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.