Phlorizin  (Synonyms: Floridzin)

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].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

436.41

C₂₁H₂₄O₁₀

60-81-1

Solid

White to off-white

O=C(C1=C(O)C=C(O)C=C1O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)CCC3=CC=C(O)C=C3

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Pajor AM, et al. Inhibitor binding in the human renal low- and high-affinity Na+/glucose cotransporters. J Pharmacol Exp Ther. 2008;324(3):985-991.  [Content Brief]

  [2]. Chang WT, et al. Evaluation of the anti-inflammatory effects of phloretin and phlorizin in lipopolysaccharide-stimulated mouse macrophages. Food Chem. 2012;134(2):972-979.  [Content Brief]

  [3]. Katsuda Y, et al. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin. Exp Anim. 2015;64(2):161-169.  [Content Brief]

  [4]. Ni T, et al. Phlorizin, an Important Glucoside: Research Progress on Its Biological Activity and Mechanism. Molecules. 2024;29(3):741. Published 2024 Feb 5.

  [5]. Ehrenkranz JR, et al. Phlorizin: a review. Diabetes Metab Res Rev. 2005 Jan-Feb;21(1):31-8.