Phlorizin: Nature, Sources, and Pharmacological Properties
Phlorizin is a naturally occurring dihydrochalcone (phenylpropanoid) compound primarily found in apple trees (Malus species), with significant pharmacological properties including inhibition of sodium-glucose transporters, which has led to its use as a prototype for developing antidiabetic medications. 1, 2
Natural Sources and Distribution
- Phlorizin was first isolated from the bark of apple trees and is predominantly found in plants of the Malus genus 1
- It has a species- and tissue-specific distribution within apple trees, with high concentrations found in the bark 2
- Few other plant species contain phlorizin, and when present, it's typically in much lower amounts compared to apple trees 2
Chemical Structure and Properties
- Phlorizin (also spelled phloridzin, phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a dihydrochalcone glycoside 2
- Chemically, it consists of phloretin (the aglycone) linked to glucose via a 2'-O-glycosidic bond 2
- It belongs to the flavonoid class of compounds with significant biological activity 3
Biosynthesis
- The biosynthesis of phlorizin involves several enzymes including:
- NADPH-dependent dehydrogenase
- Chalcone synthase
- UDP-glucose:phloretin 2'-O-glycosyltransferase 2
- This biosynthetic pathway has been confirmed through studies with recombinant enzymes and plant protein extracts 2
Extraction Methods
- Extraction methods for phlorizin are similar to those used for other phenolic compounds 1
- Common techniques include:
- High-speed countercurrent chromatography (HSCCC)
- Resin adsorption technology
- Preparative high-performance liquid chromatography (HPLC) 1
Pharmacological Properties and Mechanisms
- Phlorizin's primary pharmacological action is inhibition of sodium-glucose symporters (SGLT), particularly in:
- Proximal renal tubules (causing renal glycosuria)
- Small intestine mucosa (blocking glucose absorption) 4
- It has been identified as a flavonoid that can inhibit various enzymes and transport proteins important in drug disposition 5
- When ingested, phlorizin is hydrolyzed in the body to phloretin, which has different pharmacological properties 6
Therapeutic Applications
- Antidiabetic effects: Served as a prototype for developing SGLT inhibitors for diabetes treatment 4
- Anti-inflammatory properties: Regulates the IL-1β/IKB-α/NF-KB signaling pathway 3
- Antibacterial activity: Reduces intracellular DNA agglutination, protein synthesis, energy production, and disrupts cellular metabolism 3
- Additional reported effects include:
Clinical Significance
- Phlorizin has been used in medical research for over 150 years, particularly in diabetes and renal physiology studies 4
- It has contributed significantly to understanding fundamental concepts in renal physiology and glucose transport mechanisms 4
- Modern antidiabetic medications (SGLT2 inhibitors) were developed using phlorizin as a prototype, but with more selective inhibitory activity toward glucose transport in the kidney 6
Potential Drug Interactions
- As a flavonoid, phlorizin may decrease the activity of certain enzymes and transport proteins involved in drug metabolism 5
- It can potentially affect drug bioavailability through inhibition of intestinal cytochrome P450 3A4 (CYP3A4) 5
- However, coadministration of phlorizin with medications is not automatically contraindicated; assessment should consider:
- The amount and type of phlorizin being ingested
- Specific information about the interaction
- Whether the drug has low bioavailability 5
Phlorizin represents an important natural compound that has significantly contributed to our understanding of glucose transport mechanisms and led to the development of modern antidiabetic medications, while continuing to show promise for various therapeutic applications.