Abstract
Pinworm infections are one of the common problems in laboratory rodents and man. At present there are only few drugs against intestinal helminths, and new drugs are urgently needed to cope up any future risk of drug resistance. Interest in plant secondary metabolites (PSMs) has risen considerably in the recent years for the discovery and development of new drugs. In the present study, we explored the in vitro and in vivo anthelmintic potentials of two pentacyclic triterpenoids, ursolic acid (UA) and betulinic acid (BA), the important PSMs of many medicinal plants, against Syphacia obvelata (Nematoda: Oxyuridae), a common pinworm of mice. The results of this study indicated that in both, in vitro and in vivo assays, BA showed comparatively better anthelmintic effects than UA. In the in vitro assay, 1.00 mg/ml concentration of BA showed paralysis and mortality of worms in 1.20 ± 0.04 and 2.30 ± 0.03 h, respectively. In the in vivo assay, a single 10.00 mg/kg dose of BA, administered for 5 days, revealed 68.78% reduction in egg counts and 84.08% reduction in worm counts of infected mice. The present study suggests that BA holds a great promise to be pursued further for detailed testing against some other representative group of helminth parasites.
References
Albonico M, Bickle Q, Ramsan M, Montresor A, Savioli L, Taylor M (2003) Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bull World Health Organ 81:343–352
Anthony JP, Fyfe L, Smith H (2005) Plant active components: a resource for antiparasitic agents? Trends Parasitol 21:462–468
Caboni P, Aissani N, Demurtas M, Ntalli N, Onnis V (2015) Nematicidal activity of acetophenones and chalcones against Meloidogyne incognita and structure-activity considerations. Pest Manag Sci 72:125–130
Camurca-Vasconcelos ALF, Bevilaqua CML, Morais SM, Maciel MV, Costa CTC, Macedo ITF, Oliveira LM, Braga RR, Silva RA, Vieira LS (2007) Anthelmintic activity of Croton zehntneri and Lippia sidoides essential oils. Vet Parasitol 148:288–294
Costa CT, Bevilaqua CM, Morais SM, Camurça-Vasconcelos AL, Maciel MV, Braga RR, Oliveira LM (2010) Anthelmintic activity of Cocos nucifera L. on intestinal nematodes of mice. Res Vet Sci 88:101–103
Deepak M, Dipankar G, Prashanth D, Asha MK, Amit A, Venkataraman BV (2002) Tribulosin and beta-sitosterol-d-glucoside, the anthelmintic principles of Tribulus terrestris. Phytomedicine 9:753–756
Eloh K, Demurtas M, Deplano A, Mfopa AN, Murgia A, Maxia A, Onnis V, Caboni P (2015) In vitro nematicidal activity of aryl hydrazones and comparative GC–MS metabolomics analysis. J Agric Food Chem 63:9970–9976
Fontanay S, Grare M, Mayer J, Finance C, Duval RE (2008) Ursolic, oleanolic and betulinic acids: antibacterial spectra and selectivity indexes. J Ethnopharmacol 120:272–278
Frolova TS, Kukina TP, Sinitsyna OI (2015) Genotoxic and mutagenic properties of synthetic betulinic acid and betulonic acid. Russ J Bioorganic Chem 41:409–413
Grice RL, Prociv P (1993) In vitro embryonation of Syphacia obvelata eggs. Int J Parasitol 23:257–260
Hotez P, Gurwith M (2011) Europe’s neglected infections of poverty. Int J Infect Dis 15:611–619
Innocente AM, Silva GNS, Cruz LN, Moraes MS, Nakabashi M, Sonnet P, Gosmann G, Garcia CRS, Gnoatto SCB (2012) Synthesis and antiplasmodial activity of betulinic acid and ursolic acid analogues. Molecules 17:12003–12014
Kaplan RM (2004) Drug resistance in nematodes of veterinary importance: a status report. Trends Parasitol 20:477–481
Keiser J, Utzinger J (2010) The drugs we have and the drugs we need against major helminth infections. Adv Parasitol 73:197–230
Li JW, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325:161–165
Liu J (1995) Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 49:57–68
