Natural compounds for inhibition of human Hyal-1

Lengers I, Orlando Z, Brandt S, Melzig M.F, Buschauer A, Hensel A, Jose J

Abstract

Surface display of active Hyal-1 on Escherichia coli via Autodisplay enables the screening for potential inhibitors in a whole cell system. Based on this technique we determined the inhibitory effect of different plantextractsand natural compounds on human Hyal-1. The IC50 values of Malvae sylvestris flos, Equiseti herba, Ononidis radix and Althaea officinalis (A. officinalis) were determined between 1.4 and 7.7 mg/mL.Furthermore, the IC50 values of four saponines were determined. The obtained IC50 value for glycyrrhizic acid, a known Hyal-1 inhibitor, was 177 μM. The IC50 values for the identified novel inhibitorsgypsophila saponin 2, SA1641, and SA1657 were 108, 296 and 371 μM, respectively.[1] These extracts and compounds can be used as a starting point for the synthesis of new small molecule inhibitors targetinghuman Hyal-1. Extracts of A. officinalis are indicated for patients who suffer for dry cough to smooth mouth membranes. In an eukaryotic cell assay with a HaCaT keratinocyte cell line, the gene expression of hyal-1was determined after treatment with 125 μg/mL and 250 μg/mL of a root extract of A. officinalis for 24 h. HaCaT keratinocytes were chosen as a model cell line to represent skin and mucosal epithelial cells,considering the topical application of A. officinalis in pharmaceutical usage. It could have been shown, that treatment with the A. officinalis decreases expression of hyal-1 gene in HaCaT cells by 30 %. In conclusion,A. officinalis does not only inhibit the enzymatic activity of Hyal-1 but also led to a decrease in hyal-1 expression.