Generic placeholder image

Recent Advances in Anti-Infective Drug Discovery

Author(s): Agrima Yadav, Shikha Yadav* and Aftab Alam

DOI: 10.2174/0127724344266902231117112109

DownloadDownload PDF Flyer Cite As
A Landscape on Lymphatic Filariasis with its Effects and Recent Advanced Treatments

Page: [197 - 215] Pages: 19

  • * (Excluding Mailing and Handling)

Abstract

Lymphatic filariasis is an infection caused by parasites that poses a significant health, social, and economic burden, affecting a vast population that exceeds 120 million individuals globally. The Etiology of the infection is attributed to three nematode parasites, namely Wuchereria bancrofti, B. timori, and Brugia malayi, as well as which are phylogenetically related. These parasites are transmitted to humans via mosquitoes belonging to the Anopheles, Aedes genera, and Culex. As per the estimation provided by the WHO, the current number of individuals infected with filariasis stands at approximately 120 million across 81 countries. Furthermore, it is estimated that around 1.34 billion individuals reside in regions that are endemic to filariasis, thereby putting them at risk of contracting the disease. Different synthetic drugs such as Ivermectin, Doxycycline, Albendazole, and Suramin are used in the treatment. Some natural plants are Azadirachta indica, Tinospora cordifolia, Zingiber officinal, as well as, some marine sources are also included for better treatment. We also touch briefly on a few additional filarial diseases. Although there are only a few medications available to treat filariasis, their frequent usage may result in drug resistance. Furthermore, there is no effective vaccination for the treatment of filariasis. Due to these restrictions, it has been crucial to create new anti-filarial medications, which motivates researchers to find novel pharmaceuticals with anti-filarial action. In this article, we examine the latest achievements in the anti-filarial area, including the many forms of filariasis and their historical contexts, elimination programmes, various therapeutic classes (both synthetic and natural), investigated product-derived targets as well as clinical investigations.

Graphical Abstract

[1]
World Health Organization. Global programme to eliminate lymphatic filariasis: Progress report, 2019. Wkly Epidemiol Rec 2019; 95: 509-24.
[2]
Gordon S, Melrose W, Warner J, Buttner P, Ward L. Lymphatic filariasis: A method to identify subclinical lower limb change in PNG adolescents. PLoS Negl Trop Dis 2011; 5(7): e1242.
[http://dx.doi.org/10.1371/journal.pntd.0001242] [PMID: 21811644]
[3]
Melrose WD. Lymphatic filariasis: New insights into an old disease. Int J Parasitol 2002; 32(8): 947-60.
[http://dx.doi.org/10.1016/S0020-7519(02)00062-0] [PMID: 12076624]
[4]
Ending the neglect to attain the sustainable development goals: A road map for neglected tropical diseases 2021–2030. World Health Organization. Available at: https://www.who.int/publications-detail-redirect/9789240010352 (Accessed: 09 June 2023).
[5]
Turner HC. Health economic analyses of the global programme to eliminate lymphatic filariasis. Int Health 2020; 13 (Suppl. 1): S71-4.
[http://dx.doi.org/10.1093/inthealth/ihaa095] [PMID: 33349885]
[6]
World Health Organization. Bridging the gaps: The world health report. Geneva: The Organization 1995.
[7]
Ramaiah KD, Das PK, Michael E, Guyatt HL. The economic burden of lymphatic filariasis in India. Parasitol Today 2000; 16(6): 251-3.
[http://dx.doi.org/10.1016/S0169-4758(00)01643-4] [PMID: 10827432]
[8]
World Health Organization. Monitoring and epidemiological assessment of mass drug administration in the global programme to eliminate lymphatic filariasis: A manual for national elimination programmes 2011.
[9]
Ramaiah KD, Vanamail P, Pani SP, Yuvaraj J, Das PK. The effect of six rounds of single dose mass treatment with diethylcarbamazine or ivermectin on Wuchereria bancrofti infection and its implications for lymphatic filariasis elimination. Trop Med Int Health 2002; 7(9): 767-74.
