Trans-cinnamic Acid Alleviates High-fat Diet-induced Renal Injury via JNK/ERK/P38 MAPK pathway

Obesity-related chronic kidney disease (CKD) poses a significant risk to individuals' health and wellbeing, but the pathological mechanisms and treatment strategies are currently limited. Trans-cinnamic acid (CA) is a key active monomer found in cinnamon bark and is known for its diverse pharmacological activities. However, its effect on obesity-related renal injury remains unknown. In the current study, the in vitro and in vivo experiments were combined to investigate the beneficial effect of CA on renal injury induced by HFD or PA. We found that CA significantly reduced the obesity of zebrafish body and the accumulation of fat in kidney tissues. The histopathological changes and dysfunction induced by HFD were effectively mitigated by CA administration, as evidenced by the detection of Hematoxylin-Eosin straining, NAG activity, creatinine level, and expression of functional-related genes, respectively. Additionally, the in vitro and in vivo findings demonstrated that CA dramatically reduced the oxidative stress, inflammatory, and apoptosis in HFD-induced kidney tissues or PA-treated HEK293T and HK-2 cells. Finally, the results regarding ERK, JNK, and P38 proteins phosphorylation confirmed that CA may alleviate HFD-induced renal injury by inhibiting the phosphorylation of ERK, JNK, and P38 MAPK proteins. This theory was further supported by the results of co-treatment with anisomycin (a JNK activator) or lipopolysaccharide and CA in HEK293T cells. This study proves that CA alleviates the obesity-related CKD probably through inhibition of MAPK signaling pathway.