Anthelmintic Activities of Extract and Ellagitannins from Phyllanthus urinaria against Caenorhabditis elegans and Zoonotic or Animal Parasitic
          Nematodes

Jonathan Jato; Patrick Waindok; François Ngnodandi Belga François Ngnodandi; Emmanuel Orman; Christian Agyare; Emelia Oppong Bekoe; Christina Strube; Andreas Hensel; Eva Liebau; Verena Spiegler

doi:10.1055/a-2117-9426

Planta Medica, Inhaltsverzeichnis

Planta Med 2023; 89(13): 1215-1228
DOI: 10.1055/a-2117-9426

Biological and Pharmacological Activity

Original Papers

Anthelmintic Activities of Extract and Ellagitannins from Phyllanthus urinaria against Caenorhabditis elegans and Zoonotic or Animal Parasitic Nematodes

Jonathan Jato

¹University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany

²Kwame Nkrumah University of Science and Technology, Faculty of Pharmacy and Pharmaceutical Sciences, Kumasi, Ghana

⁵University of Health and Allied Sciences, School of Pharmacy, Ho, Ghana

⁷University of Münster, Institute of Integrative Cell Biology and Physiology, Münster, Germany

,

Patrick Waindok

³University of Veterinary Medicine Hannover, Institute for Parasitology, Centre for Infection Medicine, Hannover, Germany

,

François Ngnodandi Belga François Ngnodandi

⁴University of Ngaoundere, Faculty of Sciences, Department of Biological Sciences, Ngaoundéré, Cameroon

,

Emmanuel Orman

¹University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany

⁵University of Health and Allied Sciences, School of Pharmacy, Ho, Ghana

,

Christian Agyare

²Kwame Nkrumah University of Science and Technology, Faculty of Pharmacy and Pharmaceutical Sciences, Kumasi, Ghana

,

Emelia Oppong Bekoe

⁶University of Ghana, College of Health Science, School of Pharmacy, Accra, Ghana

,

Christina Strube^*

³University of Veterinary Medicine Hannover, Institute for Parasitology, Centre for Infection Medicine, Hannover, Germany

,

Andreas Hensel ^*

¹University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany

,

Eva Liebau^*

⁷University of Münster, Institute of Integrative Cell Biology and Physiology, Münster, Germany

,

Verena Spiegler^*

¹University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany

› Institutsangaben

Abstract

The aerial parts of Phyllanthus urinaria are used in traditional medicine in West Africa against helminthiasis, but their anthelmintic potential has not been evaluated until now. Within the current study, a hydroacetonic extract (AWE) and fractions and isolated ellagitannins from P. urinaria were, therefore, tested in vitro against Caenorhabditis elegans and the larvae of the animal parasites Toxocara canis, Ascaris suum, Ancylostoma caninum, and Trichuris suis. Compounds 1 – 13, mainly representing ellagitannins, were isolated using different chromatographic methods, and their structures were elucidated by HR-MS and ¹H/¹³C-NMR. AWE exerted concentration-dependent lethal effects (LC₅₀ of 2.6 mg/mL) against C. elegans and inhibited larval migration of all animal parasites tested (T. suis L1 IC₅₀ 24.3 µg/mL, A. suum L3 IC₅₀ 35.7 µg/mL, A. caninum L3 IC₅₀ 112.8 µg/mL, T. canis L3 IC₅₀ 1513.2 µg/mL). The anthelmintic activity of AWE was mainly related to the polar, tannin-containing fractions. Geraniin 1, the major ellagitannin in the extract, showed the strongest anthelmintic activity in general (IC₅₀ between 0.6 and 804 µM, depending on parasite species) and was the only compound active against A. caninum (IC₅₀ of 35.0 µM). Furosin 9 was least active despite structural similarities to 1. Among the parasites tested, Trichuris suis L1 larvae turned out to be most sensitive with IC₅₀ of 0.6, 6.4, 4.0, 4.8, and 2.6 µM for geraniin 1, repandusinic acid A 3, punicafolin 8, furosin 9, and phyllanthusiin A 10, respectively.

