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Traditional Kenyan herbal medicine: exploring natural products’ therapeutics against schistosomiasis

Published online by Cambridge University Press:  03 March 2022

Fidensio K. Ndegwa ,
Chaitanya Kondam ,
Samuel Y. Aboagye Open the ORCID record for Samuel Y. Aboagye [Opens in a new window] ,
Taiwo E. Esan ,
Zohra Sattar Waxali ,
Margaret E. Miller ,
Nicholas K. Gikonyo ,
Paul K. Mbugua ,
Paul O. Okemo  and
David L. Williams Open the ORCID record for David L. Williams [Opens in a new window]
...Show all authors
Fidensio K. Ndegwa
Affiliation:
Department of Pharmacognosy, Pharmaceutical Chemistry and Pharmaceutical & Industrial Pharmacy, Kenyatta University, Nairobi, Kenya
Chaitanya Kondam
Affiliation:
Department of Chemistry and Biochemistry, Northern Illinois University, 1425 West Lincoln Highway, DeKalb, IL60115-2828, USA
Samuel Y. Aboagye
Affiliation:
Department of Microbial Pathogens & Immunity, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL60612, USA
Taiwo E. Esan
Affiliation:
Department of Chemistry and Biochemistry, Northern Illinois University, 1425 West Lincoln Highway, DeKalb, IL60115-2828, USA
Zohra Sattar Waxali
Affiliation:
Department of Chemistry and Biochemistry, Northern Illinois University, 1425 West Lincoln Highway, DeKalb, IL60115-2828, USA
Margaret E. Miller
Affiliation:
Department of Chemistry and Biochemistry, Northern Illinois University, 1425 West Lincoln Highway, DeKalb, IL60115-2828, USA
Nicholas K. Gikonyo
Affiliation:
Department of Pharmacognosy, Pharmaceutical Chemistry and Pharmaceutical & Industrial Pharmacy, Kenyatta University, Nairobi, Kenya
Paul K. Mbugua
Affiliation:
Department of Plant Sciences, Kenyatta University, Nairobi, Kenya
Paul O. Okemo
Affiliation:
Department of Microbiology, Kenyatta University, Nairobi, Kenya
David L. Williams*
Affiliation:
Department of Microbial Pathogens & Immunity, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL60612, USA
Timothy J. Hagen*
Affiliation:
Department of Chemistry and Biochemistry, Northern Illinois University, 1425 West Lincoln Highway, DeKalb, IL60115-2828, USA
*
Author for correspondence: David L. Williams, E-mail: david_williams@rush.edu; Timothy J. Hagen, E-mail: thagen@niu.edu
Author for correspondence: David L. Williams, E-mail: david_williams@rush.edu; Timothy J. Hagen, E-mail: thagen@niu.edu
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Abstract

Praziquantel (PZQ) remains the only drug of choice for the treatment of schistosomiasis, caused by parasitic flatworms. The widespread use of PZQ in schistosomiasis endemic areas for about four decades raises concerns about the emergence of resistance of Schistosoma spp. to PZQ under drug selection pressure. This reinforces the urgency in finding alternative therapeutic options that could replace or complement PZQ. We explored the potential of medicinal plants commonly used by indigenes in Kenya for the treatment of various ailments including malaria, pneumonia, and diarrhoea for their antischistosomal properties. Employing the Soxhlet extraction method with different solvents, seven medicinal plants Artemisia annua, Ajuga remota, Bredilia micranta, Cordia africana, Physalis peruviana, Prunus africana and Senna didymobotrya were extracted. Qualitative phytochemical screening was performed to determine the presence of various phytochemicals in the plant extracts. Extracts were tested against Schistosoma mansoni newly transformed schistosomula (NTS) and adult worms and the schistosomicidal activity was determined by using the adenosine triphosphate quantitation assay. Phytochemical analysis of the extracts showed different classes of compounds such as alkaloids, tannins, terpenes, etc., in plant extracts active against S. mansoni worms. Seven extracts out of 22 resulted in <20% viability against NTS in 24 h at 100 μg/ml. Five of the extracts with inhibitory activity against NTS showed >69.7% and ≥72.4% reduction in viability against adult worms after exposure for 24 and 48 h, respectively. This study provides encouraging preliminary evidence that extracts of Kenyan medicinal plants deserve further study as potential alternative therapeutics that may form the basis for the development of the new treatments for schistosomiasis.

