Nitazoxanide is a thiazolide antiprotozoal and antiviral drug with an IC50 of 2.4μM against the proliferation of Giardia lamblia trophozoites. Nitazoxanide is commonly used in the study of infectious diseases and may have potential applications in the treatment of diseases such as viral gastroenteritis and parasitic infections[1]. Nitazoxanide has demonstrated anti-Japanese encephalitis virus (JEV) activity in a mouse model[2]. Additionally, Nitazoxanide possesses anti-inflammatory and immunomodulatory effects, which may contribute to its therapeutic potential in various diseases[3-4].
In vitro, Nitazoxanide (2.5–25μM) was used to treat human lung fibroblasts (MRC-5 cells) and mouse lung epithelial cells (MLE-12 cells). Nitazoxanide significantly inhibited transforming growth factor-β1 (TGF-β1)-induced cell proliferation and migration, reduced the expression levels of collagen I (Collagen-I) and α-smooth muscle actin (α-SMA), and decreased the secretion of collagen I. Furthermore, Nitazoxanide inhibited the activation of the TGF-β1-induced Smad2/3 signaling pathway and induced autophagy[5]. When human glioblastoma cells (LN229, A172, U87) and human umbilical vein endothelial cells (HUVECs) were treated with Nitazoxanide at concentrations of 100–1600μM for 48 or 72 hours, Nitazoxanide showed dose-dependent and time-dependent inhibition of cell proliferation, with reduced expression of the proliferation marker Ki67. Additionally, the colony-forming ability of cells treated with Nitazoxanide was significantly decreased[6].
In vivo, Nitazoxanide (100 and 200mg/kg) was administered orally to ApoE-/- mice with diet-induced atherosclerosis for 15 weeks. At both doses, Nitazoxanide significantly reduced the atherosclerotic plaque area in the aortic arch and aortic root, decreased serum levels of inflammatory factors IL-1β and IL-6, and inhibited the proliferation and migration of vascular smooth muscle cells as well as the activation of the NLRP3 inflammasome in macrophages[7]. Nitazoxanide (75, 100, and 150mg/kg) was administered orally to male C57BL/6J mice with dextran sulfate sodium (DSS)-induced ulcerative colitis during the DSS induction period. At all three doses, Nitazoxanide significantly improved DSS-induced colitis symptoms in a dose-dependent manner, including reducing the disease activity index (DAI), alleviating weight loss, increasing colon length, and improving pathological changes in colon tissue. Additionally, Nitazoxanide significantly reduced serum and colon tissue levels of IL-6 and IL-17, and decreased serum myeloperoxidase (MPO) activity[8].
References:
[1] Müller J, Rühle G, Müller N, et al. In vitro effects of thiazolides on Giardia lamblia WB clone C6 cultured axenically and in coculture with Caco2 cells. Antimicrob Agents Chemother. 2006 Jan;50(1):162-70.
[2] Shi Z, Wei J, Deng X, et al. Vaccaria hypaphorine impairs RANKL-induced osteoclastogenesis by inhibition of ERK, p38, JNK and NF-κB pathway and prevents inflammatory bone loss in mice. Biomed Pharmacother. 2018 Jan;97:1155-1163.
[3] Zhang T, Yan Y, Xue Y, et al. Pharmacokinetic Study of Hypaphorine, a Potential Agent for Treating Osteoclast-based Bone Loss, on Rats Using LC-MS/MS. Comb Chem High Throughput Screen. 2022;25(11):1889-1896.
[4] Bai S, Liang H, Jiang W, et al. Identifying hypaphorine as a novel antiviral compound against dengue virus. Antiviral Res. 2025 Jun 24;240:106220.
[5] Chen XY, Dong YC, Yu YY, et al. Anthelmintic nitazoxanide protects against experimental pulmonary fibrosis. Br J Pharmacol. 2023 Dec;180(23):3008-3023.
[6] Wang X, Shen C, Liu Z, et al. Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma. Cell Death Dis. 2018 Oct 9;9(10):1032.
[7] Ma MH, Li FF, Li WF, et al. Repurposing nitazoxanide as a novel anti-atherosclerotic drug based on mitochondrial uncoupling mechanisms. Br J Pharmacol. 2023 Jan;180(1):62-79.
[8] Zhu HT, Luo J, Peng Y, et al. Nitazoxanide protects against experimental ulcerative colitis through improving intestinal barrier and inhibiting inflammation. Chem Biol Interact. 2024 May 25;395:111013.
Nitazoxanide是一种噻唑烷类抗原虫和抗病毒药物，对抑制Giardia lamblia滋养体增殖的IC50为2.4μM。Nitazoxanide常被用于感染性疾病的研究，并可能在治疗病毒性胃肠炎和寄生虫感染等疾病中具有潜在应用价值[1]。Nitazoxanide 在小鼠模型中显示出抗日本脑炎病毒(JEV)活性[2]，此外，Nitazoxanide还具有抗炎和免疫调节作用，这可能有助于其在多种疾病治疗中的潜力[3-4]。
在体外，Nitazoxanide（2.5–25μM）处理人肺成纤维细胞（MRC-5细胞）和小鼠肺上皮细胞（MLE-12细胞），Nitazoxanide显著抑制了转化生长因子-β1（TGF-β1）诱导的细胞增殖和迁移，降低了胶原蛋白I（Collagen-I）和α-平滑肌肌动蛋白（α-SMA）的表达水平，并减少了胶原蛋白I的分泌。此外，Nitazoxanide还抑制了TGF-β1诱导的Smad2/3信号通路的激活，并诱导了自噬反应[5]。Nitazoxanide以100–1600μM的浓度处理人胶质母细胞瘤细胞（LN229、A172、U87）和人脐静脉内皮细胞（HUVECs）48小时或72小时，Nitazoxanide显示出剂量依赖性和时间依赖性的抑制细胞增殖的效果，且增殖标记物Ki67的表达降低。此外，Nitazoxanide处理后的细胞集落形成能力显著下降[6]。
在体内，Nitazoxanide（100和200mg/kg）通过口服给药，用于治疗饮食诱导的动脉粥样硬化ApoE-/-小鼠模型，给药时间为15周。Nitazoxanide在两个剂量下均显著减少了主动脉弓和主动脉根部的动脉粥样硬化斑块面积，降低了血清中炎症因子IL-1β和IL-6的水平，并且抑制了血管平滑肌细胞的增殖和迁移以及巨噬细胞中NLRP3炎症体的激活[7]。Nitazoxanide（75、100和150mg/kg）通过口服给药，用于治疗由葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎的雄性C57BL/6J小鼠模型，给药时间为DSS诱导期间。Nitazoxanide在所有三个剂量下均能以剂量依赖性方式显著改善DSS诱导的结肠炎症状，包括降低疾病活动指数（DAI）、减轻体重下降、增加结肠长度，并改善结肠组织的病理变化。此外，Nitazoxanide还能显著降低血清和结肠组织中IL-6和IL-17的水平，减少血清中髓过氧化物酶（MPO）的活性[8]。