Phlorizin

Names

[ CAS No. ]:
60-81-1

[ Name ]:
Phlorizin

[Synonym ]:
phlorizoside
4,6-dihydroxy-2-(β-D-glucosido)-β-(p-hydroxyphenyl)propiophenone
3,5-Dihydroxy-2-[3-(4-hydroxyphenyl)propanoyl]phenyl-β-D-glucopyranoside
1-(2,4-Dihydroxy-6-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}phenyl)-3-(4-hydroxyphenyl)-1-propanone
phloridzosid
phloridzine
Phlorrhizen
phloretin 2'-O-glucoside
1-Propanone, 1-[2-(β-D-glucopyranosyloxy)-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)-
Phlorizin
Isosalipurposide
Phloretin-2'-b-glucoside
Phloridzin
Phlorhizin
3,5-Dihydroxy-2-[3-(4-hydroxyphenyl)propanoyl]phenyl β-D-glucopyranoside
1-(2,4-Dihydroxy-6-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxyméthyl)tétrahydro-2H-pyran-2-yl]oxy}phényl)-3-(4-hydroxyphényl)-1-propanone
1-[2-(β-D-Glucopyranosyloxy)-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)-1-propanone
1-(2,4-Dihydroxy-6-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}phenyl)-3-(4-hydroxyphenyl)-1-propanon
2'-(β-D-glucopyranosyloxy)-4',6'-dihydroxy-3-(4-hydroxyphenyl)propiophenone
4,6-Dihydroxy-2-(b-D-glucosido)-b-(p-hydroxyphenyl)propiophenone
Phloretin-2'-O-glucoside
Floridzin
MFCD00006591
1-[2-(b-D-Glucopyranosyloxy)-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)-1-propanone
1-Propanone, 1-(2-(β-D-glucopyranosyloxy)-4,6-dihydroxyphenyl)-3-(4-hydroxyphenyl)-
Phloretin-2'-β-glucoside
phlorrhizin
EINECS 200-487-1

Biological Activity

[Description]:

Phlorizin is a non-selective SGLT inhibitor with Kis of 300 and 39 nM for hSGLT1 and hSGLT2, respectively. Phlorizin is also a Na+/K+-ATPase inhibitor.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Na+/K+ ATPase

Signaling Pathways >> Membrane Transporter/Ion Channel >> SGLT

Natural Products >> Flavonoids

Research Areas >> Metabolic Disease

[Target]

Ki: 300 nM (hSGLT1), 39 nM (hSGLT2)[1] Na+/K+-ATPase[2]

[In Vitro]

Phlorizin is a non-selective SGLT inhibitor with Kis of 300 and 39 nM for hSGLT1 and hSGLT2, respectively[1]. Phlorizin is also a Na+/K+-ATPase inhibitor[2]. Phlorizin at 2×10-4 M inhibits Na+ and Rb+-activated ATPase activities in human red cell membranes by 43 %. At 1 mM and 7 mM RbCl, rubidium uptake is not changed or is slightly inhibited (less than 15 %) by 2×10-4 M Phlorizin[2]. Cell viability is not significantly altered by doses of Phlorizin <100 μM. Pretreating cells with Phlorizin does not significantly reduce nitrite or PGE2 levels. Phlorizin does not suppress IL-6 or TNF-α production, although 100 μM Phlorizin can significantly inhibit TNF-α expression[3].

[In Vivo]

Prior to Phlorizin treatment, the blood glucose level in SDT fatty rats is 370±49 mg/dL. Six hours after dosing, the blood glucose level in the Phlorizin treated group decreases to an almost normal level (139±32 mg/dL). Phlorizin-treated SDT fatty rats are heavier than vehicle-treated SDT fatty rats after 12 weeks. Phlorizin treatment significantly decreases glucose excretion and delays insulin decreases. Creatinine clearance decreases significantly with Phlorizin treatment. 23 weeks of Phlorizin treatment prevents the decrease of nerve fibers (23.6±3.2 fibers/mm). Retinal abnormalities are completely prevented with Phlorizin[4].

