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      Metabolomics Study of Shaoyao Plants Decoction on the Proximal and Distal Colon in Mice with Dextran Sulfate Sodium-Induced Colitis by UPLC-Q-TOF-MS

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          Abstract

          Purpose

          Shaoyao decoction (SYD) is a traditional Chinese medicine used to treat ulcerative colitis (UC). The exact mechanism of action of SYD in UC treatment is still unclear. Here, we examined the therapeutic effects of SYD in mice with dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanism.

          Methods

          The experimental group was divided into normal control, UC, and SYD treatment groups. The UC model of C57BL/6 mice was induced using 3% (w/v) DSS for 7 days. SYD was orally administered for 7 days. The proximal and distal colonic metabolic profiles were detected using quadrupole-time-of-flight mass spectrometry-based untargeted metabolomics.

          Results

          SYD significantly increased weight, reduced disease activity index scores, and ameliorated colon length shortening and pathological damage in mice. In the distal colon, SYD increased the abundance of phosphatidic acid and lysophosphatidylethanolamine and decreased the abundance of lactosylceramide, erythrodiol 3-palmitate, and lysophosphatidylcholine. In the proximal colon, SYD increased the abundance of palmitic acid, cyclonormammein, monoacylglyceride, 13S-hydroxyoctadecadienoic acid, and ceanothine C and decreased the abundance of tetracosahexaenoic acid, phosphatidylserine, and diglyceride.

          Conclusion

          Our findings revealed that SYD could alleviate UC by regulating metabolic dysfunction, which provides a reference for further studies on SYD.

          Most cited references98

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          Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.

          Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world.
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            The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.

            Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.
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              Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases

              Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                22 December 2022
                2022
                : 16
                : 4343-4364
                Affiliations
                [1 ]The Second Clinical Medical College, Zhejiang Chinese Medical University , Hangzhou, People’s Republic of China
                [2 ]Academic Affairs Office, Zhejiang Chinese Medical University , Hangzhou, People’s Republic of China
                [3 ]The Second Affiliated Hospital of Zhejiang Chinese Medical University , Hangzhou, People’s Republic of China
                Author notes
                Correspondence: Yuyao Hu, The Second Affiliated Hospital of Zhejiang Chinese Medical University , 318 Chaowang Road, Hangzhou, People’s Republic of China, Email 20094017@zcmu.edu.cn
                Author information
                https://orcid.org/http://orcid.org/0000-0002-1269-7883
                Article
                384607
                10.2147/DDDT.S384607
                9792814
                d1ba75b1-6ed7-4b15-b40c-aeed19c16b7f
                © 2022 Luo et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 September 2022
                : 09 December 2022
                Page count
                Figures: 12, Tables: 6, References: 98, Pages: 22
                Funding
                Funded by: Zhejiang Province Traditional Chinese Medicine Science and Technology Project;
                Funded by: Zhejiang Traditional Chinese Medicine Administration;
                Funded by: Zhejiang Province Natural Science Foundation;
                This research was supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Project (No: 2021ZQ042), Zhejiang Traditional Chinese Medicine Administration (No: 2020ZZ010), and Zhejiang Province Natural Science Foundation (No: LY21H270007).
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                shaoyao decoction,ulcerative colitis,metabolomics,uplc-q-tof-ms,dss-induced colitis mouse model

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