Plant Products in the Treatment and Control of Filariasis and Other Helminth Infections and Assay Systems for Antifilarial/Anthelmintic Activity

Abstract

Lymphatic filariasis, onchocerciasis, loaisis, and other helminth infections cause serious health problems especially in resource-limited tropical and subtropical developing countries of the world, and more than 2 billion people are infected with at least one helminth species. From times immemorial, man looked up to the plant kingdom in search of anthelmintics, antifilarials, and remedies for parasite-induced health problems. Although more than 50 % of drugs in modern medicine are derived from plants or leads from plants, a success story of plant-based anthelminthics or antifilarials is yet to be told. In the last 5 decades, more than 100 plant products were reported to be beneficial in the treatment or control of these parasitic infections but they could not be developed into viable drugs for a variety of reasons. This review focuses on the plant products reported to be useful in the control and treatment of human helminth infections with the main emphasis on filariasis and the in vitro and in vivo systems available for assaying anthelmintic activity.

Key words

plant products - filariasis - helminthiasis - in vitro assays - in vivo assays

References

• 1 Harborne J B. Phytochemical methods. A guide to modern techniques of plant analysis, 3rd edition. London; Chapman & Hall 1998
• 2 Butler M S, Newman D J. Mother Nature's gifts to diseases of man: the impact of natural products on anti-infective, anticholestemics and anticancer drug discovery.  Prog Drug Res. 2008;  65 13-44
• 3 Kuhn T, Wang Y. Artemisinin – an innovative cornerstone for anti-malaria therapy.  Prog Drug Res. 2008;  66 385-422
• 4 de Silva N R, Brooker S, Hotez P J, Montresor A, Engels D, Savioli L. Soil-transmitted helminth infections: updating the global picture.  Trends Parasitol. 2003;  19 547-551
• 5 Fincham J E, Markus M B, Adams V J. Could control of soil-transmitted helminthic infection influence the HIV/AIDS pandemic.  Acta Trop. 2003;  86 315-333
• 6 Molyneux D. Lymphatic filariasis (elephantiasis) elimination: a public health success and development opportunity.  Filaria J. 2003;  2 13
• 7 WHO .The global burden of disease: 2004. Available at. http://www.who.int/healthinfo/global_burden_disease/estimates_regional/en/index.html Accessed October 10, 2010
• 8 Maizels R M, Gomez-Escobar N, Gregory W F, Murray J, Zang X. Immune evasion genes from filarial nematodes.  Int J Parasitol. 2001;  31 889-898
• 9 WHO . Onchocerciasis and its control. Report of a WHO Expert Committee on onchocerciasis control.  World Health Organ Tech Rep Ser. 1995;  852 1-104
• 10 Molyneux D H. Onchocerciasis control in West Africa: Current status and future of the onchocerciasis control programme.  Parasitol Today. 1995;  11 399-402
• 11 WHO . Soil-transmitted helminthiasis. Number of children treated 2007–2008: update on the 2010 global target.  Wkly Epidemiol Rec. 2010;  85 141-147
• 12 Stephenson L S, Latham M C, Kinoti S N, Kurz K M, Brigham H. Improvements in physical fitness of Kenyan schoolboys infected with hookworm, Trichuris trichiura and Ascaris lumbricoides following a single dose of albendazole.  Trans R Soc Trop Med Hyg. 1990;  84 277-282
• 13 Nokes C, Grantham-McGregor S M, Sawyer A W, Cooper E S, Bundy D A. Parasitic helminth infection and cognitive function in school children.  Proc Biol Sci. 1992;  247 77-81
• 14 Adams E J, Stephenson L S, Latham M C, Kinoti S N. Physical activity and growth of Kenyan school children with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved after treatment with albendazole.  J Nutr. 1994;  124 1199-1206
• 15 Koroma M M, Williams R A, de la Haye R R, Hodges M. Effects of albendazole on growth of primary school children and the prevalence and intensity of soil-transmitted helminths in Sierra Leone.  J Trop Pediatr. 1996;  42 371-372
• 16 Stoltzfus R J, Albonico M, Chwaya H M, Savioli L, Tielsch J, Schulze K, Yip R. Hemoquant determination of hookworm-related blood loss and its role in iron deficiency in African children.  Am J Trop Med Hyg. 1996;  55 399-404
• 17 Katiyar J C, Gupta S, Sharma S. Experimental models in drug development for helminthic diseases.  Rev Infect Dis. 1989;  11 638-654
• 18 Murthy P K, Tyagi K, Roy Chowdhury T K, Sen A B. Susceptibility of Mastomys natalensis (GRA strain) to a subperiodic strain of human Brugia malayi.  Indian J Med Res. 1983;  77 623-630
• 19 Murthy P K, Chowdhury T K, Sen A B. Indian cat (Felis indica) as a host to subperiodic Malaysian strain of human Brugia malayi.  J Commun Dis. 1983;  15 100-105
