Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Author(s): Sharif Alhassan Abdullahi, Ngah Zasmy Unyah, Noshariza Nordin, Rusliza Basir, Wana Mohammed Nasir, Ashraf Ahmad Alapid, Yahaya Hassan, Tijjani Mustapha and Roslaini Abd Majid*

DOI: 10.2174/1389557519666191029105736

DownloadDownload PDF Flyer Cite As
Phytochemicals and Potential Therapeutic Targets on Toxoplasma gondii Parasite

Page: [739 - 753] Pages: 15

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.

Keywords: Phytochemicals, drug target, parasite, T. gondii, toxoplasmosis, in vivo, in vitro.

Graphical Abstract

[1]
Blader, I.J.; Saeij, J.P. Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence. APMIS, 2009, 117(5-6), 458-476.
[http://dx.doi.org/10.1111/j.1600-0463.2009.02453.x] [PMID: 19400868]
[2]
Uttah, E.; Ogban, E.; Okonofua, C. Toxoplasmosis: A global infection, so widespread, so neglected. IJSRP, 2013, 3, 1-6.
[3]
Müller, J.; Hemphill, A. New approaches for the identification of drug targets in protozoan parasites. Int. Rev. Cell Mol. Biol., 2013, 301, 359-401.
[http://dx.doi.org/10.1016/B978-0-12-407704-1.00007-5] [PMID: 23317822]
[4]
Liu, Q.; Singla, L.D.; Zhou, H. Vaccines against Toxoplasma gondii: status, challenges and future directions. Hum. Vaccin. Immunother., 2012, 8(9), 1305-1308.
[http://dx.doi.org/10.4161/hv.21006] [PMID: 22906945]
[5]
Filisetti, D.; Candofi, E. Immune response to Toxoplasma gondii Ann 1st Super Sanita, 2004, 40(1), 71-80.
[6]
Nonaka, M.; Murata, Y.; Takano, R.; Han, Y.; Kabir, M.H.B.; Kato, K. Screening of a library of traditional Chinese medicines to identify anti-malarial compounds and extracts. Malar. J., 2018, 17(1), 244.
[http://dx.doi.org/10.1186/s12936-018-2392-4] [PMID: 29941026]
[7]
Gomes, TC; Andrade Júnior, HF; Lescano, SA; Amato-Neto, V In vitro action of anti-antiparasitic drugs, especially artesunate,against Toxoplasma gondii. Revista da so Sociedade Brasileira de Medicina Tropical, 2012, 45(4), 485-90.
[8]
de Oliveira, T.C.; Silva, D.A.; Rostkowska, C.; Béla, S.R.; Ferro, E.A.; Magalhães, P.M.; Mineo, J.R. Toxoplasma gondii: effects of Artemisia annua L. on susceptibility to infection in experimental models in vitro and in vivo. Exp. Parasitol., 2009, 122(3), 233-241.
[http://dx.doi.org/10.1016/j.exppara.2009.04.010] [PMID: 19389400]
[9]
Doliwa, C.; Xia, D.; Escotte-Binet, S.; Newsham, E.L.; Sanya J, S.; Aubert, D.; Randle, N.; Wastling, J.M.; Villena, I. Identification of differentially expressed proteins in sulfadiazine resistant and sensitive strains of Toxoplasma gondii using difference-gel electrophoresis (DIGE). Int. J. Parasitol. Drugs Drug Resist., 2013, 3, 35-44.
[http://dx.doi.org/10.1016/j.ijpddr.2012.12.002] [PMID: 24533291]
[10]
Antczak, M.; Dzitko, K.; Długońska, H. Human toxoplasmosis-Searching for novel chemotherapeutics. Biomed. Pharmacother., 2016, 82, 677-684.
[http://dx.doi.org/10.1016/j.biopha.2016.05.041] [PMID: 27470411]
[11]
Greif, G.; Harder, A.; Haberkorn, A. Chemotherapeutic approaches to protozoa: Coccidiae--current level of knowledge and outlook. Parasitol. Res., 2001, 87(11), 973-975.
[http://dx.doi.org/10.1007/s004360100402] [PMID: 11728025]
[12]
Alday, P.H.; Doggett, J.S. Drugs in development for toxoplasmosis: advances, challenges, and current status. Drug Des. Devel. Ther., 2017, 11, 273-293.
[http://dx.doi.org/10.2147/DDDT.S60973] [PMID: 28182168]
[13]
Aspinall, T.V.; Joynson, D.H.; Guy, E.; Hyde, J.E.; Sims, P.F. The molecular basis of sulfonamide resistance in Toxoplasma gondii and implications for the clinical management of toxoplasmosis. J. Infect. Dis., 2002, 185(11), 1637-1643.
[http://dx.doi.org/10.1086/340577] [PMID: 12023770]
[14]
Dannemann, B.; McCutchan, J.A.; Israelski, D.; Antoniskis, D.; Leport, C.; Luft, B.; Nussbaum, J.; Clumeck, N.; Morlat, P.; Chiu, J. The California Collaborative Treatment Group.Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. Ann. Intern. Med., 1992, 116(1), 33-43.
[http://dx.doi.org/10.7326/0003-4819-116-1-33] [PMID: 1727093]
[15]
Baatz, H.; Mirshahi, A.; Puchta, J.; Gümbel, H.; Hattenbach, L.O. Reactivation of toxoplasma retinochoroiditis under atovaquone therapy in an immunocompetent patient. Ocul. Immunol. Inflamm., 2006, 14(3), 185-187.
[http://dx.doi.org/10.1080/09273940600659740] [PMID: 16766403]
[16]
Boyom, F.F.; Fokou, P.V.; Tchokouaha, L.R.; Spangenberg, T.; Mfopa, A.N.; Kouipou, R.M.; Mbouna, C.J.; Donfack, V.F.; Zollo, P.H. Repurposing the open access malaria box to discover potent inhibitors of Toxoplasma gondii and Entamoeba histolytica. Antimicrob. Agents Chemother., 2014, 58(10), 5848-5854.