Michels C, Goyal P, Nieuwenhuizen N, Brombacher F (2006) Infection with Syphacia obvelata (pinworm) induces protective Th2 immune responses and influences ovalbumin-induced allergic reactions. Infect Immun 74:5926–5932
Mullauer FB, Kessler JH, Medema JP (2010) Betulinic acid, a natural compound with potent anti-cancer effects. Anticancer Drugs 21:215–227
Neto CC (2011) Ursolic acid and other pentacyclic triterpenoids: anticancer activities and occurrence in berries. In: Stoner GD, Seeram NP (eds) Berries and cancer prevention, vol 41, C. Springer Science + Business Media, LLC, Berlin. doi:10.1007/978-1-4419-7554-6_2
Oge Ayaz E, Ide T, Dalgıç S (2000) The effect of doramectin, moxidectin and netobimin against natural infections of Syphacia muris in rats. Vet Parasitol 88:299–303
Olliaro P, Seiler J, Kuesel A, Horton J, Clark JN, Don R, Keiser J (2011) Potential drug development candidates for human soil-transmitted helminthiases. PLoS Neglec Trop Dis 5:e1138
Panic G, Duthaler U, Speich B, Keiser J (2014) Repurposing drugs for the treatment and control of helminth infections. Int J Parasitol: Drugs Drug Resist 4:185–200
Tandon V, Pal P, Roy B, Rao HSP, Reddy KS (1997) In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India. Parasitol Res 83:492–498
Vijaya N, Yadav AK (2016) In vitro anthelmintic assessment of selected phytochemicals against Hymenolepis diminuta, a zoonotic tapeworm. J Parasit Dis 40:1082–1086
Villasenor IM, Angelada J, Canlas AP, Echegoyen D (2002) Bioactivity studies on beta-sitosterol and its glucoside. Phytother Res 16:417–421
Wabo PJ, Payne VK, Mbogning TG, Komtangi MC, Yondo J, Ngangout AM, Mpoame M, Bilong BCF (2013) In vitro anthelminthic efficacy of Dichrocephala integrifolia (Asteraceae) extracts on the gastro-intestinal nematode parasite of mice: Heligmosomoides bakeri (Nematoda, Heligmosomatidae). Asian Pac J Trop Biomed 3:100–104
Wang XH, Zhou SY, Qian ZZ, Zhang HL, Qiu LH, Song Z, Zhao J, Wang P, Hao XS, Wang HQ (2013) Evaluation of toxicity and single dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors. Expert Opin Drug Metab Toxicol 9:117–125
Wang G, Xiulei C, Yayun D, Zhong L, Xiaoyong X (2015) Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one derivatives against Meloidogyne incognita. J Agric Food Chem 63:6883–6889
Williams AR, Fryganas C, Ramsay A, Mueller-Harvey I, Thamsborg SM (2014a) Direct Anthelmintic effects of condensed tannins from diverse plant sources against Ascaris suum. PLoS ONE 9:e97053. doi:10.1371/journal.pone.0097053
Williams AR, Ropiak HM, Fryganas C, Desrues O, Mueller-Harvey I, Thamsborg SM (2014b) Assessment of the anthelmintic activity of medicinal plant extracts and purified condensed tannins against free-living and parasitic stages of Oesophagostomum dentatum. Parasit Vectors 7:518
Wink M (2012) Medicinal plants: a source of anti-parasitic secondary metabolites. Molecules 17:12771–12791
Yogeeswari P, Sriram D (2005) Betulinic acid and its derivatives: a review on their biological properties. Curr Med Chem 12:657–666
Acknowledgements
Vijaya thank North-Eastern Hill University, Shillong for providing her the University Grants Commission’s, New Delhi non-net fellowship.
Author information
Authors and Affiliations
Contributions
AKY conceived and supervised the study, developed the final draft; Vijaya performed the experiments, analysed the data and developed the first draft; SG wrote the supplementary information and participated in preparation of second manuscript draft.
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Vijaya, Yadav, A.K. & Gogoi, S. In vitro and in vivo anthelmintic efficacy of two pentacyclic triterpenoids, ursolic acid and betulinic acid against mice pinworm, Syphacia obvelata . J Parasit Dis 42, 144–149 (2018). https://doi.org/10.1007/s12639-017-0960-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12639-017-0960-0