• 20 Murthy P K, Srivastava A K, Joshi A, Sen A B, Murthy P S R, Ghatak S. Physiopathophysiology changes during infection in multimmate rats. I: Histological studies.  IRCS Med Sci. 1986;  14 1106-1107
• 21 Tyagi K, Murthy P K, Chatterjee R K, Sen A B. Chemotherapeutic response of Brugia malayi to antifilarials in Mastomys natalensis.  Indian J Parasitol. 1986;  10 195-207
• 22 Katiyar J C, Misra A, Gupta S, Visen P K S, Murthy P K, Sen A B. Efficacy of a substituted methyl benzimidazole carbamate against developing and adult helminth parasites.  Vet Parasitol. 1987;  23 193-204
• 23 Murthy P K, Tyagi K, Sen A B. Attempt to infect Tatera indica with sub-periodic strain of Brugia malayi.  Indian J Med Res. 1987;  85 471-472
• 24 Katiyar J C, Gupta S, Visen P K, Murthy P K, Misra A, Kumar S, Sarin J P. Methyl 5-[4-(2-pyridinyl)-1-piperazinylcarbonyl]-1H-benzimidazol- 2-yl carbamate: efficacy against developing and adult helminths by topical application.  Indian J Exp Biol. 1988;  26 715-719
• 25 Murthy P K, Tyagi K, Chatterjee R K. Indian langur (Presbytis entellus) as experimental host for Brugia malayi infection.  Curr Sci. 1990;  59 1236-1239
• 26 Murthy P K, Fatma N, Chatterjee R K. Comparative susceptibility of ivermectin against different filarial parasites. CSIR Golden Jubilee Symposium, Lucknow, India 1992
• 27 Tyagi K, Murthy P K, Chatterjee R K. Brugia malayi in Indian leaf monkey (Presbytis entellus). Response to repeated exposures of infective larvae.  Curr Sci. 1996;  70 164-167
• 28 Murthy P K, Chatterjee R K. Evaluation of two in vitro test systems employing Brugia malayi parasite for screening of potential antifilarials.  Curr Sci. 1999;  77 1084-1089
• 29 Murthy P K, Khan M A, Rajani H B, Srivastava V M L. Preadult stage of parasite is involved in the development of filarial limb edema in Brugia malayi-infected Indian leaf monkey (Presbytis entellus).  Clin Diagn Lab Immunol. 2002;  9 913-918
• 30 Dube A, Murthy P K, Puri S K, Misra-Bhattacharya S. Presbytis entellus: a primate model for parasitic disease research.  Trends Parasitol. 2004;  20 358-360
• 31 Murthy P K, Srivastava K, Murthy P S R. Responses of Brugia malayi-Presbytis entellus, a non-human primate model of filariasis, to DEC, ivermectin and CDRI compound 82–437.  Curr Sci. 2004;  86 101-108
• 32 Sahare K N, Anandharaman V, Meshram V G, Meshram S U, Gajalakshmi D, Goswami K, Reddy M V. In vitro effect of four herbal plants on the motility of Brugia malayi microfilariae.  Indian J Med Res. 2008;  127 467-471
• 33 Lakshmi V, Joseph S K, Srivastava S, Verma S K, Sahoo M K, Dube V, Mishra S K, Murthy P K. Antifilarial activity in vitro and in vivo of some flavonoids tested against Brugia malayi.  Acta Trop. 2010;  DOI: 10.1016/j.actatropica.2010.06.006 , advance online publication 6 July 2010
  
• 34 Townson S, Tagboto S, McGarry H F, Egerton G L, Taylor M J. Onchocerca parasites and Wolbachia endosymbionts: evaluation of a spectrum of antibiotic types for activity against Onchocerca gutturosa in vitro.  Filaria J. 2006;  5 4
• 35 Zahner H, Johri G N, Kohler P, Striebel H P, Franz M. In vitro effects of 2-tert-butyl-benzothiazole derivatives on microfilariae of Litomosoides carinii, Brugia malayi and Acanthocheilonema viteae.  Arzneimittelforschung. 1991;  41 764-768
• 36 Zaridah M Z, Idid S Z, Omar A W, Khozirah S. In vitro antifilarial effects of three plant species against adult worms of subperiodic Brugia malayi.  J Ethnopharmacol. 2001;  78 79-84
• 37 Tippawangkosol P, Choochote W, Na-Bangchang K, Jitpakdi A, Pitasawat B, Riyong D. Comparative assessment of the in vitro sensitivity of Brugia malayi infective larvae to albendazole, diethylcarbamazine and ivermectin alone and in combination.  Southeast Asian J Trop Med Public Health. 2004;  35 (Suppl. 2) 15-21
• 38 Rao R U, Huang Y, Fischer K, Fischer P U, Weil G J. Brugia malayi: Effects of nitazoxanide and tizoxanide on adult worms and microfilariae of filarial nematodes.  Exp Parasitol. 2009;  121 38-45
• 39 Comley J C, Townson S, Rees M J, Dobinson A. The further application of MTT-formazan colorimetry to studies on filarial worm viability.  Trop Med Parasitol. 1989;  40 311-316
• 40 Rao U R, Salinas G, Mehta K, Klei T R. Identification and localization of glutathione S-transferase as a potential target enzyme in Brugia species.  Parasitol Res. 2000;  86 908-915
• 41 Smith H L, Rajan T V. Tetracycline inhibits development of the infective-stage larvae of filarial nematodes in vitro.  Exp Parasitol. 2000;  95 265-270
