Chrysin improves diabetic nephropathy by regulating the AMPK-mediated lipid metabolism in HFD/STZ-induced DN mice

Diabetic nephropathy (DN) is a highly prevalent and severe diabetic complication. It is urgent to explore high efficiency and minor side effects therapy for DN. Chrysin is a natural flavonoid with various biological activities found in honey and propolis, and has considerable potential to improve DN. The study was designed to explore the effects and the specific underlying mechanism of chrysin for DN in high-fat-diet (HFD) and streptozotocin (STZ) induced DN mice. Firstly, the study revealed that chrysin effectively improved obesity, insulin resistance (IR), renal function, and pathological injury in DN mice. Secondly, the study found that chrysin improved the key indices and markers of lipid accumulation, oxidative stress, and inflammation which are closely related to the development or progression of DN. Moreover, chrysin markedly modulated lipid metabolism by regulating Adenosine 5' monophosphate-activated protein kinase (AMPK) and essential downstream proteins. Furthermore, AMPK inhibitor (Dorsomorphin) intervention partially suppressed the positive effects of chrysin on all testing indicators, indicating that activated AMPK is crucial for chrysin action on DN. The present study demonstrated that chrysin may improve DN by regulating lipid metabolism, and activated AMPK plays a critical role in the regulation of chrysin. PRACTICAL APPLICATIONS: The study verified the positive effects of chrysin on obesity, insulin resistance, kidney injury, renal function, lipid accumulation, inflammation, and oxidative stress, which are closely related to the development or progression of diabetic nephropathy (DN). Moreover, we explored that chrysin improves DN by regulating AMPK-mediated lipid metabolism. Furthermore, the AMPK inhibitor was used to confirm that activated AMPK plays a critical role in the effects of chrysin. These results could offer a full explanation and a potential option for adjuvant therapy of DN diabetes with chrysin.