Effects of Zhuang medicine compound Xiancao Granule on diabetic kidney disease: A multi-omics analysis

Ethnopharmacological relevance: Diabetic kidney disease (DKD) poses a severe threat to human health. Compound Xiancao Granule (CXCG), a classic Zhuang medicinal formula, is reported as highly effective in treating DKD. However, the mechanisms underlying the action of CXCG in DKD remain unclear.Aim of the study: This study aimed to investigate the mechanisms of action of CXCG against DKD using multi-omics analysis, including 16s rRNA sequencing, metabolomics, and transcriptomics. Materials and methods: The chemical compounds of CXCG were identified using ultra -high-performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry analysis. A rat model of DKD was established by combining nephrectomy of the left kidney, high-fat diet, and streptozotocin. The therapeutic effects of CXCG on DKD were assessed based on body weight, blood glucose level, renal function, inflammatory cytokine levels, and histological staining. Subsequently, 16s rRNA sequencing, liquid chromatography-tandem mass spectrometry untargeted metabolomic profiling, and RNA sequencing analysis were used to investigate the mechanisms of action of CXCG in DKD. Spearman's correlation analysis was per-formed to elucidate the correlations between efficacy indicators, gut microbiota, metabolites, and inflammation-related genes.Results: A total of 118 compounds were identified in CXCG. CXCG significantly ameliorated glucose metabolism disorders, improved renal function, attenuated inflammation, and delayed renal pathological changes in DKD rats. CXCG modulated gut microbiota dysbiosis, including Alloprevotella, Oscillibacter, Anaeroplasma, Anaerotruncus, and Faecalibacterium. In addition, metabolic disruption in DKD rats was regulated by CXCG, which is involved in the metabolism of carbohydrates and amino acids. Transcriptome analysis showed that CXCG affected DKD mainly by regulating inflammation-related genes and pathways, such as the PI3K/Akt and MAPK signaling pathways. Furthermore, there were significant correlations between efficacy indicators, gut microbiota, metabolites, and genes.Conclusion: This multi-omics association study provides novel insights into the effects of CXCG on DKD by remodeling the gut microbiota structure and restoring the metabolic homeostasis through the regulation of carbohydrate metabolism, amino acid metabolism, and inflammation-related pathways, highlighting a potential therapeutic strategy for DKD.