Cathepsin K Inhibitors Isolated from Ginger Rhizome

Zingiber officinale Roscoe, Zingiberaceae, is an herb used since ancient times as a spice and medicinal plant to treat several illnesses, particularly osteoarthritis. Some clinical/preclinical studies have highlighted the anti-arthritic effect of ginger extracts, making it promising in the search of drugs that can be used in the treatment of diseases such as arthritis and osteoarthritis. Hence, a bioassay-guided study was carried out using cathepsin K, an important target involved in these pathologies. After successive chromatographic fractionation, 15 compounds were isolated and identified from ginger dichloromethane-soluble fraction. The compounds with the greatest inhibitory effect were [10]-shogaol (IC 50 5.8 ± 0.4 μM), [10]-gingerol (IC 50 10.4 ± 0.2 μM), and [8]-shogaol (IC 50 21.1 ± 2.4 μM). For [10]-gingerol, the inhibition type was determined to be uncompetitive. [10]-Gingerol was docked on the allosteric site of the cathepsin K, which corroborated the experimentally determined inhibitory effect. Therefore, gingerols have a great potential to become candidates as natural antiresorptive drugs. Graphical abstract