Phlorizin

Phlorizin (Floridzin) is an orally active non-selective sodium-glucose cotransporter (SGLT) inhibitor, with an IC₅₀ of 0.04 μM and a K_i of 39 nM against hSGLT2, and an IC₅₀ of 0.17 μM and a K_i of 0.31 μM against hSGLT1. Phlorizin promotes GLUT4 translocation, inhibits gluconeogenesis and promotes glycogen synthesis by activating the PI3K/Akt/mTOR pathway. Phlorizin reduces DNA damage and apoptosis (apoptosis) by inhibiting the NF-κB inflammatory pathway. Phlorizin induces apoptosis via activating the Caspase pathway by antagonizing the JAK/STAT3 and PCK pathways. Phlorizin also exhibits antibacterial, anti-inflammatory and neuroprotective activities^[1][2][3][4]. IC50 & Target:Ki: 300 nM (hSGLT1), 39 nM (hSGLT2)^[1]
Na⁺/K⁺-ATPase^[2] In Vitro:Phlorizin (30 min), a competitive inhibitor, potently inhibits sodium-dependent AMG transport in COS-7 cells expressing wild-type mSGLT2, with a mean K_i of 65 nM and a mean IC₅₀ of 0.07 μM^[1].
Phlorizin (10 min) shows significantly reduced inhibitory potency against sodium-dependent AMG transport in COS-7 cells expressing the hSGLT1^C610K mutant, with a mean IC₅₀ of 1.7 μM, which is 10-fold higher than that of wild-type hSGLT1^[1].
Phlorizin (30 min) significantly enhances the inhibitory potency against sodium-dependent AMG transport in COS-7 cells expressing the hSGLT2^C615K mutant, with a mean IC₅₀ of 0.017 μM, which is 2-fold lower than that of wild-type hSGLT2^[1].
Phlorizin (30 min) significantly enhances the inhibitory potency against sodium-dependent AMG transport in COS-7 cells expressing the mSGLT2^N173A mutant, with a mean IC₅₀ of 0.018 μM^[1].
Phlorizin (1-100 μM) inhibits glucose transport in renal tubular cells and intestinal cells^[2].
Phlorizin (100-150 μg/mL) alleviates hydrogen peroxide-induced oxidative stress, DNA damage and apoptosis in human HepG2 cells by regulating the expression of Nrf2 protein and apoptosis-related genes^[4].
Phlorizin (6.25-100 μM) inhibits Zika virus infection in cell models by reducing the activities of apoptotic caspase-3/-7, decreasing the phosphorylation level of the Akt/mTOR pathway, and lowering viral titers^[4].
Phlorizin inhibits biofilm formation by up to 70% Staphylococcus aureus in RN4220 cells^[4].
Phlorizin enhances the survival rate of human SH-SY5Y neuroblastoma cells and cerebral cortical neurons exposed to hydrogen peroxide or high-glucose environments by inhibiting SGLT-mediated Na⁺ and glucose influx^[4].
Phlorizin exerts anti-tumor effects in human KYSE450 and KYSE30 esophageal cancer cells by inhibiting proliferation, invasion, migration and autophagy, and by activating apoptosis via antagonizing the JAK2/STAT3 signaling pathway^[4]. In Vivo:Phlorizin normalizes insulin sensitivity in partially pancreatectomized diabetic rats by reducing blood glucose, while it has no effect on insulin action in control rats^[2].
Phlorizin (p.o.) inhibits the increase in blood glucose levels in healthy mice following glucose loading^[2].
Phlorizin (p.o.) leads to its complete conversion to Phloretin (HY-N0142) (90% as glucuronide or sulfate conjugates) in healthy rats, followed by excretion in urine^[2].
Phlorizin (through the interior of the proximal convoluted tubule) into the proximal convoluted tubule impairs single-nephron glomerular filtration rate and renal tubular ion reabsorption function in streptozotocin-induced diabetic rats, but exerts no effect on normal control rats^[2].
