cause the death of nematodes and paralysis leading to expulsion from the gastro-intestinal tract. Flavonoids from Chenopodium album L and Mangifera indica L act through the action of phosphodiesterase and Ca²⁺-ATPase, and flavonoids and tannins have been shown to act synergistically and are complementary to praziquantel. Artemisinins from Artemisia cina O. Berg are known to disrupt mitochondrial ATP production. Terpenoids from Cucurbita moschata L disrupt neurotransmission leading to paralysis as well as disruption of egg hatching. Yeast particle encapsulated terpenes are effective for the control of albendazole-resistant helminths.

Keywords: ethnoveterinary; medicine; nematodes; parasites; plant; safety; synthetic; toxicity.

FIGURE 1

(A) 4-O-Caffeoylquinic acid and 5-O-caffeoylquinic acids are examples of phenolic acids in green coffee beans (Wei and Tanokura, 2015). (B) (1) Condensed Tannins cause paralysis and death of helminths. (2) Flavonoids affect the calcium pump and ATPase leading to the death of the helminth. (3) Phenolic acids affect cell signaling pathways and gene expressions leading to the death of the helminth. The blue circle shows possible synergistic actions between Condensed Tannins and Flavonoids.

FIGURE 2

(A) The structure of morphine (Verpoorte, 2005). (B) Benzo (c) phenanthridine or isoquinoline alkaloids damage helminth neurons leading to the death of the helminth.

FIGURE 3

(A) The structure of digitalin is an example of steroidal saponins (Morgan and Wilson, 1999). (B) Saponins affect mitochondrial action and also alter the permeability of the cell membrane leading to death of the helminth.

FIGURE 4

(A) The structure of gibberellic acid (Sponsel, 2003). (B) Yeast encapsulated terpenes inhibit neurotransmission and lead to helminth paralysis, they also inhibit hatching of helminths eggs.

FIGURE 5

(A) The structure of Benzyl glucosinolate, metabolites of glucosinolates (Akram et al., 2021). (B) BITC causes helminth DNA and cuticle damage.

FIGURE 6

(A) The structure of daidzein (Hampl et al., 2009). (B) Isoflavones cause helminth paralysis and inhibit energy utilization.

FIGURE 7

(A) The structure of artemisinin (Zeyuan, Yulin, and Meiyi, 2018). (B) Artemisinin and its derivatives inhibit neurotransmission resulting into worm paralysis (1) and can affect mitochondrial action resulting into worm death (2).

FIGURE 8

General mechanism of resistance to anthelmintic drugs. Genetic modifications in the parasite occur following decades of application of allopathic anthelmintics. DNA replication errors subsequently promote evolutionary changes in the gene of the parasites to form stable DNA (1). This undergoes transcription (2), and translation (3) with substitution of primary amino acids associated with susceptibility with those which favour resistances against anthelmintics. Subsequent protein modifications (4) favour expression of receptors which inhibit or reduce anthelmintic binding thus protecting the parasite from anthelmintic action. These genetic modifications are transferred to the offspring, favouring selective evolutionary changes which produce metabolic enzymes which degrade anthelmintics (5). A modified genotype is subsequently created which produces subsequent offsprings which are completely resistant to anthelmintics.