ZHOU Rongbin and JIANG Wei from University of Science and Technology of China of Chinese Academy of Sciences, collaborating with DENG Xianming from Xiamen University, showed how Oridonin (Ori), the major ingredient of Chinese medicinal herb Rabdosia rubescens, targets NLRP3 to exert its anti-inflammatory activity, which shed light on treatment for NLRP3-related diseases.
NLRP3 inflammasome is a multiple protein complex whose activation contributes to the progress of several human diseases, such as type 2 diabetes (T2D), atherosclerosis and neurodegenerative diseases. However, no clinical medicine targeting to NLPR3 has been found.
Inspired by the wide use of traditional Chinese medicinal herbs in anti-inflammatory treatment, researchers tested the effect of Ori in blocking NLRP3 activation and revealed the mechanism behind.
Study showed that Ori forms a covalent bond with the cysteine 279 of NLRP3 in NACHT domain to block the interaction between NLRP3 and NEK7, thereby inhibiting NLRP3 inflammasome assembly and activation.
Scientists also conducted experiments on mice. Results suggested that Ori has both preventive and therapeutic effects on mouse models of peritonitis, gouty arthritis and T2D, via inhibition of NLRP3 activation.
This discovery caters for both industrial and academical need in intervening NLRP3-driven diseases. The study was published in Nature Commuication.
In the future, Ori might serve as a lead in developing new therapies and help more patients.
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