期刊
FRONTIERS IN PHARMACOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.00151
关键词
catechol; quinone; electrophiles; NRF2; KEAP1; cytoprotection; oxidative stress; inflammation
资金
- Spanish Ministry of Economy and Competiveness [SAF2016-76520-R]
- Spanish Tatiana de Guzman el Bueno Foundation [P-024-FTPGB 2018]
- European Regional Development Fund, Competitiveness Operational Program 2014-2020 [P_37_732/2016]
- Consejo Nacional de Ciencia y Tecnologia (CONACY, Mexico)
- Posgrado en Ciencias Biologicas at UNAM
- Comunidad Autonoma de Madrid [B2017/BMD-3827]
Nordihydroguaiaretic acid (NDGA) is a phenolic lignan obtained from Larrea tridentata, the creosote bush found in Mexico and USA deserts, that has been used in traditional medicine for the treatment of numerous diseases such as cancer, renal, cardiovascular, immunological, and neurological disorders, and even aging. NDGA presents two catechol rings that confer a very potent antioxidant activity by scavenging oxygen free radicals and this may explain part of its therapeutic action. Additional effects include inhibition of lipoxygenases (LOXs) and activation of signaling pathways that impinge on the transcription factor Nuclear Factor Erythroid 2-related Factor (NRF2). On the other hand, the oxidation of the catechols to the corresponding quinones my elicit alterations in proteins and DNA that raise safety concerns. This review describes the current knowledge on NDGA, its targets and side effects, and its synthetic analogs as promising therapeutic agents, highlighting their mechanism of action and clinical projection towards therapy of neurodegenerative, liver, and kidney disease, as well as cancer.
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