• 42 Tiwari P, Tripathi L M, Raghu K G, Srivastava V M. Acanthocheilonema viteae: octopamine and its physiological role.  Exp Parasitol. 2004;  108 53-58
• 43 Walter R D, Wittich R M, Kuhlow F. Filaricidal effect of mefloquine on adults and microfilariae of Brugia patei and Brugia malayi.  Trop Med Parasitol. 1987;  38 55-56
• 44 Davies K P, Zahner H, Kohler P. Litomosoides carinii: mode of action in vitro of benzothiazole and amoscanate derivatives with antifilarial activity.  Exp Parasitol. 1989;  68 382-391
• 45 Singhal K C, Saxena P N, Johri M B. Studies on the use of Setaria cervi for in vitro antifilarial screening.  Jpn J Pharmacol. 1973;  23 793-797
• 46 Comley J C, Szopa T M, Strote G, Buttner M, Darge K, Buttner D W. A preliminary assessment of the feasibility of evaluating promising antifilarials in vitro against adult Onchocerca volvulus.  Parasitology. 1989;  99 (Pt. 3) 417-425
• 47 Townson S, Shay K E, Dobinson A R, Connelly C, Comley J C, Zea-Flores G. Onchocerca gutturosa and O. volvulus: studies on the viability and drug responses of cryopreserved adult worms in vitro.  Trans R Soc Trop Med Hyg. 1989;  83 664-669
• 48 Comley J C. New macrofilaricidal leads from plants?.  Trop Med Parasitol. 1990;  41 1-9
• 49 Strote G, Darge K, Bonow I. Morphological alterations of male Onchocerca volvulus after in vitro exposure to mel w and milbemycin a confirming the results of viability tests.  Trop Med Parasitol. 1990;  41 429-436
• 50 Cho-Ngwa F, Daggfeldt A, Titanji V P, Gronvik K O. Preparation and characterization of specific monoclonal antibodies for the detection of adult worm infections in onchocerciasis.  Hybridoma (Larchmt). 2005;  24 283-290
• 51 Mukherjee M, Misra S, Chatterjee R K. Development of in vitro screening system for assessment of antifilarial activity of compounds.  Acta Trop. 1998;  70 251-255
• 52 Singh D P, Misra S, Chatterjee R K. A new technique of in vitro assay of antifilarials using different life-forms of Acanthocheilonema viteae.  Jpn J Exp Med. 1990;  60 303-309
• 53 Singh B K, Mishra M, Saxena N, Yadav G P, Maulik P R, Sahoo M K, Gaur R L, Murthy P K, Tripathi R P. Synthesis of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines as a new class of antifilarial agents.  Eur J Med Chem. 2008;  43 2717-2723
• 54 Nisha M, Kalyanasundaram M, Paily K P, Abidha, Vanamail P, Balaraman K. In vitro screening of medicinal plant extracts for macrofilaricidal activity.  Parasitol Res. 2007;  100 575-579
• 55 Awasthi S K, Mishra N, Dixit S K, Singh A, Yadav M, Yadav S S, Rathaur S. Antifilarial activity of 1,3-diarylpropen-1-one: effect on glutathione-S-transferase, a phase II detoxification enzyme.  Am J Trop Med Hyg. 2009;  80 764-768
• 56 Rao R, Well G J. In vitro effects of antibiotics on Brugia malayi worm survival and reproduction.  J Parasitol. 2002;  88 605-611
• 57 Gunawardena N K, Fujimaki Y, Aoki Y, Mishima N, Ezaki T, Uni S, Kimura E. Differential effects of diethylcarbamazine, tetracycline and the combination on Brugia pahangi adult females in vitro.  Parasitol Int. 2005;  54 253-259
• 58 Fujimaki Y, Kamachi T, Yanagi T, Caceres A, Maki J, Aoki Y. Macrofilaricidal and microfilaricidal effects of Neurolaena lobata, a Guatemalan medicinal plant, on Brugia pahangi.  J Helminthol. 2005;  79 23-28
• 59 Batra S, Chatterjee R K, Srivastava V M. Antioxidant system of Litomosoides carinii and Setaria cervi: effect of a macrofilaricidal agent.  Vet Parasitol. 1992;  43 93-103
• 60 Tyagi K, Murthy P K, Sen A B. Sequential changes in the antibody response of Mastomys natalensis consequent to Brugia malayi infection.  Indian J Med Res. 1985;  81 269-274
• 61 Tyagi K, Murthy P K, Sen A B. Effect of some known antifilarials on the immune responses of Mastomys natalensis infected with Brugia malayi.  Indian J Med Res. 1986;  83 155-161
• 62 Srivastava A K, Murthy P K, Joshi A, Sen A B, Murthy P S R, Ghatak S. Physiopathological changes during infection in multimammate rats. II. Enzyme studies.  IRCS Med Sci. 1986;  14 1108-1109
• 63 Culbertson J T, Rose H M. Chemotherapy of filariasis in the cotton rat by administration of neostam.  Science. 1944;  99 245
• 64 Tropical Disease Research-TDR. Seventh Programme Report. Chapter 4 Filariasis. Geneva; WHO 1985: 1-20
• 65 Ash L R, Riley J M. Development of subperiodic Brugia malayi in the jird, Meriones unguiculatus, with notes on infections in other rodents.  J Parasitol. 1970;  56 969-973
• 66 Murthy P K, Murthy P S, Tyagi K, Chatterjee R K. Fate of infective larvae of Brugia malayi in the peritoneal cavity of Mastomys natalensis and Meriones unguiculatus.  Folia Parasitol (Praha). 1997;  44 302-304
