Nephroprotective Role of Boerhavia diffusa: A Mechanistic Review of Gene Expression and Signaling Cascades

Drug induced nephrotoxicity is a major clinical challenge, arising from diverse therapeutic agents such as cisplatin, aminoglycosides, streptozotocin, NSAIDs, antivirals, methotrexate, calcineurin inhibitors, and radiocontrast media. These agents damage renal tissue through overlapping mechanisms including oxidative stress, mitochondrial dysfunction, apoptosis, inflammation, and fibrosis, leading to acute kidney injury and progression to chronic kidney disease. Conventional mitigation strategies remain limited, prompting growing interest in plantderived secondary metabolites with multitargeted protective effects. Boerhavia diffusa Linn. (Punarnava), a traditional herb, has demonstrated nephroprotective potential through its diverse phytoconstituents such as boeravinones, punarnavine, flavonoids, saponins, and phenolic acids. These compounds modulate key signaling pathways including Nuclear Factor Erythroid 2Related Factor 2/ Antioxidant Response Elements (Nrf2/ARE), Nuclear Factor Kappa B (NFκB), MitogenActivated Protein Kinase, Phosphoinositide 3Kinase/ Protein Kinase B (MAPK, PI3K/Akt), and Transforming Growth Factor Beta (TGFβ/Smad), thereby attenuating oxidative damage, suppressing inflammation, regulating apoptosis, and reducing fibrosis. This review synthesizes mechanistic insights into druginduced nephrotoxicity and highlights the translational relevance of B. diffusa as a multitarget nephroprotective agent.