[http://dx.doi.org/10.1128/AAC.02541-14] [PMID: 25049259]
[17]
Bauri, R.K.; Tigga, M.N.; Kullu, S.S. A review on use of medicinal plants to control parasites. Indian J. Nat. Prod. Resources (IJNPR)[Formerly: Nat. Prod. Radiance (NPR)],, 2015, 6(4), 268-277.
[18]
Sepulveda-Arias, J.C.; Veloza, L.A.; Mantilla-Muriel, L.E. Anti-Toxoplasma activity of natural products: a review. Recent Pat Antiinfect Drug Discov, 2014, 9(3), 186-194.
[http://dx.doi.org/10.2174/1574891X10666150410120321] [PMID: 25858302]
[19]
Al Nasr, I.; Ahmed, F.; Pullishery, F.; El-Ashram, S.; Ramaiah, V.V. Toxoplasmosis and anti-Toxoplasma effects of medicinal plant extracts-A mini-review. Asian Pac. J. Trop. Med., 2016, 9(8), 730-734.
[http://dx.doi.org/10.1016/j.apjtm.2016.06.012] [PMID: 27569880]
[20]
Sharif, M.; Sarvi, S.; Pagheh, A.S.; Asfaram, S.; Rahimi, M.T.; Mehrzadi, S.; Ahmadpour, E.; Gholami, S.; Daryani, A. The efficacy of herbal medicines against Toxoplasma gondii during the last 3 decades: a systematic review. Can. J. Physiol. Pharmacol., 2016, 94(12), 1237-1248.
[http://dx.doi.org/10.1139/cjpp-2016-0039] [PMID: 27564395]
[21]
Pillai, S.; Mahmud, R.; Lee, W.C.; Perumal, S. Anti-parasitic activity of Myristica fragrans Houtt. Essential oil against Toxoplasma gondii parasite. APCBEE Procedia, 2012, 2, 92-96.
[http://dx.doi.org/10.1016/j.apcbee.2012.06.017]
[22]
Kavitha, N.; Noordin, R.; Chan, K-L.; Sasidharan, S. In vitro anti-Toxoplasma gondii activity of root extract/fractions of Eurycoma longifolia Jack. BMC Complement. Altern. Med., 2012, 12, 91.
[http://dx.doi.org/10.1186/1472-6882-12-91] [PMID: 22781137]
[23]
Yang, X.; Huang, B.; Chen, J.; Huang, S.; Zheng, H.; Lun, Z.R.; Shen, J.; Wang, Y.; Lu, F. In vitro effects of aqueous extracts of Astragalus membranaceus and Scutellaria baicalensis GEORGI on Toxoplasma gondii. Parasitol. Res., 2012, 110(6), 2221-2227.
[http://dx.doi.org/10.1007/s00436-011-2752-2] [PMID: 22179265]
[24]
Lee, W.C.; Mahmud, R.; Noordin, R.; Piaru, S.P.; Perumal, S.; Ismail, S. Alkaloids content, cytotoxicity and anti-Toxoplasma gondii activity of Psidium guajava L. and Tinospora crispa. Bangladesh J. Pharmacol., 2012, 7(4), 272-276.
[http://dx.doi.org/10.3329/bjp.v7i4.12499]
[25]
Choi, W.; Jiang, M.; Chu, J. Antiparasitic effects of Zingiber officinale (Ginger) extract against Toxoplasma gondii. J. Appl. Biomed., 2013, 11(1), 15-26.
[http://dx.doi.org/10.2478/v10136-012-0014-y]
[26]
Choi, K.M.; Gang, J.; Yun, J. Anti-Toxoplasma gondii RH strain activity of herbal extracts used in traditional medicine. Int. J. Antimicrob. Agents, 2008, 32(4), 360-362.
[http://dx.doi.org/10.1016/j.ijantimicag.2008.04.012] [PMID: 18619816]
[27]
Weiss, L.M.; Kim, K. The development and biology of bradyzoites of Toxoplasma gondii. Frontiers in bioscience. J. Virtual Lib., 2000, 5, 391.
[28]
Al-Zanbagi, N.A. In vivo effect of some home spices extracts on the toxoplasma gondii tachyzoites. J. Family Community Med., 2009, 16(2), 59-65.
[PMID: 23012192]
[29]
Leesombun, A.; Boonmasawai, S.; Nishikawa, Y. Effects of Thai piperaceae plant extracts on Neospora caninum infection. Parasitol. Int., 2017, 66(3), 219-226.
[http://dx.doi.org/10.1016/j.parint.2017.01.017] [PMID: 28137670]
[30]
Devanthran, K.; Unyah, Z.; Majid, R.A.; Abdullah, W.O. In vitro activity of Piper sarmentosum ethanol leaf extract against Toxoplasma gondii tachyzoites. Trop. J. Pharm. Res., 2017, 16(11), 2667-2673.
[http://dx.doi.org/10.4314/tjpr.v16i11.14]
[31]
Daryani, A.; Ebrahimzadeh, M.A.; Sharif, M.; Ahmadpour, E.; Edalatian, S.; Rahimi Esboei, B. Anti-Toxoplasma activities of methanolic extract of Sambucus nigra (Caprifoliaceae) fruits and leaves. Rev. Biol. Trop., 2015, 63(1), 7-12.
[http://dx.doi.org/10.15517/rbt.v63i1.14545] [PMID: 26299111]
[32]
Benoit-Vical, F.; Santillana-Hayat, M.; Kone-Bamba, D.; Mallie, M.; Derouin, F. Anti-Toxoplasma activity of vegetal extracts used in West African traditional medicine. Parasite, 2000, 7(1), 3-7.
[http://dx.doi.org/10.1051/parasite/2000071003] [PMID: 10743641]
[33]
Melo, E.J.T.; Vilela, K.J.; Carvalho, C.S. Effects of aqueous leaf extracts of Azadirachta indica A. Juss.(neem) and Melia azedarach L.(Santa Barbara or cinnamon) on the intracellular development of Toxoplasma gondii. Rev. Bras. Plantas Med., 2011, 13(2), 215-222.
