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With the increasing prevalence of anthelmintic resistance in animals recorded globally, and the threat of resistance in human helminths, the need for novel anthelmintic drugs is greater than ever. Most research aimed at discovering novel anthelmintic leads relies on high throughput screening (HTS) of large libraries of synthetic small molecules in industrial and academic settings in developed countries, even though it is the tropical countries that are most plagued by helminth infections. Tropical countries, however, have the advantage of possessing a rich flora that may yield natural products (NP) with promising anthelmintic activity. Focusing on South Asia, which produces one of the world's highest research outputs in NP and NP-based anthelmintic discovery, we find that limited basic research and funding, a lack of awareness of the utility of model organisms, poor industry-academia partnerships and lack of technological innovations greatly limit anthelmintics research in the region. Here we propose that utilizing model organisms including the free-living nematode Caenorhabditis elegans, that can potentially allow rapid target identification of novel anthelmintics, and Oscheius tipulae, a closely related, free-living nematode which is found abundantly in soil in hotter temperatures, could be a much-needed innovation that can enable cost-effective and efficient HTS of NPs for discovering compounds with anthelmintic/antiparasitic potential in South Asia and other tropical regions that historically have devoted limited funding for such research. Additionally, increased collaborations at the national, regional and international level between parasitologists and pharmacologists/ethnobotanists, setting up government-industry-academia partnerships to fund academic research, creating a centralized, regional collection of plant extracts or purified NPs as a dereplication strategy and HTS library, and holding regional C. elegans/O. tipulae-based anthelmintics workshops and conferences to share knowledge and resources regarding model organisms may collectively promote and foster a NP-based anthelmintics landscape in South Asia and beyond., Competing Interests: Declaration of Competing Interest The authors declare that no conflict of interest exists., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Worldwide, traditional usage of herbal medicines is a common practice to treat various parasitic infections. In India, bark decoction of Oroxylum indicum (L.) Kurz. (Bignoniaceae) is used as a traditional medicine to cure intestinal-helminthic infections. This study investigated the anthelmintic efficacy of methanolic bark extract of O. indicum on Hymenolepis diminuta (Cestoda), using both in vitro and in vivo methods. Utilizing a mini-questionnaire, first, we collected information about the pattern of anthelmintic use of this plant. Later, in vitro efficacy of extract was tested at 10, 20 and 30 mg/ml on both the artificially excysted juveniles and adult H. diminuta worms. Herein, scanning electron microscopy (SEM) was also utilized to determine the possible effects of extract on tegumental surfaces of juvenile and adult cestode. In vivo, extract was tested at 250, 500 and 1000 mg/kg in H. diminuta albino rat model, against juvenile and adult cestode. Praziquantel (PZQ) served as reference drug in anthelmintic assays. The acute toxicity of extract was determined as per the OECD guidelines. The field questionnaire data revealed that 78 % of people in the area use O. indicum stem bark against intestinal helminths, and of these, 75 % of people also believed it highly efficacious anthelmintic remedy. In vitro testing of extract revealed significant effects on juvenile worms, and 30 mg/ml of extract caused mortality of juveniles at the initial period (0.25 ± 0.00 h). Conversely, PZQ (1 mg/ml) showed paralysis and mortality of juvenile cestodes in 0.44 ± 0.04 and 1.11 ± 0.06 h, respectively. As determined by SEM, in vitro exposure to extract showed substantial effects on both juveniles and adult worms in the form of wrinkled scolex, distorted tegument and eroded microtriches. In vivo study revealed better efficacy of extract against juveniles than adult stages of parasite. Treatment of rats with 1000 mg/kg of extract caused 79.3 % reduction in EPG counts and 70.8 % of reduction in worm counts, which compared well to PZQ efficacy. In acute toxicity study, administration of a single oral dose of 2000 mg/kg of extract to mice did not cause any signs of toxicity or mortality within 2-week observation. Hence, the LD50 of extract was estimated to be greater than 2000 mg/kg. In conclusion, the bark extract of O. indicum possesses concentration-dependent effects against the larval and adult H. diminuta worms, and thus the extract holds promise in the control of intestinal helminthiases. This also supports the common belief of people about the reputation of this plant as anthelmintic in traditional medicine. There is a need to standardize the formulations of this plant for their possible use as standardized herbal anthelmintic agents in the future.

