OA DKD

The MCC algorithm was applied to evaluate the importance of each node. The nodes are displayed from yellow to red, indicating their MCC scores from low to high.(D) Screening of the top 7 hub targets based on the highest MCC values. Figure 2.

GO functional annotation and KEGG pathway enrichment analysis of the core targets of OA against DKD. (A-C) GO enrichment analysis of the potential targets. The top significantly enriched terms in (A) BP, (B) CC, and (C) MF are displayed.

The x-axis represents the gene count enriched in each category. (D) KEGG pathway enrichment analysis showing the top 5 enriched signaling pathways. The color of the bubbles represents the significance of enrichment, ranging from blue to red.

The size of the bubbles indicates the number of targets involved in each term or pathway. Figure 3. Network visualization of the mechanism and molecular docking verification.

(A) The Target-Pathway network constructed based on KEGG enrichment analysis. (B) The panoramic view showing the binding position of OA (yellow sticks) within 5IJB. The ligand is located in the hydrophobic pocket of the MD-2 subunit.

(C) Detailed view of the binding interface. The surrounding residues within 5 Å are rendered as spheres to visualize the hydrophobic enclosure and steric complementarity. OA is shown as yellow sticks.

Figure 4. Hematoxylin and eosin staining of each group (magnification ×200). The tubular lesions in the T2DM group were more serious than that of group NC.

The tubular lesions in the OAL and OAH group were milder. Figure 5. OA improved renal function in DN rats.

Ultrastructure of kidneys observed by TEM in each group(×20000).Images showing structure of the glomerular basement membrane (GBM) in the different groups. Black arrows show podocyte foot process morphology. Figure 6 RT-PCR detection of mRNA levels of inflammation-related indicators in rat kidney tissue.

(A) TNF-α（B）IL-6（C）IL-10 #P<0.0001 Figure 7 Expression of NLRP3,GSDMD,Caspase-1,NF-κB,TLR4 detected by Western blot. (A）Representative blot images for each protein.（B） Quantitative comparison of protein expression levels among groups. *P＜0.01； #P<0.001 Supplementary Table S1 SwissTargetPrediction Supplementary Table S2 MCC Score Supplementary Table S3 Molecular docking parameters of Oleanolic Acid with TLR4MD-2 complex Table 1.Software and database for network Pharmacology Table.2 RNA primer sequences Table.3 Comparison of Scr、TC、TG、FBG、UA 、KI and 24h UMA among various groups.

Values are the mean ± SD;*P<0.01 vs NC,#P<0.01 vs T2DM,&P<0.01 vs OAL