• 67 Petranyi G, Mieth H, Leitner I. Mastomys natalensis as an experimental host for Brugia malayi subperiodic.  Southeast Asian J Trop Med Public Health. 1975;  6 328-337
• 68 Zahner H, Schares G. Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi.  Acta Trop. 1993;  52 221-266
• 69 Mak J W, Navaratnam V, Ramachandran C P. Experimental chemotherapy of lymphatic filariasis. A review.  Ann Trop Med Parasitol. 1991;  85 131-137
• 70 Hewitt R I, Wallace W S, White E, Subbarow Y. Experimental chemotherapy of filariasis; experimental methods for testing drugs against naturally acquired filarial infections in cotton rats and dogs.  J Lab Clin Med. 1947;  32 1293-1303
• 71 Sewell P, Hawking F. Chemotherapy of experimental filariasis.  Br J Pharmacol Chemother. 1950;  5 239-260
• 72 Chatterjee R K, Fatma N, Agarwal V K, Sharma S, Anand N. Comparative antifilarial efficacy of the N-oxides of diethylcarbamazine and two of its analogues.  Trop Med Parasitol. 1989;  40 474-475
• 73 Fatma N, Sharma S, Chatterjee R K. 2,2′-Dicarbomethoxyamino-5,5′-dibenzimidazolyl ketone – a new antifilarial agent.  Acta Trop. 1989;  46 311-321
• 74 Srivastava S K, Chauhan P M, Bhaduri A P, Murthy P K, Chatterjee R K. Secondary amines as new pharmacophores for macrofilaricidal drug design.  Bioorg Med Chem Lett. 2000;  10 313-314
• 75 Stables J N, Lees G M, Rankin R. The potential of mice as animal models for antifilarial screening.  Trop Med Parasitol. 1988;  39 25-28
• 76 Singh D P, Rathore S, Misra S, Chatterjee R K, Ghatak S, Sen A B. Studies on the causation of adverse reactions in microfilaraemic host following diethylcarbamazine therapy (Dipetalonema viteae in Mastomys natalensis).  Trop Med Parasitol. 1985;  36 21-24
• 77 Kinnamon K E, Klayman D L, Poon B T, McCall J W, Dzimianski M T, Rowan S J. Filariasis testing in a jird model: new drug leads from some old standbys.  Am J Trop Med Hyg. 1994;  51 791-796
• 78 Kinnamon K E, Engle R R, Poon B T, Ellis W Y, McCall J W, Dzimianski M T. Anticancer agents suppressive for adult parasites of filariasis in Mongolian jirds.  Proc Soc Exp Biol Med. 2000;  224 45-49
• 79 Fujimaki Y, Sithithaworn P, Mitsui Y, Aoki Y. Delayed macrofilaricidal activity of diethylcarbamazine against Brugia pahangi in Mongolian jirds.  J Helminthol. 2004;  78 293-295
• 80 Lammler G, Herzog H, Gruner D. Development of chemotherapeutic agents of parasitic diseases. Amsterdam; North Holland Publishing Company 1975: 157
• 81 Sadanaga A, Hayashi Y, Tanaka H, Nogami S, Shirasaka A. Evaluation of the transplantation method of adult Brugia malayi into the jird, Meriones unguiculatus, for testing macrofilaricides.  Jpn J Exp Med. 1984;  54 275-277
• 82 Gaur R L, Dixit S, Sahoo M K, Khanna M, Singh S, Murthy P K. Anti-filarial activity of novel formulations of albendazole against experimental brugian filariasis.  Parasitology. 2007;  134 537-544
• 83 Tiwari V K, Tewari N, Katiyar D, Tripathi R P, Arora K, Gupta S, Ahmad R, Srivastava A K, Khan M A, Murthy P K, Walter R D. Synthesis and antifilarial evaluation of N1,Nn-xylofuranosylated diaminoalkanes.  Bioorg Med Chem. 2003;  11 1789-1800
• 84 Mak J W, Lam P L, Rain A N, Suresh K. Effect of ivermectin against subperiodic Brugia malayi infection in the leaf monkey, Presbytis cristata.  Parasitol Res. 1988;  74 383-385
• 85 Mak J W, Lam P L, Choong M F, Suresh K. Antifilarial activity of intravenous suramin and oral diethylcarbamazine citrate on subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata.  J Helminthol. 1990;  64 96-99
• 86 Murthy P K, Tyagi K, Sen A B. Susceptibility of Macaca mulatta to a subperiodic strain of Brugia malayi.  Indian J Parasitol. 1986;  10 189-192
• 87 Misra S, Tyagi K, Chatterjee R K. Experimental transmission of nocturnally periodic Wuchereria bancrofti to Indian leaf monkey (Presbytis entellus).  Exp Parasitol. 1997;  86 155-157
• 88 Schacher J F. Laboratory models in filariasis: a review of filarial life-cycle patterns.  Southeast Asian J Trop Med Public Health. 1973;  4 336-349
• 89 Huber W, Koella J C. A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites.  Acta Trop. 1993;  55 257-261
• 90 Page C, Page M, Noel C. A new fluorimetric assay for cytotoxicity measurements in vitro.  Int J Oncol. 1993;  3 473-476
• 91 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 92 Duwel D. Laboratory methods in the screening of anthelmintics.  Prog Drug Res. 1975;  19 48-63
• 93 Colgrave M L, Kotze A C, Kopp S, McCarthy J S, Coleman G T, Craik D J. Anthelmintic activity of cyclotides: In vitro studies with canine and human hookworms.  Acta Trop. 2009;  109 163-166
