Affiliation:
1. Department of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
2. School of Chinese Ethnic Medicine, Guizhou Minzu University, Guiyang 550025, China
Abstract
Ulcerative colitis (UC) is an intractable disease prevalent worldwide. While ethyl acetate extract from decoction of Sargentodoxa cuneata (EAdSc) has potential anti-inflammatory activity, its effects on UC remain unknown. In this study, the constituent compounds discussed in the literature and identified by gas chromatography and mass spectrometry (GC–MS) were collected, and the blood-soluble components of EAdSc were identified by liquid chromatography–mass spectrometry. The network pharmacology analysis and molecular docking analysis were performed to explore the potential underlying mechanism and active ingredients of EAdSc against UC. Furthermore, mice with dextran sulfate sodium (DSS)-induced UC were used to study the therapeutic effects and validate the mechanism of EAdSc against UC. A total of 53 compounds from EAdSc were identified in the literature and by GC–MS, and 22 blood-soluble EAdSc components were recognized. Network pharmacology analysis revealed that multiple inflammatory signaling pathways are involved in EAdSc’s anti-UC activity. Furthermore, molecular docking analysis showed that the eleutheroside A, liriodendrin, epicatechin, 2-methoxy-4-vinylphenol, catechin, androsin, coumaroyltyramine, and catechol may be active against UC through the TLR4/NF-κB/NLRP3 pathway. EAdSc reduced the disease activity, macroscopic colon damage, and histological damage indices, as well as inhibiting DSS-induced spleen enlargement and colon shortening. In addition, EAdSc decreased the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17, as well as the expression of TLR4, NF-κB p65, NLRP3, and Caspase-1 mRNA in colon tissues. These results provide insights into the anti-UC effects and underlying mechanisms of EAdSc and help elucidate the active ingredients of EAdSc in the treatment of UC.
Funder
Guizhou Provincial Basic Research Program
Guizhou University of Traditional Chinese Medicine 2021 National Natural Science Foundation of China Post-subsidy Fund Scientific Research Innovation Exploration Special Project
Scholarship Fund from the China Scholarship Council
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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