[http://dx.doi.org/10.1590/S1516-05722011000200014]
[34]
De Pablos, L.M.; González, G.; Rodrigues, R.; García Granados, A.; Parra, A.; Osuna, A. Action of a pentacyclic triterpenoid, maslinic acid, against Toxoplasma gondii. J. Nat. Prod., 2010, 73(5), 831-834.
[http://dx.doi.org/10.1021/np900749b] [PMID: 20441162]
[35]
Dahbi, A.; Bellete, B.; Flori, P.; Hssaine, A.; Elhachimi, Y.; Raberin, H.; Chait, A.; Tran Manh Sung, R.; Hafid, J. The effect of essential oils from Thymus broussonetii Boiss on transmission of Toxoplasma gondii cysts in mice. Parasitol. Res., 2010, 107(1), 55-58.
[http://dx.doi.org/10.1007/s00436-010-1832-z] [PMID: 20336317]
[36]
Eraky, M.A.; El-Fakahany, A.F.; El-Sayed, N.M.; Abou-Ouf, E.A.R.; Yaseen, D.I. Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a mouse model. Parasitol. Res., 2016, 115(7), 2863-2871.
[http://dx.doi.org/10.1007/s00436-016-5041-2] [PMID: 27098159]
[37]
Mirzaalizadeh, B.; Sharif, M.; Daryani, A.; Ebrahimzadeh, M.A.; Zargari, M.; Sarvi, S.; Mehrzadi, S.; Rahimi, M.T.; Mirabediny, Z.; Golpour, M.; Montazeri, M. Effects of Aloe vera and Eucalyptus methanolic extracts on experimental toxoplasmosis in vitro and in vivo. Exp. Parasitol., 2018, 192, 6-11.
[http://dx.doi.org/10.1016/j.exppara.2018.07.010] [PMID: 30031121]
[38]
Gubbels, M.J.; Li, C.; Striepen, B. High-throughput growth assay for Toxoplasma gondii using yellow fluorescent protein. Antimicrob. Agents Chemother., 2003, 47(1), 309-316.
[http://dx.doi.org/10.1128/AAC.47.1.309-316.2003] [PMID: 12499207]
[39]
Jin, C.; Jung, S.Y.; Kim, S.Y.; Song, H.O.; Park, H. Simple and efficient model systems of screening anti-Toxoplasma drugs in vitro. Expert Opin. Drug Discov., 2012, 7(3), 195-205.
[http://dx.doi.org/10.1517/17460441.2012.660479] [PMID: 22468951]
[40]
Jin, C.; Kaewintajuk, K.; Jiang, J.; Jeong, W.; Kamata, M.; Kim, H.S.; Wataya, Y.; Park, H. Toxoplasma gondii: a simple high-throughput assay for drug screening in vitro. Exp. Parasitol., 2009, 121(2), 132-136.
[http://dx.doi.org/10.1016/j.exppara.2008.10.006] [PMID: 18977350]
[41]
Gautam, B.; Singh, G.; Wadhwa, G.; Farmer, R.; Singh, S.; Singh, A.K.; Jain, P.A.; Yadav, P.K. Metabolic pathway analysis and molecular docking analysis for identification of putative drug targets in Toxoplasma gondii: novel approach. Bioinformation, 2012, 8(3), 134-141.
[http://dx.doi.org/10.6026/97320630008134] [PMID: 22368385]
[42]
Reddy, P.J.; Rao, A.A.; Malhotra, D.; Sharma, S.; Kumar, R.; Jain, R. A simple protein extraction method for proteomic analysis of diverse biological specimens. Curr. Proteomics, 2013, 10, 298-311.
[http://dx.doi.org/10.2174/15701646113106660004]
[43]
Rahman, A.H.M.M.; Gulshana, M.I.A. Taxonomy and medicinal uses on amaranthaceae family of Rajshahi, Bangladesh. Appl. Ecol. Environ. Sci., 2014, 2(2), 54-59.
[http://dx.doi.org/10.12691/aees-2-2-3]
[44]
Anju, Dhiman Jugnu G, Kavita S, Arun N, Sandeep D. A review on medicinal prospective of Andrographis paniculata Nees. J. Pharmaceut. Scientif. Innovat., 2012, 1(1), 1-4.
[45]
Dua, V.K.; Ojha, V.P.; Roy, R.; Joshi, B.C.; Valecha, N.; Devi, C.U.; Bhatnagar, M.C.; Sharma, V.P.; Subbarao, S.K. Anti-malarial activity of some xanthones isolated from the roots of Andrographis paniculata. J. Ethnopharmacol., 2004, 95(2-3), 247-251.
[http://dx.doi.org/10.1016/j.jep.2004.07.008] [PMID: 15507344]
[46]
Chao, W.W.; Lin, B.F. Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chin. Med., 2010, 5(1), 17.
[http://dx.doi.org/10.1186/1749-8546-5-17] [PMID: 20465823]
[47]
Mistry, K.N.; Joshi, B.B.; Patel, C.Y. Evaluation of phytochemicals accountable for antimicrobial activity of Andrographis paniculata and Tinospora cordifoli extracts. World J. Pharm. Pharm. Sci., 2016, 5(8), 838-847.
[48]
Najib Nik A Rahman, N.; Furuta, T.; Kojima, S.; Takane, K.; Ali Mohd, M. Antimalarial activity of extracts of Malaysian medicinal plants. J. Ethnopharmacol., 1999, 64(3), 249-254.
[http://dx.doi.org/10.1016/S0378-8741(98)00135-4] [PMID: 10363840]
[49]
Zheng, K.; Li, C.; Shan, X.; Liu, H.; Fan, W.; Wang, Z. A study on isolation of chemical constituents from Sophora flavescens Ait. and their anti-glioma effects. Afr. J. Tradit. Complement. Altern. Med., 2013, 11(1), 156-160.