• 94 Hounzangbe-Adote S, Fouraste I, Moutairou K, Hoste H. In vitro effects of four tropical plants on the activity and development of the parasitic nematode, Trichostrongylus colubriformis.  J Helminthol. 2005;  79 29-33
• 95 Bizimenyera E S, Githiori J B, Eloff J N, Swan G E. In vitro activity of Peltophorum africanum Sond. (Fabaceae) extracts on the egg hatching and larval development of the parasitic nematode Trichostrongylus colubriformis.  Vet Parasitol. 2006;  142 336-343
• 96 Alonso-Diaz M A, Torres-Acosta J F, Sandoval-Castro C A, Capetillo-Leal C, Brunet S, Hoste H. Effects of four tropical tanniniferous plant extracts on the inhibition of larval migration and the exsheathment process of Trichostrongylus colubriformis infective stage.  Vet Parasitol. 2008;  153 187-192
• 97 Alonso-Diaz M A, Torres-Acosta J F, Sandoval-Castro C A, Aguilar-Caballero A J, Hoste H. In vitro larval migration and kinetics of exsheathment of Haemonchus contortus larvae exposed to four tropical tanniniferous plant extracts.  Vet Parasitol. 2008;  153 313-319
• 98 Maphosa V, Masika P J, Bizimenyera E S, Eloff J N. In-vitro anthelminthic activity of crude aqueous extracts of Aloe ferox, Leonotis leonurus and Elephantorrhiza elephantina against Haemonchus contortus.  Trop Anim Health Prod. 2010;  42 301-307
• 99 Tandon V, Pal P, Roy B, Rao H S, Reddy K S. In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India.  Parasitol Res. 1997;  83 492-498
• 100 Marquez-Navarro A, Nogueda-Torres B, Hernandez-Campos A, Soria-Arteche O, Castillo R, Rodriguez-Morales S, Yepez-Mulia L, Hernandez-Luis F. Anthelmintic activity of benzimidazole derivatives against Toxocara canis second-stage larvae and Hymenolepis nana adults.  Acta Trop. 2009;  109 232-235
• 101 Keiser J. In vitro and in vivo trematode models for chemotherapeutic studies.  Parasitology. 2010;  137 589-603
• 102 Xue J, Xiao S H, Xu L L, Qiang H Q. The effect of tribendimidine and its metabolites against Necator americanus in golden hamsters and Nippostrongylus braziliensis in rats.  Parasitol Res. 2010;  106 775-781
• 103 Albonico M, Allen H, Chitsulo L, Engels D, Gabrielli A F, Savioli L. Controlling soil-transmitted helminthiasis in pre-school-age children through preventive chemotherapy.  PLoS Negl Trop Dis. 2008;  2 e126
• 104 Boray J C, Happich F A, Andrews J C. Studies on the suitability of the albino rat for testing anthelminthic activity against Fasciola hepatica.  Ann Trop Med Parasitol. 1967;  61 104-111
• 105 Campbell W C, Fisher M H, Stapley E O, Albers-Schonberg G, Jacob T A. Ivermectin: a potent new antiparasitic agent.  Science. 1983;  221 823-828
• 106 Behm C A, Bendig M M, McCarter J P, Sluder A E. RNAi-based discovery and validation of new drug targets in filarial nematodes.  Trends Parasitol. 2005;  21 97-100
• 107 Chatterjee R K, Fatma N, Murthy P K, Sinha P, Kulshreshtha D K, Dhawan B N. Macrofilaricidal activity of the stem bark of Streblus asper and its major active constituents.  Drug Dev Res. 1992;  26 67-78
• 108 Misra N, Sharma M, Raj K, Dangi A, Srivastava S, Misra-Bhattacharya S. Chemical constituents and antifilarial activity of Lantana camara against human lymphatic filariid Brugia malayi and rodent filariid Acanthocheilonema viteae maintained in rodent hosts.  Parasitol Res. 2007;  100 439-448
• 109 Dalziel J M. The useful plants of west tropical Africa. London; The Crown Agents for the Colonies 1937: 612
• 110 Burkill H M. The useful plants of west tropical Africa, 2nd edition. Kew; Royal Botanic Gardens 1985: 960
• 111 Kiuchi F, Miyashita N, Tsuda Y, Kondo K, Yoshimura H. Studies on crude drugs effective on visceral larva migrans. I. Identification of larvicidal principles in betel nuts.  Chem Pharm Bull (Tokyo). 1987;  35 2880-2886
• 112 Murthy P K. Anthelmintics from medicinal plants. Sood ML Helminthology in India. India; International Book Distributors 2003: 377-392
• 113 Singh N P, Singh V K. Streblus asper Lour. – An ancient Indian drug for the cure of filariasis.  Acta Bot Indica. 1987;  15 108-109
• 114 Singh N P, Ram E R. Filaria and its herbal cure.  New Botanist. 1988;  15 201-205
• 115 Kilian H D. Preliminary data on the effects of an extract from Cassia aubrevellei in onchocerciasis. Hamburg; Liberia Research Unit of the Tropical Institute 1987: 33-34
• 116 Kilian H D, John K, Buttner D W, Kraus L. In vivo and in vitro effects of extracts of Cassia aubrevillei in onchocerciasis. O-NOW Symposium on Onchocerciasis, Leiden, Netherlands 1989