Keywords

Traditional medicineArtemisia annuaAjuga remotaBredilia micrantaCordia africanaPhysalis peruvianaPrunus africanaSenna didymobotryaschistosomiasis
Type
Research Paper
Information
Journal of Helminthology , Volume 96 , 2022 , e16
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Introduction

Schistosomiasis or bilharzia is one of the most common parasitic neglected tropical diseases. It is caused by the flatworms in the genus Schistosoma. The World Health Organization (WHO) estimates that more than 230 million people from 78 countries including the Middle East, South America, East Asia and sub-Saharan Africa are at risk with about 200,000 deaths each year (World Health Organization, 2022). The main burden of the disease is in sub-Saharan Africa, which accounts for over 90% of all incident cases (Colley et al., Reference Colley, Bustinduy, Secor and King2014). The primary schistosome species infecting humans are Schistosoma mansoni, Schistosoma haematobium and Schistosoma japonicum and transmission is mainly by contact with contaminated freshwater, whereby infective larvae released from freshwater snails, for instance, Biomphalaria glabrata, penetrate the host skin, develop within circulation and mature into Schistosoma adult worms in the mesenteric or bladder veins of human host (Colley et al., Reference Colley, Bustinduy, Secor and King2014). The egg deposition within the liver and or bladder and in some cases the central nervous system and pulmonary systems of the human host evokes immunological responses with associated disease pathophysiology (Colley et al., Reference Colley, Bustinduy, Secor and King2014).

There is no vaccine for schistosomiasis treatment and the only existing drug recommended by the WHO for chemotherapy praziquantel (PZQ) has been utilized for the past four decades. The widespread use of PZQ monotherapy in African endemic communities has raised concerns about the selection of drug resistant schistosomes. Even though evidence of clinically relevant emergence of PZQ resistance is lacking, low cure rates in response to PZQ in the field after extensive mass drug administration in Egypt and Senegal have been reported (Simoben et al., Reference Simoben, Ntie-Kang, Akone and Sippl2018). Furthermore, S. mansoni isolates from Kenyan patients showed lower susceptibility to PZQ, including one isolate from a patient who was never fully cured after repeated PZQ treatment over several years and PZQ-resistance can be generated in the laboratory (Fallon & Doenhoff, Reference Fallon and Doenhoff1994; Bergquist et al., Reference Bergquist, Utzinger and Keiser2017). The continual administration of PZQ most likely will select for schistosomes with reduced susceptibility, which could accelerate the emergence of resistance as large reservoirs of untreated schistosomes become exposed to PZQ. There is, therefore, the need for alternative therapeutic options that could be used in place of or to complement PZQ.

Plants, bacteria and fungi are good sources of pharmacologically active natural products used in the treatment of various diseases (Simoben et al., Reference Simoben, Ntie-Kang, Akone and Sippl2018) and traditional, plant-based medicines are a potential source for new drugs. Research efforts have intensified in search of new, potent, affordable and effective drugs to treat parasitic diseases due to the limited treatment options and the lack of vaccines targeting the parasitic diseases. Plant parts have been used as traditional medicine for schistosomiasis for centuries in many African countries. Phytolacca dodecandra berries are used as a molluscicide to control schistosomiasis in Ethiopia (Esser et al., Reference Esser, Semagn and Wolde-Yohannes2003). Breonia decaryana, Citrus reticulata, Dalbergia monticola, Senna alata and Zingiber zerumbet are used for schistosomiasis treatment in Madagascar (Rakotoarivelo et al., Reference Rakotoarivelo, Rakotoarivony, Ramarosandratana, Jeannoda, Kuhlman, Randrianasolo and Bussmann2015). In Mali, Cissus quadrangularis and Stylosanthes erecta (Bah et al., Reference Bah, Diallo, Dembele and Paulsen2006), Rauvolfia vomitoria (Tekwu et al., Reference Tekwu, Bosompem and Anyan2017), Elephantorrhiza goetzei and Pilistigma thonningii are used as remedies for schistosomiasis (Maroyi, Reference Maroyi2013). Due to the enormous therapeutic properties shown by many plants, in this study we explored the potential of seven plants used in Kenya for treating malaria, pneumonia, and diarrhoea for their schistosomicidal activity: Artemisia annua (Anibogwu et al., Reference Anibogwu, Jesus, Pradhan, Pashikanti, Mateen and Sharma2021); Ajuga remota (Cocquyt et al., Reference Cocquyt, Cos, Herdewijn, Maes, Van den Steen and Laekeman2011; Yikna & Yehualashet, Reference Yikna and Yehualashet2021); Bredilia micranta (Maroyi, Reference Maroyi2017); Cordia africana (Lelamo, Reference Lelamo2021); Physalis peruviana (Kasali et al., Reference Kasali, Tusiimire, Kadima, Tolo, Weisheit and Agaba2021); Prunus africana (Kathambi et al., Reference Kathambi, Mutie, Rono, Wei, Munyao, Kamau, Gituru, Hu and Wang2020); and Senna didymobotrya (Schmelzer et al., Reference Schmelzer and Gurib-Fakim2008).

