Apples have often been associated with ‘keeping the good doctor at bay’ and one of the reasons would be the presence of phloretin and phloridzin. The epidemiology studies of Knecht (1996) & Mennen (2004) on the ingestion of apples might be due to the presence of these agents. Phloretin and its glucoside phloridzin are abundant in apples, especially the peel (Escarpa & González, 1998; Tsao et al., 2003). Structurally, it is a dihydrochalcone derivative. For many years the occurrence of phloretin was considered to be restricted to apples but it has also been identified and isolated from strawberries. This certainly extends our knowledge of the natural sources of this polyphenolic compound (Hilt et al., 2003) and is likely to be found to varying extents in other fruit.
The main biological action of phloretin is the inhibition of the glucose cotransporter1 (Raja et al, 2003; Xiao & Cant, 2003) which makes it a universal glucose modulator. Phloretin furthermore possesses antioxidative properties because studies revealed that apples generally exert these activities, attributed to phytochemicals present in the skin (Eberhardt et al., 2000). Phloretin and phloridzin thus accounts in part for the antioxidative capacity of apples (Lee et al., 2003). Other studies have established the pharmacophore responsiblefor the antioxidative activity of phloretin (Rezk et al., 2002; Nakamura et al., 2003). It also has antipyretic action being able to modulate fever.
The biochemical evidence has focussed on its glucose modulation activity. In the small intestine, phloridzin affects glucose uptake through competitive interactions with enteric sugar transport and the facilitated transporters for glucose in GLUT2 for example. Phloridzin has a higher binding affinity for these transporters. In the kidney, it inhibits active transporters such as SGLT1 and 2 in the renal proximal tubular cells and so promotes renal glycosuria. One study in diabetic dogs showed phloridzin induced polyuria, weight loss and normalisation on insulin resistance. In muscles, phloridzin decreases GLUT4 availability (Ehrenkranz et al., 2005).
Phloridzin also affects hormonal levels. Its hypoglycaemic action could be modulated by levels of glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP). Given phloridzin can delay glucose absorption. Where the liver is concerned, phloridzin delays hepatic glucose release and the corresponding post-prandial peak by lowering levels of GIP in the proximal region and increasing GLP-1 in the distal region of the small intestine. Such hormones belong to the incretin family and influence insulin release with concomitant decrease in the synthesis of glucagon. Other studies show that GLUTn transporters are inhibited by phloridzin so lowering fat deposition (Frerichs and Ball, 1964).
References
Eberhardt, M. V., Lee, C. Y. & Liu, R. H. (2000) Antioxidant activity of fresh apples. Nature 405 pp. 903-904.
Ehrenkranz, J.R., Lewis, N.G., Kahn, C.R. Roth, J. (2005) Phlorizin: a review. Diabetics Metab. Res. Rev. 21 pp. 31-38 doi: 10.1002/dmrr.532
Escarpa, A. & González, M. C. (1998) High-performance liquid chromatography with diode-array detection for the determination of phenolic compounds in peel and pulp from different apple varieties. J. Chromatogr. A 823 pp. 331-337
Frerichs, H. Ball, E.G. (1964) Studies on the metabolism of adipose tissue. XVI. Inhibition by phlorizin and phloretin of the insulin-stimulated uptake of glucose. Biochemistry 3 pp. 981-085.
Hilt, P., Schieber, A., Yildirim, C., Arnold, G., Klaiber, I., Conrad, J., Beifuss, U. & Carle, R. (2003) Detection of phloridzin in strawberries (Fragaria x ananassa Duch.) by HPLC-PDA-MS/MS and NMR spectroscopy. J. Agric. Food Chem. 51 pp. 2896-2899
Lee, K. W., Kim, Y. J., Kim, D. O., Lee, H. J. & Lee, C. Y. (2003) Major phenolics in apple and their contribution to the total antioxidant capacity. J. Agric. Food Chem. 51 pp. 6516-6520
Raja, M. M., Tyagi, N. K. & Kinne, R.K.H. (2003) Phlorizin recognition in a C-terminal fragment of SGLT1 studied by tryptophan scanning and affinity labeling. J. Biol. Chem. 278 pp. 49154-49163
Rezk, B. M., Haenen, G.R.M.M., van der Vijgh, W.J.F. & Bast, A. (2002) The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids. Biochem. Biophys. Res. Commun. 295 pp. 9-13.
Nakamura, Y., Watanabe, S., Miyake, N., Kohno, H. & Osawa, T. (2003) Dihydrochalcones: evaluation as novel radical scavenging antioxidants. J. Agric. Food Chem. 51: pp. 3309-3312
Stangl et al., (2005) The Flavonoid Phloretin Suppresses Stimulated Expression of Endothelial Adhesion Molecules and Reduces Activation of Human Platelets. J. Nutr. 135 (February) pp. 172-178
Tsao, R., Yang, R., Young, J. C. & Zhu, H. (2003) Polyphenolic profiles in eight apple cultivars using high-performance liquid chromatography (HPLC). J. Agric. Food Chem. 51 pp. 6347-6353
Xiao, C. & Cant, J. P. (2003) Glucose transporter in bovine mammary epithelial cells is an asymmetric carrier that exhibits cooperativity and trans-stimulation. Am. J. Physiol. Cell Physiol. 285 C1226-C1234.
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