Idiopathic membranous nephropathy (IMN) is an autoimmune glomerular disease. Current immunosuppressive therapies often cause side effects and high recurrence rates, highlighting the need for new treatments. Baicalin (BAI), a flavonoid isolated from Scutellaria baicalensis, has anti-inflammatory and antioxidant properties. This study examined effects of BAI on IMN using in vitro mouse podocyte clone-5 (MPC-5) cells treated with zymosan-activated serum (ZAS) and in vivo mouse models induced with cationic bovine serum albumin (BSA). Treatments included the BAI and advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE) agonist, advanced glycation end products - bovine serum albumin (AGE-BSA). Assessments included cell viability, apoptosis, reactive oxygen species (ROS), inflammatory cytokines, oxidative stress markers, renal function, and histopathology. Potential targets and pathways involved in BAI's effect on IMN were identified using network pharmacology. Compared to the ZAS-induced MPC-5 cell group, BAI increased cell viability and reduced apoptosis in injured cells. Meantime, BAI significantly reduced the release of pro-inflammatory cytokines tumor necrosis factor α, monocyte chemotactic protein 1, and interleukin 6 and enhanced antioxidant capacity by increasing total superoxide dismutase levels while simultaneously decreasing oxidative stress markers ROS, malondialdehyde, and lactate dehydrogenase in IMN cell models. Similarly, BAI exhibited anti-inflammatory and anti-oxidative effects in an in vitro IMN model and protected renal function in IMN mice with IMN. In addition, BAI downregulated AGE and RAGE in both IMN cell models and mice, and reduced CD68 levels in IMN mice. However, the activation of the AGE/RAGE pathway by AGE-BSA weakened the protective effects of BAI in these IMN models. Collectively, BAI mitigated inflammation and oxidative stress in IMN by repressing the AGE/RAGE pathway, suggesting its potential as a promising therapeutic agent for IMN.
Lou et al. (Mon,) studied this question.