Material and methods

Collection and preparation of plant material

The botanical information on the traditional medicinal plants of Kenya used in this study are presented in table 1. Dry powdered material of seven plants (A. remota, B. micrantha, S. didymobotrya, C. africana, P. peruviana, P. africana, and A. annua) were obtained from the Department of Pharmacognosy, Pharmaceutical Chemistry and Pharmaceutical & Industrial Pharmacy, Kenyatta University, Nairobi, Kenya. The plant material was first extracted with boiling water by decoction and then sequentially extracted with methanol and hexane in a Soxhlet apparatus. Plant material was also extracted non-sequentially using acetone with Soxhlet extraction. The extraction solvents (methanol, acetone and hexane) were evaporated under nitrogen gas, and water extracts were dried by lyophilization. Depending on sample availability and extraction yield, the samples were tested for anti-schistosomal activity. The yields of crude extracts are shown in table 2.

Table 1. Botanical information of medicinal plants used for anti-schistosomal study.

Table 2. Crude extraction yield from Kenyan medicinal plants.

Evaluation of schistosomicidal activity

Preparation of schistosomula

Biomphalaria glabrata (strain NMRI) infected with S. mansoni (strain NMRI) were obtained from the National Institute of Allergy and Infectious Diseases Schistosomiasis Resource Center of the Biomedical Research Institute. After infections were patent, snails were exposed to bright light for 1 h to obtain cercariae. Cercariae were mechanically transformed to schistosomula as described (Lombardo et al., Reference Lombardo, Pasche, Panic, Endriss and Keiser2019). Briefly, cercariae were placed on ice for 30 min and then centrifuged at 350 × g for 10 min. The supernatant was decanted and 2 ml of serum-free M199 medium was added to cercarial pellets and vortexed for 1 min until cercarial tails were detached. Newly transformed schistosomula (NTS) were purified by layering on 4°C Percoll gradient suspension containing Eagle's minimum essential medium, penicillin–streptomycin (10,000 U per ml penicillin/10,000 U per ml streptomycin), and 1 M 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid in 0.85% sodium chloride with cercariae suspension and centrifuged at 500 × g for 15 min. Cercarial pellets were resuspended and washed thrice in serum-free M199 medium and collected at 100 × g for 5 min. NTS (240) were transferred to U-bottom 96 well assay plates containing 200 μl of M199 medium supplemented with 5.5 mm D-glucose, penicillin–streptomycin and 5% heat inactivated fetal bovine serum and incubated at 37°C in a 5% carbon dioxide (CO2) incubator overnight.

Preparation of adult worms

Swiss Webster mice (Charles River) housed in the Comparative Research Center of Rush University Medical Center were infected by percutaneous tail exposure to about 200 S. mansoni cercariae through natural transdermal penetration of the cercariae for one hour (Tucker et al., Reference Tucker, Karunaratne, Lewis, Freitas and Liang2013). Mice were euthanized 7-weeks post infection using a lethal dose of 0.018 ml of Euthasol and 5.85 mg/ml heparin to prevent blood coagulation (injection volume of 400 μl). Perfusion was performed by flushing pre-warmed Roswell Park Memorial Institute (RPMI) containing phenol red and L-glutamine through a 25- and 3/8-gauge needle placed into the aorta attached to Tygon® tubing aided by the Masterflex™ L/S perfusion pump as described (Tucker et al., Reference Tucker, Karunaratne, Lewis, Freitas and Liang2013). Adult worms were carefully washed in phenol red free RPMI medium and subsequently incubated in phenol red free RPMI medium supplemented with 5.5 mm D-glucose, penicillin–streptomycin and 5% heat inactivated fetal bovine serum and at 37°C in a 5% CO2 incubator overnight.

Schistosomicidal activity of extracts against S. mansoni schistosomula and adult worms

The dimethyl sulphoxide (DMSO) formulated plant extracts were diluted with phenol red free M199 medium or RPMI medium for NTS and adult worms, respectively, at <1% DMSO final concentrations. NTS and adult worms from overnight cultures were tested against extracts in triplicate at 100 μg/ml. Controls were treated with DMSO alone or 5 μM auranofin as a positive control in appropriate medium (Kuntz et al., Reference Kuntz, Davioud-Charvet, Sayed, Califf, Dessolin, Arnér and Williams2007). NTS and adult worm viability was assessed at 24 h by measuring adenosine triphosphate (ATP) content of worms using the CellTiter-Glo® Assay (Promega) following manufacturer's instructions as described (Lalli et al., Reference Lalli, Guidi, Gennari, Altamura, Bresciani and Ruberti2015).

