1. TARGET IDENTIFICATION AND VALIDATION OF (+)-2-(l-HYDROXYL-4-OXOCYCLOHEXYL) ETHYL CAFFEATE, AN ANTI-INFLAMMATORY NATURAL PRODUCT.
- Author
-
L. LI, H-W. ZENG, F. LIU, J-G. ZHANG, R-C. YUE, W-Q. LU, X. YUAN, W-X. DAI, H. YUAN, Q-Y. SUN, J. HUANG, H-L. LI, Y-S. LI, L. SHAN, and W-D. ZHANG
- Subjects
- *
ANTI-inflammatory agents , *NATURAL products , *BIGNONIACEAE , *INFLAMMATION , *ENZYMATIC analysis , *ARACHIDONIC acid , *LIPOXYGENASES , *THERAPEUTICS - Abstract
(+)-2-(l-hydroxyl-4-oxocyclohexyl) ethyl caffeate (HOEC) was isolated from Incarvillea mairei var. grandiflora (Wehrhahn) Grierson. The plants of the Incarvillea genus have long been used as folk medicines for the treatment of inflammation-related diseases in China. 5-Lipoxygenase (5-LOX), a key enzyme in the arachidonic acid (AA) cascade, was identified as a potential target of HOEC by a pulldown assay, and then extensively validated by biosensor-based affinity detection, enzyme-based activity assays, cell-based AA metabolite analysis and computer-aided AA network simulation. Further in vivo studies of AA-induced ear oedema, ovalbumin (OVA)-induced lung inflammation and collagen-induced arthritis demonstrated the anti-inflammatory potency and validated the therapeutic target of HOEC. This work revealed that HOEC acted as an anti-inflammatory agent targeting 5-LOX, which not only confirmed the key role of 5-LOX in inflammation but also provided a paradigm for the exploration of natural product mechanisms of action. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF