Abstract
We aimed to uncover the underlying mechanisms contributing to the therapeutic efficacy of Astragalus mongholicus Polysaccharides (mAPS) in alleviating diabetic nephropathy (DN). The rat model of DN was subjected to a high-sugar and high-fat diet (HSHFD) coupled with streptozotocin (STZ) injection. Our findings revealed that mAPS administration decreased fasting blood glucose (FBG), BUN, SCR, UA, and MDA levels, while elevating serum GSH, GSH-PX, and SOD activities in DN rats (p < 0.05). Furthermore, there was a notable rise in the mRNA and protein expression of renal Nrf-2, GCLC, NQO1, and HO-1 post mAPS treatment (p < 0.05). Additionally, mAPS supplementation led to reduced protein expression of TLR4, NLRP3, p-NF-κB, TGF-β, and Smad4. Concurrently, mAPS exerted a modulatory effect on gut microbiota, as evidenced by the increased abundance of Muribaculaceae, Ruminococcus_1, Phascolarctobacterium, and Lachnoclostridium-related genera. Spearman correlation analysis illustrated a negative association between the abundance of microbiota (Muribaculaceae, Lachnospiraceae_NK4A136, Ruminococcus_1, Clostridiales) and the levels of serum parameters (BUN, CR, UA, TC, TG). In summary, our data robustly attests to the potential of mAPS in modulating oxidative stress, inflammation, and gut microbiota, ultimately resulting in improved renal function in DN rats.