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

Hongyang Wang; Fuzhen Pan; Jie Liu; Juncheng Zhang; Fuli Zhang; Yu Wang

doi:10.1016/j.jep.2023.117328

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

J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117328. doi: 10.1016/j.jep.2023.117328. Epub 2023 Oct 20.

Authors

Hongyang Wang¹, Fuzhen Pan², Jie Liu², Juncheng Zhang², Fuli Zhang², Yu Wang³

Affiliations

¹ School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Heilongjiang Univ Tradit Chinese Med, Harbin, Heilongjiang, 150000, China.
² Heilongjiang Univ Tradit Chinese Med, Harbin, Heilongjiang, 150000, China.
³ Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563006, China; Inner Mongolia Minzu University, Tongliao, Inner Mongolia, 028000, China. Electronic address: wangyu@imun.edu.cn.

PMID: 37865275
DOI: 10.1016/j.jep.2023.117328

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: For this reason, this study was performed to uncover the effects and mechanism of action of HYWD on T2DM.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Huayuwendan decoction; IL-17/NF-κB signaling pathway; Mechanism; Network pharmacology; Type 2 diabetes mellitus.

MeSH terms

Animals
Blood Glucose
Cholesterol, LDL
Diabetes Mellitus, Experimental* / drug therapy
Diabetes Mellitus, Type 2* / drug therapy
Inflammation / drug therapy
Interleukin-17
Male
NF-kappa B
Rats
Rats, Wistar
Signal Transduction

Substances

NF-kappa B
Interleukin-17
Blood Glucose
Cholesterol, LDL