Key words

Phyllanthus urinaria - Phyllanthaceae - nematodes - ellagitannins - geraniin

Volltext

Referenzen

References
1 World Health Organization (WHO). WHO Factsheet: Soil-transmitted helminth infections. Accessed June 15, 2022 at: https://www.who.int/news-room/fact-sheets/detail/soil-transmitted-helminth-infections
2 Ochola EA, Karanja DMS, Elliott SJ. The impact of neglected tropical diseases (NTDs) on health and wellbeing in Sub-Saharan Africa (SSA): A case study of Kenya. PLoS Negl Trop Dis 2021; 15: 1-19
3 Hotez PJ, Fenwick A, Savioli L, Molyneux DH. Rescuing the bottom billion through control of neglected tropical diseases. Lancet 2009; 373: 1570-1575
4 Leslie J, Garba A, Oliva EB, Barkire A, Tinni AA, Djibo A, Mounkaila I, Fenwick A. Schistosomiaiss and soil-transmitted helminth control in Niger: cost effectiveness of school based and community distributed mass drug administration. PLoS Negl Trop Dis 2011; 5: e1326
5 Tinkler SH. Preventive chemotherapy and anthelmintic resistance of soil-transmitted helminths – Can we learn nothing from veterinary medicine?. One Health 2020; 9: 100106
6 Tabi MM, Powell M, Hodnicki D. Use of traditional healers and modern medicine in Ghana. Int Nurs Rev 2006; 53: 52-58
7 World Health Organization (WHO). WHO global report on traditional and complementary medicine 2019. Accessed March 16, 2023 at: https://apps.who.int/iris/handle/10665/312342
8 Jato J, Orman E, Duah Boakye Y, Oppong Bekoe E, Oppong Bekoe S, Asare-Nkansah S, Spiegler V, Hensel A, Liebau E, Agyare C. Anthelmintic agents from African medicinal plants: review and prospects. Evid Based Complement Alternat Med 2022; 2022: 8023866
9 Agyare C, Spiegler V, Sarkodie H, Asase A, Liebau E, Hensel A. An ethnopharmacological survey and in vitro confirmation of the ethnopharmacological use of medicinal plants as anthelmintic remedies in the Ashanti region, in the central part of Ghana. J Ethnopharmacol 2014; 158: 255-263
10 Burke JM, Miller JE. Sustainable approaches to parasite control in ruminant livestock. Vet Clin North Am Food Anim Pract 2020; 36: 89-107
11 Hoste H, Torres-Acosta JFJ, Sandoval-Castro CA, Mueller-Harvey I, Sotiraki S, Louvandin H, Thamsborg SM, Terrill TH. Tannin containing legumes as a model for nutraceuticals against digestive parasites in livestock. Vet Parasitol 2015; 212: 5-17
12 Khanbabaee K, van Ree T. Tannins: Classification and definition. Nat Prod Rep 2001; 18: 641-649
13 Spiegler V, Liebau E, Hensel A. Medicinal plant extracts and plant-derived polyphenols with anthelmintic activity against intestinal nematodes. Nat Prod Rep 2017; 34: 627-643
14 Karonen M, Ahern JR, Legroux L, Suvanto J, Engström MT, Sinkkonen J, Salminen JP, Hoste H. Ellagitannins inhibit the exsheathment of Haemonchus contortus and Trichostrongylus colubriformis larvae: The efficiency increases together with the molecular size. J Agric Food Chem 2020; 68: 4176-4186
15 Xu M, Zha ZJ, Qin XL, Zhang XL, Yang CR, Zhang YJ. Phenolic antioxidants from the whole plant of Phyllanthus urinaria . Chem Biodivers 2007; 4: 2246-2252
16 Satyan KS, Prakash A, Signh RP, Srivastava RS. Phthalic acid bis-ester and other phytoconstituents of Phyllanthus urinaria . Planta Med 1995; 61: 293-294
17 Geethangili M, Ding ST. A review of the phytochemistry and pharmacology of Phyllanthus urinaria L. Front Pharmacol 2018; 9: 1-20
18 Katiki LM, Ferreira JFS, Zajac AM, Masler C, Lindsay DS, Carolina A, Chagas S, Amarante AFT. Caenorhabditis elegans as a model to screen plant extracts and compounds as natural anthelmintics for veterinary use. Vet Parasitol 2011; 182: 264-268
19 Mahdy MAK, Lim YAL, Ngui R, Fatimah MS, Choy SH, Yap NJ, Al-Mekhlafi HM, Ibrahim J, Surin J. Prevalence and zoonotic potential of canine hookworms in Malaysia. Parasit Vectors 2012; 5: 1-7
