Advancement on discovery of anti-arthritis using Chinese herbal medicine by the Macau University of Science and Technology

Group photo with Chair Professor Liu Liang and the research team
Group photo with Chair Professor Liu Liang and the research team

Following the “2012 National Science and Technology Progress Award”, the research team led by Chair Professor Liu Liang on anti-arthritis using Chinese herbal medicine from the Macau University of Science and Technology, have recently identified a compound derived from medicinal herb, dihydromyricetin (DMY), to be potent directly in suppressing the kinase activity of an inflammatory protein IKK-b via cysteine-46 residue, leading to inhibition of IKK-b-NF-kB signaling pathway, and thereby produces anti-arthritis effect. The discovery of novel drug binding site “Cys-46” of IKK-b was recently granted for innovation patent by the Australia government. These innovative findings also provided important information in developing the drug screening platform for the discovery of new IKK-b inhibitors.

IKK-b is a key regulatory protein kinase for activation of T lymphocytes and other immune-component cells, while activation of IKK-b-NF-kB signaling has been proven to play a central role in the progression of cancers, autoimmune disease like rheumatoid arthritis and various inflammatory diseases. Therefore, discovery of IKK-b inhibitors has become the most promising area of research for medical science and pharmaceutical industry. In the past years, the Cys-179 residue and ATP binding site are the most well-known targeted sites of the existing IKK-b inhibitors, therefore, small-molecules and natural compounds which can target one of these drug binding sites, are capable to inhibit the kinase activity of IKK-b, and thereby suppressing inflammatory diseases and cancers. Recently, the research team led by Chair Professor Liu has successfully identified a novel drug binding site, Cys-46 residue of IKK-b, and generated the gene mutant mice harboring the C46A mutation on IKK-b. Their findings could be further developed and applied in the new arena of target drug discovery for treatment of inflammatory diseases and cancers.

Inflammatory diseases and cancers are the major health threat of humans. At the same time, IKK-b and IKK-b-NF-kB signalling activation have been proven as the common and major pathogenesis of those diseases. Nowadays, research on personalized medicine which emphasizes the study on the individual gene expression and mutation profile, has become an hot topic in medical science and played an important role for identifying suitable and specific target drugs for treating individual patients with lung, colon or breast cancer. However, due to the fact that the genes expression profile and mutation pattern are varied among individual patients, the existing target therapy drugs may only show promising efficacy in particular group of patients, but not all. As a result, those patients harbouring specific gene expression pattern or gene mutation are still lacking of effective drug. For instance, the Cys-179 residue and ATP binding site are the most well-known targeted sites of the existing IKK-b inhibitors. Mutation of these two drug binding sites on IKK-b prevents those inhibitors from suppressing the kinase activity, while binding of DMY onto the Cys-46 residue of IKK-b is able to overcome the drug resistant phenotype of IKK-b mutants with mutations on the Cys-179 residue and ATP binding region. In this connection, identification of a new drug binding site, Cys-46 on IKK-b protein, may provide a new technical platform for screening anti-inflammatory and anti-cancer agents.

All inventors of this innovative patent are come from the State Key Laboratory of Quality Research in Chinese Medicine, including Chair Professor Liang Liu, Dr. Ting Li, Dr. Vincent Kam Wai Wong, Professor Zhi Hong Jiang and Dr. Hua Zhou.