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Simiao Decoction Alleviates Gouty Arthritis by Modulating Proinflammatory Cytokines and the Gut Ecosystem.

ABSTRACT: Simiao decoction, a classical traditional Chinese medicine (TCM) formula, has been widely used for thousands of years due to its safety and efficiency in treating gouty arthritis. Utilizing serum proinflammatory cytokines and gut ecosystems, this study elucidated the mechanisms of alleviating gouty arthritis by Simiao decoction. Simiao decoction (4.0, 8.0, and 16.0 g/kg) was orally administered to gouty arthritis mice and febuxostat was given as a positive control. The spleen, kidney, and liver indexes indicated that Simiao decoction was safe for the treatment of gouty arthritis in C57BL/6 mice. Besides, our study demonstrated that Simiao decoction was effective for reducing the level of serum uric acid and decreasing MPO, XOD, and ADA activity, as well as alleviating gouty-related symptoms, such as foot swelling and pain. Moreover, Simiao decoction could also reduce some specific serum proinflammatory cytokines including IL-1?, IL-9, IFN-?, MIP-1? and MIP-1?. We then surveyed the effects of Simiao decoction on the gut ecosystems in a systematic manner by combining network pharmacology, ELISA, western blot, and illumina sequencing. In the murine of model of gouty arthritis, Simiao decoction could suppress NLRP3 inflammasomes expression, reduce gut apoptosis through modulating TNF-?, Caspase 8, and AIFM1 protein expressions, affect lipid metabolism by regulating APOB, LPL, PPAR? protein expressions and restore gut microbiota via reducing potential pathogens. Overall, these findings suggested that Simiao decoction was an effective therapeutic drug for gouty arthritis and the gut ecosystem might act as a potential anti-inflammatory target of Simiao decoction.

SUBMITTER: Lin X

PROVIDER: S-EPMC7327538 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Simiao Decoction Alleviates Gouty Arthritis by Modulating Proinflammatory Cytokines and the Gut Ecosystem.

Lin Xiaoying X Shao Tiejuan T Huang Lin L Wen Xianghui X Wang Mingzhu M Wen Chengping C He Zhixing Z

Frontiers in pharmacology 20200624

Simiao decoction, a classical traditional Chinese medicine (TCM) formula, has been widely used for thousands of years due to its safety and efficiency in treating gouty arthritis. Utilizing serum proinflammatory cytokines and gut ecosystems, this study elucidated the mechanisms of alleviating gouty arthritis by Simiao decoction. Simiao decoction (4.0, 8.0, and 16.0 g/kg) was orally administered to gouty arthritis mice and febuxostat was given as a positive control. The spleen, kidney, and liver ...[more]

PMID: 32670069

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Project description:BackgroundGout is considered one of the most painful acute conditions caused by deposition of monosodium urate (MSU) crystals within joints. Recent studies have shown that interleukin (IL)-1β is a key inflammatory mediator in acute gouty arthritis (GA), and its level is regulated by microRNAs (miRNAs). However, the molecular mechanisms of the regulation remain unclear.MethodsA miRNA microarray was used to analyze the miRNA expression profiles in peripheral white blood cells (WBCs) of patients with GA. THP-1 cells were transfected with miRNA mimics, stimulated by MSU crystals, and then subjected to quantitative real-time polymerase chain reaction or Western blot analysis. Levels of IL-1β, IL-8, and tumor necrosis factor (TNF)-α in culture supernatants of THP-1 cells were measured by enzyme-linked immunosorbent assay. A luciferase reporter assay was conducted to confirm the interaction of miRNA and IL-1β 3'-untranslated regions (UTRs).ResultsCombining bioinformatics and miRNA expression profiles, we found five miRNAs (hsa-miR-30c-1-3p, hsa-miR-488-3p, hsa-miR-550a-3p, hsa-miR-663a, and hsa-miR-920) that possibly target IL-1β. Then, we demonstrated that miR-488 and miR-920 were significantly decreased in the WBCs of patients with GA and that MSU crystals could inhibit expression of miR-488 and miR-920. Upregulation of miR-488 and miR-920 could suppress MSU-induced IL-1β protein expression in THP-1 cells, but no significant difference in IL-1β messenger RNA levels was observed. Moreover, we found that miR-488 and miR-920 could directly target the 3'-UTR of IL-1β. Overexpression of miR-488 and miR-920 could significantly inhibit the gene and protein expression of IL-8 and TNF-α in MSU-induced THP-1 cells.ConclusionsThis study demonstrates the roles of miR-488 and miR-920 in regulating the production of proinflammatory cytokines in the pathogenesis of GA. These findings suggest that miR-488 and miR-920 could serve as potential therapeutic targets in the treatment of GA.

Project description:BackgroundThe prevalence rates of gout worldwide have increased annually. Acute gouty arthritis (AGA) accounts for a large proportion of gout patients and causes severe physical and mental pain in patients. Controlling the occurrence and development of gout inflammation is the first step in the treatment of gout. The main treatment drugs in gout are non-steroid anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids, but these treatments have many adverse reactions which limit their clinical application. Baihu and Guizhi decoction (BHGZ) is one of the classic prescriptions in the Synopsis of the Golden Chamber and is a good prescription for AGA. Previous clinical studies have shown that BHGZ confers a strong benefit for treating AGA. However, the literature shows a lack of high-quality RCT research on BHGZ with respect to AGA. Therefore, in this study, we use a randomized, double-blind, controlled study with a placebo to evaluate the clinical efficacy and safety of BHGZ on the AGA of moist heat arthralgia spasm syndrome.MethodsThis study is a randomized, double-blind, controlled clinical trial. A total of 102 adult participants with AGA of moist heat arthralgia spasm syndrome will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be BHGZ plus the low-dose colchicine, and the control intervention will be placebo plus the low-dose colchicine for 10 days. To study the clinical efficacy (including VAS score; joint tenderness, joint swelling, joint movement disorder; TCM evidence efficacy score) and the changes of inflammatory indexes. At the same time, the improvement of joint inflammation in patients with AGA will be observed from musculoskeletal ultrasound imaging, and the safety evaluation will be carried out.DiscussionThis study will be the first placebo-controlled RCT to assess whether BHGZ plus low-dose colchicine have beneficial effects on changing reducing inflammation of joints for patients with AGA of moist heat arthralgia spasm syndrome. The results of this trial will help to provide evidence-based recommendations for clinicians.Trial registrationChinese Clinical Trials Register ChiCTR1900024974 . Registered on 5 August 2019.

Dataset Information

Simiao Decoction Alleviates Gouty Arthritis by Modulating Proinflammatory Cytokines and the Gut Ecosystem.

Publications

Simiao Decoction Alleviates Gouty Arthritis by Modulating Proinflammatory Cytokines and the Gut Ecosystem.

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