20 Nejsum P, Betson M, Bendall RP, Thamsborg SM, Stothard JR. Assessing the zoonotic potential of Ascaris suum and Trichuris suis: Looking to the future from an analysis of the past. J Helminthol 2012; 86: 148-155
21 Overgaauw PAM, van Knapen F. Veterinary and public health aspects of Toxocara spp. Vet Parasitol 2013; 193: 398-403
22 Agyare C, Lechtenberg M, Deters A, Petereit F, Hensel A. Ellagitannins from Phyllanthus muellerianus (Kuntze) Exell.: Geraniin and furosin stimulate cellular activity, differentiation and collagen synthesis of human skin keratinocytes and dermal fibroblasts. Phytomedicine 2011; 18: 617-624
23 Foo LY. Amariinic acid and related ellagitannins from Phyllanthus amarus . Phytochemistry 1995; 39: 217-224
24 Trinh BTD, Staerk D, Jäger AK. Screening for potential α-glucosidase and α-amylase inhibitory constituents from selected Vietnamese plants used to treat type 2 diabetes. J Ethnopharmacol 2016; 186: 189-195
25 de Paula Carlis MS, Féboli A, de Laurentiz AC, da Silva Filardi R, de Oliveira AHP, Andrade E Silva ML, dos Anjos LA, Guidi Magalhães L, da Silva de Laurentiz R. In vitro anthelmintic activity of the crude hydroalcoholic extract of Piper cubeba fruits and isolated natural products against gastrointestinal nematodes in sheep. Vet Parasitol 2019; 275: 108932
26 Pullan RL, Brooker SJ. The global limits and population at risk of soil-transmitted helminth infections in 2010. Parasit Vectors 2012; 5: 1-14
27 Abaka-Yawson A, Senoo D, Aboagye EA, Hotorvi C, Tawiah PA, Sosu SQ, Kwadzokpui PK. High prevalence of intestinal helminthic infection among children under 5 years in a rural Ghanaian community: an urgent call for attention. J Parasit Dis 2020; 44: 625-632
28 Hu Y, Ellis BL, Yiu YY, Miller MM, Urban JF, Shi LZ, Aroian RV. An extensive comparison of the effect of anthelmintic classes on diverse nematodes. PLoS One 2013; 8: 1-12
29 Spiegler V, Liebau E, Peppler C, Raue K, Werne S, Strube C, Heckendorn F, Agyare C, Stark T, Hofmann T, Hensel A. A hydroalcoholic extract from Paullinia pinnata L. roots exerts anthelmintic activity against free-living and parasitic nematodes. Planta Med 2016; 82: 1173-1179
30 Wimmersberger D, Tritten L, Keiser J. Development of an in vitro drug sensitivity assay for Trichuris muris first-stage larvae. Parasit Vectors 2013; 6: 1-8
31 Brunet S, Fourquaux I, Hoste H. Ultrastructural changes in the third-stage, infective larvae of ruminant nematodes treated with sainfoin (Onobrychis viciifolia) extract. Parasitol Int 2011; 60: 419-424
32 Cheng HS, Ton SH, Abdul Kadir K. Ellagitannin geraniin: A review of the natural sources, biosynthesis, pharmacokinetics and biological effects. Phytochem Rev 2017; 16: 159-193
33 Ademola IO, Fagbemi BO, Idowu SO. Anthelmintic activity of extracts of Spondias mombin against gastrointestinal nematodes of sheep: studies in vitro and in vivo . Trop Anim Health Prod 2005; 37: 223-235
34 Morais-Costa F, Vasconcelos VO, Duarte ER, dos Santos Lima W. Plants from Cerrado for the Control of Gastrointestinal Nematodes of Ruminants. In: Anthelmintics: Clinical Pharmacology, uses in Veterinary Medicine and Efficacy. New York: Nova Science Publishers; 2014: 89-108
35 Lone BA, Bandh SA, Chishti MZ, Bhat FA, Tak H, Nisa H. Anthelmintic and antimicrobial activity of methanolic and aqueous extracts of Euphorbia helioscopia L. Trop Anim Health Prod 2013; 45: 743-749
36 Scott G, Springfield EP, Coldrey N. A pharmacognostical study of 26 South African plant species used as traditional medicines. Pharm Biol 2004; 42: 186-213
