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

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.

Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway

“…In recent years, there has been growing interest in the role of imbalanced intestinal macrophage polarization in the development of UC. Que, a natural compound found in various traditional Chinese medicines, has been shown to modulate macrophage polarization and is known for its effectiveness in treating inflammatory conditions, including UC ( Huang et al, 2021 ; Wu et al, 2022 ; Zhou H. F. et al, 2023 ). While the activation of the cGAS-STING pathway has been linked to macrophage polarization imbalance and tissue damage in the heart, its role in macrophage polarization in UC has remained unclear ( Cao et al, 2018 ; Decout et al, 2021 ; Tsai et al, 2021 ).…”

The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis

“…Eight hundred microliters of methanol was added to 200 μL plasma, vortexed for 3 min and centrifuged at 14,000 rpm for 10 min (4°C). 19 The supernatant was transferred to a new tube, then evaporated to dryness. The residue was redissolved by 50 μL 60% methanol and centrifuged at 14,000 rpm for 10 min for subsequent analysis.…”

Chinmedomics: a potent tool for the evaluation of traditional Chinese medicine efficacy and identification of its active components

“…However, whether the selected compounds can be absorbed into serum and exert their bioactivities still needs further verification. In addition, many disease targets have been obtained by previous methods, how to lock core therapeutic targets and key pathways from numerous disease targets has become an important issue [ 8 , 9 ].…”