[http://dx.doi.org/10.1046/j.1365-3156.2002.00935.x] [PMID: 12225508]
[10]
Gyapong JO, Owusu IO, da-Costa Vroom FB, Mensah EO, Gyapong M. Elimination of lymphatic filariasis: current perspectives on mass drug administration. Res Rep Trop Med 2018; 9: 25-33.
[http://dx.doi.org/10.2147/RRTM.S125204] [PMID: 30050352]
[11]
Anitha K, Shenoy RK. Treatment of lymphatic filariasis: current trends. Indian J Dermatol Venereol Leprol 2001; 67(2): 60-5.
[PMID: 17664709]
[12]
Taylor MJ, Bandi C, Hoerauf A. Wolbachia bacterial endosymbionts of filarial nematodes. Adv Parasitol 2005; 60: 245-84.
[http://dx.doi.org/10.1016/S0065-308X(05)60004-8] [PMID: 16230105]
[13]
Brady M. Seventh meeting of the Global Alliance to Eliminate Lymphatic Filariasis: Reaching the vision by scaling up, scaling down, and reaching out. Parasit Vectors 2014; 7(1): 46.
[http://dx.doi.org/10.1186/1756-3305-7-46]
[14]
Babu BV, Behera DK, Kerketta AS, et al. Use of an inclusive-partnership strategy in urban areas of Orissa, India, to increase compliance in a mass drug administration for the control of lymphatic filariasis. Ann Trop Med Parasitol 2006; 100(7): 621-30.
[http://dx.doi.org/10.1179/136485906X118521] [PMID: 16989688]
[15]
Kakkar RS, Mehta D, Sisodia A. Radiological and functional outcome of unstable bimalleolar fractures through surgical treatment using baird–jackson scoring system. Int J Sci Res 2019; 8(10): 1076-81.
[16]
Siriyasatien P, Intayot P, Sawaswong V, et al. Description of potential vectors of zoonotic filarial nematodes, Brugia pahangi, Setaria digitata, and Setaria labiatopapillosa in Thai mosquitoes. Heliyon 2023; 9(2): e13255.
[http://dx.doi.org/10.1016/j.heliyon.2023.e13255] [PMID: 36846682]
[17]
Lymphatic filariasis [Internet]. World Health Organization; [cited 2023 Jun 9]. Available from: https://www.who.int/news-room/fact-sheets/detail/lymphatic-filariasis
[18]
Gordon C, Jones M, McManus D. The history of Bancroftian lymphatic filariasis in Australasia and Oceania: Is there a threat of re-occurrence in mainland Australia? Trop Med Infect Dis 2018; 3(2): 58.
[http://dx.doi.org/10.3390/tropicalmed3020058] [PMID: 30274454]
[19]
Small ST, Ramesh A, Bun K, et al. Population genetics of the filarial worm wuchereria bancrofti in a post-treatment region of Papua New Guinea: Insights into diversity and life history. PLoS Negl Trop Dis 2013; 7(7): e2308.
[http://dx.doi.org/10.1371/journal.pntd.0002308] [PMID: 23875043]
[20]
Fact sheets (no date) World Health Organization Available at: https://www.who.int/news-room/fact-sheets (Accessed: 11 June 2023).
[21]
Gordon CA, McManus DP, Jones MK, Gray DJ, Gobert GN. The increase of exotic zoonotic helminth infections: The impact of urbanization, climate change and globalization. Adv Parasitol 2016; 91: 311-97.
[http://dx.doi.org/10.1016/bs.apar.2015.12.002] [PMID: 27015952]
[22]
Boreham PFL, Marks EN. Human filariasis in Australia: Introduction, investigation and elimination. R Soc Qld 1986; 97: 23-52.
[23]
Sasa M. Human filariasis. In: A global survey of epidemiology and control. University Park Press 1976.
