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Purity: ≥98%
Phlorizin (phloridzin), a glucoside of phloretin which is a dihydrochalcone and a family of bicyclic flavonoids, is a potent and non-selective competitive SGLT inhibitor with Kis of 300 and 39 nM for hSGLT1 and hSGLT2, respectively. Moreover, phenolizin inhibits the activity of Na+/K+-ATPase. Due to its ability to compete with D-glucose for binding to the transporter/carrier, phenorizin is a competitive inhibitor of SGLT1 and SGLT2, which lowers blood glucose levels by reducing renal glucose transport. Phlorizin was researched as a possible medication for type 2 diabetes, but more promising and selective synthetic analogs, like canagliflozin and dapagliflozin, have since supplanted it.
| Targets |
hSGLT2 ( Ki = 39 nM ); hSGLT1 ( Ki = 300 nM ); Na+/K+-ATPase
- Sodium-glucose cotransporter 1 (SGLT1) (Ki = 0.2 μM in rabbit intestinal brush-border membranes) [4] - Sodium-glucose cotransporter 2 (SGLT2) (IC50 = 0.39 μM in rat renal cortex) [3] |
|---|---|
| ln Vitro |
Phlorizin is a dihydrochalcone that can be found in the bark of fruit trees such as cherries, apples, and pears (Pyrus communis). As a competitive inhibitor of SGLT1 and SGLT2, phenorizin lowers blood glucose levels by decreasing renal glucose transport.[1] The main pharmacological effects of phenylurizin include the production of renal glycosuria and the inhibition of intestinal glucose absorption via the sodium-glucose symporters found in the small intestine's mucosa and proximal renal tubule. These effects are beneficial for the treatment of diabetes, obesity, and stress hyperglycemia.[2]
- Inhibition of intestinal glucose absorption: Phloridzin (0.1-10 μM) inhibited Na+-dependent glucose uptake in rabbit intestinal brush-border membrane vesicles, with maximum inhibition (~80%) at 10 μM. This effect was competitive with glucose, as indicated by increased Km values for glucose uptake without changing Vmax [4] - Inhibition of renal glucose reabsorption: In rat renal cortex slices, Phloridzin (1-50 μM) reduced Na+-dependent glucose uptake in a concentration-dependent manner, with 50% inhibition at 3.9 μM. It had no significant effect on Na+-independent glucose transport [3] |
| ln Vivo |
Before root bark dye treatment, the SDT contaminant concentration was 370±49 mg/dL. Six hours after labeling, the formaldehyde concentration in the root bark dye-treated group was close to normal levels (139±32 mg/dL). After 12 weeks, the specific gravity of SDT treated with root bark cherry was heavier than that treated with active substances. Root bark cherry treatment significantly reduced neuronal excretion and delayed insulin reduction. Muscle clearance was significantly reduced after root bark cherry treatment. Skin granule treatment for 23 weeks prevented the reduction of nerve fibers (23.6±3.2 fibers/mm). Phloridzin [4] can completely prevent nerve fiber abnormalities.
- Antihyperglycemic effect in diabetic rats: In streptozotocin-induced diabetic rats, intravenous administration of Phloridzin (5-20 mg/kg) dose-dependently reduced blood glucose levels by 30-60% within 1 hour, accompanied by a 5-10-fold increase in urinary glucose excretion. The effect lasted for 2-4 hours [2] - Glucose tolerance improvement: In normal rats, oral Phloridzin (50 mg/kg) administered 30 minutes before an oral glucose load (2 g/kg) reduced the postprandial glucose peak by ~40% and blunted the glucose excursion over 2 hours [2] - Effect on insulin and glucagon: In diabetic rats, Phloridzin (10 mg/kg, i.v.) increased plasma insulin levels by ~25% and decreased glucagon levels by ~20% at 1 hour post-administration, possibly due to improved glucose utilization [1] |
| Enzyme Assay |
After red cells are hemolyzed, sealed ghosts can be obtained by adding 4×10-3 M ATP and 5×10-3 M MgCl2, either with or without 5×10-4 M Phlorizin (final concentration). After incubating ghosts equivalent to 0.4-0.45 mL of the original blood cells for 45 or 90 minutes with 0.9 mL of Medium A and 86RbCl, the radioactivity in 200 μL of the supernatant is measured. After incubation, the increase in inorganic phosphate indicates the ATPase activity in the resealed ghosts.
- SGLT activity in brush-border membranes: Rabbit intestinal brush-border membrane vesicles were prepared and incubated with Phloridzin (0.1-100 μM) in the presence of [¹⁴C]-glucose and Na+ gradient. After 10 minutes, vesicles were filtered, and radioactivity was measured. Kinetic parameters (Km, Vmax) were calculated to determine competitive inhibition [4] - Renal SGLT inhibition assay: Rat renal cortex slices were incubated with Phloridzin (1-50 μM) and [¹⁴C]-glucose in Na+-containing or Na+-free buffer. Glucose uptake was measured after 30 minutes, and IC50 was determined from the dose-response curve [3] |
| Cell Assay |
The cell line derived from murine macrophages, RAW264.7, is utilized. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is used to determine the viability of cells. In 96-well plates, cells (105 cells/well) are cultivated and exposed to different Phlorizin concentrations for a full day. After removing the supernatant, the cells are incubated at 37°C for 4 hours with 50 mg/mL of MTT. After washing the plates and adding isopropanol to dissolve the formazone crystals, a microplate reader is used to measure the absorbance values at 570 nm.
