Berberine ameliorates renal impairment and inhibits podocyte dysfunction by targeting the PI3K/Akt pathway in diabetic rat.
J Diabetes Investig. 2019 Jul 23. Epub 2019 Jul 23. PMID: 31336024
AIMS: Amelioration of renal impairment is the key to diabetic nephropathy (DN) therapy. The progression of DN is closely related to podocyte dysfunction, but the detailed mechanism has not yet been clarified. This study aims to explore the renal impairment amelioration effect of berberine and related mechanism targeting podocyte dysfunction under diabetic state.
MATERIALS AND METHODS: Streptozotocin (35 mg·kg) were used to built DN rat model together with high glucose/lipid diet. Renal functional parameters and glomerular ultrastructure changes have been recorded. The alterations of PI3K, Akt and p-Akt in kidney cortex were determined by western blot. Meantime, podocyte dysfunction was induced and treated with berberine and LY294002. After that, podocyte adhesion functional parameters, protein biomarker as well as the alterations of PI3K/Akt pathway were detected.
RESULTS: Berberine declines the increased levels of biochemical indicators and significantly improves the abnormal expression of PI3K, Akt and p-Akt in model rat kidney. In vitro, co-stimulating factor could obviously reduce the podocyte adhesion activity, including the decreases expression of nephrin, podocin and adhesion moleculeα3β1 levels, to induce the podocyte dysfunction, and the trends were markedly reversed by the therapy of berberine and LY294002. Moreover, reduction of PI3K and p-Akt levels were observed in the berberine (30 and 60 μM) and LY294002 (40 μM) treatment group, but the Akt protein expression showedlittle change.
CONCLUSIONS: Berberine could ameliorate the renal impairment and inhibit the podocyte dysfunction in diabetic rat, and the underlying molecular mechanisms may be involved in the regulation of PI3K/Akt signaling pathway. This article is protected by copyright. All rights reserved.