ABSTRACT
Cathepsin K (CTSK) is considered a critical pharmaceutical target in the treatment of osteoporosis. CTSK exerts proteolytic activities against regulatory proteins besides its collagenase function, which may account for some of the adverse reactions when blocked by active site-directed inhibitors. Exosite inhibitors that can discriminate between the therapeutic collagenase and other biological activities of CTSK specifically inhibit the collagenase activity of CTSK without interfering with the other proteolytic activities of the protease. Active recombinant CTSK was expressed in Pichia pastoris, and purified by n-butyl sepharose and SP sepharose column chromatography. Herba Ecliptae is a common traditional Chinese medicine in the treatment of bone diseases. Collagenase assay and benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin (Z-FR-MCA) substrate assay based on CTSK are applied to verify the exosite inhibitors. n-Butanol extract of Herba Ecliptae are the most active fraction and eclalbasaponin IX isolated from n-butanol fraction is the potential exosite inhibitor of CTSK.
ABSTRACT
Erzhiwan includes two components of Chinese herbal medicines - Ligustri Lucidi Fructus and Herba Eclip-tae .Ligustri Lucidi Fructus ,Herba Ecliptae and their formulation have various hepatoprotective effects .There are many ac-tive ingredients in the formulation ,such as triterpenes ,iridoids ,phenethyl alcohol-glucosides ,coumarin ethers ,etc .They can resist various chemistry-induced hepatic injury ,ischemia reperfusion induced hepatic injury ,and hepatic fibrosis .The mecha-nisms of hepatoprotective effect include anti-oxidative stress ,anti-inflammatory ,inhibition of hyperplasia and activation of liver stellate cell ,motivating the apoptosis of liver stellate cell ,influencing the metabolic processes of liver cell ,ect .We reviewed and summarized the hepatoprotective effects of Erzhiwan and its components Ligustri Lucidi Fructus and Herba Ecliptae and explore the mechanisms of hepatoprotective effect in order to provide information for further research of pharmacodynamic ma-terial base .