[24]
Jeremiah CJ, Aboltins CA, Stanley PA. Lymphatic filariasis in Australia: an update on presentation, diagnosis and treatment. Med J Aust 2011; 194(12): 655-7.
[http://dx.doi.org/10.5694/j.1326-5377.2011.tb03154.x] [PMID: 21692728]
[25]
Kline K, McCarthy JS, Pearson M, Loukas A, Hotez PJ. Neglected tropical diseases of Oceania: review of their prevalence, distribution, and opportunities for control. PLoS Negl Trop Dis 2013; 7(1): e1755.
[http://dx.doi.org/10.1371/journal.pntd.0001755] [PMID: 23383349]
[26]
de la Santé MO. World Health Organization. Summary of global update on preventive chemotherapy implementation in 2016: Weekly Epidemiological Record= Relevé épidémiologique hebdomadaire 2017; 92(40): 589-93.
[27]
Global Programme to eliminate lymphatic filariasis: Progress report 2020. [Internet]. World Health Organization; [cited 2023 Jun 12]. Available from: https://www.who.int/publications/i/item/who-wer9641-497-508
[28]
Jayakumar K, Bindu R. International Journal of scientific research
[29]
Edeson JF. The epidemiology and treatment of infection due to Brugia malayi. Bull World Health Organ 1962; 27(4-5): 529-41.
[PMID: 20604131]
[30]
Al-shaham AA, Sood S. Recurrent furunculosis as a cause of isolated penile lymphedema: a case report. J Med Case Reports 2010; 4(1): 196.
[http://dx.doi.org/10.1186/1752-1947-4-196] [PMID: 20584337]
[31]
Kabatereine NB, Malecela M, Lado M, Zaramba S, Amiel O, Kolaczinski JH. How to (or not to) integrate vertical programmes for the control of major neglected tropical diseases in sub-Saharan Africa. PLoS Negl Trop Dis 2010; 4(6): e755.
[http://dx.doi.org/10.1371/journal.pntd.0000755] [PMID: 20614017]
[32]
Addiss DG. Global elimination of lymphatic filariasis: Addressing the public health problem. PLoS Negl Trop Dis 2010; 4(6): e741.
[http://dx.doi.org/10.1371/journal.pntd.0000741] [PMID: 20614015]
[33]
Schissel DJ, Hivnor C, Elston DM. Elephantiasis nostras verrucosa. Cutis 1998; 62(2): 77-80.
[PMID: 9714902]
[34]
Sisto K, Khachemoune A. Elephantiasis nostras verrucosa: A review. Am J Clin Dermatol 2008; 9(3): 141-6.
[http://dx.doi.org/10.2165/00128071-200809030-00001] [PMID: 18429642]
[35]
Boyd J, Sloan S, Meffert J. Elephantiasis nostrum verrucosa of the abdomen: Clinical results with tazarotene. J Drugs Dermatol 2004; 3(4): 446-8.
[PMID: 15303792]
[36]
Castellani A. Research on elephantiasis nostras and elephantiasis tropica with special regard to their initial stage of recurring lymphangitis (lymphangitis recurrens elephantogenica). Arch Ital Sci Med Trop Parassitol 1969; 50(7): 171-95.
[PMID: 5363963]
[37]
Sanders LJ, Slomsky JM, Burger-Caplan C. Elephantiasis nostras: An eight-year observation of progressive nonfilarial elephantiasis of the lower extremity. Cutis 1988; 42(5): 406-11.
[PMID: 3058397]
[38]
Erickson QL, Kobayashi T, Vogel PS. Photo quiz. Woody edema of the legs. Am Fam Physician 2003; 67(3): 583-4.
[PMID: 12588081]
[39]
Yoho RM, Budny AM, Pea AS. Elephantiasis nostras verrucosa. J Am Podiatr Med areas were Assoc 2006; 96(5): 442-4.