[Kinase Assay]

Resealed ghosts are obtained with the addition of 4×10-3 M ATP and 5×10-3 M MgCl2 with or without 5×10-4 M Phlorizin (final concentration) when red cells are hemolyzed. Ghosts corresponding to 0.4-0.45 mL of the original blood cells are incubated with 0.9 mL of Medium A and 86RbCl for 45 or 90 min and the radioactivity in 200 μL of the supernatant is determined. The ATPase activity in the resealed ghosts is determined from the increase in inorganic phosphate after incubation[1].

[Cell Assay]

The RAW264.7 murine macrophage-derived cell line is used. Cell viability is measured using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells (105 cells/well) are cultured in 96-well plates and treated with varying concentrations of Phlorizin for 24 h. Next, the supernatant is removed and the cells are incubated with MTT (50 mg/mL) for 4 h at 37°C. The plates are washed and isopropanol is added to dissolve formazone crystals, then the absorbance values are measured at 570 nm using a microplate reader[3].

[Animal admin]

Female SDT fatty rats are used in this study. At six weeks of age, SDT fatty rats are divided into two groups (n=8); a Phlorizin treated group and a vehicle treated group. Age-matched female Sprague-Dawley (SD) rats are used as control animals (n=8). Animals are housed in a climate-controlled room (temperature 23±3°C, humidity 55±15%, 12 h lighting cycle) and allowed free access to basal diet and water. Phlorizin is injected subcutaneously once daily (100 mg/kg/day) to animals in the Phlorizin treated group for 23 weeks. Twenty % propylene glycol is administered to animals in the vehicle treated group and control SD rats[4].

[References]

[1]. Pajor AM, et al. Inhibitor binding in the human renal low- and high-affinity Na+/glucose cotransporters. J Pharmacol Exp Ther. 2008 Mar;324(3):985-91.

[2]. Nakagawa A, et al. Localization of the phlorizin site on Na, K-ATPase in red cell membranes. J Biochem. 1977 May;81(5):1511-5.

[3]. Chang WT, et al. Evaluation of the anti-inflammatory effects of phloretin and phlorizin in lipopolysaccharide-stimulated mouse macrophages. Food Chem. 2012 Sep 15;134(2):972-9.

[4]. 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):161-9.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Boiling Point ]:
770.0±60.0 °C at 760 mmHg

[ Melting Point ]:
113-114 °C(lit.)

[ Molecular Formula ]:
C₂₁H₂₄O₁₀

[ Molecular Weight ]:
436.409

[ Flash Point ]:
270.7±26.4 °C

[ Exact Mass ]:
436.136932

[ PSA ]:
177.14000

[ LogP ]:
0.45

[ Vapour Pressure ]:
0.0±2.8 mmHg at 25°C

[ Index of Refraction ]:
1.686

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UC2080000

CHEMICAL NAME :: 1-Propanone, 1-(2-(beta-D-glucopyranosyloxy)-4,6-dihydroxyphenyl)- 3-(4-hydroxyphenyl)-

CAS REGISTRY NUMBER :: 60-81-1

LAST UPDATED :: 199512

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C21-H24-O10

MOLECULAR WEIGHT :: 436.45

WISWESSER LINE NOTATION :: T6OTJ B1Q CQ DQ EQ FOR CQ EQ BV2R DQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CBCCT* "Summary Tables of Biological Tests," National Research Council Chemical-Biological Coordination Center. (National Academy of Science Library, 2101 Constitution Ave., NW, Washington, DC 20418) Volume(issue)/page/year: 6,226,1954 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 600 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: 85DJA5 "Malformations Congenitales des Mammiferes," Tuchmann-Duplessis, H., Paris, Masson et Cie, 1971 Volume(issue)/page/year: -,95,1971

Safety Information

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S36

[ WGK Germany ]:
3

[ RTECS ]:
UC2080000

Phlorizin

Names

Biological Activity

Chemical & Physical Properties

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

Safety Information

Synthetic Route

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Precursor & DownStream

Precursor

DownStream

Related Compounds