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Potent and specific inhibitors of hyaluronidases, a group of enzymes preferentially catalysing the hydrolysis of hyaluronic acid, are not known so far. Such compounds could be useful as pharmacological tools for studying the physiological and pathophysiological role of both hyaluronan and hyaluronidases. The effects of sulphated and non-sulphated structurally different oligosaccharides on bovine testicular hyaluronidase, hyaluronidase from bee venom and hyaluronate lyase from Streptococcus agalactiae (hylB (4755)) were studied with the Morgan-Elson reaction. Several active compounds were identified within a series of sulphated beta-(1,4)-galacto-oligosaccharides. The determined IC (50) values of these sulphated oligosaccharides ranged from 4 microM to 630 microM for all hyaluronan-degrading enzymes. Sulphated oligosaccharides like verbascose, planteose and neomycin showed comparable inhibition on all hyaluronidases, thereby possessing 100 - 500 times the activity of the widely accepted hyaluronidase inhibitor apigenin.

The ethanolic extract of Ilex aquifolium L. (Aquifoliaceae) concentration-dependently inhibited leukotriene B4 biosynthesis in isolated bovine PMNL with an IC50 value of about 60 micrograms/ml, whereas the effect on epidermal 12(S)-HETE biosynthesis was much less pronounced. The extract also inhibited the non-enzymatic, peroxyl radical-stimulated lipid peroxidation in model membranes and was further a scavenger of the iron-dependent generation of hydroxyl radicals from hydrogen peroxide as determined by protection against deoxyribose degradation. While inhibition of leukotriene biosynthesis was not mediated by its known phenolic constituents such as hyperoside, rutoside, and chlorogenic acid, these compounds were responsible for the inhibitory effects of I. aquifolium against non-enzymatic lipid peroxidation and deoxyribose degradation.