Background: Diabetic nephropathy (DN) serves as the major etiological factor of end-stage renal disease (ESRD) in DM patients. Balanophora involucrata Hook.f. & Thomson (BI) is a traditional medicine of the Tujia ethnic group in China, with good therapeutic effects on kidney diseases. However, both its effectiveness in the context of DN and the regulatory mechanism remain to be further clarified.
Purpose: To elucidate the role of BI in DN mice, with a focus on exploring the intrinsic mechanism responsible for this process.
Methods: UPLC-MS/MS was employed to identify the main ingredients of BI. The DN model was established using C57BLKS/J db/db mice, which received BI treatment. Serum/urine parameters, renal histology, and ultrastructure were assessed. Intrinsic microbial composition and corresponding metabolites were analyzed via 16S rDNA gene sequencing and nontargeted metabolomics. HK-2 cells were treated with high glucose to simulate DN and then treated with BI-containing drug serum and ferrostatin-1 (fer-1). Cell viability was assessed by CCK-8 assay, and lipid peroxidation was evaluated using the Bodipy 581/591 C11 fluorescence assay. Commercial kits were used to detect MDA and other ferroptosis-related indicators. Protein levels were analyzed by Western blotting.
Results: Terpenoids and flavonoids were the main identified components of BI. Fasting blood glucose was reduced, and lipid metabolism disorders were corrected by BI in DN mice. It also ameliorated renal injury in these mice. Meanwhile, BI regulated serum metabolites, and remodeled gut microbiota in DN mice. Furthermore, Nrf2, GPX4, FPN1, FTH1, and SLC7A11 were activated by BI, whereas TFR1 and ACSL4 were suppressed.
Conclusions: BI ameliorates DN by regulating serum metabolites, remodeling the gut microbiota, and inhibiting ferroptosis.
Keywords: Balanophora involucrata Hook.f. & Thomson; Diabetic nephropathy; Ferroptosis; Gut microbiota; Serum metabolites.
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