Integrated Metabonomics and Network Pharmacology to Reveal the Action Mechanism Effect of Shaoyao Decoction on Ulcerative Colitis

Jin Wu; Yiting Luo; Yan Shen; Yuyao Hu; Fangyuan Zhu; Jiaqian Wu; Yingchao Liu

doi:10.2147/DDDT.S375281

Integrated Metabonomics and Network Pharmacology to Reveal the Action Mechanism Effect of Shaoyao Decoction on Ulcerative Colitis

Drug Des Devel Ther. 2022 Oct 27:16:3739-3776. doi: 10.2147/DDDT.S375281. eCollection 2022.

Authors

Jin Wu¹, Yiting Luo¹, Yan Shen², Yuyao Hu², Fangyuan Zhu¹, Jiaqian Wu¹, Yingchao Liu³

Affiliations

¹ The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
² Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, People's Republic of China.
³ Academic Affairs Office, Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.

Abstract

Background: Traditional Chinese medicine (TCM) has the advantage of multi-component and multi-target, which becomes a hot spot in the treatment of numerous diseases. Shaoyao decoction (SYD) is a TCM prescription, which is mainly used to treat damp-heat dysentery clinically, with small side effects and low cost. However, its mechanism remains elusive. The purpose of this study is to explore the mechanism of SYD in the treatment of mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through metabolomics and network pharmacology, and verify through molecular docking and immunohistochemistry, so as to provide a scientific basis for the role of SYD in the treatment of UC.

Materials and methods: Firstly, DSS-induced UC models were established and then untargeted metabolomics analysis of feces, livers, serum and urine was performed to determine biomarkers and metabolic pathways closely related to the role of SYD. Besides, network pharmacology was applied to screen the active components and UC-related targets, which was verified by molecular docking. Finally, metabonomics and network pharmacology were combined to draw the metabolite-pathway-target network and verified by immunohistochemistry.

Results: Metabolomics results showed that a total of 61 differential metabolites were discovered in SYD-treated UC with 3 main metabolic pathways containing glycerophospholipid metabolism, sphingolipid metabolism and biosynthesis of unsaturated fatty acids, as well as 8 core targets involving STAT3, IL1B, IL6, IL2, AKT1, IL4, ICAM1 and CCND1. Molecular docking demonstrated that the first five targets had strong affinity with quercetin, wogonin, kaempferol and baicalein. Combined with metabolomics and network pharmacology, sphingolipid signaling pathway, PI3K/AKT-mTOR signaling pathway and S1P3 pathway were identified as the main pathways.

Conclusion: SYD can effectively ameliorate various symptoms and alleviate intestinal mucosal damage and metabolic disorder in DSS induced UC mice. Its effect is mainly related to sphingolipid metabolism, PI3K/AKT-mTOR signaling pathway and S1P3 pathway.

Keywords: Shaoyao decoction; UPLC-Q-TOF-MS; metabolomics; network pharmacology; ulcerative colitis.

MeSH terms

Animals
Colitis, Ulcerative* / chemically induced
Colitis, Ulcerative* / drug therapy
Drugs, Chinese Herbal* / chemistry
Metabolomics
Mice
Molecular Docking Simulation
Network Pharmacology
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Sphingolipids
TOR Serine-Threonine Kinases

Substances

Drugs, Chinese Herbal
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Sphingolipids

Grants and funding

This research was supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Project (No: Z2021ZQ042), Zhejiang Traditional Chinese Medicine Administration (No: 2020ZZ010), and Zhejiang Province Natural Science Foundation (No: LY21H270007).