[40]
Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: Skin physiology and skin manifestations of obesity. J Am Acad Dermatol 2007; 56(6): 901-16.
[http://dx.doi.org/10.1016/j.jaad.2006.12.004] [PMID: 17504714]
[41]
Weil GJ, Lammie PJ, Weiss N. The ICT filariasis test: A rapid-format antigen test for diagnosis of bancroftian filariasis. Parasitol Today 1997; 13(10): 401-4.
[http://dx.doi.org/10.1016/S0169-4758(97)01130-7] [PMID: 15275155]
[42]
Amaral F, Samico SC, Figueredo-Silva J, et al. Live adult worms detected by ultrasonography in human Bancroftian filariasis. Am J Trop Med Hyg 1994; 50(6): 753-7.
[http://dx.doi.org/10.4269/ajtmh.1994.50.753] [PMID: 8024070]
[43]
Shenoy RK, John A, Hameed S, Suma TK, Kumaraswami V. Apparent failure of ultrasonography to detect adult worms of Brugia malayi. Ann Trop Med Parasitol 2000; 94(1): 77-82.
[http://dx.doi.org/10.1080/00034983.2000.11813515] [PMID: 10723526]
[44]
McCarthy J. Diagnosis of lymphatic filarial infection. 2000; 15: 127-50.
[45]
Freedman DO, Filho PJA, Besh S, Silva MCM, Braga C, Maciel A. Lymphoscintigraphic analysis of lymphatic abnormalities in symptomatic and asymptomatic human filariasis. J Infect Dis 1994; 170(4): 927-33.
[http://dx.doi.org/10.1093/infdis/170.4.927] [PMID: 7523538]
[46]
Dreyer G, Addiss D, Noroes J, Amaral F, Rocha A, Coutinho A. Ultrasonographic assessment of the adulticidal efficacy of repeat high-dose ivermectin in bancroftian filariasis. Trop Med Int Health 1996; 1(4): 427-32.
[http://dx.doi.org/10.1046/j.1365-3156.1996.d01-79.x] [PMID: 8765448]
[47]
Norões J, Dreyer G, Santos A, Mendes VG, Medeiros Z, Addiss D. Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg 1997; 91(1): 78-81.
[http://dx.doi.org/10.1016/S0035-9203(97)90405-3] [PMID: 9093637]
[48]
Andrade LD, Medeiros Z, Pires ML, et al. Comparative efficacy of three different diethylcarbamazine regimens in lymphatic filariasis. Trans R Soc Trop Med Hyg 1995; 89(3): 319-21.
[http://dx.doi.org/10.1016/0035-9203(95)90561-8] [PMID: 7660449]
[49]
Shenoy RK, Kumaraswami V, Suma TK, Rajan K, Radhakuttyamma G. A double-blind, placebo-controlled study of the efficacy of oral penicillin, diethylcarbamazine or local treatment of the affected limb in preventing acute adenolymphangitis in lymphoedema caused by brugian filariasis. Ann Trop Med Parasitol 1999; 93(4): 367-77.
[http://dx.doi.org/10.1080/00034983.1999.11813433] [PMID: 10656038]
[50]
Shenoy RK, Suma TK, Rajan K, Kumaraswami V. Prevention of acute adenolymphangitis in brugian filariasis: comparison of the efficacy of ivermectin and diethylcarbamazine, each combined with local treatment of the affected limb. Ann Trop Med Parasitol 1998; 92(5): 587-94.
[http://dx.doi.org/10.1080/00034983.1998.11813316] [PMID: 9797832]
[51]
Ottesen EA, Ismail MM, Horton J. The role of albendazole in programmes to eliminate lymphatic filariasis. Parasitol Today 1999; 15(9): 382-6.
[http://dx.doi.org/10.1016/S0169-4758(99)01486-6] [PMID: 10461168]
[52]
Division of Control of Tropical Diseases, Communicable Diseases Report from informal consultation on albendazole research findings in lymphatic filariasis; WHO/FIL/98194; (closed document). Geneva: World Health Organization 1998.