[http://dx.doi.org/10.4314/ajtcam.v11i1.24] [PMID: 24653570]
[50]
Krishna, P.M. KNV, R. and Banji, D. A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae. Rev. Bras. Farmacogn., 2012, 22(5), 1145-1154.
[http://dx.doi.org/10.1590/S0102-695X2012005000043]
[51]
Youn, H.J.; Lakritz, J.; Rottinghaus, G.E.; Seo, H.S.; Kim, D.Y.; Cho, M.H.; Marsh, A.E. Anti-protozoal efficacy of high performance liquid chromatography fractions of Torilis japonica and Sophora flavescens extracts on Neospora caninum and Toxoplasma gondii. Vet. Parasitol., 2004, 125(3-4), 409-414.
[http://dx.doi.org/10.1016/j.vetpar.2004.08.002] [PMID: 15482896]
[52]
Zhang, X.; Jin, L.; Cui, Z.; Zhang, C.; Wu, X.; Park, H.; Quan, H.; Jin, C. Antiparasitic effects of oxymatrine and matrine against Toxoplasma gondii in vitro and in vivo. Exp. Parasitol., 2016, 165, 95-102.
[http://dx.doi.org/10.1016/j.exppara.2016.03.020] [PMID: 26993085]
[53]
Bhargava, S.; Dhabhai, K.; Batra, A.; Sharma, A.; Malhotra, B. Zingiber officinale: Chemical and phytochemical screening and evaluation of its antimicrobial activities. J. Chem. Pharm. Res., 2012, 4(1), 360-364.
[54]
Riaz, H.; Begum, A.; Raza, S.A.; Khan, Z.M.U.D.; Yousaf, H.; Tariq, A. Antimicrobial property and phytochemical study of ginger found in local area of Punjab, Pakistan. Int. Curr. Pharm. J., 2015, 4(7), 405-409.
[http://dx.doi.org/10.3329/icpj.v4i7.23591]
[55]
Iqbal, H. Comparative efficacy of Aloe vera and Tamarix aphylla against cutaneous leishmaniasis. Int. J. Basic Med. Sci. Pharm.,, 2012, 2(2)
[56]
Bhat, R.; Karim, A.A. Tongkat Ali (Eurycoma longifolia Jack): a review on its ethnobotany and pharmacological importance. Fitoterapia, 2010, 81(7), 669-679.
[http://dx.doi.org/10.1016/j.fitote.2010.04.006] [PMID: 20434529]
[57]
Khanam, Z.; Wen, C.S.; Bhat, I.U.H. Phytochemical screening and antimicrobial activity of root and stem extracts of wild Eurycoma longifolia Jack (Tongkat Ali). J. King Saud Univ.-. Sci., 2015, 27(1), 23-30.
[http://dx.doi.org/10.1016/j.jksus.2014.04.006]
[58]
Chan, K.L.; Choo, C.Y.; Abdullah, N.R.; Ismail, Z. Antiplasmodial studies of Eurycoma longifolia Jack using the lactate dehydrogenase assay of Plasmodium falciparum. J. Ethnopharmacol., 2004, 92(2-3), 223-227.
[http://dx.doi.org/10.1016/j.jep.2004.02.025] [PMID: 15138004]
[59]
Joseph, B.; Priya, M. Review on nutritional, medicinal and pharmacological properties of guava (Psidium guajava Linn.). Int. J. Pharma Bio Sci., 2011, 2(1), 53-69.
[60]
Obaineh, O.M.; Shadrach, A. Phytochemical constituents and medicinal properties of different extracts of Anacardium occidentale and Psidium guajava. Asian J. Biomed. Pharmaceut. Sci., 2013, 3(16), 20.
[61]
Morais-Braga, M.F.B.; Carneiro, J.N.P.; Machado, A.J.T.; Dos Santos, A.T.L.; Sales, D.L.; Lima, L.F.; Figueredo, F.G.; Coutinho, H.D. Psidium guajava L., from ethnobiology to scientific evaluation: Elucidating bioactivity against pathogenic microorganisms. J. Ethnopharmacol., 2016, 194, 1140-1152.
[http://dx.doi.org/10.1016/j.jep.2016.11.017] [PMID: 27845266]
[62]
Adeyemi, O.S.; Sykes, M.L.; Akanji, M.A.; Avery, V.M. Anti-trypanosomal and cytotoxic activity of ethanolic extracts of Psidium guajava leaves in Alamar Blue based assays. Vet. Arh., 2011, 81(5), 623-633.
[63]
Kaushik, N.K.; Bagavan, A.; Rahuman, A.A.; Zahir, A.A.; Kamaraj, C.; Elango, G.; Jayaseelan, C.; Kirthi, A.V.; Santhoshkumar, T.; Marimuthu, S.; Rajakumar, G.; Tiwari, S.K.; Sahal, D. Evaluation of antiplasmodial activity of medicinal plants from North Indian Buchpora and South Indian Eastern Ghats. Malar. J., 2015, 14(1), 65.
[http://dx.doi.org/10.1186/s12936-015-0564-z] [PMID: 25879738]
[64]
Lee, W.C.; Mahmud, R.; Noordin, R.; Pillai Piaru, S.; Perumal, S.; Ismail, S. Free radicals scavenging activity, cytotoxicity and anti-parasitic activity of essential oil of Psidium guajava L. leaves against Toxoplasma gondii J. Essent. Oil Bear. Plants, 2013, 16, 32-38.
[65]
Abood, W.N.; Fahmi, I.; Abdulla, M.A.; Ismail, S. Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8. BMC Complement. Altern. Med., 2014, 14(1), 205.
[http://dx.doi.org/10.1186/1472-6882-14-205] [PMID: 24969238]
[66]
Amom, Z.; Bahari, H.; Isemaail, S.; Ismail, N.A.; Shah, Z.M.; Arsyad, M.S. Nutritional composition, antioxidant ability and flavonoid content of Tinospora crispa stem. Adv. Nat. Appl. Sci., 2009, 3(1), 88-95.
