Nifuroxazide

Nifuroxazide is a cell-permeable and orally available nitrofuran-based antidiarrheal agent that effectively suppresses the activation of cellular STAT1/3/5 transcription activity with IC50 of 3 μM against IL-6-induced STAT3 activation in U3A cells

Open Clinical Trial on Using Nifuroxazide Compared to Probiotics in Treating Acute Diarrhoeas in Adults.[Pubmed:28144199]

Mater Sociomed. 2016 Dec;28(6):454-458.

BACKGROUND: Nifuroxazide is well known and often used anti-diarrhoeal medicine which has been pushed back from routine practice in recent years and often replaced with probiotics. Even probiotics are accepted and placed in some therapeutic guidelines for diarrhoea treatment, there are no enough evidence for its effectiveness and no comparative efficacy data with Nifuroxazide in treatment of acute diarrhea. PATIENTS AND METHODS: In open, prospective observational study, the efficacy and safety of Nifuroxazide were compared with a probiotic containing lactic acid bacteria in the treatment of acute diarrhoea. A total number of 169 adult patients were included in this study, who administered Nifuroxazide in the dose of 200 mg/4 times a day, while they took preparation containing lactic acid bacteria (1,2 x 10(7) live lyophilised lactic-acid bacteria) three times a day for three days. RESULTS: Mean time to last unformed stool (TLUS) in a group which was treated with Nifuroxazide was two days, while it took five days for the stool normalisation in the group using probiotic (p=0.0001). CONCLUSIONS: Orally administered Nifuroxazide has demonstrated better efficiency as compared to probiotic in treating acute diarrhoea, and both medicines have shown the same safety and tolerance in this study.

Combined nifuroxazide and SAT05f therapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation.[Pubmed:27906171]

Cell Death Dis. 2016 Dec 1;7(12):e2507.

Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and Nifuroxazide may be the novel strategies for aGvHD therapy. The results showed combined therapy significantly decreased the severity of aGvHD and prolonged the survival rate. Furthermore, after treatment, the activation of CD4(+) effect T cells was reduced, whereas Treg cells was increased, and the cytokine release was inhibited. In conclusion, combined therapy of Nifuroxazide with SAT05f may be potential for the prevention or treatment of aGvHD, providing theoretic and experimental basis.

Inhibition of Stat3 signaling pathway by nifuroxazide improves antitumor immunity and impairs colorectal carcinoma metastasis.[Pubmed:28055016]

Cell Death Dis. 2017 Jan 5;8(1):e2534.

Colorectal carcinoma (CRC) is the one of the most common cancers with considerable metastatic potential, explaining the need for new drug candidates that inhibit tumor metastasis. The signal transducers and activators of the transcription 3 (Stat3) signaling pathway has an important role in CRC and has been validated as a promising anticancer target for CRC therapy. In the present study, we report our findings on Nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3. Our studies showed that Nifuroxazide decreased the viability of three CRC cell lines and induced apoptosis of cancer cells in a concentration-dependent manner. Moreover, western blot analysis demonstrated that the occurrence of its apoptosis was correlated with the activation of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. In addition, Nifuroxazide markedly impaired CRC cell migration and invasion by downregulating phosphorylated-Stat3(Tyr705), and also impaired the expression of matrix metalloproteinases (MMP-2 and MMP-9). Furthermore, our studies showed that Nifuroxazide also significantly inhibited the tumor metastasis in lung and abdomen metastasis models of colon cancer. Meanwhile, Nifuroxazide functionally reduced the proliferation index, induced tumor apoptosis and impaired metastasis. Notably, Nifuroxazide reduced the number of myeloid-derived suppressor cells in the blood, spleens and tumors, accompanied by the increased infiltration of CD8(+) T cells in the tumors. Importantly, a marked decrease in the number of M2-type macrophages in tumor in the abdomen metastasis model was also observed. Taken together, our results indicated that Nifuroxazide could effectively inhibit tumor metastasis by mediating Stat3 pathway and it might have a therapeutic potential for the treatment of CRC.

Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma.[Pubmed:26830149]

Sci Rep. 2016 Feb 2;6:20253.

Melanoma is a highly malignant neoplasm of melanocytes with considerable metastatic potential and drug resistance, explaining the need for new candidates that inhibit tumor growth and metastasis. The signal transducer and activator of the transcription 3 (Stat3) signaling pathway plays an important role in melanoma and has been validated as promising anticancer target for melanoma therapy. In this study, Nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3, was evaluated for its anti-melanoma activity in vitro and in vivo. It had potent anti-proliferative activity against various melanoma cell lines and could induce G2/M phase arrest and cell apoptosis. Moreover, Nifuroxazide markedly impaired melanoma cell migration and invasion by down-regulating phosphorylated-Src, phosphorylated-FAK, and expression of matrix metalloproteinase (MMP) -2, MMP-9 and vimentin. It also significantly inhibited tumor growth without obvious side effects in the A375-bearing mice model by inducing apoptosis and reducing cell proliferation and metastasis. Notably, Nifuroxazide significantly inhibited pulmonary metastases, which might be associated with the decrease of myeloid-derived suppressor cells (MDSCs). These findings suggested that Nifuroxazide might be a potential agent for inhibiting the growth and metastasis of melanoma.