Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Renal interstitial fibrosis (RIF) is a critical pathological outcome of chronic kidney disease (CKD). Aconitine has been shown to induce RIF, with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway potentially playing a key role in this process. Quercetin, a natural flavonoid compound, exhibits anti-fibrotic effects that may be associated with this pathway. However, there is no clear evidence yet regarding its role in aconitine-induced RIF. Objectives: This study aimed to investigate the intervention effect of quercetin on aconitine-induced RIF and the role of PI3K/Akt pathway in its mechanism. Methods: A mouse model of RIF was established and the animals were randomly assigned to the following groups: normal control, aconitine model, low-dose quercetin, medium-dose quercetin, high-dose quercetin and high-dose quercetin combined with the PI3K inhibitor S27673-MA. The extent of fibrosis and the expression of key molecules in the PI3K/Akt pathway were evaluated using histopathology, qPCR and Western blot. Results: Compared to the model group, the high-dose quercetin group exhibited an approximately 60% reduction in fibrotic area (P<0.01). Moreover, quercetin significantly suppressed the overexpression of phospho-PI3K (p-PI3K), phospho-AKT (p-AKT), neutrophil elastase (NE) and nuclear factor kappa B p65 (NF-?B p65) at both transcriptional and protein levels in renal tissues (P<0.05). The use of the PI3K inhibitor S27673-MA further enhanced the anti-fibrotic effect of quercetin and its inhibitory effect on the aforementioned molecules. Conclusion: Quercetin ameliorates aconitine-induced RIF by inhibiting the PI3K/Akt pathway and its downstream NE/NF-?B axis.