[53]
Horton J. Albendazole: A review of anthelmintic efficacy and safety in humans. Parasitology 2000; 121(S1) (Suppl.): S113-32.
[http://dx.doi.org/10.1017/S0031182000007290] [PMID: 11386684]
[54]
GlaxoSmithKline. Lymphatic filariasis programme: eliminating lymphatic filariasis. www.gsk.com/filariasis/eliminating.htm (accessed October 2002).
[55]
Jayakody RL, DeSilva CS, Weerasinghe WM. Treatment of bancroftian filariasis with albendazole: Evaluation of efficacy and adverse reactions. Trop Biomed 1993; 10: 19.
[56]
Shenoy RK, John A, Babu BS, Suma TK, Kumaraswami V. Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations. Ann Trop Med Parasitol 2000; 94(6): 607-14.
[http://dx.doi.org/10.1080/00034983.2000.11813583] [PMID: 11064762]
[57]
Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: A double-blind, randomised placebo-controlled trial. Lancet 2005; 365(9477): 2116-21.
[http://dx.doi.org/10.1016/S0140-6736(05)66591-9] [PMID: 15964448]
[58]
Debrah AY, Mand S, Specht S, et al. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis. PLoS Pathog 2006; 2(9): e92.
[http://dx.doi.org/10.1371/journal.ppat.0020092] [PMID: 17044733]
[59]
Debrah AY, Mand S, Marfo-Debrekyei Y, et al. Macrofilaricidal effect of 4 weeks of treatment with doxycycline on Wuchereria bancrofti. Trop Med Int Health 2007; 12(12): 1433-41.
[http://dx.doi.org/10.1111/j.1365-3156.2007.01949.x] [PMID: 18076549]
[60]
Turner JD, Mand S, Debrah AY, et al. A randomized, double-blind clinical trial of a 3-week course of doxycycline plus albendazole and ivermectin for the treatment of Wuchereria bancrofti infection. Clin Infect Dis 2006; 42(8): 1081-9.
[http://dx.doi.org/10.1086/501351] [PMID: 16575724]
[61]
Hoerauf A. Filariasis: New drugs and new opportunities for lymphatic filariasis and onchocerciasis. Curr Opin Infect Dis 2008; 21(6): 673-81.
[http://dx.doi.org/10.1097/QCO.0b013e328315cde7] [PMID: 18978537]
[62]
Subrahmanyam D. Antifilarials and their mode of action. Ciba Found Symp 1987; 127: 246-64. [Chichester, UK: John Wiley & Sons, Ltd.].
[PMID: 3297557]
[63]
Harder A. Chemotherapeutic approaches to schistosomes: Current knowledge and outlook. Parasitol Res 2002; 88(5): 395-7.
[http://dx.doi.org/10.1007/s00436-001-0588-x] [PMID: 12049454]
[64]
Jentsch KD, Hunsmann G, Hartmann H, Nickel P. Inhibition of human immunodeficiency virus type I reverse transcriptase by suramin-related compounds. J Gen Virol 1987; 68(8): 2183-92.
[http://dx.doi.org/10.1099/0022-1317-68-8-2183] [PMID: 2440983]
[65]
Chijioke CP, Umeh RE, Mbah AU, Nwonu P, Fleckenstein LL, Okonkwo PO. Clinical pharmacokinetics of suramin in patients with onchocerciasis. Eur J Clin Pharmacol 1998; 54(3): 249-51.
[http://dx.doi.org/10.1007/s002280050454] [PMID: 9681668]
[66]
Sangshetti JN, Shinde DB, Kulkarni A, Arote R. Two decades of antifilarial drug discovery: A review. RSC Advances 2017; 7(33): 20628-66.
[http://dx.doi.org/10.1039/C7RA01857F]
[67]
Walter RD, Schulz-Key H. Onchocerca volvulus: Effect of suramin on lactate dehydrogenase and malate dehydrogenase. Tropenmed Parasitol 1980; 31(1): 55-8.
