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

Abstract

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.

Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks

“…Evidence suggests that propolis and its bioactive constituents can influence nutrient-sensing pathways, prompting an examination of their potential therapeutic benefits across different health domains and in addressing age-associated diseases. A study showed that chrysin’s beneficial effects on diabetic nephropathy involve the modulation of lipid metabolism through the activation of AMPK in HFD/STZ-induced diabetic mice [ 247 ]. In a parallel manner, a 4-week regimen of chrysin treatment in rats successfully reversed glucose elevation, inflammation, and the decline in serum insulin levels associated with aging, indicating that chrysin helps preserve islet function [ 248 ].…”

Nutritional Strategies against Diabetic Nephropathy: Insights from Animal Studies and Human Trials

“…Chrysin aids in managing obesity and improving insulin sensitivity by altering lipid metabolism via the activation of AMPK and its downstream, such as SREBP-1 [ 27 ]. Anti-obesogenic and anti-lipogenic effects were observed when an AMPK inhibitor was administered to a rat model of DN [ 28 ]. Resveratrol, a polyphenolic compound in fruits like grapes, nuts, and berries, possesses antioxidant properties and provides multiple health benefits, including anti-inflammatory and anticancer effects [ 29 ].…”

Diabetic nephropathy: An outline on molecular mechanism and protective pathways of phytoconstituents

“…Chrysin controlled lipid metabolism by altering downstream proteins including adenosine 52 monophosphateactivated protein kinase (AMPK). A study revealed that lipid metabolic modulation by way of activated AMPK plays a role in how chrysin improves DN (Zhou et al, 2022). Chrysin controlled mesenchymal and epithelial markers, which prevented excessive hyperglycemia from causing EMT.…”