Statistical analysis for schistosomicidal activity

Schistosome viability in the presence of the crude extracts were assessed using this formula:

$$\% {\rm viability} = \displaystyle{{{\rm Averages}\,{\rm of}\,{\rm Test}} \over {{\rm Averages}\,{\rm of}\,{\rm DMSO}\,{\rm Control}}} \times 100$$

Phytochemical analysis

Qualitative phytochemical characterization was performed by placing 5 μl of solution onto a silica plate and then subjecting to standard reagents used for phytochemical analysis. The following reagents were used for the phytochemical analysis: anisaldehyde/sulphuric acid reagent for steroids (Xu & Liu, Reference Xu and Liu2021); Dragendorff reagent for alkaloids (Dube et al., Reference Dube, van Heerden, Zachariades, Uyi and Munyai2021); potassium hydroxide (Bornträger reaction) (Henzelyová et al., Reference Henzelyová, Antalová, Nigutová, Logoida, Schreiberová, Kusari and Čellárová2020) for coumarins (365 nm) and anthraquinones (vis. and 365 nm); 5% ethanolic solution of sulphuric acid (H2SO4) for cardiac glycosides (Onyema, Reference Onyema2019); aluminium chloride (AlCl3) solution (1% ethanolic AlCl3) for flavonoids (Gwatidzo et al., Reference Gwatidzo, Dzomba and Mangena2018); iron (III) chloride (FeCl3) reagent (3% FeCl3) for tannins and phenolic compounds (Fu & Chen, Reference Fu and Chen2019); ninhydrin for amino acids, amines and amino sugars (0.2% ethanolic ninhydrin solution) (Tyagi et al., Reference Tyagi, Dwivedi and Bagchi2019); phenol/ H2SO4 solution for carbohydrates (Su et al., Reference Su, Lu, Lu, Lai and Ng2020; Oh et al., Reference Oh, Lee and Kim2021); and vanillin/H2SO4 solution for terpenes/terpenoids (Jiang et al., Reference Jiang, Kempinski and Chappell2016).

Results

Schistosomicidal activity of crude extracts of Kenyan medicinal plants

Seven Kenyan medicinal plants were extracted with various solvents resulting in 22 different crude extracts (table 2). These were evaluated for schistosomicidal activity against S. mansoni NTS. Following 24-hour exposure of NTS to 100 μg/ml of each extract worm viability was determined by ATP quantitation. We observed variable viabilities among the crude extracts analysed. Greater than 80% reduction in NTS viability was detected after treatment with A. annua (acetone) – 97.9%, P. africana (acetone) – 96.4% B. micrantha (water) – 89.9%, P. peruviana (acetone) – 89.5%, B. micrantha (methanol) – 88.6%, A. remota (hexane) – 82.5%, and S. didymobotrya (acetone) – 82.4% compared to the DMSO treated NTS negative control as shown in fig. 1. While treatment with most of the extracts resulted in moderate viability reductions, treatment with A. remota (water) (4.2% reduction) and B. micrantha (hexane) (9.2% reduction) had minimal activity against NTS.

Fig. 1. Schistosoma mansoni newly transformed schistosomula viability against crude extracts from Kenyan medicinal plants. The error bars represent the standard deviation of three independent experiments.

We further tested all nine extracts that showed >80% decrease in viability against NTS for activity against S. mansoni adult worms. Viability was determined for each extract after 24-hour and 48-hour exposure to adult worms. After 24-hour exposure, all extracts showed ≤36% viability against adult worms except A. annua (acetone) (48%) and B. micrantha (methanol) (51.5%) (fig. 2). Upon 48-hour exposure, about 10% increased reduction in viability was observed among the seven tested extracts with all compounds resulting in >55% mortality. The most active extract against S. mansoni adult worms was B. micrantha (water) with 81.6% reduction in viability (fig. 2).

Fig. 2. Schistosoma mansoni adult worm viability after treatment with crude plant extracts with potent newly transformed schistosomula-killing activity. Viability (%) after 24 h () or 48 h () treatment with extract. The error bars represent the standard deviation of three independent experiments.

Qualitative phytochemical screening results

Qualitative analysis of crude plant extracts showed the presence of various phytochemicals (table 3). The level of phytochemicals was categorized as high, moderate, low, or absent. Artemisia annua plant extracts showed high levels of steroids, tannins, anthraquinones and terpenes/terpenoids. Moderate levels of glycosides and flavonoids were present in A. annua extracts. Steroids and tannins were present at high levels in B. micrantha extracts. Alkaloids, anthraquinones and glycosides were moderately present in B. micrantha plant extracts. Cordia africana plant extracts showed steroids, tannins and proteins at high levels whereas glycosides and anthraquinones were scarcely present. Ajuga remota plant extracts showed steroids, flavonoids, terpenes/terpenoids, glycosides, proteins and anthraquinones eminently whereas tannins were scarcely present. Prunus africana plant extracts showed steroids, glycosides and anthraquinones at high levels whereas tannins, terpenes/terpenoids and flavonoids were present at low levels. Senna didymobotrya plant extracts showed steroids, glycosides and anthraquinones at high levels whereas tannins, alkaloids and flavonoids were present at low levels or absent. Physalis peruviana plant extracts showed high levels of steroids and terpenes/terpenoids whereas tannins, flavonoids, and anthraquinones were present at low levels or absent.