[PMID: 7376252]
[68]
Walter RD, Albiez EJ. Inhibition of NADP-linked malic enzyme from Onchocerca volvulus and Dirofilaria immitis by suramin. Mol Biochem Parasitol 1981; 4(1-2): 53-60.
[http://dx.doi.org/10.1016/0166-6851(81)90028-1] [PMID: 7322187]
[69]
Shankar PR. Essential medicines and health products information portal [Internet]. U.S. NLM 2014. [cited 2023 Jun 12]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917174/
[70]
Miller MJ. Use of levamisole in parasitic infections. Drugs 1980; 20(2): 122-30.
[http://dx.doi.org/10.2165/00003495-198020020-00005] [PMID: 6995094]
[71]
Temu SE, McMahon JE. Chemotherapy with spaced doses of diethylcarbamazine preceded by levamisole in Bancroftian filariasis. Trans R Soc Trop Med Hyg 1981; 75(6): 835-7.
[http://dx.doi.org/10.1016/0035-9203(81)90424-7] [PMID: 7036437]
[72]
Aceves J, Erlij D, Martínez-Marañón R. The mechanism of the paralysing action of tetramisole on Ascaris somatic muscle. Br J Pharmacol 1970; 38(3): 602-7.
[http://dx.doi.org/10.1111/j.1476-5381.1970.tb10601.x] [PMID: 5445688]
[73]
Harrow ID, Gration KAF. Mode of action of the anthelmintics morantel, pyrantel and levamisole on muscle cell membrane of the nematode Ascaris suum. Pestic Sci 1985; 16(6): 662-72.
[http://dx.doi.org/10.1002/ps.2780160612]
[74]
Gupta J, Misra S, Mishra SK, et al. Antifilarial activity of marine sponge Haliclona oculata against experimental Brugia malayi infection. Exp Parasitol 2012; 130(4): 449-55.
[http://dx.doi.org/10.1016/j.exppara.2012.01.009] [PMID: 22306280]
[75]
Lakshmi V, Srivastava S, Mishra S, Misra S, Verma M, Misra-Bhattacharya S. In vitro and in vivo antifilarial potential of marine sponge, Haliclona exigua (Kirkpatrick), against human lymphatic filarial parasite Brugia malayi. Parasitol Res 2009; 105(5): 1295-301.
[http://dx.doi.org/10.1007/s00436-009-1555-1] [PMID: 19626340]
[76]
Lakshmi V, Kumar R, Gupta P, et al. The antifilarial activity of a marine red alga, Botryocladia leptopoda, against experimental infections with animal and human filariae. Parasitol Res 2004; 93(6): 468-74.
[http://dx.doi.org/10.1007/s00436-004-1159-8] [PMID: 15243801]
[77]
Mukherjee N, Saini P, Mukherjee S, Roy P, Sinha Babu SP. In vitro antifilarial activity of Azadirachta indica aqueous extract through reactive oxygen species enhancement. Asian Pac J Trop Med 2014; 7(11): 841-8.
[http://dx.doi.org/10.1016/S1995-7645(14)60147-4] [PMID: 25441981]
[78]
Saxena K, Dube V, Kushwaha V, et al. Antifilarial efficacy of Hibiscus sabdariffa on lymphatic filarial parasite Brugia malayi. Med Chem Res 2011; 20(9): 1594-602.
[http://dx.doi.org/10.1007/s00044-010-9419-x]
[79]
Singh R, Singhal KC, Khan NU. Antifilarial activity of Mallotus philippensis Lam. on Setaria cervie (Nematoda: Filarioidea) in vitro. Indian J Physiol Pharmacol 1997; 41(4): 397-403.
[PMID: 10235663]
[80]
Sashidhara KV, Singh SP, Misra S, Gupta J, Misra-Bhattacharya S. Galactolipids from Bauhinia racemosa as a new class of antifilarial agents against human lymphatic filarial parasite, Brugia malayi. Eur J Med Chem 2012; 50: 230-5.
