Safflower injection against obesity-induced mice podocyte injury by improving insulin resistance through increasing renal INSR and eNOS expression.

Background: Podocyte injury is a common pathologic mechanism in obesity-related glomerulopathy (ORG). Safflower injection (SFI), scientifically extracted and refined from safflower, is used to treat diabetic kidney disease according to clinical guideline. Our previous study confirmed that the main active compounds of SFI ameliorated high glucose-induced podocyte injury. It is uncertain whether SFI has an effect on ORG-related podocyte injury.

Objectives: This study aimed to explore the pharmacological effects and related mechanisms of SFI on podocyte injury of ORG mice.

Methods: First, by combining ultra-high performance liquid chromatography tandem mass spectrometry analysis with online databases, the pathway enrichment, target-pathway analysis, and human protein-protein interaction network were conducted to discover the possible crucial mechanism of SFI against ORG. Then, ORG mice model was established by high-fat diet and biochemical assays, histopathology and western blot were used to explore the effects of SFI on obesity and podocyte injury. Finally, system pharmacology-based findings were evaluated in ORG mice.

Results: The results of system pharmacology suggested that SFI could alleviate ORG through insulin resistance (IR)-related pathway by regulating insulin receptor (INSR) and endothelial nitric oxide synthase (eNOS) expressions. The in vivo experiment confirmed that SFI ameliorated obesity, lipid metabolism-related indicators, podocyte injury of ORG mice. The mechanism relationships among IR, INSR, and eNOS were further verified in ORG mice.

Conclusions: Our findings imply that by up-regulating the expression of renal INSR and eNOS, thereby inhibiting IR, SFI may be a promising candidate for the treatment of ORG.