Table 3. Phytochemical analysis from seven Kenyan plant extracts.

+++ = high, ++ = moderate, + = low, − = absent.

Discussion

The lack of a vaccine or alternative drugs to PZQ for the management of schistosomiasis has necessitated the need to search for novel anti-infective agents. Even though the efficacy of PZQ for the past four decades has not been in doubt, concerns about the possible emergence of resistance due to selective drug pressure are inevitable, reinforcing the urgency towards the discovery of new schistosomicidal agents. Furthermore, PZQ has poor activity against migrating juvenile worms and treatment often results in incomplete cures (Pica-Mattoccia & Cioli, Reference Pica-Mattoccia and Cioli2004). Plants have served as active components of many pharmacological products due to their broad spectrum of biological activity including cytotoxic, antiparasitic and antimicrobial properties (Heinrich & Lee Teoh, Reference Heinrich and Lee Teoh2004; Wright, Reference Wright2010). In most healthcare resource-limited settings, indigenes rely extensively on plant medicines for primary healthcare services. We, therefore, explored the therapeutic potential of seven Kenyan herbal plants commonly used in the treatment of malaria, pneumonia and chest pains. We report herein the schistosomicidal properties of A. annua, B. micrantha, P. peruviana, A. remota, S. didymobotrya and P. africana, with a demonstrated potential to be repurposed as treatment for schistosomiasis.

The antimalarial, anti-inflammatory, antibacterial and analgesic properties of these extracts are known; however, their schistosomicidal properties are unclear. Our findings show that 100 μg/ml of acetone extracts of A. annua, P. africana, P. peruviana and S. didymobotrya, 100 μg/ml of water and methanol extracts of B. micrantha and 100 μg/ml of hexane extracts of A. remota had significant worm killing activity (>90%) against S. mansoni NTS after 24-hour exposure. These extracts further showed ≥69.7% and ≥72.5% killing activity in S. mansoni adult worms after 24 and 48-hours of exposure, respectively. The extracts show promise as possible leads by their killing potential on both the larval stage and adult worms of S. mansoni. Since PZQ is primarily active against only adult worms, combination therapy with the extracts may inhibit all the developmental stages of the parasite and may overcome the problem of drug resistance. Ethanolic extracts of A. annua has been shown to have schistosomicidal activity at 2 mg/ml (Ferreira et al., Reference Ferreira, Peaden and Keiser2011). In China, artemisinin extracted from A. annua and its derivatives artemether, artesunate and dihydroartemisinin, have efficacy against S. japonicum. Multiple doses of artemisinin at 6 mg/kg body weight showed preventive efficacies as high as 65–97% (Liu et al., Reference Liu, Wu, Liang, Jie, Wang, Wang and Huang2014). The extract dose of 100 μg/ml used in this study was comparatively lower in relation to similar studies where doses within the ranges of 1.25–2.5 mg/mL of different plant extracts resulted in 90% of the killing of Paramphistomum cervi, the causative agent of enteritis and anaemia in livestock mammals (Elango & Rahuman, Reference Elango and Rahuman2011).

Phytochemical analyses of the extracts detected different classes of compounds comprising steroids, tannins, anthraquinones, glycosides and terpenoids mediating the observed S. mansoni worm killing. Bioactive components of plants display variable activities against different stages of pathogens (Ferreira et al., Reference Ferreira, Peaden and Keiser2011). The acetone extracts of A. annua which contained steroids, anthraquinones and terpenoids and P. africana with steroids, anthraquinones and glycosides as major compounds showed complete killing of NTS. However, worm killing activity was reduced after 48-hours of exposure against S. mansoni adult worms in some of the extracts. The reduced activity influenced by variable susceptibilities of the bioactive components could be as a result of poor uptake or efflux of the compounds by the adult worm. We observed a strong correlation in the worm killing activity of a water decoction extract of B. micrantha. After 24-hour exposure to extracts, 90.1% of NTS were killed while 72.2% and 81.6% adult worms were killed after 24 and 48-hour exposure, respectively. This suggests that tannins, the major phytochemical component in B. micrantha, possess schistosomicidal properties. Tannins obtained from Lotus corniculatus, Hedysarum coronarium and Onobrychis viciifolia, caused a remarkable reduction in Trichostrongylus colubriformis hatched eggs and inhibited the development of eggs in gastrointestinal nematodes (Molan et al., Reference Molan, Hoskin, Barry and McNabb2000, Reference Molan, Waghorn and McNabb2002). Tannins have been shown to inhibit parasites by minimizing the formation of infective stage larvae, reduction of eggs excretion by the adult worms and reduction of eggs’ development (Athanasiadou et al., Reference Athanasiadou, Kyriazakis, Jackson and Coop2001). Simple tannins such as (-)-epicatechin are orally bioavailable (Zhu et al., Reference Zhu, Chen and Li2000; Serrano et al., Reference Serrano, Puupponen-Pimia, Dauer, Aura and Saura-Calixto2009) suggesting that they may be active against blood dwelling schistosome worms; similar tannins were identified in this study.

