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Soyasaponin Bb acts as aldose reductase differential inhibitor

 

Saponins are amphiphilic compounds of plant origin composed of a steroidal or triterpenoid aglycone moiety linked to sugar chains. They are biologically active and have anti-inflammatory, immunomodulatory, hypocholesterolemic and cytotoxic properties. Saponins are also antioxidants, have anti-diabetic action and were shown to inhibit aldose reductase (AHR1B1). 

Aldose reductase is a cytosolic NADPH-dependent oxidoreductase catalysing the reduction of hydrophilic and hydrophobic aldehydes. It is a drug target for counteraction of secondary diabetic complications since it contributes to production of ROS in hyperglycemic conditions. 

A recent paper examined saponin extracts from Zolfino bean and performed kinetic studies on the inhibition of human recombinant aldose reductase (hAHR1B1) with soyasaponins. 

Saponin extracts from Zolfino bean were screened for their inhibitory activity on aldose reductase. Known compounds in the active fractions were identified as soyasaponin Ba and Bb. Kinetic studies were performed with purified soyasaponins from Carbosynth to investigate whether they preferentially inhibit the reduction of sugar molecules. 

Inhibition curves of aldose reductase activity were performed with two different substrates, L-idose from Carbosynth and 4-hydroxynonenal. This experimental designed allowed the distinction between broad spectrum aldose reductase inhibitor (ARI), affecting reduction of hydrophilic and hydrophobic aldehydes, and aldose reductase differential inhibitor (ARDI), which preferentially inhibits reduction of sugar molecules. 

Substrate

Soyasaponin Ba

Soyasaponin Bb

L-idose

IC50 = 40 μM

IC50 = 170 μM

4-hydroxynonenal

IC50 = 47 μM

IC50 = 360 μM

Table 1. Half maximal inhibitor concentrations (IC50) obtained from kinetic studies with human recombinant aldose reductase. 

 

The results showed that soyasaponin Ba behaves as an ARI because it inhibits L-idose  and HNE reduction with the same effectiveness. Soyasaponin Bb showed ARDI properties since it inhibited L-idose reduction more efficiently than HNE reduction.

 

For more details, read the original paper published in the Journal of Enzyme Inhibition and Medicinal Chemistry: Balestri et al., 2018

 

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