Raspberry ameliorates renal fibrosis in rats with chronic kidney disease via the PI3K/Akt pathway

Background: Renal fibrosis is a hallmark of chronic kidney disease (CKD). In traditional Chinese medicine, Rubus chingii Hu (raspberry) is believed to have kidney-tonifying properties. However, whether raspberry can effectively treat CKD, along with the specific active compounds and underlying mechanisms, remains unclear. Purpose: This study aims to investigate the potential of raspberries in treating CKD and elucidate the mechanisms involved. Methods: CKD model was established in rats using adenine. The effects of raspberry treatment on CKD were assessed through macroscopic observations and pathological changes in the kidney. The expression of fibrotic proteins in renal tissues was analyzed to evaluate the impact of raspberry on renal fibrosis. Data mining combined with compositional analysis were employed to identify the active ingredients, targets, and pathways of raspberry that may improve CKD. Subsequently, Western blotting and immunofluorescence analysis were conducted to confirm the involvement of the PI3K/AKT signaling pathway in the renoprotective mechanism of raspberry. Results: Raspberry treatment significantly alleviated renal pathological damage, fibrosis and inflammation in model rats, showing effects comparable to irbesartan (Avapro). Chemical composition analysis and network pharmacology predicted AKT1 as the core target, and the PI3K/AKT pathway plays a pivotal role in mediating the therapeutic effects of raspberry extract in CKD. Molecular docking studies further confirmed that active compounds in raspberry have a strong binding affinity with AKT1. Western blotting and immunofluorescence results demonstrated that raspberry inhibited phosphorylation, thereby suppressing the PI3K/AKT pathway, leading to its antifibrotic effect on the kidney. Conclusion: Raspberry was firstly discovered to potentially treat CKD by alleviating renal fibrosis through inhibition of the PI3K/AKT pathway. Raspberry, as a medicinal and edible traditional herb, could serve as a promising therapeutic agent or health supplement for improving renal fibrosis and slowing CKD progression.