[67]
Ahmad, W.; Jantan, I.; Bukhari, S.N. Tinospora crispa (L.) Hook. f. & Thomson: A review of its ethnobotanical, phytochemical, and pharmacological aspects. Front. Pharmacol., 2016, 7, 59.
[http://dx.doi.org/10.3389/fphar.2016.00059] [PMID: 27047378]
[68]
Niljan, J.; Jaihan, U.; Srichairatanakool, S.; Uthaipibull, C.; Somsak, V. Antimalarial activity of stem extract of Tinospora crispa against plasmodium berghei infection in mice. J. Health Res., 2014, 28(3), 199-204.
[69]
Rungruang, T.; Boonmars, T. In vivo antiparasitic activity of the Thai traditional medicine plant--Tinospora crispa--against Plasmodium yoelii. Southeast Asian J. Trop. Med. Public Health, 2009, 40(5), 898-900.
[PMID: 19842370]
[70]
Zirihi, G.N.; Mambu, L.; Guédé-Guina, F.; Bodo, B.; Grellier, P. In vitro antiplasmodial activity and cytotoxicity of 33 West African plants used for treatment of malaria. J. Ethnopharmacol., 2005, 98(3), 281-285.
[http://dx.doi.org/10.1016/j.jep.2005.01.004] [PMID: 15814260]
[71]
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(1), 79-84.
[http://dx.doi.org/10.1016/S0378-8741(01)00286-0] [PMID: 11585692]
[72]
Elford, B.C. L-Glutamine influx in malaria-infected erythrocytes:A target for antimalarials? Parasitol. Today (Regul. Ed.),, 1986, (11), 309-312.
[http://dx.doi.org/10.1016/0169-4758(86)90126-2] [PMID: 15462745]
[73]
Abdullahi, S.A.; Abd Majid, R.; Unyah, N.Z.; Nordin, N.; Basir, R.; Wana, M.N.; Alapid, A.A.; Yahaya, H.; Mustapha, T. In vitro anti-toxoplasmal activities of ethanolic extracts from Andrographis paniculata and Tinospora crispa against Toxoplasma gondii parasite. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM ‘18) “Seizing Opportunities and Addressing Challenges of Precision Medicine’, 2019.
[http://dx.doi.org/10.3389/conf.fphar.2018.63.00046]
[74]
Hossain, M.A.; Al-Toubi, W.A.; Weli, A.M.; Al-Riyami, Q.A.; Al-Sabahi, J.N. Identification and characterization of chemical compounds in different crude extracts from leaves of Omani neem. J. Taibah Univ. Sci., 2013, 7(4), 181-188.
[http://dx.doi.org/10.1016/j.jtusci.2013.05.003]
[75]
Quelemes, P.V.; Perfeito, M.L.; Guimarães, M.A.; dos Santos, R.C.; Lima, D.F.; Nascimento, C.; Silva, M.P.; Soares, M.J.; Ropke, C.D.; Eaton, P.; de Moraes, J.; Leite, J.R. Effect of neem (Azadirachta indica A. Juss) leaf extract on resistant Staphylococcus aureus biofilm formation and Schistosoma mansoni worms. J. Ethnopharmacol., 2015, 175, 287-294.
[http://dx.doi.org/10.1016/j.jep.2015.09.026] [PMID: 26408045]
[76]
Al-Jadidi, H.S.; Hossain, M.A. Studies on total phenolics, total flavonoids and antimicrobial activity from the leaves crude extracts of neem traditionally used for the treatment of cough and nausea. Beni-Suef Univ. J. Basic Appl. Sci., 2015, 4(2), 93-98.
[http://dx.doi.org/10.1016/j.bjbas.2015.05.001]
[77]
Bedri, S.; Khalil, E.A.; Khalid, S.A.; Alzohairy, M.A.; Mohieldein, A.; Aldebasi, Y.H.; Seke Etet, P.F.; Farahna, M. Azadirachta indica ethanolic extract protects neurons from apoptosis and mitigates brain swelling in experimental cerebral malaria. Malar. J., 2013, 12(1), 298.
[http://dx.doi.org/10.1186/1475-2875-12-298] [PMID: 23984986]
[78]
Belaqziz, R.; Harrak, R.; Romane, A.; Oufdou, K.; ElFels, M.A. antimicrobial and insecticidal activities of the endemic thymus broussonetti Boiss. and Thymus maroccanus ball. Rec. Nat. Prod., 2010, 4(4), 230-237.
[79]
Boubaker, H.; Karim, H.; El Hamdaoui, A.; Msanda, F.; Leach, D.; Bombarda, I. Chemical characterization and antifungal activities of four Thymus species essential oils against postharvest fungal pathogens of citrus. Ind. Crops Prod., 2016, 86, 95-101.
[http://dx.doi.org/10.1016/j.indcrop.2016.03.036]
[80]
Fadli, M.; Saad, A.; Sayadi, S.; Chevalier, J.; Mezrioui, N.E.; Pagès, J.M.; Hassani, L. Antibacterial activity of Thymus maroccanus and Thymus broussonetii essential oils against nosocomial infection - bacteria and their synergistic potential with antibiotics. Phytomedicine, 2012, 19(5), 464-471.
[http://dx.doi.org/10.1016/j.phymed.2011.12.003] [PMID: 22257599]
[81]
Sayout, A.; Bahi, F.; Ouknin, M.; Arjouni, Y.; Majidi, L.; Romane, A. Phytochemical screening and antioxidant activity of four Moroccan Thymus species: T. leptobotrys Murb., T. pallidus Batt., T. broussonetti Boiss. and T. maroccanus Ball. Arab. J. Med. Aromat. Plants, 2015, 1(2), 117-128.
[82]
Dahbi, A.; Bellete, B.; Flori, P.; Hssaine, A.; Elhachimi, Y.; Raberin, H.; Chait, A.; Tran Manh Sung, R.; Hafid, J. The effect of essential oils from Thymus broussonetii Boiss on transmission of Toxoplasma gondii cysts in mice. Parasitol. Res., 2010, 107(1), 55-58.
