Protandim – Perhaps A Nrf2 activator and hazardous?
Protandim® is a patented blend of 5 herbal ingredients with antioxidant activity: milk thistle (Silybum marianum) extract (225 mg), bacopa (Bacopa monnieri) extract (150 mg), ashwagandha (Withania somnifera) root (150 mg), green tea (Camellia sinensis) extract (75 mg), and turmeric (Curcuma longa) extract (75 mg).
Cell culture studies have indicated that Protandim® can protect a variety of cell types (cartilage, heart cells, endothelial cells, chondrocytes) from oxidative stress damage and activate the Nrf2 antioxidant pathway when Protandim® is applied to the cells directly[4; 5; 6]. According to the manufacturer, Protandim can cause allergic responses, gastrointestinal disturbances (stomach ache, diarrhea, vomiting), headache, and rash of the hands and feet.
HOWEVER, NRF2 activation promotes the recurrence of dormant tumour cells through regulation of redox and nucleotide metabolism [Nature Metabolism volume 2, pages318–334 (2020)]. AND burgeoning evidence has revealed a detrimental role of Nrf2 in cardiac pathological remodeling and dysfunction toward heart failure. In this mini-review, we outline recent advances in structural features of Nrf2 and regulation of Nrf2 activity and discuss the emerging dark side of Nrf2 in the heart as well as the potential mechanisms of Nrf2-mediated myocardial damage and dysfunction.
Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) is a critical transcription factor that regulates the expression of over 1000 genes in the cell under normal and stressed conditions. These transcripts can be categorized into different groups with distinct functions, including antioxidative defense, detoxification, inflammatory responses, transcription factors, proteasomal and autophagic degradation, and metabolism. Nevertheless, Nrf2 has been historically considered as a crucial regulator of antioxidant defense to protect against various insult-induced organ damage and has evolved as a promising drug target for the treatment of human diseases, such as heart failure. However, burgeoning evidence has revealed a detrimental role of Nrf2 in cardiac pathological remodeling and dysfunction toward heart failure
