Huayuwendan decoction ameliorates inflammation via IL-17/NF-κB signaling pathway in diabetic rats

Huayuwendan decoction (HYWD) is a broad used traditional Chinese medicine and therapeutic effects against type 2 diabetes mellitus (T2DM). The mechanism of HYWD on the treatment of T2DM is still unclear. For this reason, this study was performed to uncover the effects and mechanism of action of HYWD on T2DM. Male Wistar rats were chosen to set up the T2DM model. This study was randomly divided into six groups: CON (control), MOD (model), HYWDL (Huayuwendan decoction Low Dose), HYWDM (Huayuwendan decoction Middle Dose), HYWDH (Huayuwendan decoction High Dose), and MET (Metformin). Body weight gains were estimated. Using H&E staining, pathological alterations was explored. The serums of fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2 h PG) were detected by Roche blood glucose meter. LDL-C and HDL-C were analyzed by automatic biochemical analyzer. Network pharmacology analyzed the active ingredients, drug targets, and key pathways of HYWD in T2DM treatment. The islet function and inflammation related factors were determined by ELISA. NF-κB signaling pathway or IL-17 signaling pathway related proteins were analyzed by Western blotting. IL-17RA were determined by immunohistochemistry analyze. HYWD inhibited weight gain in T2DM rats. Histopathological results showed that HYWD inhibits liver injury. HYWD suppressed LDL-C and enhanced HDL-C in serum of T2DM rats. HYWD reduce FPG and 2 h PG, inhibit Fins, GSP and IRI, but enhance IAI in serum of T2DM rats. In addition, the network pharmacology results identified 292 chemical compounds in HYWD. 279 candidate targets were recognized, including IL-17A, IL-1β, NFкB, stats, mmp3, and cxcl2. The pathways revealed that the possible target of HYWD related with the regulation of IL-17 signaling pathway and NF-κB pathway. Then in vivo study, HYWD reduced the levels of IL-6, TNF-α, IL-17 and IL-1β in serum and inhibit the protein expression involved in IL-17/NF-κB signaling pathway. The study demonstrates that HYWD may improve T2DM by repressing with the IL-17/NF-κB signaling pathway, which offer encouraging support for using alternative medicine of type 2 diabetes mellitus.