[http://dx.doi.org/10.1007/s00436-010-1832-z] [PMID: 20336317]
[83]
Dwivedi, V.; Tripathi, S. Review study on potential activity of Piper betle. J. Pharmacogn. Phytochem., 2014, 3(4), 93-98.
[84]
Al-Adhroey, A.H.; Nor, Z.M.; Al-Mekhlafi, H.M.; Amran, A.A.; Mahmud, R. Antimalarial activity of methanolic leaf extract of Piper betle L. Molecules, 2010, 16(1), 107-118.
[http://dx.doi.org/10.3390/molecules16010107] [PMID: 21189459]
[85]
Misra, P.; Kumar, A.; Khare, P.; Gupta, S.; Kumar, N.; Dube, A. Pro-apoptotic effect of the landrace Bangla Mahoba of Piper betle on Leishmania donovani may be due to the high content of eugenol. J. Med. Microbiol., 2009, 58(Pt 8), 1058-1066.
[http://dx.doi.org/10.1099/jmm.0.009290-0] [PMID: 19528177]
[86]
Mohd Zainudin, M.; Zakaria, Z.; Megat Mohd Nordin, N.A. The use of Piper sarmentosum leaves aqueous extract (Kadukmy™) as antihypertensive agent in spontaneous hypertensive rats. BMC Complement. Altern. Med., 2015, 15(1), 54.
[http://dx.doi.org/10.1186/s12906-015-0565-z] [PMID: 25887182]
[87]
Rukachaisirikul, T.; Siriwattanakit, P.; Sukcharoenphol, K.; Wongvein, C.; Ruttanaweang, P.; Wongwattanavuch, P.; Suksamrarn, A. Chemical constituents and bioactivity of Piper sarmentosum. J. Ethnopharmacol., 2004, 93(2-3), 173-176.
[http://dx.doi.org/10.1016/j.jep.2004.01.022] [PMID: 15234750]
[88]
Mohamad, S.; Zin, N.M.; Wahab, H.A.; Ibrahim, P.; Sulaiman, S.F.; Zahariluddin, A.S.M.; Noor, S.S.M. Antituberculosis potential of some ethnobotanically selected Malaysian plants. J. Ethnopharmacol., 2011, 133(3), 1021-1026.
[http://dx.doi.org/10.1016/j.jep.2010.11.037] [PMID: 21094237]
[89]
Samaha, H.A.M.; Ali, N.A.A.; Mansi, I.; Abu-El-Halawa, R. Antimicrobial, antiradical and xanthine oxidase inhibitory activities of Juniperus procera plant extracts from Albaha. World J. Pharm. Pharm. Sci., 2017, 6(2), 232-242.
[90]
Kayser, O.; Kiderlen, A.F.; Croft, S.L. Natural products as antiparasitic drugs. Parasitol. Res., 2003, 90(2)(Suppl. 2), S55-S62.
[http://dx.doi.org/10.1007/s00436-002-0768-3] [PMID: 12937967]
[91]
Kim, J.T.; Park, J.Y.; Seo, H.S.; Oh, H.G.; Noh, J.W.; Kim, J.H.; Kim, D.Y.; Youn, H.J. In vitro antiprotozoal effects of artemisinin on Neospora caninum. Vet. Parasitol., 2002, 103(1-2), 53-63.
[http://dx.doi.org/10.1016/S0304-4017(01)00580-5] [PMID: 11751000]
[92]
Lans, C.; Turner, N.; Khan, T.; Brauer, G. Ethnoveterinary medicines used to treat endoparasites and stomach problems in pigs and pets in British Columbia, Canada. Vet. Parasitol., 2007, 148(3-4), 325-340.
[http://dx.doi.org/10.1016/j.vetpar.2007.06.014] [PMID: 17628343]
[93]
Ferreira, J.F.; Luthria, D.L.; Sasaki, T.; Heyerick, A. Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules, 2010, 15(5), 3135-3170.
[http://dx.doi.org/10.3390/molecules15053135] [PMID: 20657468]
[94]
Squires, J.M.; Ferreira, J.F.; Lindsay, D.S.; Zajac, A.M. Effects of artemisinin and Artemisia extracts on Haemonchus contortus in gerbils (Meriones unguiculatus). Vet. Parasitol., 2011, 175(1-2), 103-108.
[http://dx.doi.org/10.1016/j.vetpar.2010.09.011] [PMID: 20943323]
[95]
Bamunuarachchi, G.S.; Ratnasooriya, W.D.; Premakumara, S.; Udagama, P.V. Antimalarial properties of Artemisia vulgaris L. ethanolic leaf extract in a Plasmodium berghei murine malaria model. J. Vector Borne Dis., 2013, 50(4), 278-284.
[PMID: 24499850]
[96]
Islamuddin, M.; Chouhan, G.; Tyagi, M.; Abdin, M.Z.; Sahal, D.; Afrin, F.; Afrin, F. Leishmanicidal activities of Artemisia annua leaf essential oil against Visceral Leishmaniasis. Front. Microbiol., 2014, 5, 626.
[http://dx.doi.org/10.3389/fmicb.2014.00626] [PMID: 25505453]
[97]
Okeke, C.U.; Ezeabara, C.A.; Okoronkwo, O.F.; Udechukwu, C.D.; Uka, C.J.; Aziagba, B.O. Determination of nutritional and phytochemical compositions of two variants of a bitter leaf (Vernonia amygdalina Del). J. Human Nutrit. Food Sci., 2015, 3(3), 1065.
[98]
Udochukwu, U.; Omeje, F.I.; Uloma, I.S.; Oseiwe, F.D. Phytochemical analysis of Vernonia amygdalina and Ocimum gratissimum extracts and their antibacterial activity on some drug resistant bacteria. Am. J. Res. Communicat., 2015, 3(5), 225-235.
[99]
Hashmi, M.A.; Khan, A.; Hanif, M.; Farooq, U.; Perveen, S. Traditional uses, phytochemistry, and pharmacology of Olea europaea (olive). Evid. Based Complement. Alternat. Med., 2015.