37 Engström MT, Karonen M, Ahern JR, Baert N, Payré B, Hoste H, Salminen JP. Chemical structures of plant hydrolyzable tannins reveal their in vitro activity against egg hatching and motility of Haemonchus contortus nematodes. J Agric Food Chem 2016; 64: 840-851
38 Haslam E. Natural polyphenols (vegetable tannins) as drugs: Possible modes of action. J Nat Prod 1996; 59: 205-215
39 Castagna F, Bava R, Musolino V, Piras C, Cardamone A, Carresi C, Lupia C, Bosco A, Rinaldi L, Cringoli G, Palma E, Musella V, Britti D. Potential new therapeutic approaches based on Punica granatum fruits compared to synthetic anthelmintics for the sustainable control of gastrointestinal nematodes in sheep. Animals 2022; 12: 2883
40 Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F. Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: The evidence so far. Evid Based Complement Alternat Med 2013; 2013: 270418
41 Martínez-Ortíz-de-Montellano C, Arroyo-López C, Fourquaux I, Torres-Acosta JFJ, Sandoval-Castro CA, Hoste H. Scanning electron microscopy of Haemonchus contortus exposed to tannin-rich plants under in vivo and in vitro conditions. Exp Parasitol 2013; 133: 281-286
42 Jikai L, Yue H, Henkel T, Weber K. One step purification of corilagin and ellagic acid from Phyllanthus urinaria using high-speed countercurrent chromatography. Phytochem Anal 2002; 13: 1-3
43 Yoshida T, Iton H, Matsunaga S, Tanaka R, Okuda T. Tannins and related polyphenols of euphorbiaceous plants. IX: hydrolyzable tannins with C4 glucose core from Phyllanthus flexuosus Muell. Arg. Chem Pharm Bull 1992; 40: 53-60
44 Pfundstein B, El Desouky SK, Hull WE, Haubner R, Erben G, Owen RW. Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): Characterization, quantitation and determination of antioxidant capacities. Phytochemistry 2010; 71: 1132-1148
45 Fernandez J, Reyes R, Ponce H, Oropeza M, Van Calsteren MR, Jankowski C, Campos MG. Isoquercitrin from Argemone platyceras inhibits carbachol and leukotriene D4-induced contraction in guinea-pig airways. Eur J Pharmacol 2005; 522: 108-115
46 Tanaka T, Nonaka GI, Nisioka I. Punicafolin, an ellagitannin from the leaves of Punica granatum . Phytochemistry 1985; 24: 2075-2078
47 Miguel OG, Calixto JB, Santos ARS, Messana I, Ferrari F, Cechinel Filho V, Pizzolatti MG, Yunes RA. Chemical and preliminary analgesic evaluation of geraniin and furosin isolated from Phyllanthus sellowianus . Planta Med 1996; 62: 146-149
48 Zhang LZ, Guo YJ, Tu GZ, Guo WB, Miao F. Isolation and identification of a novel ellagitannin from Phyllanthus urinaria L. Yao Xue Xue Bao 2004; 39: 119-122
49 Yoshida T, Maruyama Y, Memon MU, Shingu T, Okuda T. Gemins D, E and F, ellagitannins from Geum janponicum . Phytochemistry 1985; 24: 1041-1046
50 Moraes LS, Donza MRH, Rodrigues APD, Silva BJM, Brasil DSB, Zoghbi MDGB, Andrade EHA, Guilhon GMSP, Silva EO, Schmidt TJ. Leishmanicidal activity of (+)-Phyllanthidine and the phytochemical profile of Margaritaria nobilis (Phyllanthaceae). Molecules 2015; 20: 22157-22169
51 Rajapakse RPVJ, Vasanthathilake VWSM, Lloyd S, Fernando ST. Collection of eggs and hatching and culturing second-stage larvae of Toxocara vitulorum in vitro . J Parasitol 1992; 78: 1090-1092
52 Raulf MK, Lepenies B, Strube C. Toxocara canis and Toxocara cati somatic and excretory-secretory antigens are recognised by c-type lectin receptors. Pathogens 2021; 10: 1-17
53 Ebner F, Hepworth MR, Rausch S, Janek K, Niewienda A, Kühl A, Henklein P, Lucius R, Hamelmann E, Hartmann S. Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease. Allergy 2014; 69: 1489-1497
54 Rabel B, Mcgregor R, Douch PGC. Improved bioassay for estimation of inhibitory effects of ovine gastrointestinal mucus and anthelmintics on nematode larval migration. Int J Parasitol 1994; 24: 671-676

Zusatzmaterial

Ergänzendes Material