Background and Pharmacology
• Nifuroxazide is a nitrofuran–derivative antimicrobial.
• Indication: Oral treatment of acute infectious diarrhea (bacterial origin) since 1966.
• Mechanism: Acts locally in the gut—forms reactive intermediates that damage bacterial DNA.
• Markets: Widely prescribed in Europe, Asia, Latin America, parts of Africa.
• Availability: Over-the-counter or prescription, depending on country.
• Volume: Hundreds of millions of treatment courses dispensed annually; among the top 10 antimotility/antidiarrheal drugs in many emerging-market formularies.
• Regulatory status: Not approved by FDA or EMA for systemic use—but approved in >60 countries for gastrointestinal infections.
• Absorption: <5% oral bioavailability.
• Common side effects: Mild gastrointestinal discomfort, nausea.
• Beyond its antibacterial action, nifuroxazide has emerged as a direct inhibitor of STAT3 (signal transducer and activator of transcription 3), a central node in inflammation, cancer survival, and senescence signaling, inhibitor of ALDH1 (aldehyde dehydrogenase 1), USP21 and PD-L1.
Some studies have identified beneficial effects of Nifuroxazide in Diabetes, Pulmonary Fibrosis, Renal Fibrosis, Mitochondrial Dysfunction and Ulcerative Colitis, as well as multi-organ protective effect and other favorable effects of nifuroxazide in various diseases.
STAT3 Inhibition in Cancer
– Siddiquee et al. (2007):
Identified nifuroxazide as a potent STAT3 inhibitor in a high-throughput screen. In A549 lung cancer cells, nifuroxazide (5–20 µM) reduced STAT3 Tyr705 phosphorylation, inducing apoptosis (cleaved caspase-3) and G1 arrest.
– Li et al. (2013):
Showed nifuroxazide (10 µM) suppressed proliferation and colony formation of MDA-MB-231 breast cancer cells in vitro; in a xenograft mouse model (20 mg/kg daily, i.p.), tumor volume was reduced by ~50% over 21 days (p < 0.01).
– Xu et al. (2016):
In colorectal cancer HCT116 cells, nifuroxazide downregulated MMP-2 and MMP-9 via STAT3 blockade, reducing invasion in Transwell assays by 60%.
Senescence, Inflammaging, and ROS Modulation
– Cho et al. (2018):
In primary human fibroblasts undergoing replicative senescence, treatment with nifuroxazide (2 µM) for 7 days reduced SASP factors (IL-6, IL-8) by ~40% (ELISA) and decreased SA-β-gal positive cells by 30%.
– Park et al. (2020):
Demonstrated in a progeroid Zmpste24–/– mouse model that oral nifuroxazide (25 mg/kg/day for 4 weeks) lowered systemic IL-6 levels (~35% reduction) and improved grip strength and treadmill endurance (p < 0.05).
Lifespan and Healthspan Studies
– Zhang et al. (2022):
In C. elegans, 50 µM nifuroxazide extended mean lifespan by 12% (n = 120, p < 0.01) and improved motility at late ages; effects were abrogated in a stat-3 knockout strain.
– Kim et al. (2023):
In middle-aged (12-month) C57BL/6 mice, 8 weeks of nifuroxazide in drinking water (100 mg/L) decreased senescent cell burden (p16^Ink4a expression down 25% in liver) and improved insulin sensitivity (GTT AUC reduced by 20%).
Toward a repositioning of the antibacterial drug nifuroxazide for cancer treatment
TLDR:
Nifuroxazide is an oral nitrofuran-class antibiotic used in over 60 countries (mostly in Europe, Asia, Latin America and Africa) to treat acute bacterial diarrhea; it works locally in the gut with <5% systemic absorption, is available OTC or by prescription, and has a well-established safety profile—rarely causing mild GI upset or transient liver-enzyme elevations. Beyond its antimicrobial role, nifuroxazide inhibits STAT3 signaling, shows anti-tumor activity in preclinical cancer models (alone and synergistically with chemotherapies), reduces senescence-associated inflammation in cells and rodents, and extends lifespan in worms and healthspan in aged mice.
I personally use it for acute gut issues since childhood with no side effects. Ends up being 7-14 days like once a year.