State Key Laboratory of Component-based Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
State Key Laboratory of Component-based Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
Phytomedicine. 2022 Jul;101:154100. doi: 10.1016/j.phymed.2022.154100. Epub 2022 Apr 17.
A number of studies have shown that gastrointestinal manifestations co-exist with respiratory symptoms in coronavirus disease 2019 (COVID-19) patients. Xuanfei Baidu decoction (XFBD) was recommended by the National Health Commission to treat mild and moderate COVID-19 patients and proved to effectively alleviate intestinal symptoms. However, the exact mechanisms remain elusive.
This study aimed at exploring potential mechanisms of XFBD by utilizing a mouse model of dextran sulfate sodium (DSS)-induced acute experimental colitis, mimicking the disease conditions of intestinal microecological disorders.
The network pharmacology approach was employed to identify the potential targets and pathways of XFBD on the intestinal disorders. Mice with DSS-induced intestinal disorders were utilized to evaluate the protective effect of XFBD in vivo, including body weight, disease activity index (DAI) score, colon length, spleen weight, and serum tumor necrosis factor-α (TNF-α) level. Colon tissues were used to perform hematoxylin-eosin (H&E) staining, western blot analysis, and transcriptome sequencing. Macrophages, neutrophils and the proportions of T helper cell (Th) 1 and Th2 cells were measured by flow cytometry. Intestinal contents were collected for 16S rRNA gene sequencing.
Network pharmacology analysis indicated that XFBD inhibited the progression of COVID-19-related intestinal diseases by repressing inflammation. In mice with DSS-induced intestinal inflammation, XFBD treatment significantly reduced weight loss, the spleen index, the disease activity index, TNF-α levels, and colonic tissue damage, and prevented colon shortening. Transcriptomics and flow cytometry results suggested that XFBD remodeled intestinal immunity by downregulating the Th1/Th2 ratio. Western blot analysis showed that XFBD exerted its anti-inflammatory effects by blocking the nuclear factor-κB (NF-κB) signaling pathway. Indicator analysis of microbiota showed that 75 operational taxonomic units (OTUs) were affected after XFBD administration. Among them, Akkermansia, Muribaculaceae, Lachnospiraceae, and Enterorhabdus were simultaneously negatively correlated with intestinal disorders' parameters, and Bacteroides, Escherichia-Shigella, Eubacterium nodatum,Turicibacter, and Clostridium sensu stricto 1, showed positive correlations with intestinal disorders' parameters.
Our data indicate that XFBD treatment attenuated intestinal disorders associated with inhibiting inflammation, remodeling of intestinal immunity, and improving intestinal flora. These findings provide a scientific basis for the clinical use of XFBD and offer a potential therapeutic approach for the treatment of COVID-19 patients with intestinal symptoms.
多项研究表明，在 2019 年冠状病毒病（COVID-19）患者中，胃肠道表现与呼吸道症状并存。宣肺败毒汤（XFBD）被国家卫生健康委员会推荐用于治疗轻度和中度 COVID-19 患者，并已被证明能有效缓解肠道症状。然而，确切的机制仍不清楚。
本研究旨在利用葡聚糖硫酸钠（DSS）诱导的急性实验性结肠炎小鼠模型，模拟肠道微生态失调的疾病状况，探讨 XFBD 的潜在作用机制。
采用网络药理学方法鉴定 XFBD 对肠道紊乱的潜在靶点和途径。利用 DSS 诱导的肠道紊乱小鼠模型，评估 XFBD 在体内的保护作用，包括体重、疾病活动指数（DAI）评分、结肠长度、脾脏重量和血清肿瘤坏死因子-α（TNF-α）水平。采用苏木精-伊红（H&E）染色、蛋白质印迹分析和转录组测序检测结肠组织。采用流式细胞术检测巨噬细胞、中性粒细胞和 Th1 和 Th2 细胞比例。收集肠道内容物进行 16S rRNA 基因测序。
网络药理学分析表明，XFBD 通过抑制炎症来抑制 COVID-19 相关肠道疾病的进展。在 DSS 诱导的肠道炎症小鼠中，XFBD 治疗可显著减轻体重减轻、脾脏指数、疾病活动指数、TNF-α水平和结肠组织损伤，并防止结肠缩短。转录组学和流式细胞术结果表明，XFBD 通过下调 Th1/Th2 比值重塑肠道免疫。蛋白质印迹分析表明，XFBD 通过阻断核因子-κB（NF-κB）信号通路发挥抗炎作用。微生物指示分析表明，XFBD 给药后有 75 个操作分类单元（OTUs）受到影响。其中，阿克曼菌属、穆里氏菌科、lachnospiraceae 科和 Enterorhabdus 同时与肠道紊乱参数呈负相关，而拟杆菌属、埃希氏-志贺氏菌属、Eubacterium nodatum、Turicibacter 和 Clostridium sensu stricto 1 与肠道紊乱参数呈正相关。
我们的数据表明，XFBD 治疗可减轻与抑制炎症、重塑肠道免疫和改善肠道菌群相关的肠道紊乱。这些发现为 XFBD 的临床应用提供了科学依据，并为治疗 COVID-19 患者肠道症状提供了一种潜在的治疗方法。