Although there are several effective drugs available for the treatment of intestinal helminths, the fact remains that they continue to remain out of reach to a vast majority of people in the world, especially in developing countries. On the other hand, there are a great many herbal remedies that are effective against common intestinal worms and are easily available to common people in developing countries. Clerodendrum colebrookianum Walp. (Lamiaceae) is a perennial shrub which is native to South and Southeast Asia. Traditionally, the leaves of this plant are used by the indigenous people of Northeast India as a remedy for the treatment of intestinal tapeworm infections. The aim of this study was to evaluate and authenticate the anthelmintic efficacy of C. colebrookianum leaf extract in experimentally induced Hymenolepis diminuta (a zoonotic tapeworm) infections in Wistar rats. The efficacy of the plant extract was assessed by monitoring the eggs per gram of faeces (EPG) counts and worm recovery rates of experimental animals, following treatment with the leaf extract of this plant at three different doses, i.e. 200, 400 and 800 mg/kg body weight, each given singly for 5 days. The results obtained revealed that the leaf extract of C. colebrookianum possesses a dose-dependent efficacy against the larval, immature and adult stages of H. diminuta. However, the efficacy of the extract was found to be considerably high only against the adult stages of the parasite. For this stage, a single 800-mg/kg dose of extract, given for 5 days, resulted into 68.42% reduction in the EPG counts and 62.50% reduction in the worm counts in the extract-treated group of animals, as compared to the control. The reference drug, praziquantel (5 mg/kg, single dose), however, showed slightly better efficacy and caused 95.16 and 87.00% reductions in the EPG and worm counts of treated animals, respectively. Unlike the adult stages, the efficacy of the plant extract was recorded to be comparatively low against the larval and immature stages of the parasite, as the treatment of animals with the highest dose of extract (800 mg/kg) could cause only 37.50 and 54.00% reductions in worm counts, respectively. The experimental evidence obtained in this study suggests that leaves of C. colebrookianum possess significant anthelminthic properties and supports their use against intestinal tapeworm infections in traditional medicine.

Although there are many effective drugs available to treat intestinal worms, the fact remains that they remain out of reach to a majority of the population in many areas of the world. On the other hand, traditional plant-based remedies continue to be an important therapeutic aid for treating worm infections throughout the world, especially in the developing nations. Solanum myriacanthum Dunal is a perennial shrub that is used in the folk medicine of Tangkhul Naga tribe of India for treating intestinal worms. This study evaluates the anthelmintic activity of its ripe fruit extract using experimental Hymenolepis diminuta (a zoonotic tapeworm) infections in albino rats. The efficacy of extract was adjudged by monitoring the eggs per gram (EPG) count of parasite as well as by the direct count of surviving worms in the intestine following treatment with methanol fruit extract of this plant to different groups of rats harbouring H. diminuta infections. The plant extract showed a dose-dependent reduction of both EPG as well as worm counts for all the developmental stages of H. diminuta in rats. However, the effects of the extract were more apparent on the adult stages than larval or immature stages of the parasite. Against the adult stage, a single oral dose of 800 mg/kg of extract, given for 3 days, showed 60.49% reduction in the EPG counts and 56.60% reduction in the worm counts in the extract-treated group as compared to untreated control. In comparison, the reference drug praziquantel (5 mg/kg) showed 51.81% and 70.00% reduction in the EPG and worm counts, respectively. The LD50 (oral) of the extract was determined to be 3,093.24 mg/kg in rats, and no significant changes were observed in the values of serum glutamate oxalate transaminase, serum glutamate pyruvate transaminase, cholesterol and total protein between the extract-treated and control groups of animals. These findings indicate that ripe fruits of S. myriacanthum possess significant anthelmintic property, without any adverse effects to the experimental animals. This may provide a scientific rationale for the traditional use of this plant against intestinal worms.

The leaves ofGynura angulosaDC (Compositae) have been widely used in the indigenous system of medicine of Naga tribes in India for curing intestinal-helminth infections. In this study, the anthelmintic effects ofG. angulosaleaf extract were investigatedin-vitroandin-vivoagainstHymenolepis diminuta, a zoonotic tapeworm species. Inin-vitrostudy, the anthelmintic effects of extract were judged on the basis of paralysis and mortality of test worms, at 5, 10, 20 and 40 mg/ml concentrations, while inin-vivostudy, the leaf extract was tested at 200, 400 and 800 mg/kg doses against experimentally inducedH. diminutainfections in rats. The results revealed thatG. angulosaleaf extract possesses dose-dependent anthelmintic effects. Inin-vitrostudy, at 40 mg/kg concentration, the leaf extract showed mortality of test worms in as early as 2.92 h. Inin-vivostudy, the effects of extract were found to be more prominent against the adult stage than the larval stage of test parasite. Against the adult worm, the 800 mg/kg dose of extract, given for 5 days, resulted into 78.60 % reduction in eggs per gram of faeces (EPG) counts and 70.75 % reduction in worm counts of treated animals. In both the assays, the effects of extract were found to be quite comparable with that of a reference anthelmintic drug, praziquantel. These results prove thatG. angulosaleaves possesses significant anthelmintic properties. Therefore, this plant may be useful in the treatment of intestinal helminth infections and could also be a potential source of new anthelmintic compound. [ABSTRACT FROM AUTHOR]