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CDDO and Its Role in Chronic Diseases
1Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina, 29208, USA.
Advances in Experimental Medicine and Biology
|October 25, 2016
Summary
Oleanolic acid derivatives, like CDDO, show promise in treating inflammation and kidney disease by activating the Nrf2 antioxidant pathway. Further research is needed for cancer and cardiovascular applications.
Area of Science:
- Translational research
- Natural product chemistry
- Medicinal chemistry
Background:
- Oleanolic acid, a traditional Chinese medicine, is a precursor for novel therapeutic agents.
- Chemical modification of oleanolic acid yielded 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO).
- CDDO exhibits enhanced anti-inflammatory activity and potential in treating diverse diseases.
Purpose of the Study:
- To investigate the therapeutic potential of CDDO and its derivatives.
- To elucidate the mechanism of action involving the Nrf2 pathway.
- To contextualize current clinical trial outcomes for future therapeutic development.
Main Methods:
- Chemical modification of oleanolic acid to synthesize CDDO.
- Investigating CDDO's effect on the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
- Reviewing preclinical and clinical trial data for various conditions.
Main Results:
- CDDO significantly increases anti-inflammatory activity compared to oleanolic acid.
- CDDO upregulates Nrf2 by altering the Keap1-Nrf2 interaction, activating antioxidant genes.
- Positive outcomes observed in laboratory and clinical trials for lung injury, inflammation, and chronic kidney disease.
Conclusions:
- CDDO derivatives represent a promising class of compounds targeting the Nrf2 pathway.
- While effective for certain conditions, CDDO's efficacy in cancer and cardiovascular diseases requires further investigation.
- Continued research is essential to optimize CDDO-based therapies and address limitations.
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