Cannabidiol regulates L-carnitine and butyric acid metabolism by modulating the gut microbiota to ameliorate collagen-induced arthritis

IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2024-11-19 DOI:10.1016/j.phymed.2024.156270
Qishun Geng , Zhaoran Wang , Tong Shi , Chaoying Wen , Jiahe Xu , Yi Jiao , Wenya Diao , Jienan Gu , Zihan Wang , Lu Zhao , Tingting Deng , Cheng Xiao
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Abstract

Background

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting multiple systems in the body. Cannabidiol (CBD) is one of the most medically valuable active ingredients in cannabis. At present, CBD has been shown to alleviate the progression of RA; however, owing to its multiple targets, the mechanism of CBD is not clear.

Methods

On the basis of the gut microbiota, we explored the mechanism by which CBD inhibits RA progression. Metagenomic and nontargeted metabolomic analyses were used to determine the changes in the intestinal ecology and plasma metabolites of collagen-induced arthritis (CIA) rats after CBD treatment.

Results

CBD reversed gut dysbiosis in CIA rats, notably altering the abundances of Allobaculum_unclassified, Allobaculum_fili, and Prevotella_unclassified. In addition, metabolomic analysis confirmed that CBD increased the contents of butyric acid and L-carnitine. Allobaculum could produce butyric acid and Prevotella could accelerate the metabolism of L-carnitine. In addition, in vitro experiments demonstrated that L-carnitine participated in the regulation of neutrophils, macrophages and RA-fibroblast-like synoviocytes (RA-FLSs), which was consistent with the synovial changes in CIA rats caused by CBD.

Conclusion

In summary, CBD increased the plasma contents of butyric acid and L-carnitine by altering the abundances of gut microbiota, thereby inhibiting inflammation in neutrophils, macrophages and RA-FLSs. Our study is the first to explain the mechanism by which CBD alleviates progression in CIA rats from the perspective of gut microbes and metabolites, providing new views into CBD mechanisms, which warrants clinical attention.

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大麻二酚通过调节肠道微生物群来调节左旋肉碱和丁酸代谢,从而改善胶原蛋白诱发的关节炎
背景类风湿性关节炎(RA)是最常见的自身免疫性疾病之一,影响人体多个系统。大麻二酚(CBD)是大麻中最具医疗价值的活性成分之一。目前,CBD 已被证明可减轻 RA 的进展;然而,由于其具有多个靶点,CBD 的作用机制尚不清楚。方法在肠道微生物群的基础上,我们探索了 CBD 抑制 RA 进展的机制。结果CBD逆转了CIA大鼠的肠道菌群失调,显著改变了Allobaculum_unclassified、Allobaculum_fili和Prevotella_unclassified的丰度。此外,代谢组分析证实,CBD 增加了丁酸和左旋肉碱的含量。Allobaculum能产生丁酸,Prevotella能加速左旋肉碱的代谢。结论综上所述,CBD 通过改变肠道微生物群的丰度来增加血浆中丁酸和左旋肉碱的含量,从而抑制中性粒细胞、巨噬细胞和 RA-FLS 的炎症反应。我们的研究首次从肠道微生物和代谢产物的角度解释了 CBD 缓解 CIA 大鼠病情进展的机制,为 CBD 的作用机制提供了新的视角,值得临床关注。
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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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