Tizoxanide is the main active metabolite of nitazoxanide. Nitazoxanide and tizoxanide have a broad-spectrum anti-infective effect, including parasites, bacteria, and virus. Tizoxanide exerts anti-inflammatory effects, by inhibiting the production of pro-inflammatory cytokines and suppressing of the activation of the NF-κB and the MAPK signaling pathways in LPS-treated (lipopolysaccharide) macrophage cells[3]. Tizoxanide (TIZ) inhibited virus replication of all CIVs (canine influenza virus) with 90% inhibitory concentrations ranging from 0.60 to 0.76 μM, and it is effective against CIV and may be useful for treatment of canine influenza in dogs[4]. TIZ exhibited potent inhibition of both HBV (hepatitis B virus) and HCV (hepatitis C virus) replication[5]. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested. Median EC50 values (±IQR) of 0.48 μM (0.33-0.71), 0.62 μM (0.56-0.75), 0.66 μM (0.62-0.69), and 0.60 μM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively[6].
Tizoxanide/替唑尼特 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PC3 cells
20 µM
16 hours
Inhibited SKP2 expression, leading to G1 cell cycle arrest
Cell Rep Med. 2025 Jan 21;6(1):101890
22Rv1 cells
20 µM
48 hours
Induced apoptosis
Cell Rep Med. 2025 Jan 21;6(1):101890
DU145 cells
20 µM
16 hours
Inhibited cell growth
Cell Rep Med. 2025 Jan 21;6(1):101890
C4-2 cells
20 µM
16 hours
Inhibited E2F1-mediated gene expression, including genes involved in cell cycle progression, DNA synthesis, and lipid synthesis
Cell Rep Med. 2025 Jan 21;6(1):101890
HepG2 cells
1, 5, 10, 25 µM
24 hours
Induced mild mitochondrial uncoupling and activated AMPK
Acta Pharm Sin B. 2022 Mar;12(3):1322-1338
U87MG cells
1 and 10 µM
24 hours
TIZ significantly inhibited the phosphorylation levels of CDK1 Thr161
Front Pharmacol. 2022 May 25;13:895573
Rat chondrocytes
0.5 µM
24 hours
To evaluate the effect of Tiz on IL-1β-induced inflammatory response and cartilage matrix degradation, results showed that Tiz could alleviate IL-1β-induced inflammatory response and cartilage matrix degradation.
Heliyon. 2023 Aug 26;9(9):e19472
Rat chondrocytes
0.125, 0.25, 0.5 µM
24 hours
To evaluate the effect of Tiz on chondrocyte viability, results showed that Tiz at 0.125, 0.25 and 0.5 μM had no toxic effects on cells.
Heliyon. 2023 Aug 26;9(9):e19472
Vero cells
0.5 μg/mL
24 hours
To study the effect of TIZ on the proteome of Vero cells, identifying 15 differentially expressed proteins involved in various biological processes including translation, intracellular trafficking, RNA processing and modification, and signal transduction.
Sci Rep. 2020 Sep 7;10(1):14733
A172 cells
0.01 to 10 µM
24, 48, and 72 hours
TIZ dose-dependently inhibited cell proliferation with an IC50 of 0.73 µM at 48 h
Front Pharmacol. 2022 May 25;13:895573
U118MG cells
0.01 to 10 µM
24, 48, and 72 hours
TIZ dose-dependently inhibited cell proliferation with an IC50 of 2.31 µM at 48 h
Front Pharmacol. 2022 May 25;13:895573
U87MG cells
0.01 to 10 µM
24, 48, and 72 hours
TIZ dose-dependently inhibited cell proliferation with an IC50 of 1.10 µM at 48 h
Front Pharmacol. 2022 May 25;13:895573
MCF-7 cells
30 µM
3 hours or 24 hours
Induced autophagosome formation, assessed by increased punctate EGFP-LC3 fluorescence and increased EGFP-LC3II lipidation product
PLoS Pathog. 2012;8(5):e1002691
Marc-145-GFP cells
5 µM
36 hours
Evaluate the inhibitory effect of Tizoxanide on PRRSV proliferation, results showed Tizoxanide significantly inhibited PRRSV proliferation at 5 μM
Nat Commun. 2024 Jun 6;15(1):4813.
Vero E6 cells
3.19 µM
48 hours
Evaluate the antiviral activity of Tizoxanide against SARS-CoV-2, showing an EC50 of 7.48 µM
EBioMedicine. 2022 Aug;82:104148
Fusobacterium nucleatum
0.06–0.5 μg/ml
48 hours
To determine the minimum inhibitory concentration (MIC) of Tizoxanide against Fusobacterium nucleatum, showing an MIC range of 0.06–0.5 μg/ml.
To evaluate the inhibitory effect of Tizoxanide on DENV-2 replication, results showed TIZ could inhibit virus replication with IC50 of 1.38 μM and IC90 of 4.8 μM
Viruses. 2023 Mar 7;15(3):696
Tizoxanide/替唑尼特 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Male SD rats
OA model induced by anterior cruciate ligament resection and partial medial meniscus removal
Intra-articular injection
0.5 μM
Once a week for 8 weeks
To evaluate the effect of Tiz on cartilage damage in rat OA model, results showed that intra-articular injection of Tiz could significantly alleviate the progression of cartilage damage.
Heliyon. 2023 Aug 26;9(9):e19472
Caenorhabditis elegans
Wild-type N2 strain and various mutants (e.g., aak-2, daf-16, sir-2.1, rsks-1, akt-1, akt-2)
Administered via OP50 E. coli diet
10, 100, 500 μM and 1 mM
Continuous treatment for 12 days starting from L4 stage or lifelong treatment
Tizoxanide extends lifespan and healthspan in C. elegans, improves high glucose-induced lifespan shortening via Akt/AMPK/sir-2.1/daf-16 pathway, enhances motility, reduces lipofuscin accumulation, improves mitochondrial morphology and function, and activates AMPK-dependent autophagy.
Acta Pharm Sin B. 2024 Jul;14(7):3266-3280
BALB/C nude mice
Subcutaneous and intracranial orthotopic xenograft models
Intraperitoneal injection
5 and 15 mg/kg
Three times per week for 3 weeks
TIZ significantly suppressed the growth of GBM, prolonged the survival of nude mice without obvious side effects
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