Chemical Properties
Crystalline Solid
Chemical Properties
White to pale yellow solid.
Uses
A calcium channel protein inhibitor.
Uses
antidiabetic, inhibits glucose transport
Uses
antioxidant cosmetic use
Uses
The aglucon of Phlorizin. A glucose transport inhibitor. Also inhibits protein kinase C and has been shown to inhibit the entry of five enveloped viruses into human fibroblasts.
Definition
ChEBI: A member of the class of dihydrochalcones that is dihydrochalcone substituted by hydroxy groups at positions 4, 2', 4' and 6'.
General Description
Phloretin is a dihydrochalcone?flavonoid with antioxidant activity usually found in apples and apple-derived products. It is extensively used for peroxynitrite scavenging and the inhibition of?lipid peroxidation.
Biological Activity
phloretin is a dihydrochalcone, a type of natural phenols which can be found in apple tree leaves and manchurian apricot. phloretin inhibits the active transport of glucose into cells via sodium-glucose linked transporter (sglt) 1 and 2 with ic50 value of 49±12 μm [2].sglts are a family of glucose transporter which is found in the small intestine mucosa (sglt 1) and nephron proximal tubule (sglt 2). they contribute to the renal glucose reabsorption.after treatment of phloretin, differentiated 3t3-l1 cells exhibited significantly enhanced glycerol and the inhibition of adipogenesis-related transcription factor that were regulated by sglts. additionally, phloretin promoted phosphorylation of amp-activated protein kinase and increased activity of adipose triglyceride lipase and hormone-sensitive lipase [1]. when raw 263.7 cells were cultured from differentiated 3t3-l1 cell media, pt suppressed the sglt-associated nuclear transcription factor kappab and mitogen-activated protein kinase pathways [1].in streptozotocin-induced rat model of diabetes type i, oral administration of phloridzin (5/10/20/40 mg/kg/day) resulted in signi?cant reduction of blood glucose levels and improved dyslipidemia. additionally, administration of phloridzin reduced urine volume and water intake in a dose-dependent manner [3].
Biochem/physiol Actions
Reacts with vic-dicarbonyl compounds such as glyoxal and methylglyoxal, preventing cytotoxic conjugation with biological macromolecules.
Synthesis
Phloretin biosynthesis originates from phenylalanine or tyrosine. In the natural plant pathway, chalcone synthase (CHS) catalyzes the decarboxylative condensation of phloretoyl-CoA with three molecules of malonyl-CoA to form phloretin[4][5][6]. Artificial biosynthetic pathways have been established in yeast and Escherichia coli. These systems produce phloretin by assembling p-coumaroyl-CoA ligase (4CL) and CHS genes, using 3-(4-hydroxyphenyl) propanoic acid as a low-cost raw material. Optimization of these pathways, including stepwise culture and fed-batch fermentation, has achieved production titers up to 619.5 mg/L[5][6].
Purification Methods
Crystallise phloretin from aqueous EtOH. [Zemplen & Bognár Chem Ber 75 1040 1942, Zemplén Chem Ber 76 386 1943, Beilstein 8 IV 3518.]
References
[1] huang w c et al. , phloretin and phlorizin promote lipolysis and inhibit inflammation in mouse 3t3-l1 cells and in macrophage-adipocyte co-cultures. mol nutr food res. 2013, 57: 1807-1817.
[2] kasahara t, kasahara m. expression of the rat glut1 glucose transporter in the yeast saccharomyces cerevisiae. biochem j. 1996, 315 ( pt 1):177-182.
[3] najafian m, jahromi m z, nowroznejhad m j, phloridzin reduces blood glucose levels and improves lipids metabolism in streptozotocin-induced diabetic rats. mol biol rep. 2012, 39(5): 5299-306.