Renal cell glucose uptake assay: Primary cultures of rat renal proximal tubule cells were treated with Phloridzin (5-50 μM) and [³H]-glucose in medium with or without Na+. After 1 hour, cells were lysed, and radioactivity was counted to assess Na+-dependent glucose uptake [3] |
| Animal Protocol |
This study uses female SDT fatty rats. Six weeks of age are used to split the eight SDT fatty rats into two groups: one treated with phenol and the other with a vehicle. Eight female Sprague-Dawley (SD) rats of the same age are used as the control group. Housed in a climate-controlled room with a temperature of 23±3°C, humidity of 55±15%, and a 12-hour lighting cycle, the animals are given unrestricted access to water and their basal diet. For 23 weeks, animals in the Phlorizin treated group receive one subcutaneous injection of phenol (100 mg/kg/day). The animals in the vehicle treated group and the SD rats under control are given 20% propylene glycol.
- Diabetic rat model: Streptozotocin-induced diabetic rats (blood glucose >300 mg/dL) were anesthetized, and Phloridzin (5, 10, 20 mg/kg) was administered via tail vein injection. Blood glucose was measured at 0, 30, 60, 120, and 240 minutes using a glucometer. Urine was collected over 4 hours to quantify glucose excretion via colorimetric assay [2] - Oral glucose tolerance test: Normal rats were fasted overnight, then given Phloridzin (50 mg/kg) by oral gavage. Thirty minutes later, they received an oral glucose load (2 g/kg). Blood glucose was measured at 0, 30, 60, 90, and 120 minutes [2] |
| ADME/Pharmacokinetics |
- Oral absorption: Phloridzin has low oral bioavailability (~10%) in rats due to hydrolysis by intestinal β-glucosidases, producing phloretin and glucose [2]
- Metabolism: In vivo, Phloridzin is rapidly metabolized to phloretin (aglycone) in the intestine and liver, which is further conjugated with glucuronic acid [2] - Excretion: In rats, intravenously administered Phloridzin (10 mg/kg) is excreted primarily in urine (60-70%) within 24 hours, mostly as metabolites [2] |
| Toxicity/Toxicokinetics |
- Acute toxicity: In mice, the LD50 of Phloridzin after intraperitoneal injection is ~500 mg/kg, with death occurring within 24 hours due to severe hypoglycemia [2]
- Chronic toxicity: Rats treated with Phloridzin (20 mg/kg/day, i.p.) for 4 weeks showed no significant changes in liver or kidney function tests, but slight weight loss (~5%) was observed [1] 6072 mouse LD intraperitoneal >500 mg/kg Summary Tables of Biological Tests, National Research Council Chemical-Biological Coordination Center., 6(226), 1954 |
| References | |
| Additional Infomation |
Phlorizin is an aryl beta-D-glucoside that is phloretin attached to a beta-D-glucopyranosyl residue at position 2' via a glycosidic linkage. It has a role as a plant metabolite and an antioxidant. It is an aryl beta-D-glucoside, a member of dihydrochalcones and a monosaccharide derivative. It is functionally related to a phloretin.
Phlorizin has been reported in Lithocarpus pachyphyllus, Malus doumeri, and other organisms with data available. - Phloridzin is a natural glycoside isolated from apple tree bark (Malus pumila). It was one of the first identified SGLT inhibitors and serves as a prototype for the development of SGLT2 inhibitors used in type 2 diabetes treatment [1][2] - Its mechanism of action involves blocking renal glucose reabsorption and intestinal glucose absorption, thereby reducing blood glucose levels through increased urinary glucose excretion [3][4] |
| Molecular Formula |
C21H24O10
|
|---|---|
| Molecular Weight |
436.4093
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| Exact Mass |
436.136
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| Elemental Analysis |
C, 57.80; H, 5.54; O, 36.66
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| CAS # |
60-81-1
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| Related CAS # |
Phlorizin dihydrate; 7061-54-3
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| PubChem CID |
6072
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| Appearance |
White to light yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
770.0±60.0 °C at 760 mmHg
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| Melting Point |
113-114 °C(lit.)
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| Flash Point |
270.7±26.4 °C
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| Vapour Pressure |
0.0±2.8 mmHg at 25°C
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| Index of Refraction |
1.686
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| LogP |
0.45
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| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
581
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1[C@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])O[H])OC1=C([H])C(=C([H])C(=C1C(C([H])([H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H])=O)O[H])O[H]
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| InChi Key |
IOUVKUPGCMBWBT-QNDFHXLGSA-N
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| InChi Code |
InChI=1S/C21H24O10/c22-9-16-18(27)19(28)20(29)21(31-16)30-15-8-12(24)7-14(26)17(15)13(25)6-3-10-1-4-11(23)5-2-10/h1-2,4-5,7-8,16,18-24,26-29H,3,6,9H2/t16-,18-,19+,20-,21-/m1/s1
|
| Chemical Name |
1-[2,4-dihydroxy-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]-3-(4-hydroxyphenyl)propan-1-one
|
| Synonyms |
NSC-2833; NSC 2833; Phlorizoside; Floridzin; Phlorrhizin; Phloretin 2'-glucoside; Phlorrhizen; ...; 60-81-1; NSC2833; Phlorizin; phloridzin; phloretin-2'-β-D-glucopyranoside; AI3-19835; Phloretin 2'-glucoside; Phloretin-2'-O-beta-glucoside; Phlorizoside; Phlorrhizin
|
| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~87 mg/mL (~199.4 mM)
Ethanol: ~87 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1.75 mg/mL (4.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). Solubility in Formulation 5: 15.15 mg/mL (34.72 mM) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2914 mL | 11.4571 mL | 22.9142 mL | |
| 5 mM | 0.4583 mL | 2.2914 mL | 4.5828 mL | |
| 10 mM | 0.2291 mL | 1.1457 mL | 2.2914 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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