• 117 Titanji V P K, Evehe M S, Ayafor J F, Kimbu S F. Novel Onchocerca volvulus filarcides from Carapa procera, Polyalthia suaveolens and Pachypodanthium staudii. O-NOW Symposium on Onchocerciasis, Leiden, Netherlands 1989
• 118 Suresh M, Kaleysa Raj R. Cardol: The antifilarial principle from Anacardium occidentale.  Curr Sci. 1990;  59 477-479
• 119 Kulangara A C, Subramanian R. Preliminary studies on the effects of certain compounds on the filarial worm of the lizard, including an estimate of the toxicity of sodium flouride.  Indian J Med Res. 1960;  48 698-704
• 120 Dutta A, Sukul N C. Filaricidal properties of a wild herb, Andrographis paniculata.  J Helminthol. 1982;  56 81-84
• 121 Datta A, Sukul N C. Antifilarial effect of Zingiber officinale on Dirofilaria immitis.  J Helminthol. 1987;  61 268-270
• 122 Titanji V P K, Ayafor J F, Mulufi J P, Mbacham W F. In vitro killing of Onchocerca volvulus (Filaroidea) adults and microfilariae by selected Cameroonian medicinal plant extracts.  Fitoterpia. 1987;  58 338-339
• 123 Parveen N, Singhal K C, Khan N U. Screening of some plant extracts for their potential antifilarial activity using Setaria cervi as test organism. International Conference on Recent Advances in Medicinal, Aromatic and Spice Crops, New Delhi, India 1989
• 124 Singh R, Singhal K C, Khan N U. Antifilarial activity of the leaves of Mallotus philippensis Lam. on Setaria cervi (Nematode Filarioidea) in vitro.  Indian J Physiol Pharmacol. 1997;  41 397-403
• 125 Ampofo O. “Plants that heal” World Health.  The Magazine of the World Health Organization. 1977;  26-30
• 126 Khunkitti W, Fujimaki Y, Aoki Y. In vitro antifilarial activity of extracts of the medicinal plant Cardiospermum halicacabum against Brugia pahangi.  J Helminthol. 2000;  74 241-246
• 127 Sahare K N, Anandhraman V, Meshram V G, Meshram S U, Reddy M V, Tumane P M, Goswami K. Anti-microfilarial activity of methanolic extract of Vitex negundo and Aegle marmelos and their phytochemical analysis.  Indian J Exp Biol. 2008;  46 128-131
• 128 Lakshmi V, Saxena A, Pandey K, Bajpai P, Misra-Bhattacharya S. Antifilarial activity of Zoanthus species (Phylum Coelenterata, Class Anthzoa) against human lymphatic filaria, Brugia malayi.  Parasitol Res. 2004;  93 268-273
• 129 Mathew N, Misra-Bhattacharya S, Perumal V, Muthuswamy K. Antifilarial lead molecules isolated from Trachyspermum ammi.  Molecules. 2008;  13 2156-2168
• 130 Gaur R L, Sahoo M K, Dixit S, Fatma N, Rastogi S, Kulshreshtha D K, Chatterjee R K, Murthy P K. Antifilarial activity of Caesalpinia bonducella against experimental filarial infections.  Indian J Med Res. 2008;  128 65-70
• 131 Haerdi F. Die Eingeborenen-Heilpflanzen des Ulanga-Distriktes Tanganjikas (Ostafrika).  Acta Trop Suppl 8. 1964;  1-278
• 132 Oguakwa J U, Galeffi C, Messana I, Patamia M, Nicoletti M, Marini-Bettolo G B. Research on African medicinal plants. III New alkaloids from Alstonia boonei De Wild Gazzetta.  Chim Ital. 1983;  113 533-535
• 133 Oliver-Bever B E P. Anti-infective activity of higher plants. Medicinal plants in Tropical West Africa. Cambridge; Cambridge University Press 1986: 123-190
• 134 Ojewole J A O. Studies on the pharmacology of echitamine, an alkaloid from the stem bark of Alstonia booneri L. (Apocynaceae).  Int J Crude Drugs Res. 1984;  22 121-143
• 135 Farnsworth N R, Akerele O, Bingel A S, Soejarto D D, Guo Z. Medicinal plants in therapy.  Bull World Health Organ. 1985;  63 965-981
• 136 Guha Bakshi D N, Sensarma P, Pal D C. A lexicon of medicinal plants in India. Calcutta; Naya Prokash 1999: 290
• 137 Watt J M M, Breyer-Brandwijk G. The medicinal and poisonous plants of Southern and Eastern Africa, 2nd edition. London; E. & S. Livingstone, Ltd. 1962
• 138 Githens T S. Drug plants of Africa, African handbooks No. 8. Philadelphia; University of Pennsylvania Press 1948: 125
• 139 Satyavati G V, Gupta A K, Tandon N. Medicinal plants of India. New Delhi, India; Indian Council of Medical Research 1986
• 140 Banu M J, Nellaiappan K, Dhandayuthapani S. Mitochondrial malate dehydrogenase and malic enzyme of a filarial worm Setaria digitata: some properties and effects of drugs and herbal extracts.  Jpn J Med Sci Biol. 1992;  45 137-150
• 141 Ayensu E S. Medicinal plants of West Africa. Algonac, Michigan; Reference Publications Inc. 1978: 330
• 142 Deka L, Majumdar R, Dutta A M. Some Ayurvedic important plants from district Karnrup (Assam).  Ancient Sci Life. 1983;  3 108-115
• 143 Al-Yahya M A, Al-Meshal I A, Mossa J S, Tariq M. Phytochemical and pharmacological studies on Calotropis procera. 3rd International Conference of Traditional and Folk Medicine, Lecatecas, Mexico; 1985. 