In summary, this study has found that extracts of seven plants used for the treatment of a variety of conditions in Kenya have schistosomicidal activity against cultured S. mansoni worms. Further studies of these extracts to identify the active components will provide promising lead compounds that can be developed to meet the urgent need for new drugs for the treatment of schistosomiasis.

Acknowledgements

Biomphalaria glabrata snails infected with Schistosoma mansoni were provided by the National Institute of Allergy and Infectious Diseases (NIAID) Schistosomiasis Resource Center of the Biomedical Research Institute (Rockville, MD) through National Institutes of Health–NIAID Contract HHSN272201000005I for distribution through Biodefense and Emerging Infections Research Resources.

Financial support

The authors acknowledge Northern Illinois University for supporting and funding this work. The study was partially funded by National Institutes of Health (D.L.W. AI127635).

Conflicts of interest

No conflict of interest was reported by the authors.

Ethical standards

This study was approved by the Institutional Animal Care and Use Committee of Rush University Medical Center (20-069; Department of Health and Human Services animal welfare assurance number A-3120−01).

Footnotes

*

These authors contributed equally.

References

Anibogwu, R, Jesus, K, Pradhan, S, Pashikanti, S, Mateen, S and Sharma, K (2021) Extraction, isolation and characterization of bioactive compounds from Artemisia and their biological significance: a review. Molecules 26(22), 6995.CrossRefGoogle ScholarPubMed
Athanasiadou, S, Kyriazakis, I, Jackson, F and Coop, RL (2001) Direct anthelmintic effects of condensed tannins towards different gastrointestinal nematodes of sheep: in vitro and in vivo studies. Veterinary Parasitology 99(3), 205–219.CrossRefGoogle ScholarPubMed
Bah, S, Diallo, D, Dembele, S and Paulsen, BS (2006) Ethnopharmacological survey of plants used for the treatment of schistosomiasis in Niono District, Mali. Journal of Ethnopharmacology 105(3), 387–399.CrossRefGoogle ScholarPubMed
Bergquist, R, Utzinger, J and Keiser, J (2017) Controlling schistosomiasis with praziquantel: how much longer without a viable alternative? Infectious Diseases of Poverty 6(1), 74.CrossRefGoogle ScholarPubMed
Cocquyt, K, Cos, P, Herdewijn, P, Maes, L, Van den Steen, PE and Laekeman, G (2011) Ajuga remota Benth.: from ethnopharmacology to phytomedical perspective in the treatment of malaria. Phytomedicine 18(14), 1229–1237.CrossRefGoogle ScholarPubMed
Colley, DG, Bustinduy, AL, Secor, WE and King, CH (2014) Human schistosomiasis. Lancet 383(9936), 2253–2264.CrossRefGoogle ScholarPubMed
Dube, N, van Heerden, FR, Zachariades, C, Uyi, OO and Munyai, TC (2021) First record of pyrrolizidine alkaloids in the southern African biotype of Chromolaena odorata (Asteraceae). South African Journal of Botany 139, 19–25.CrossRefGoogle Scholar
Elango, G and Rahuman, AA (2011) Evaluation of medicinal plant extracts against ticks and fluke. Parasitology Research 108(3), 513–519.CrossRefGoogle ScholarPubMed
Esser, KB, Semagn, K and Wolde-Yohannes, L (2003) Medicinal use and social status of the soap berry endod (Phytolacca dodecandra) in Ethiopia. Journal of Ethnopharmacology 85(2–3), 269–277.CrossRefGoogle ScholarPubMed
Fallon, PG and Doenhoff, MJ (1994) Drug-resistant schistosomiasis: resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific. American Journal of Tropical Medicine and Hygiene 51(1), 83–88.CrossRefGoogle ScholarPubMed
Ferreira, JF, Peaden, P and Keiser, J (2011) In vitro trematocidal effects of crude alcoholic extracts of Artemisia annua, A. absinthium, Asimina triloba, and Fumaria officinalis: trematocidal plant alcoholic extracts. Parasitology Research 109(6), 1585–1592.CrossRefGoogle ScholarPubMed
Fu, Z and Chen, R (2019) Study of complexes of tannic acid with Fe(III) and Fe(II). Journal of Analytical Methods in Chemistry 2019, 3894571. Available at https://www.hindawi.com/journals/jamc/2019/3894571/ (accessed 1 December 2021).CrossRefGoogle Scholar
