Nephroprotective activity of natural products against chemical toxicants: The role of Nrf2/ARE signaling pathway

Nephropathy can occur following exposure of the kidneys to oxidative stress. Oxidative stress is the result of reactive oxygen species (ROS) formation due to intracellular catabolism or exogenous toxicant exposure. Many natural products (NPs) with antioxidant properties have been used to demonstrate that oxidative damage-induced nephrotoxicity can be ameliorated or at least reduced through stimulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Nrf2 is a basic leucine zipper (bZip) transcription factor that regulates gene expression of the antioxidant response elements (ARE). Nrf2 is involved in the cellular antioxidant-detoxification machinery. Nrf2 activation is a major mechanism of nephroprotective activity for these NPs, which facilitates its entry into the nucleus, primarily by inhibiting Kelch like-ECH-associated protein 1 (Keap1). The purpose of this article was to review the peer-reviewed literature of NPs that have shown mitigating effects on renal disorder by stimulating Nrf2 and thereby suggesting potential new therapeutic or prophylactic strategies against kidney-damaging xenobiotics.