Genistein as a renoprotective agent: mechanistic insights into antioxidant, anti-inflammatory, and fibrosis-regulating pathways.

Kidney diseases refer to a group of disorders that affect the structure and function of the kidneys, impairing their ability to filter waste products, excess fluids, and toxins from the blood. These diseases can be acute and chronic, and if left untreated, can lead to kidney failure. Their progression is closely associated with inflammation and oxidative stress. Key signaling cascades, such as TLR-4/MAPK and TLR-4/NF-κB, are instrumental in fostering renal inflammation. Excessive ROS production worsens kidney damage, whereas activation of the Nrf-2/ARE pathway mitigates this by enhancing antioxidant defense. Moreover, the TGF-β/Smad pathway is heavily implicated in driving renal fibrosis, a major factor in disease progression. Additionally, elevated uric acid levels exacerbate inflammatory signaling, thereby worsening renal injury and dysfunction. Current treatments for kidney diseases have several concerns, including the need for routine monitoring, side effects, and long-term regimens. Several natural compounds have shown promise in supporting kidney health by modulating these key molecular targets. Genistein is a naturally occurring isoflavone predominantly found in soybeans and soy-based products, such as tofu, soy milk, and tempeh. It has demonstrated beneficial effects in various renal disorders, including both acute and chronic conditions, by regulating key molecular mediators involved in tissue injury, fibrosis, and cellular defense mechanisms. These mediators include TLR-4, MAPK, NF-κB, TGF-β, Smads, ACE, angiotensin, SIRT1, Nrf-2, ROS, SERBP, JAK/STAT and cytokines, among others. Considering the potential of genistein in modulating these mediators, the current review investigates the mechanistic interactions among these mediators in mediating its renoprotective effects.