Gwatidzo, L, Dzomba, P and Mangena, M (2018) TLC separation and antioxidant activity of flavonoids from Carissa bispinosa, Ficus sycomorus, and Grewia bicolar fruits. Nutrire 43(1), 3.CrossRefGoogle Scholar
Heinrich, M and Lee Teoh, H (2004) Galanthamine from snowdrop—the development of a modern drug against Alzheimer's disease from local Caucasian knowledge. Journal of Ethnopharmacology 92(2–3), 147–162.CrossRefGoogle ScholarPubMed
Henzelyová, J, Antalová, M, Nigutová, K, Logoida, M, Schreiberová, A, Kusari, S and Čellárová, E (2020) Isolation, characterization and targeted metabolic evaluation of endophytic fungi harbored in 14 seed-derived Hypericum species. Planta Medica 86(13–14), 997–1008.Google ScholarPubMed
Jiang, Z, Kempinski, C and Chappell, J (2016) Extraction and analysis of terpenes/terpenoids. Current Protocols in Plant Biology 1, 345–358.CrossRefGoogle ScholarPubMed
Kasali, FM, Tusiimire, J, Kadima, JN, Tolo, CU, Weisheit, A and Agaba, AG (2021) Ethnotherapeutic uses and phytochemical composition of Physalis peruviana L.: an overview. Scientific World Journal 2021, 5212348. Available at https://fjps.springeropen.com/articles/10.1186/s43094-021-00306-3 (accessed 1 December 2021).CrossRefGoogle ScholarPubMed
Kathambi, V, Mutie, FM, Rono, PC, Wei, N, Munyao, JN, Kamau, P, Gituru, RW, Hu, GW and Wang, QF (2020) Traditional knowledge, use and conservation of plants by the communities of Tharaka-Nithi County, Kenya. Plant Diversity 42(6), 479–487.CrossRefGoogle ScholarPubMed
Kuntz, AN, Davioud-Charvet, E, Sayed, AA, Califf, LL, Dessolin, J, Arnér, ESJ and Williams, DL (2007) Thioredoxin glutathione reductase from Schistosoma mansoni: An essential parasite enzyme and a key drug target. PLOS Neglected Tropical Diseases 4(6), e206.Google Scholar
Lalli, C, Guidi, A, Gennari, N, Altamura, S, Bresciani, A and Ruberti, G (2015) Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni. PLOS Neglected Tropical Diseases 9(1), e0003484.CrossRefGoogle ScholarPubMed
Lelamo, LL (2021) A review on the indigenous multipurpose agroforestry tree species in Ethiopia: Management, their productive and service roles and constraints. Heliyon 7(9), e07874.CrossRefGoogle ScholarPubMed
Liu, YX, Wu, W, Liang, YJ, Jie, ZL, Wang, H, Wang, W and Huang, YX (2014) New uses for old drugs: The tale of artemisinin derivatives in the elimination of schistosomiasis japonica in China. Molecules 19(9), 15058–15074.CrossRefGoogle ScholarPubMed
Lombardo, FC, Pasche, V, Panic, G, Endriss, Y and Keiser, J (2019) Life cycle maintenance and drug-sensitivity assays for early drug discovery in Schistosoma mansoni. Nature Protocols 14(2), 461–481.CrossRefGoogle ScholarPubMed
Maroyi, A (2013) Traditional use of medicinal plants in south-central Zimbabwe: review and perspectives. Journal of Ethnobiology and Ethnomedicine 9, 31.CrossRefGoogle ScholarPubMed
Maroyi, A (2017) Ethnopharmacology and therapeutic value of Bridelia micrantha (Hochst.) Baill. in tropical Africa: a comprehensive review. Molecules 22(9), 1493.CrossRefGoogle ScholarPubMed
Molan, AL, Hoskin, SO, Barry, TN and McNabb, WC (2000) Effect of condensed tannins extracted from four forages on the viability of the larvae of deer lungworms and gastrointestinal nematodes. The Veterinary Record 147(2), 44–48.CrossRefGoogle ScholarPubMed
Molan, AL, Waghorn, GC and McNabb, WC (2002) Effect of condensed tannins on egg hatching and larval development of Trichostrongylus colubriformis in vitro. The Veterinary Record 150(3), 65–69.CrossRefGoogle ScholarPubMed
Oh, J-H, Lee, C-Y, Kim, J-E, et al. (2021) Effect of characterized Green tea extraction methods and formulations on enzymatic starch hydrolysis and intestinal glucose transport. Journal of Agricultural and Food Chemistry 69(50), 15208–15217.CrossRefGoogle ScholarPubMed
Onyema, AM (2019) Extraction, phytochemical, physicochemical and toxicological study of ginger lily (Costus afer Ker Gawl) leaf and snail (Archachatina marginata) slime for potential use as anti-diabetic drug delivery. IOSR Journal of Applied Chemistry 12(9), 8–19.Google Scholar
