Dietary secoisolariciresinol diglucoside alleviates chronic kidney disease in offspring rats caused by maternal trans-fatty acid exposure by regulating the Bcl-2/Bax/caspase-3 signaling axis
MA Siyu
CHEN Meiqing
WU Tianyu
ZHAO Wenhong
Abstract：Objective To investigate the potential mechanism underlying the protective effect of secoisolariciresinol diglucoside(SDG)against chronic kidney disease(CKD)in offspring mice caused by maternal exposure to trans fatty acids(TFA)during pregnancy and lactation.Methods Thirty female C57BL/6 mice were randomized into control group,TFA model group,and 3 TFA model groups treated with SDG at low,medium and high doses(10,20 and 30 mg/kg,respectively).The changes in blood urea nitrogen(BUN)and serum creatinine(CRE)levels of the mice were measured.Network pharmacology analysis was conducted to explore protective mechanism of SDG against TFA-induced renal injury,and molecular docking was used to assess the binding affinity of SDG to Bcl-2,Bax,and caspase-3.The protein expressions of cleaved caspase-3,Bax,and Bcl-2 in the renal tissues of the offspring mice were detected with Western blotting.Result The mice in TFA group showed significantly higher BUN and CRE levels than those in the control group.Treatment with SDG at the medium and high doses significantly reduced BUN and CRE levels in the mouse models.Network pharmacology and molecular docking suggested that SDG ameliorated renal injury by targeting the apoptosis-related Bcl-2/Bax/caspase-3 axis.The results of Western blotting showed the mouse models in TFA exposure group had increased renal cell apoptosis with elevated expression levels of cleaved caspase-3 protein and a decreased Bcl-2/Bax ratio(P<0.05),and intervention with SDG at all the 3 doses significantly reduced renal cell apoptosis and renal expression of cleaved caspase-3 and increased the Bcl-2/Bax ratio in the mouse models.Conclusion Maternal TFA exposure during gestation and lactation induces renal injury in offspring mice.Dietary SDG intervention can mitigate TFA-induced renal injury in offspring mice possibly by suppressing renal cell apoptosis via regulating the Bcl-2/Bax/caspase-3 signaling axis.
Keywords：secoisolariciresinol diglucosidetrans-fatty acidchronic kidney diseasenutrition interventionsapoptosisBcl-2/Bax/caspase-3
Publication Date：2025-12-20
Online Publishing Date：2025-12-31(First online date of this platform, not the publication date of the document)
Pages：9( 2658-2666 )