Therapeutic potential of tanshinone IIA in folic acid-induced acute kidney injury: a network pharmacology approach

Acute kidney injury (AKI) is a clinical syndrome that can be caused by a variety of factors, leading to rapid decline of kidney function and increased morbidity and mortality, whilst also exerting significant economic burden on the affected patient. <i>Salvia miltiorrhiza</i> is a highly valued plant in traditional Chinese medicine (TCM). Tanshinone IIA (Tan IIA) is an important active compound that can be extracted from salvia miltiorrhiza, which has reported anti-inflammatory effects. The objective of the present investigation was to explore the potential effects of Tan IIA on folic acid-induced AKI and elucidate its underlying mechanism. A comprehensive analysis was conducted utilizing the TCM Systematic Pharmacology Database and Analytical Platform database to screen for chemical components and their corresponding targets. Subsequently, by using network pharmacology techniques and Cytoscapes 3.7.2 software, a protein-protein interaction (PPI) network was constructed and analyzed. Through Venn diagram analysis of the DeGeNET, OMIM, PharmGKB, and GeneCards databases using the key word "acute kidney injury," a total of 76 overlapping targets were obtained. Building upon this, a compound-target gene network was constructed and analyzed by Cytoscapes 3.7.2 software, revealing TP53, STAT3, CASP3, VEGFA, and JUN to be pivotal therapeutic targets. Subsequently, an AKI mouse model was established to investigate the renal effects of Tan IIA. By immunohistochemistry, Western blot results showed the Tan IIA ameliorated kidney function by alleviating inflammation, mitigating necrosis of renal tubular cells, promoting their proliferation and attenuating kidney injury. These beneficial effects were found to be achieved by inhibiting the PI3K/AKT signaling pathway and inhibiting the expression of TP53 by Western blot. In conclusion, TP53may be a potential target for folic acid-induced AKI, whilst Tan IIA exerts its renoprotective effects and improves renal function by PI3K/AKT signaling pathways.