Preparative isolation and identification of tyrosinase inhibitors from the seeds of Garcinia kola by high-speed counter-current chromatography.

In continuation of our search for bioactive natural products that can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation, 50 extracts/fractions from 21 families of medicinal plants from West and Central Africa were evaluated for inhibitory activity against tyrosinase (E:C:1.14.18.1), the rate-limiting enzyme in melanin synthesis. Four extracts including the methanol extract of Garcinia kola seeds at 100 microg/ml displayed >60% inhibition of tyrosinase activity. Preparative high-speed counter-current chromatography with solvent system composed of n-hexane-ethyl acetate-methanol-water (3:5:3:5) successfully separated the most active extract from G. kola seed. By stepwise increase of the flow-rate of the mobile phase, five major biflavanones including GB-I-glucoside (1) GB-1a (2), GB-1 (3), GB-2 (4), kolaflavonone (5) were successfully isolated in 6 h. Compound (4) was the most potent (IC(50) 582 microM) and compared favorably with a reference tyrosinase inhibitor (kojic acid, IC(50) 130 microM).

Protease inhibitors and their peptidomimetic derivatives as potential drugs.

Precise spatial and temporal regulation of proteolytic activity is essential to human physiology. Modulation of protease activity with synthetic peptidomimetic inhibitors has proven to be clinically useful for treating human immunodeficiency virus (HIV) and hypertension and shows potential for medicinal application in cancer, obesity, cardiovascular, inflammatory, neurodegenerative diseases, and various infectious and parasitic diseases. Exploration of natural inhibitors and synthesis of peptidomimetic molecules has provided many promising compounds performing successfully in animal studies. Several protease inhibitors are undergoing further evaluation in human clinical trials. New research strategies are now focusing on the need for improved comprehension of protease-regulated cascades, along with precise selection of targets and improved inhibitor specificity. It remains to be seen which second generation agents will evolve into approved drugs or complementary therapies.