[http://dx.doi.org/10.1016/j.ejmech.2012.01.057] [PMID: 22348826]
[81]
Deshmukh M, Sahare KN, Patidar RK, Mahajan B, Singh V. Antifilarial activity of Butea monosperma L. leaves extracts against Setaria cervi. Trends in Vector Research and Parasitology 2014; 1(1): 1-5.
[http://dx.doi.org/10.7243/2054-9881-1-1]
[82]
Chandhoke N, Ghatak BJ. Pharmacological investigations of angelecin-a tranquillosedative and anticonvulsant agent. Indian J Med Res 1975; 63(6): 833-41.
[PMID: 1213780]
[83]
Qamaruddin A, Parveen N, Khan NU, Singhal KC. Potential antifilarial activity of the leaves and seeds extracts of Psoralea corylifolia on cattle filarial parasite Setaria cervi. J Ethnopharmacol 2002; 82(1): 23-8.
[http://dx.doi.org/10.1016/S0378-8741(02)00141-1] [PMID: 12169401]
[84]
Gnanapragasam A, Ebenezar K, Sathish V, Govindaraju P, Devaki T. Protective effect of Centella asiatica on antioxidant tissue defense system against adriamycin induced cardiomyopathy in rats. Life Sci 2004; 76(5): 585-97.
[http://dx.doi.org/10.1016/j.lfs.2004.09.009] [PMID: 15556170]
[85]
Zainol MK, Abd-Hamid A, Yusof S, Muse R. Antioxidative activity and total phenolic compounds of leaf, root and petiole of four accessions of Centella asiatica (L.) Urban. Food Chem 2003; 81(4): 575-81.
[http://dx.doi.org/10.1016/S0308-8146(02)00498-3]
[86]
Sheeba MS, Asha VV. Effect of Cardiospermum halicacabum on ethanol-induced gastric ulcers in rats. J Ethnopharmacol 2006; 106(1): 105-10.
[http://dx.doi.org/10.1016/j.jep.2005.12.009] [PMID: 16469462]
[87]
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(3): 241-6.
[http://dx.doi.org/10.1017/S0022149X00000342] [PMID: 10953224]
[88]
Lakshmi V, Misra-Bhattacharya S. Bangladesh. Pharm J 2016; 19: 44-7.
[89]
Tanaka T, Ito T, Iinuma M, Takahashi Y, Naganawa H. Dimeric chalcone derivatives from Mallotus philippensis. Phytochemistry 1998; 48(8): 1423-7.
[http://dx.doi.org/10.1016/S0031-9422(98)00131-9]
[90]
Mathew N, Paily KP. Abidha, Vanamail P, Kalyanasundaram M, Balaraman K. Macrofilaricidal activity of the plant Plumbago indica/rosea in vitro. Drug Dev Res 2002; 56(1): 33-9.
[http://dx.doi.org/10.1002/ddr.10056]
[91]
Kaewbumrung S, Panichayupakaranant P. Antibacterial activity of plumbagin derivative-rich Plumbago indica root extracts and chemical stability. Nat Prod Res 2014; 28(11): 835-7.
[http://dx.doi.org/10.1080/14786419.2013.879585] [PMID: 24483166]
[92]
Tripathi S, Singh N, Shakya S, et al. Landrace/gender-based differences in phenol and thiocyanate contents and biological activity in Piper betle L. Curr Sci 2006; 91(6): 746-9.
[93]
Singh M, Shakya S, Soni VK, Dangi A, Kumar N, Bhattacharya SM. The n-hexane and chloroform fractions of Piper betle L. trigger different arms of immune responses in BALB/c mice and exhibit antifilarial activity against human lymphatic filarid Brugia malayi. Int Immunopharmacol 2009; 9(6): 716-28.
