:Phlorizin
{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 464204632
| ImageFile = Phlorhizin.svg
| ImageSize = 200px
| IUPACName = 1-[2-(β-D-Glucopyranosyloxy)-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one
| SystematicName = 1-(2,4-Dihydroxy-6-
| OtherNames = Isosalipurposide
| Section1 = {{Chembox Identifiers
| IUPHAR_ligand = 4757
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = CU9S17279X
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 245067
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 60-81-1
| PubChem = 6072
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 8113
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 16498836
| SMILES = c1cc(ccc1CCC(=O)c2c(cc(cc2O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)O)O)O)O)O
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = IOUVKUPGCMBWBT-QNDFHXLGSA-N
}}
| Section2 = {{Chembox Properties
| C=21 | H=24 | O=10
| Appearance = White solid
| Density =
| MeltingPtC = 106 to 109
| BoilingPtC = 200
| BoilingPt_notes = decomposition
| Solubility = water, low MW alcohols
}}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}
Phlorizin is a glucoside of phloretin, a dihydrochalcone. A white solid, samples often appear yellowing to impurities. It is of sweet taste and contains four molecules of water in the crystal. It is poorly soluble in ether and cold water, but soluble in ethanol and hot water. Upon prolonged exposure to aqueous solutions phlorizin hydrolyzes to phloretin and glucose.
Occurrence
Phlorizin is found primarily in unripe Malus (apple){{cite journal |last1=Makarova |first1=Elina |last2=Górnaś |first2=Paweł |last3=Konrade |first3=Ilze |last4=Tirzite |first4=Dace |last5=Cirule |first5=Helena |last6=Gulbe |first6=Anita |last7=Pugajeva |first7=Iveta |last8=Seglina |first8=Dalija |last9=Dambrova |first9=Maija |display-authors=7 |date=2015 |title=Acute anti-hyperglycaemic effects of an unripe apple preparation containing phlorizin in healthy volunteers: A preliminary study |journal=Journal of the Science of Food and Agriculture |volume=95 |issue=3 |pages=560–568 |doi=10.1002/jsfa.6779 |pmid=24917557}} root bark of apple,{{cite journal |last=Bays |first=Harold |date=2013 |title=Sodium glucose co-transporter type 2 (SGLT2) inhibitors: Targeting the kidney to improve glycemic control in diabetes mellitus |journal=Diabetes Therapy |volume=4 |issue=2 |pages=195–220 |doi=10.1007/s13300-013-0042-y |doi-access=free |pmc=3889318 |pmid=24142577}} and trace amounts have been found in strawberry.{{cite journal |last1=Hilt |first1=Petra |last2=Schieber |first2=Andreas |last3=Yildirim |first3=Caner |last4=Arnold |first4=Gabi |last5=Klaiber |first5=Iris |last6=Conrad |first6=Jürgen |last7=Beifuss |first7=Uwe |last8=Carle |first8=Reinhold |display-authors=7 |date=2003 |title=Detection of phloridzin in strawberries (Fragaria x ananassa Duch.) by HPLC–PDA–MS/MS and NMR spectroscopy |journal=Journal of Agricultural and Food Chemistry |volume=51 |issue=10 |pages=2896–2899 |doi=10.1021/jf021115k |pmid=12720368}} In Malus, it is most abundant in vegetative tissues (such as leaves and bark) and seeds. Closely related species, such as pear (Pyrus communis), cherry, and other fruit trees in the Rosaceae do not contain phlorizin.{{cite journal |last1=Gosch |first1=Christian |last2=Halbwirth |first2=Heidi |last3=Stich |first3=Karl |date=2010 |title=Phloridzin: Biosynthesis, distribution and physiological relevance in plants |journal=Phytochemistry |volume=71 |issue=8–9 |pages=838–843 |doi=10.1016/j.phytochem.2010.03.003 |pmid=20356611}} Phlorizin is a phytochemical that belongs to the class of polyphenols. In natural sources, it may occur with other polyphenols such as quercetin, catechin, epicatechin, procyanidins, and rutin.
Pharmacology
Phlorizin is an inhibitor of SGLT1 and SGLT2 because it competes with D-glucose for binding to the carrier; this action reduces renal glucose transport, lowering the amount of glucose in the blood.{{cite journal |last1=Rossetti |first1=Luciano |last2=Smith |first2=Douglas |last3=Shulman |first3=Gerald I. |last4=Papachristou |first4=Dimitrios |last5=DeFronzo |first5=Ralph A. |date=1987 |title=Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats |journal=The Journal of Clinical Investigation |volume=79 |issue=5 |pages=1510–1515 |doi=10.1172/JCI112981 |doi-access=free |pmc=424427 |pmid=3571496}}{{cite journal |last1=Tatoń |first1=Jan |last2=Piątkiewicz |first2=Paweł |last3=Czech |first3=Anna |date=2010 |title=Molecular physiology of cellular glucose transport – A potential area for clinical studies in diabetes mellitus |journal=Endokrynologia Polska |url=https://journals.viamedica.pl/endokrynologia_polska/article/view/25386 |volume=61 |issue=3 |pages=303–310 |pmid=20602306}} Phlorizin was studied as a potential pharmaceutical treatment for type 2 diabetes, but has since been superseded by more selective and more promising synthetic analogs, such as empagliflozin, canagliflozin and dapagliflozin.{{cite journal |last1=Chao |first1=Edward C. |last2=Henry |first2=Robert R. |date=2010 |title=SGLT2 inhibition – A novel strategy for diabetes treatment |journal=Nature Reviews Drug Discovery |volume=9 |issue=7 |pages=551–559 |doi=10.1038/nrd3180 |pmid=20508640}} Phlorizin is not an effective drug because when orally consumed, it is nearly entirely converted into phloretin by hydrolytic enzymes in the small intestine.{{cite journal |last1=Idris |first1=Iskandar |last2=Donnelly |first2=Richard |date=2009 |title=Sodium–glucose co-transporter-2 inhibitors: An emerging new class of oral antidiabetic drug |journal=Diabetes, Obesity and Metabolism |volume=11 |issue=2 |pages=79–88 |doi=10.1111/j.1463-1326.2008.00982.x |doi-access= |pmid=19125776}}{{cite journal |last1=Crespy |first1=Vanessa |last2=Aprikian |first2=Olivier |last3=Morand |first3=Christine |last4=Besson |first4=Catherine |last5=Manach |first5=Claudine |last6=Demigné |first6=Christian |last7=Rémésy |first7=Christian |date=2001 |title=Bioavailability of phloretin and phloridzin in rats |journal=The Journal of Nutrition |volume=131 |issue=12 |pages=3227–3230 |doi=10.1093/jn/131.12.3227 |doi-access=free |pmid=11739871}}
References
{{Reflist}}
{{Dihydrochalcones}}
{{Purine receptor modulators}}
{{Sodium-glucose transporter modulators}}