• 144 Al-Yahya M A. Phytochemical studies on the plants used in traditional medicine of Saudi Arabia.  Fitoterapia. 1986;  47 179-182
• 145 Sahu T R. Less known uses of weeds as medicinal plants.  Ancient Sci Life. 1984;  4 245-249
• 146 Hedberg I, Hedberg O, Madati P J, Mshigeni K E, Mshiu E N, Samuelsson G. Inventory of plants used in traditional medicine in Tanzania. II. Plants of the families Dilleniaceae – Opiliaceae.  J Ethnopharmacol. 1983;  9 105-127
• 147 Iwu M M. Empirical investigation of dietary plants used in Igbo Ethnomedicine. New York; Nina Etkined Redgroove Publishing Company 1986: 116
• 148 Hedberg I, Hedberg O, Madati P J, Mshigeni K E, Mshiu E N, Samuelsson G. Inventory of plants used in traditional medicine in Tanzania. Part III. Plants of the families Papilionaceae-Vitaceae.  J Ethnopharmacol. 1983;  9 237-260
• 149 Maheshwari J K, Singh K K, Saba S. Ethno-medicinal uses of plants by the Thurus of Kheri District, U.P.  Bull Med Ethnobot Res. 1980;  1 318-337
• 150 Whistler W A. Traditional and herbal medicine in the Cook Islands.  J Ethnopharmacol. 1985;  13 239-280
• 151 Baoua M, Fayn J, Bassiere J. Preliminary phytochemical testing of some medical plants of Niger.  Planta Med. 1976;  10 251-266
• 152 Dragendorff G. Die Heilpflanzen der verschiedenen Völker und Zeiten. Stuttgart; Ferdinand Enke 1898
• 153 Lewis W H, Manony P F E. Medical botany: plants affecting man's health. New York; John Wiley and Sons 1977: 240
• 154 Vasileva B. Plantes mediques Conakryinales de Guinea. Republic de Guinea; Conakry 1969
• 155 Kokward J O. Medicinal plants of East Africa. Nairobi, Kenya; East Africa Literature Bureau 1976
• 156 Kerharo J, Adam J G. Pharmacopée sénégalaise traditionelle. Paris; Vigot 1974
• 157 Parveen N, Singhal K C, Khan N U, Singhal P. Potential antifilarial activity of Streblus asper against Setaria cervi (Nematoda : Filaroidea).  Indian J Pharmacol. 1989;  21 16-21
• 158 Kliks M M. Studies on the traditional herb anthelmintic Chenopodium ambrosoides L. Ethnopharmacological evaluation and clinical field trials.  Soc Sci Med. 1985;  21 879-886
• 159 Ibrahim M A, Nwude N, Ogunsui R A, Aliu Y O. Screening of West African plants for anthelmintic activity.  ILCA Bull. 1984;  17 19-23
• 160 Takki S. Anthelminitic effect of fern preparations and their action on some liver function tests in man.  Ann Med Exp Fenn. 1967;  45 341-351
• 161 Navarrete A, Hong E. Anthelmintic properties of alpha-sanshool from Zanthoxylum liebmannianum.  Planta Med. 1996;  62 250-251
• 162 Raj R K, Kurup P A. Anthelmintic activity, toxicity and other pharmacological properties of palasonin, the active principle of Butea frondosa seeds and its piperazine salt.  Indian J Med Res. 1968;  56 1818-1825
• 163 Rastogi R P, Mehrotra B N. Compendium of Indian medicinal plants.  New Delhi: CDRI/CSIR/PID;. 1995;  125 435
• 164 de Amorin A, Borba H R, Carauta J P, Lopes D, Kaplan M A. Anthelmintic activity of the latex of Ficus species.  J Ethnopharmacol. 1999;  64 255-258
• 165 Bogh H O, Andreassen J, Lemmich J. Anthelmintic usage of extracts of Embelia schimperi from Tanzania.  J Ethnopharmacol. 1996;  50 35-42
• 166 Perrett S, Whitfield P J, Sanderson L, Bartlett A. The plant molluscicide Millettia thonningii (Leguminosae) as a topical antischistosomal agent.  J Ethnopharmacol. 1995;  47 49-54
• 167 Galal M, Bashir A K, Salih A M, Adam S E. Activity of water extracts of Albizzia anthelmintica and A. lebbek barks against experimental Hymenolepis diminuta infection in rats.  J Ethnopharmacol. 1991;  31 333-337
