高大麻酚大麻提取物可在炎症性肠病模型中缓和结肠炎并调节微生物组。

IF 3.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacology and Experimental Therapeutics Pub Date : 2024-08-19 DOI:10.1124/jpet.124.002204
Benjamin D Anderson, Diana E Sepulveda, Rahul Nachnani, Alonso Cortez-Resendiz, Matthew D Coates, Aviauna Beckett, Jordan E Bisanz, Joshua J Kellogg, Wesley M Raup-Konsavage
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引用次数: 0

摘要

大麻(Cannabis sativa L.)的药用历史悠久,尤其适用于胃肠道疾病。炎症性肠病(IBD)患者报告使用大麻来控制症状,尽管几乎没有数据支持使用大麻或大麻产品来治疗这种疾病。在本研究中,我们利用小鼠结肠炎的右旋糖酐硫酸钠(DSS)模型来评估市售、非兴奋性、高大麻酚(CBG)大麻提取物(20 毫克/毫升大麻酚、20.7 毫克/毫升大麻二酚、1 毫克/毫升大麻色烯)对 IBD 活动和结肠微生物组的影响。在饮用水中添加 2% 的 DSS 给小鼠饮用 5 天,然后再添加 2 天的普通饮用水。在这 7 天中,小鼠每天服用高浓度 CBG 大麻提取物或与之匹配的药物对照组。通过降低疾病活动指数、增加结肠长度和降低结肠组织损伤百分比等指标,每天使用高CBG大麻提取物可显著降低组织学和机体层面的疾病严重程度。粪便微生物群的 16S rRNA 基因测序显示,高 CBG 大麻提取物治疗会导致微生物群的改变,这可能对结肠炎有益。最后,通过对粪便颗粒进行代谢组学分析,我们发现接受高CBG大麻提取物治疗的小鼠的几种代谢途径趋于正常,包括那些参与炎症的途径。这些数据表明,高CBG大麻提取物可为患者提供一种新的治疗选择。意义声明 我们使用 DSS 结肠炎模型表明,使用高 CBG 大麻提取物治疗可减轻结肠炎相关症状的严重程度。此外,我们还表明,治疗可调节粪便微生物群和代谢组,具有潜在的功能意义。
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High Cannabigerol Hemp Extract Moderates Colitis and Modulates the Microbiome in an Inflammatory Bowel Disease Model.

Cannabis sativa L. has a long history of medicinal use, particularly for gastrointestinal diseases. Patients with inflammatory bowel disease (IBD) report using cannabis to manage their symptoms, despite little data to support the use of cannabis or cannabis products to treat the disease. In this study, we use the well-described dextran sodium sulfate (DSS) model of colitis in mice to assess the impact of commercially available, noneuphorigenic, high cannabigerol (CBG) hemp extract (20 mg/mL cannabigerol, 20.7 mg/mL cannabidiol, 1 mg/mL cannabichromene) on IBD activity and the colonic microbiome. Mice were given 2% DSS in drinking water for 5 days, followed by 2 days of regular drinking water. Over the 7 days, mice were dosed daily with either high CBG hemp extract or matched vehicle control. Daily treatment with high CBG hemp extract dramatically reduces the severity of disease at the histological and organismal levels as measured by decreased disease activity index, increased colon length, and decreases in percent colon tissue damage. 16S rRNA gene sequencing of the fecal microbiota reveals high CBG hemp extract treatment results in alterations in the microbiota that may be beneficial for colitis. Finally, using metabolomic analysis of fecal pellets, we find that mice treated with high CBG hemp extract have a normalization of several metabolic pathways, including those involved in inflammation. Taken together, these data suggest that high CBG hemp extracts may offer a novel treatment option for patients. SIGNIFICANCE STATEMENT: Using the dextran sodium sulfate model of colitis, the authors show that treatment with high cannabigerol hemp extract reduces the severity of symptoms associated with colitis. Additionally, they show that treatment modulates both the fecal microbiota and metabolome with potential functional significance.

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来源期刊
CiteScore
6.90
自引率
0.00%
发文量
115
审稿时长
1 months
期刊介绍: A leading research journal in the field of pharmacology published since 1909, JPET provides broad coverage of all aspects of the interactions of chemicals with biological systems, including autonomic, behavioral, cardiovascular, cellular, clinical, developmental, gastrointestinal, immuno-, neuro-, pulmonary, and renal pharmacology, as well as analgesics, drug abuse, metabolism and disposition, chemotherapy, and toxicology.
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