Salvianolic acid B and tanshinone IIA synergistically improve early diabetic nephropathy through regulating PI3K/Akt/NF-κB signaling pathway

Abstract

Ethnopharmacological relevanceDiabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which lacks effective treatment. Salviae Miltiorrhizae Radix Et Rhizoma is one of the key compatible traditional Chinese medicine in the prescription for the treatment of DN. Salvianolic acid B and tanshinone IIA are two monomer active components with high content and clear structure in Salvia miltiorrhiza, which can effectively improve early (DN), respectively. Aim of the studyTo evaluate the compatible effect of salvianolic acid B and tanshinone IIA on early DN rats and elucidate the mechanism. MethodsEarly DN rats were induced by streptozotocin combined with high glucose and high fat diet, and intervened by salvianolic acid B, tanshinone IIA and their combinations. The pathological sections of kidney, liver and biochemical indexes were analyzed. Network pharmacology method was used to predict the possible mechanism. The mechanisms were elucidated by metabolomics, Elisa, and Western blot. ResultsGiven our analysis, salvianolic acid B and tanshinone IIA can synergistically regulate 24 h UTP, Urea and Scr and improve kidney damage in early DN rats. The metabolic abnormalities of early DN rats were improved by regulating the biosynthesis of saturated fatty acids, glycerol phospholipid metabolism, steroid biosynthesis, alanine, and arachidonic acid. Salvianolic acid B combined with tanshinone IIA at a mass ratio of 13.4:1 can significantly reduce kidney inflammation, up-regulate p-PI3K/PI3K and p-Akt/Akt and down-regulate p-NF-κB/NF-κB, which better than the single-used group and can be reversed by PI3K inhibitor LY294002. ConclusionSalvianolic acid B and tanshinone IIA can synergistically improve glucose and lipid disorders, liver and kidney damage, and resist kidney inflammation in early DN rats, and the mechanism may be related to regulating PI3K/Akt/NF-κB signaling pathway.