[http://dx.doi.org/10.1016/j.intimp.2009.02.012] [PMID: 19281872]
[94]
Singh R, Khan NU, Singhall KC. In vitro antifilarial activity of Sencio nudicaulis Buch. Ham. Effect on Setaria cervi (Nematoda Filarioidea). Indian J Physiol Pharmacol 1996; 40(3): 231-6.
[PMID: 8950138]
[95]
Ghosh S, Saha S. Tinospora cordifolia: One plant, many roles. Anc Sci Life 2012; 31(4): 151-9.
[http://dx.doi.org/10.4103/0257-7941.107344] [PMID: 23661861]
[96]
Polasa K, Nirmala K. Ginger: Its role in xenobiotic metabolism. Icmr Bull 2003; 33(6): 57-62.
[97]
Mishra V, Parveen N, Singhal KC, Khan NU. Antifilarial activity of Azadirachta indica on cattle filarial parasite Setaria cervi. Fitoterapia 2005; 76(1): 54-61.
[http://dx.doi.org/10.1016/j.fitote.2004.10.010] [PMID: 15664463]
[98]
Koh HL, Tan CH, Chua TK. Guide to medicinal plants, a: An illustrated scientific and medicinal approach. World scientific 2009.
[99]
Tripathi A, Chandrasekaran N, Raichur AM, Mukherjee A. Antibacterial applications of silver nanoparticles synthesized by aqueous extract of Azadirachta indica (Neem) leaves. J Biomed Nanotechnol 2009; 5(1): 93-8.
[http://dx.doi.org/10.1166/jbn.2009.038] [PMID: 20055111]
[100]
Othman F, Motalleb G, Lam Tsuey Peng S, Rahmat A, Fakurazi S, Pei Pei C. Extract of Azadirachta indica (Neem) leaf induces apoptosis in 4T1 breast cancer BALB/c mice. Cell J 2011; 13(2): 107-16.
[PMID: 23507990]
[101]
Schumacher M, Cerella C, Reuter S, Dicato M, Diederich M. Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway. Genes Nutr 2011; 6(2): 149-60.
[http://dx.doi.org/10.1007/s12263-010-0194-6] [PMID: 21484152]
[102]
Lucantoni L, Yerbanga RS, Lupidi G, Pasqualini L, Esposito F, Habluetzel A. Transmission blocking activity of a standardized neem (Azadirachta indica) seed extract on the rodent malaria parasite Plasmodium berghei in its vector Anopheles stephensi. Malar J 2010; 9(1): 66.
[http://dx.doi.org/10.1186/1475-2875-9-66] [PMID: 20196858]
[103]
Aziz Q. To Study the anti-ulcer effect of Azadirachta indica leaf extract and isolated compound of neem Nimolicine (NC) in comparison with ulcer healing drugs on gastric mucosa of albino rats
[104]
Misra S, Singh DP, Chatterjee RK. Studies on Alteration in antibody level of filarious host 1988; 30(1): 1-1.
[105]
Stolk WA, Van Oortmarssen GJ, De Vlas SJ, et al. Effects of ivermectin and diethylcarbamazine on microfilariae and overall microfilaria production in bancroftian filariasis. Am J Trop Med Hyg 2005; 73(5): 881-7.
[http://dx.doi.org/10.4269/ajtmh.2005.73.881] [PMID: 16282298]
[106]
Minqiang Du. A kind of Chinese medicine composition treating anal cryptitis CN106266699A, 2016.
[107]
Robert F., Etchegaray JP, Gerard W., Patrick L., Mazars RJ. Medicinal products and pure preparations of melarsomine dihydrochloride, process for obtaining them and intermediate products obtained US5770733A, 1995.
[108]
Wing KD. Anthelmintic N'-substituted-N,N'-disubstitutedhydrazines US5424333A, 1991.
[109]
Tsipouras A, Ostlind DA, Deborah Z. Novel fermentation product with antiparasitic activity. US5089530A, 1990.