[100]
Kar, S.K.; Bera, T.K. Phytochemical constituents of aloe vera and their multifunctional properties: A comprehensive review. Int. J. Pharm. Sci. Res., 2018, 9(4), 1416-1423.
[101]
Arunkumar, S.; Muthuselvam, M. Analysis of phytochemical constituents and antimicrobial activities of Aloe vera L. against clinical pathogens. World J. Agric. Sci., 2009, 5(5), 572-576.
[102]
Wintola, O.A.; Afolayan, A.J. Phytochemical constituents and antioxidant activities of the whole leaf extract of Aloe ferox Mill. Pharmacogn. Mag., 2011, 7(28), 325-333.
[http://dx.doi.org/10.4103/0973-1296.90414] [PMID: 22262936]
[103]
Benzidia, B; Barbouchi, M; Hammouch, H; Belahbib, N; Zouarhi, M; Erramli, H Chemical composition and antioxidant activity of tannins extract from green rind of Aloe vera (L.) Burm. F. J. King Saud Univ. Sci., 2018.
[104]
Matsuura, H.N.; Fett-Neto, A.G. Plant alkaloids: Main features,toxicity, and mechanisms of action 2017.
[http://dx.doi.org/10.1007/978-94-007-6464-4_2]
[105]
Wirasathien, L.; Boonarkart, C.; Pengsuparp, T.; Suttisri, R. Biological Activities of Alkaloids from Pseuduvaria setosa. Pharm. Biol., 2006, 44(4), 274-278.
[http://dx.doi.org/10.1080/13880200600714111]
[106]
Vennerstrom, J.L.; Lovelace, J.K.; Waits, V.B.; Hanson, W.L.; Klayman, D.L. Berberine derivatives as antileishmanial drugs. Antimicrob. Agents Chemother., 1990, 34(5), 918-921.
[http://dx.doi.org/10.1128/AAC.34.5.918] [PMID: 2360830]
[107]
Lala, S.; Pramanick, S.; Mukhopadhyay, S.; Bandyopadhyay, S.; Basu, M.K. Harmine: evaluation of its antileishmanial properties in various vesicular delivery systems. J. Drug Target., 2004, 12(3), 165-175.
[http://dx.doi.org/10.1080/10611860410001712696] [PMID: 15203896]
[108]
Fournet, A.; Barrios, A.A.; Muñoz, V.; Hocquemiller, R.; Cavé, A. Effect of some bisbenzylisoquinoline alkaloids on American Leishmania sp. in BALB/c mice. Phytother. Res., 1993, 7(4), 281-284.
[http://dx.doi.org/10.1002/ptr.2650070404]
[109]
Rivas, P.; Cassels, B.K.; Morello, A.; Repetto, Y. Effects of some β-carboline alkaloids on intact Trypanosoma cruzi epimastigotes. Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol., 1999, 122(1), 27-31.
[http://dx.doi.org/10.1016/S0742-8413(98)10069-5] [PMID: 10190025]
[110]
Ferreira, R.A.; de Oliveira, A.B.; Gualberto, S.A.; Miguel Del Corral, J.M.; Fujiwara, R.T.; Gazzinelli Guimarães, P.H.; de Almeida Vitor, R.W. New naphthoquinones and an alkaloid with in vitro activity against Toxoplasma gondii RH and EGS strains. Exp. Parasitol., 2012, 132(4), 450-457.
[http://dx.doi.org/10.1016/j.exppara.2012.09.003] [PMID: 23000485]
[111]
Alomar, M.L.; Rasse-Suriani, F.A.; Ganuza, A.; Cóceres, V.M.; Cabrerizo, F.M.; Angel, S.O. In vitro evaluation of β-carboline alkaloids as potential anti-Toxoplasma agents. BMC Res. Notes, 2013, 6(1), 193.
[http://dx.doi.org/10.1186/1756-0500-6-193] [PMID: 23663567]
[112]
Cushnie, T.P.; Cushnie, B.; Lamb, A.J. Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities. Int. J. Antimicrob. Agents, 2014, 44(5), 377-386.
[http://dx.doi.org/10.1016/j.ijantimicag.2014.06.001] [PMID: 25130096]
[113]
Wink, M.; Roberts, M.F. Compartmentation of alkaloid synthesis, transport, and storage. Alkaloids; Springer: Boston, MA, 1998, pp. 239-262.
[http://dx.doi.org/10.1007/978-1-4757-2905-4_10]
[114]
Wink, M. Medicinal plants: a source of anti-parasitic secondary metabolites. Molecules, 2012, 17(11), 12771-12791.
[http://dx.doi.org/10.3390/molecules171112771] [PMID: 23114614]
[115]
Ralph, S.A.; D’Ombrain, M.C.; McFadden, G.I. The apicoplast as an antimalarial drug target. Drug Resist. Updat., 2001, 4(3), 145-151.
[http://dx.doi.org/10.1054/drup.2001.0205] [PMID: 11768328]
[116]
Samoylenko, V.; Ashfaq, M.K.; Jacob, M.R.; Tekwani, B.L.; Khan, S.I.; Manly, S.P. Indolizidine, antiinfective and antiparasitic compounds from Prosopis glandulosa Torr. Var. glandulosa. Planta Med., 2009, 75(04), 48.
[http://dx.doi.org/10.1055/s-2009-1216486]
[117]
Wei, F.; Wang, W.; Liu, Q. Protein kinases of Toxoplasma gondii: functions and drug targets. Parasitol. Res., 2013, 112(6), 2121-2129.
[http://dx.doi.org/10.1007/s00436-013-3451-y] [PMID: 23681193]
[118]
Li, Y.; Liang, F.; Jiang, W.; Yu, F.; Cao, R.; Ma, Q.; Dai, X.; Jiang, J.; Wang, Y.; Si, S. DH334, a β-carboline anti-cancer drug, inhibits the CDK activity of budding yeast. Cancer Biol. Ther., 2007, 6(8), 1193-1199.