• 168 Satrija F, Nansen P, Murtini S, He S. Anthelmintic activity of papaya latex against patent Heligmosomoides polygyrus infections in mice.  J Ethnopharmacol. 1995;  48 161-164
• 169 Barrau E, Fabre N, Fouraste I, Hoste H. Effect of bioactive compounds from Sainfoin (Onobrychis viciifolia Scop.) on the in vitro larval migration of Haemonchus contortus: role of tannins and flavonol glycosides.  Parasitology. 2005;  131 531-538
• 170 Del Rayo Camacho M, Sanchez B, Quiroz H, Contreras J L, Mata R. Pinocembrine: a bioactive flavanone from Teloxys graveolens.  J Ethnopharmacol. 1991;  31 383-389
• 171 Ayers S, Zink D L, Mohn K, Powell J S, Brown C M, Murphy T, Brand R, Pretorius S, Stevenson D, Thompson D, Singh S B. Flavones from Struthiola argentea with anthelmintic activity in vitro.  Phytochemistry. 2008;  69 541-545
• 172 Eguale T, Tilahun G, Debella A, Feleke A, Makonnen E. In vitro and in vivo anthelmintic activity of crude extracts of Coriandrum sativum against Haemonchus contortus.  J Ethnopharmacol. 2007;  110 428-433
• 173 Booth S, Johns T, Lopez-Palacios C Y. Factors influencing self-diagnosis and treatment of perceived helminthic infection in a rural Guatemalan community.  Soc Sci Med. 1993;  37 531-539
• 174 Jain S K, Sinha B K, Saklani A. Some interesting medicinal plants known among several tribes of India.  Ethnobotany. 1989;  1 89-100
• 175 Rastogi R P, Mehrotra B N. Compendium of Indian medicinal plants. New Delhi; CDRI/CSIR/PID 1990
• 176 Molan A L, Sivakumaran S, Spencer P A, Meagher L P. Green tea flavan-3-ols and oligomeric proanthocyanidins inhibit the motility of infective larvae of Teladorsagia circumcincta and Trichostrongylus colubriformis in vitro.  Res Vet Sci. 2004;  77 239-243
• 177 Rastogi R P, Mehrotra B N. Compendium of Indian medicinal plants. New Delhi; CDRI/CSIR/PID 1993
• 178 Satrija F, Nansen P, Bjorn H, Murtini S, He S. Effect of papaya latex against Ascaris suum in naturally infected pigs.  J Helminthol. 1994;  68 343-346
• 179 Rastogi R P, Mehrotra B N. Compendium of Indian medicinal plants. New Delhi; CDRI/CSIR/PID 1991
• 180 Dhar M L, Dhar M M, Dhawan B N, Mehrotra B N, Ray C. Screening of Indian plants for biological activity.  Indian J Exp Biol. 1968;  6 232-247
• 181 Hansson A, Veliz G, Naquira C, Amren M, Arroyo M, Arevalo G. Preclinical and clinical studies with latex from Ficus glabrata HBK, a traditional intestinal anthelminthic in the Amazonian area.  J Ethnopharmacol. 1986;  17 105-138
• 182 Shiramizu K, Tuchida T, Aru M. Anthelmintic effect of cude preparation containing the root of Matteuccia orientalis on bovine fasciolosis.  J Jpn Vet Med Assoc. 1993;  46 561-564
• 183 Perrett S, Whitfield P J, Bartlett A, Sanderson L. Attenuation of Schistosoma mansoni cercariae with a molluscicide derived from Millettia thonningii.  Parasitology. 1994;  109 (Pt. 5) 559-563
• 184 Asuzu I U, Onu U O. Anthelmintic activity of the ethanolic extract of Piliostigma thonningii bark in Ascaridia galli infected chickens.  Fitoterapia. 1994;  65 291-297
• 185 Muddathir A K, Balansard G, Timon-David P, Babadjamian A, Yogoub A K, Julien M J. Anthelmintic properties of Polygonum glabrum.  J Pharm Pharmacol. 1987;  39 296-300
• 186 Stadler M, Dagne E, Anke H. Nematicidal activities of two phytoalexins from Taverniera abyssinica.  Planta Med. 1994;  60 550-552
• 187 Aye T, Mya B, Saw H, Tin M, Marlar L, Po Aung S. Screening of some medicinal plants reputed for anthelminthic activity on in vitro test models.  Myanmar Health Sci Res J. 1993;  5 79-84