Phlorizin (administered into the fourth ventricle) increases feeding behavior in healthy rats^[2].
Phlorizin (intracerebroventricular administration; single dose) induces FOS expression in periventricular glial cells of healthy rats and activates the transcriptional activity of multiple neurons in the central nervous system within 2 hours after administration^[2].
Phlorizin (1 mM, administered via endotracheal intubation) reduces alveolar fluid absorption in healthy rats^[2].
Phlorizin enhances memory in healthy rats and mice in passive avoidance tasks, and this effect is independent of blood glucose or cerebral glucose uptake^[2].
Phlorizin enhances learning ability in healthy mice and blocks insulin-induced memory impairment when administered after learning^[2].
Phlorizin (chronic administration) induces glycosuria, polyuria and weight loss in healthy dogs, mimicking the symptoms of human diabetes^[2].
Phlorizin (100 mg/kg; subcutaneous injection; once daily for 23 weeks) adequately controls hyperglycemia in female obese SDT rats, completely prevents peripheral neuropathy and retinal/ocular complications, and partially reduces indicators associated with diabetic nephropathy^[3].
Phlorizin (20-40 mg/kg) exerts antioxidant effects in D-Galactose (HY-N0210)-induced senescent mice by regulating the IL-1β/IκB-α/NF-κB signaling pathway; doses of 20 and 40 mg/kg increase the activity of antioxidant enzymes and reduce malondialdehyde levels^[4].
Phlorizin (6.25-25 mg/kg) inhibits BVDV infection in mice at doses of 6.25, 12.5, and 25 mg/kg by regulating the levels of innate immune cytokines and pattern recognition receptors^[4].
Phlorizin (20 mg/kg) improves blood glucose control and lipid metabolism in db/db type 2 diabetic mice, reduces levels of FBG, TC, TG and LDL-C, and increases HDL-C level^[4].
Phlorizin (30-120 mg/kg) alleviates streptozotocin (STZ) (HY-13753)-induced diabetes in rats at doses of 30, 60, and 120 mg/kg by improving glycolipid metabolic profiles, protecting pancreatic islets, and regulating glycogen synthase kinase-3 and the ubiquitin-proteasome pathway^[4].
Phlorizin (200 mg/kg) inhibits the JAK2/STAT3 signaling pathway in STZ-induced conscious diabetic rats at a dose of 200 mg/kg^[4].
Phlorizin (10 mg/kg) exerts anti-tumor activity in HepG2 tumor xenograft mice by inhibiting PKC expression and regulating apoptosis^[4].
Phlorizin (1-5 μmol/200 μL) blocks the ERK signaling pathway by inactivating NF-κB-induced COX-2 expression, thereby inhibiting TPA (HY-18739)-induced skin tumor formation in mice at doses of 1 and 5 μmol/200 μL^[4].
Phlorizin (0.4 g/kg) restores glycemic control and ameliorates non-alcoholic steatohepatitis (NASH) in MSG (HY-W250122)-induced obese type 2 diabetic mice at a dose of 0.4 g/kg^[4].
Phlorizin inhibits UVB-induced skin damage in nude mice by regulating the MAPK/NF-κB apoptotic signaling pathway^[4].
Phlorizin (intracerebroventricular administration) reduces cerebral infarction volume in MCAO model mice via inhibition of SGLT and anti-apoptotic signaling pathways when administered intracerebroventricularly^[4].
Phlorizin alleviates DSS (HY-116282C)-induced acute colitis in mice, reduces disease symptoms and improves intestinal morphology^[4].
Phlorizin (i.p.) reduces BCAO-induced hippocampal cell death and improves learning/memory abilities in male ddY mice, and its mechanism of action may involve inhibiting the expression of SGLT family genes^[4].
Phlorizin inhibits ischemic contracture and ischemia-induced arrhythmia in guinea pig myocardium by regulating voltage-dependent calcium channels and blocking Ca²⁺ influx^[4].