Ligustrazine Alleviates Kidney Injury in a Rat Model of Uremia via Attenuation of Wnt/β-Catenin Signaling Pathway

Uremia is associated with kidney injury and contributes to chronic renal failure. Ligustrazine, a bioactive alkaloid from traditional Chinese herb Ligusticum wallichii Franchat, exerts renal-protective effect against acute kidney injury. The role of ligustrazine in uremia-associated kidney injury was investigated. To induce uremia, rats were subjected to 5/6 nephrectomy and intravenously administered with saline. Survival rate of rats was decreased by 5/6 nephrectomy, and levels of blood urea nitrogen, serum creatinine, and 24 h urine protein were elevated. Daily administration of ligustrazine to these rats increased the survival rate and reduced levels of blood urea nitrogen, serum creatinine, and 24 h urine protein output. Moreover, analysis of kidney histology showed that ligustrazine also ameliorated pathological changes in kidney. Finally, ligustrazine reduced levels of proinflammatory cytokines and suppressed renal apoptosis in the kidney tissues of uremic rats. In addition, ligustrazine downregulated protein expression of Wnt1 and beta-catenin and inhibited nuclear distribution of beta-catenin in uremic rats. In conclusion, ligustrazine protects rats against uremia-associated kidney injury and renal inflammation through inactivation of Wnt1/beta-catenin pathway.