Pica-Mattoccia, L and Cioli, D (2004) Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment. International Journal of Parasitology 34(4), 527–533.CrossRefGoogle ScholarPubMed
Rakotoarivelo, NH, Rakotoarivony, F, Ramarosandratana, AV, Jeannoda, VH, Kuhlman, AR, Randrianasolo, A and Bussmann, RW (2015) Medicinal plants used to treat the most frequent diseases encountered in ambalabe rural community, Eastern Madagascar. Journal of Ethnobiology and Ethnomedicine 11, 68.CrossRefGoogle ScholarPubMed
Schmelzer, GH, Gurib-Fakim, A, PROTA Foundation, Technical Centre for Agricultural and Rural Cooperation. (2008) Medicinal plants. Wageningen, Netherlands: PROTA Foundation.Google Scholar
Serrano, J, Puupponen-Pimia, R, Dauer, A, Aura, AM and Saura-Calixto, F (2009) Tannins: current knowledge of food sources, intake, bioavailability and biological effects. Molecular Nutrition & Food Research 53(Suppl 2), S310–S329.CrossRefGoogle ScholarPubMed
Simoben, CV, Ntie-Kang, F, Akone, SH and Sippl, W (2018) Compounds from African medicinal plants with activities against selected parasitic diseases: schistosomiasis, trypanosomiasis and leishmaniasis. Natural Products and Bioprospecting 8(3), 151–169.CrossRefGoogle Scholar
Su, C-H, Lu, M-K, Lu, T-J, Lai, M-N and Ng, L-T (2020) A (1→6)-branched (1→4)-β-d-glucan from Grifola frondosa inhibits lipopolysaccharide-induced cytokine production in RAW264.7 macrophages by binding to TLR2 rather than dectin-1 or CR3 receptors. Journal of Natural Products 83(2), 231–242.CrossRefGoogle ScholarPubMed
Tekwu, EM, Bosompem, KM, Anyan, WK, et al. (2017) In vitro assessment of anthelmintic activities of Rauwolfia vomitoria (Apocynaceae) stem bark and roots against parasitic stages of Schistosoma mansoni and cytotoxic study. Journal of Parasitology Research 2017, 2583969.CrossRefGoogle ScholarPubMed
Tucker, MS, Karunaratne, LB, Lewis, FA, Freitas, TC and Liang, Y-s (2013) Schistosomiasis. Current Protocols in Immunology 103, 19.11.11–19.11.58.CrossRefGoogle ScholarPubMed
Tyagi, U, Dwivedi, SP and Bagchi, S (2019) Characterization of anti-oxidant and anti-microbial properties of Tamarindus indica bark extract on various pathogenic micro-organisms. Asian Journal of Biological Sciences 12(3), 499–505.CrossRefGoogle Scholar
World Health Organization (2022) Fact sheet schistosomiasis Secondary Fact sheet schistosomiasis. Available at: https://www.who.int/news-room/fact-sheets/detail/schistosomiasis (accessed 13 January 2022).Google Scholar
Wright, CW (2010) Recent developments in research on terrestrial plants used for the treatment of malaria. Natural Product Reports 27, 961–968.CrossRefGoogle ScholarPubMed
Xu, L and Liu, S (2021) Forecasting structure of natural products through color formation process by thin layer chromatography. Food Chemistry 334, 127496.CrossRefGoogle ScholarPubMed
Yikna, BB and Yehualashet, AS (2021) Medicinal plant extracts evaluated In vitro and In vivo for antidiabetic activities in Ethiopia: Bases for future clinical trials and related investigations. Evidence-Based Complementary and Alternative Medicine 2021, 9108499. Available at https://www.hindawi.com/journals/ecam/2021/9108499/ (accessed 1 December 2021).CrossRefGoogle ScholarPubMed
Zhu, M, Chen, Y and Li, RC (2000) Oral absorption and bioavailability of tea catechins. Planta Medica 66(5), 444–447.CrossRefGoogle ScholarPubMed
Figure 0

Table 1. Botanical information of medicinal plants used for anti-schistosomal study.

Figure 1

Table 2. Crude extraction yield from Kenyan medicinal plants.

Figure 2

Fig. 1. Schistosoma mansoni newly transformed schistosomula viability against crude extracts from Kenyan medicinal plants. The error bars represent the standard deviation of three independent experiments.

Figure 3

Fig. 2. Schistosoma mansoni adult worm viability after treatment with crude plant extracts with potent newly transformed schistosomula-killing activity. Viability (%) after 24 h () or 48 h () treatment with extract. The error bars represent the standard deviation of three independent experiments.

Figure 4

Table 3. Phytochemical analysis from seven Kenyan plant extracts.