Phloridzin Effectively Inhibits Glucose Uptake and Traps Advanced Glycation End Products (AGEs)

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Phloridzin, also known as Phlorizin, is a glucoside of phloretin, a dihydrochalcone, in the family of bicyclic flavonoids.  It is chemically known as phloretin-2′-β-D-glucopyranoside. 

Phloridzin is primarily found in the skins of apples, in particular, the Malus species.  It is also found in the leaves, bark and seeds of the Malus species.

Phloridzin has been shown to be very effective against glycation and advanced glycation end products (AGEs).  Glycation is considered a main factor in the aging process, which is irreversible when it occurs but can be controlled by diet and supplementation. 

Glycation can form either outside the body through various cooking methods of certain foods and/or inside the body by certain chemical metabolic reactions.  Glycation that occurs outside the body is called exogenous glycation and glycation occuring inside the body is called endogenous glycation. 

Endogenous glycation is the chemical result of the bonding of a sugar molecule with a protein or lipid molecule that produces nonfunctioning and deformed molecules known as advanced glycation end products (AGEs).

Figure 1.  Formation of AGEs  (Source: Glycation and ageing: measurement and treatment from Prime-Journal)

AGEs that stem from a glycation reaction, produces cells that are stiffer and less pliable and more subject to damage and premature aging. When glycated proteins fuse together, this is known as cross-linking. The skin, eyes and heart are particular organs subject to cross-linking.

Exogenous glycation occurs when AGEs are formed by heating proteins and lipids with sugar. Certain forms of cooking can accelerate the exogenous glycation process, such as grilling and frying.

Figure 2. AGEs  (Source: Glycation and ageing: measurement and treatment from Prime-Journal)

AGEs have a range of pathological effects, such as:

  • Increased vascular permeability.
  • Oxidizing LDL.
  • Binding cells—including macrophage, endothelial, and mesangial—to induce the secretion of a variety of cytokines – promoting chronic inflammation.
  • Inhibition of vascular dilation by interfering with nitric oxide.
  • Enhanced oxidative stress – free radicals.

Once an AGE is produced through the endogenous glycation process, it is irreversible. It is therefore important to seek ways to prevent glycation, both endogenously and exogenously.

Mechanism of Phloridzin Against Endogenous Glycation

Phloridzin attacks endogenous glycation in two steps. 

First, phloridzin inhibits glucose uptake by 52%.  1  It inhibits glucose from attaching to the lining cells of the intestine and then blocks the active transport of some, but not all, glucose out of those intestinal lining cells into the bloodstream.  2  3

Second, the glucose that is transported to the bloodstream is responsible for the formation of the dangerous carbonyl molecules that react with proteins and DNA to form AGEs.  4

The formation of these AGEs are prevented by phloridzin by trapping the remaining AGEs that are generated.  This lessens the chain reaction that can occur with AGEs detrimentally reacting with other molecules in the body.  5

In an important study from 2008, researchers found that both phloretin and its glucoside, phloridzin, could efficiently trap certain reactive AGEs called MGO and GO, under physiological conditions.

More than 80% MGO was trapped within 10 min, and 68% GO was trapped within 24 h by phloretin. Phloridzin also had strong trapping efficiency by quenching more than 70% MGO and 60% GO within 24 h. 

This study suggests that dietary flavonoids that have the same A ring structure as phloretin may have the potential to trap reactive dicarbonyl species and therefore inhibit the formation of AGEs.   6