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DOI: 10.1055/s-0033-1352012
Plant-derived inhibitors of human hyaluronidases
There is a rich tradition in application of natural products in various medical areas: as anti-inflammatory drugs up to drugs in cancer treatment.
Hyaluronidases (HAases) appear to be important in many pathophysiological processes, though they are poorly characterized. HAases degrade Hyaluronan (HA), which is a crucial component of the extracellular matrix. Various studies of HAases and HA suggest that an imbalance of HA metabolism has an influence on cell differentiation, skin aging, formation and progression of arthritic diseases and multiple sclerosis and on cancer biology [1].
Concerning their importance in HA metabolism human HAases offer opportunities for drug development. However there is a challenge to obtain catalytically active HAases for in vitro studies. All attempts to gain recombinant active Hyaluronidases in Escherichia coli were unsuccessful. Furthermore, expression in eukaryotic systems provides only low amounts of protein at high expenses [2].
Via Autodisplay technology we express functional human Hyaluronidases at the surface of E. coli. These surface displayed enzymes are then available for investigation and high-throughput screening of inhibitors [3]. In this study we report about Glycyrrhizic acid and curcumin as inhibitors toward human Hyaluronidases and we focus on new plant-derived inhibitors. These substances could serve as starting point leading to the development of new plant drugs against diseases associated with Hyaluronidase activity.
References:
[1] Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: An information-rich system. Eur J of Cell Biology 85: 699 – 715.
[2] Hofinger ESA, Bernhardt G, Buschauer A (2007a) Kinetics of Hyal-1 and PH-20 hyaluronidases: Comparison of minimal substrates and analysis of the transglycosylation reaction. Glycobiology 17:963 – 971.
[3] Kaeßler A, Olgen S, Jose J (2011) Autodisplay of catalytically active human hyaluronidase hPH-20 and testing of enzyme inhibitors. Eur J of Pharmaceutical Sciences 42:138 – 147.