[http://dx.doi.org/10.4161/cbt.6.8.4382] [PMID: 17622795]
[119]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: an overview. Scientif. World J.,, 2013, 2013162750
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[120]
Kitdamrongtham, W.; Ishii, K.; Ebina, K.; Zhang, J.; Ukiya, M.; Koike, K.; Akazawa, H.; Manosroi, A.; Manosroi, J.; Akihisa, T. Limonoids and flavonoids from the flowers of Azadirachta indica var. siamensis, and their melanogenesis-inhibitory and cytotoxic activities. Chem. Biodivers., 2014, 11(1), 73-84.
[http://dx.doi.org/10.1002/cbdv.201300266] [PMID: 24443427]
[121]
Kerboeuf, D.; Riou, M.; Guégnard, F. Flavonoids and related compounds in parasitic disease control. Mini Rev. Med. Chem., 2008, 8(2), 116-128.
[http://dx.doi.org/10.2174/138955708783498168] [PMID: 18289094]
[122]
Dobbin, C.A.; Smith, N.C.; Johnson, A.M. Heat shock protein 70 is a potential virulence factor in murine toxoplasma infection via immunomodulation of host NF-κ B and nitric oxide. J. Immunol., 2002, 169(2), 958-965.
[http://dx.doi.org/10.4049/jimmunol.169.2.958] [PMID: 12097402]
[123]
Mead, J.; McNair, N. Antiparasitic activity of flavonoids and isoflavones against Cryptosporidium parvum and Encephalitozoon intestinalis. FEMS Microbiol. Lett., 2006, 259(1), 153-157.
[http://dx.doi.org/10.1111/j.1574-6968.2006.00263.x] [PMID: 16684116]
[124]
MacLaren, A.; Attias, M.; de Souza, W. Aspects of the early moments of interaction between tachyzoites of Toxoplasma gondii with neutrophils. Vet. Parasitol., 2004, 125(3-4), 301-312.
[http://dx.doi.org/10.1016/j.vetpar.2004.07.006] [PMID: 15482886]
[125]
Kato, K.; Sugi, T.; Iwanaga, T. Roles of Apicomplexan protein kinases at each life cycle stage. Parasitol. Int., 2012, 61(2), 224-234.
[http://dx.doi.org/10.1016/j.parint.2011.12.002] [PMID: 22209882]
[126]
Tasdemir, D.; Brun, R.; Perozzo, R.; Dönmez, A.A. Evaluation of antiprotozoal and plasmodial enoyl-ACP reductase inhibition potential of turkish medicinal plants. Phytother. Res., 2005, 19(2), 162-166.
[http://dx.doi.org/10.1002/ptr.1648] [PMID: 15852483]
[127]
Mazumdar, J.; H Wilson, E.; Masek, K.; A Hunter, C.; Striepen, B. Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii. Proc. Natl. Acad. Sci. USA, 2006, 103(35), 13192-13197.
[http://dx.doi.org/10.1073/pnas.0603391103] [PMID: 16920791]
[128]
Tasdemir, D.; Kaiser, M.; Brun, R.; Yardley, V.; Schmidt, T.J.; Tosun, F.; Rüedi, P. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob. Agents Chemother., 2006, 50(4), 1352-1364.
[http://dx.doi.org/10.1128/AAC.50.4.1352-1364.2006] [PMID: 16569852]
[129]
Elmadfa, I.; Wagner, K.H. Non-nutritive bioactive food constituents of plants: tocopherols (vitamin E). Int. J. Vitam. Nutr. Res., 2003, 73(2), 89-94.
[http://dx.doi.org/10.1024/0300-9831.73.2.89] [PMID: 12747215]
[130]
Paduch, R.; Kandefer-Szerszeń, M.; Trytek, M.; Fiedurek, J. Terpenes: substances useful in human healthcare. Arch. Immunol. Ther. Exp. (Warsz.), 2007, 55(5), 315-327.
[http://dx.doi.org/10.1007/s00005-007-0039-1] [PMID: 18219762]
[131]
Popova, M.P.; Chinou, I.B.; Marekov, I.N.; Bankova, V.S. Terpenes with antimicrobial activity from Cretan propolis. Phytochemistry, 2009, 70(10), 1262-1271.
[http://dx.doi.org/10.1016/j.phytochem.2009.07.025] [PMID: 19698962]
[132]
Sülsen, V. P.; Lizarraga, E.; Mamadalieva, N. Z.; Lago, J. H. G. Potential of terpenoids and flavonoids from asteraceae as Anti-inflammatory, antitumor, and antiparasitic agents. Evid.-Based Complement. Alternat. Med., , 2017, 2017
[133]
Gershenzon, J.; Dudareva, N. The function of terpene natural products in the natural world. Nat. Chem. Biol., 2007, 3(7), 408-414.
[http://dx.doi.org/10.1038/nchembio.2007.5] [PMID: 17576428]
[134]
Luo, S.; Ruiz, F.A.; Moreno, S.N. The acidocalcisome Ca2+-ATPase (TgA1) of Toxoplasma gondii is required for polyphosphate storage, intracellular calcium homeostasis and virulence. Mol. Microbiol., 2005, 55(4), 1034-1045.
[http://dx.doi.org/10.1111/j.1365-2958.2004.04464.x] [PMID: 15686552]
[135]
Williams, A.R.; Fryganas, C.; Ramsay, A.; Mueller-Harvey, I.; Thamsborg, S.M. Direct anthelmintic effects of condensed tannins from diverse plant sources against Ascaris suum. PLoS One, 2014, 9(5)e97053
[http://dx.doi.org/10.1371/journal.pone.0097053] [PMID: 24810761]
[136]
Min, B.R.; Hart, S.P. Tannins for suppression of internal parasites. J. Anim. Sci., 2003, 81(14)(Suppl. 2), 102-109.
[137]
Macáková, K.; Kolečkář, V.; Cahlíková, L.; Chlebek, J.; Hošt’álková, A.; Kuča, K. Tannins and their influence on health. In: Recent Adv; Med. Chem, 2015; pp. 159-208.