Nephroprotective Effects of Cardamonin on Renal Ischemia Reperfusion Injury/UUO-Induced Renal Fibrosis

• DOI: 10.1021/acs.jafc.3c01880
• Publication Date: 2023-08-30T11:50:33Z
• Authors: Banghua Zhang; Zhi-Yuan Chen; Zhengyu Jiang; Shiyu Huang; Xiu-Heng Liu; Lei Wang
• Keywords: Sirius Red; Renal ischemia

Acute kidney injury and chronic renal fibrosis are intractable pathological processes to resolve, yet limited strategies able effectively address them. Cardamonin (CAD) is a flavonoid with talented antioxidant, anti-inflammatory capacity, satisfactory biosafety. In our study, animal cellular models of ischemia/reperfusion (I/R) unilateral ureteral obstruction (UUO) were successfully constructed confirm whether CAD confers protective effects underlying mechanisms. Animal experiments demonstrated that application (100 mg/kg) distinctly ameliorated tissue damage improved function. Meanwhile, the continuous oral administration after UUO surgery efficiently inhibited as confirmed by hematoxylin-eosin (H&E), Sirius red, Masson staining well downregulated mRNA protein expression collagen I, α-smooth muscle actin (α-SMA), III, fibronectin. Interestingly, in transforming growth factor β1 (TGF-β1)-stimulated hypoxia/reoxygenation (H/R)-exposed human kidney-2 (HK-2) cells, again authenticated. we performed bioinformatics analysis "ingredient-target-pathway-disease" network conclude potential mechanisms protection may be through regulation oxidative stress, inflammation, apoptosis, mitogen-activated kinase (MAPK) pathway. Furthermore, experimental data validated evidently decreased reactive oxygen species (ROS) production malondialdehyde (MDA) content while depressing inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Il-1β) inhibiting apoptosis evidenced levels P53, BAX, cleaved caspase-3, apoptotic rate I/R models. addition, impact on restraining stress inflammation was attributed its ability elevate antioxidant enzyme activities including catalase, superoxide dismutase 1 (SOD1), 2 (SOD2) inhibit inflammation-associated MARK/nuclear factor-κB (MAPK/NF-κB) signaling conclusion, cardamonin restored antioxidative capacity block suppressed MAPK/NF-κB pathway alleviate response, thus mitigating I/R-generated acute injury/UUO-induced vivo vitro, which indicated therapeutic advantage attenuating injuries.