Activity of several kinds of drugs against Toxoplasma gondii
QIAN Wei-feng1,2, SHAN Dan2, HAO Pan2, LIU Jing2, LIU Qun2
1. College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471003,China; 2. College of Veterinary Medicine, China Agricultural University, Beijing 100193,China
Abstract：In order to screen the effective anti-toxoplasmosis drugs, HFF cells and Toxoplasma gondii RH strain expressing green fluorescent protein (Tg-GFP) were used as evaluation system. Traditional Chinese medicines (curcumin and artemether), herbicides (atrazine), other anti-parasitic drugs (toltrazuril, ponazuril, diminazene aceturate and praziquantel) and anti-cancer drugs (cyclophosphamide) were selected and preliminarily evaluated for anti-T. gondii activity in vitro. The effect of curcumin against T. gondii in vivo was also tested by the treatment of acute T. gondii infection in mice. The results showed that curcumin, artemether, toltrazuril and ponazuril were active against T. gondii replication (P<0.05), and curcumin was also effective against host cell invasion (P<0.05). Atrazine was also active against T. gondii proliferation, but there is no significant difference (P>0.05). Curcumin, artemether, toltrazuril, ponazuril and atrazine exhibited inhibitory activity with 50% growth inhibitory concentration (IC50) of (0.7+0.2)μg/mL, (0.86+0.2)μg/mL, (14.2+2.8)μg/mL, (16.7+4.0)μg/mL, (59.4+4.1)μg/mL, respectively. In the growth inhibition assay, T. gondii growth was inhibited by these 5 drugs directly, not through indirect effects on HFF cells. Diminazene aceturate, praziquantel and cyclophosphamide did not inhibit the proliferation or invasion of T. gondii at the maximum safe concentrations (0.2 g/mL, 100 g/mL, and 50 g/mL). Curcumin did not prolong the survival time of mice with acute toxoplasmosis at the concentration of 50~150 mg/kg body weight. In conclusion, curcumin, artemether, toltrazuril and ponazuril were shown in anti-T. gondii activity in vitro, providing important information for further studies on anti- T. gondii drugs.
钱伟锋, 山丹, 郝攀, 刘晶, 刘群. 几种药物抗弓形虫活性的检测[J]. 中国人兽共患病学报, 2020, 36(11): 907-912.
QIAN Wei-feng, SHAN Dan, HAO Pan, LIU Jing, LIU Qun. Activity of several kinds of drugs against Toxoplasma gondii. Chinese Journal of Zoonoses, 2020, 36(11): 907-912.
[1] Dubey JP.Toxoplasmosis of animals and humans [M]. Second ed. Boca Raton, FL: CRC Press, 2010:73-174. [2] Mccabe, RE. Antitoxoplasma chemotherapy. Toxoplasmosis: a comprehensive clinical guide[M]. United Kingdom, Cambridge: Cambridge University Press, 2005:319-359. [3] Ribeiro M, Franco PS, Lopes-Maria JB, et al.Azithromycin treatment is able to control the infection by two genotypes of Toxoplasma gondii in human trophoblast BeWo cells[J]. Exp Parasitol, 2017, 181:111-118. DOI: 10.1016/j.exppara.2017.08.004 [4] Adeyemi OS, Atolani O, Awakan OJ, et al.In vitro screening to identify Anti-Toxoplasma compounds and in silico modeling for bioactivities and toxicity[J]. Yale J Biol Med,2019, 92(3): 369-383. [5] Nagamune K, Hicks LM, Fux B, et al.Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii[J]. Nature, 2008, 451:207-210. DOI: 10.1038/nature06478 [6] Zuther E, Johnson JJ, Haselkorn R, et al.Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase[J]. Proc Natl Acad Sci, 1999, 96: 13387-13392. DOI: 10.1073/pnas.96.23.13387 [7] D’angelo JG, Bordon C, Posner GH, et al.Artemisinin derivatives inhibit Toxoplasma gondii in vitro at multiple steps in the lytic cycle[J]. J Antimicrob Chemother, 2009, 63:146-150. DOI: 10.1093/jac/dkn451 [8] Saito H, Murata Y, Nonaka M, et al.Screening of a library of traditional Chinese medicines to identify compounds and extracts which inhibit Toxoplasma gondii growth[J]. J Vet Med Sci, 2020,82(2):184-187. DOI: 10.1292/jvms.19-0241. DOI10.1292/jvms.19-0241 [9] Estes R, Vogel N, Mack D, et al.Paclitaxel arrests growth of intracellular Toxoplasma gondii[J]. Antimicrob Agents chemother, 1998,42:2036-2040. DOI: 10.1128/AAC.42.8.2036 [10] Marc-Jan G, Catherine L, Boris S.High-throughput Growth Assay for Toxoplasma gondii using yellow fluorescent protein[J]. Antimicrob Agents Chemother, 2003, 47(1), 309-316. DOI: 10.1128/aac.47.1.309-316.2003 [11] Qian W, Wang H, Shan D, et al.Activity of several kinds of drugs against Neospora caninum[J]. Parasitol Int, 2015, 64(6): 597-602. DOI: 10.1016/j.parint.2015.08.002 [12] Fouladvand M, Barazesh A, Tahmaseb I.Evaluation of in vitro antileishmanial a ctivity of curcumin and its derivatives “gallium curcumin, indium curcumin and diacethyle curcumin”[J]. Eur Rev Med Pharmacol Sci, 2013, 17: 3306-3308. [13] Shahiduzzaman M, Dyachenko V, Khalafalla RE, et al.Daugschies, effects of curcumin on Cryptosporidium parvum in vitro[J]. Parasitol Res, 2009, 105: 1155-1161. DOI: 10.1007/s00436-009-1535-5 [14] Dohutia C, Chetia D, Gogoi K, et al.Design, in silico and in vitro evaluation of curcumin analogues against Plasmodium falciparum[J]. Exp Parasitol, 2017, 175: 51-58. DOI: 10.1016/j.exppara.2017.02.006 [15] Rangel-Castañeda IA, Hernández-Hernández JM, Pérez-Rangel A, et al.Amoebicidal activity of curcumin on Entamoeba histolytica trophozoites[J]. J Pharm Pharmacol, 2018, 70(3): 426-433. DOI: 10.1111/jphp.12867 [16] Asadpour M, Namazi F, Razavi SM, et al.Comparative efficacy of curcumin and paromomycin against Cryptosporidium parvum infection in a BALB/c model[J].Vet Parasitol, 2018, 250: 7-14. DOI: 10.1016/j.vetpar.2017.12.008 [17] Akhtar F, Rizvi MM, Kar SK.Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice[J]. Biotechnol Adv, 2012, 30: 310-320. DOI: 10.1016/j.biotechadv.2011.05.009 [18] Amaral AC, Gomes LA, Silva JR, et al.Liposomal formulation of turmerone-rich hexane fractions from Curcuma longa enhances their antileishmanial activity[J]. Biomed Res Int, 2014, 694934. DOI: 10.1155/2014/694934 [19] Ke OY, Krug EC, Marr JJ, et al.Inhibition of growth of Toxoplasma gondii by qinghaosu and derivatives[J]. Antimicrob Agents Chemother, 1990, 34: 1961-1965. DOI: 10.1128/aac.34.10.1961 [20] Mitchell SM, Zajac AM, Davis WL, et al.The effects of ponazuril on development of apicomplexans in vitro[J]. J Eukaryot Microbiol, 2005, 52: 231-235. DOI: 10.1111/j.1550-7408.2005.00029.x
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