Phloridzin

Phloridzin is a natural product, a dihydrochalcone glucoside found in apples (Malus domestica) and related species, particularly in the bark, leaves, and unripe fruits. It is the glucoside form of phloretin, consisting of phloretin bound to glucose at the 2' position (phloretin 2'-O-glucoside).

Chemically, phloridzin is a glycoside of the dihydrochalcone phloretin. It is hydrolyzed in vivo by glucosidases to yield phloretin and glucose, with the aglycone phloretin capable of interacting with various cellular transporters.

Biologically, phloridzin inhibits sodium-glucose cotransporters SGLT1 in the intestine and SGLT2 in the kidney in vitro, reducing glucose uptake. In vivo, its effects largely arise from hydrolysis to phloretin, which inhibits additional glucose transporters such as GLUT1 and GLUT2. Because of this, phloridzin is primarily used as a research tool to study glucose transport rather than as a therapeutic agent.

Occurrence and chemistry notes: it is found in the bark and leaves of apple trees and in some other members of the Rosaceae family. As a glycoside, it is readily hydrolyzed to release phloretin and glucose.

History and use: phloridzin was identified in the 19th century from apple-derived extracts. Although it was historically important as a natural SGLT inhibitor, its clinical use is limited due to instability, rapid hydrolysis to phloretin, and non-specific transporter inhibition. It remains a common reagent in laboratory studies of glucose transport.