Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Hebei North University, Zhangjiakou, Hebei, People's Republic of China.
Drug Des Devel Ther. 2024 Sep 24;18:4273-4289. doi: 10.2147/DDDT.S473688. eCollection 2024.
Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that lacks effective treatments. Qingchang Wenzhong Decoction (QCWZD) is a clinically effective herbal prescription that has been proven to attenuate intestinal inflammation in IBD. However, its molecular mechanism of action has not been clearly elucidated.
We aimed to probe the mechanism of QCWZD for the treatment of IBD.
The dextran sulfate sodium (DSS)-induced mouse model of IBD was used to identify the molecular targets involved in the mechanism of action of QCWZD. Metagenomics sequencing was utilized to analyze the differences in gut microbiota and the functional consequences of these changes. Network pharmacology combined with RNA sequencing (RNA-seq) were employed to predict the molecular targets and mechanism of action of QCWZD, and were validated through in vivo experiments.
Our results demonstrated that QCWZD treatment alleviated intestinal inflammation and accelerated intestinal mucosal healing that involved restoration of microbial homeostasis. This hypothesis was supported by the results of bacterial metagenomics sequencing that showed attenuation of gut dysbiosis by QCWZD treatment, especially the depletion of the pathogenic bacterial genus , while increasing the beneficial microorganism that led to altered bacterial gene functions, such as metabolic regulation. Network pharmacology and RNA-seq analyses showed that Th17 cell differentiation plays an important role in QCWZD-based treatment of IBD. This was confirmed by in vivo experiments showing a marked decrease in the percentage of CD3CD4IL-17 (Th17) cells. Furthermore, our results also showed that the key factors associated with Th17 cell differentiation (IL-17, NF-κB, TNF-α and IL-6) in the colon were significantly reduced in QCWZD-treated colitis mice.
QCWZD exerted beneficial effects in the treatment of IBD by modulating microbial homeostasis while inhibiting Th17 cell differentiation and its associated pathways, providing a novel and promising therapeutic strategy for the treatment of IBD.
炎症性肠病（IBD）是一种慢性复发性炎症性疾病，缺乏有效的治疗方法。清肠温中汤（QCWZD）是一种临床有效的草药方剂，已被证明可减轻 IBD 中的肠道炎症。然而，其作用机制尚不清楚。
探究 QCWZD 治疗 IBD 的作用机制。
采用葡聚糖硫酸钠（DSS）诱导的 IBD 小鼠模型，鉴定 QCWZD 作用机制涉及的分子靶点。采用宏基因组测序分析肠道微生物群的差异及其变化的功能后果。采用网络药理学结合 RNA 测序（RNA-seq）预测 QCWZD 的分子靶点和作用机制，并通过体内实验进行验证。
研究结果表明，QCWZD 治疗可缓解肠道炎症，加速肠道黏膜愈合，涉及微生物群稳态的恢复。这一假说得到了细菌宏基因组测序结果的支持，表明 QCWZD 治疗可减轻肠道菌群失调，特别是减少致病性细菌属 ，同时增加有益微生物 ，导致细菌基因功能发生改变，如代谢调节。网络药理学和 RNA-seq 分析表明，Th17 细胞分化在 QCWZD 治疗 IBD 中起重要作用。体内实验结果显示，CD3CD4IL-17（Th17）细胞的百分比明显降低，证实了这一假说。此外，我们的结果还表明，在 QCWZD 治疗结肠炎小鼠中，与 Th17 细胞分化相关的关键因素（IL-17、NF-κB、TNF-α 和 IL-6）在结肠中显著减少。
QCWZD 通过调节微生物群稳态，抑制 Th17 细胞分化及其相关途径，对 IBD 的治疗具有有益作用，为 IBD 的治疗提供了一种新的有前途的治疗策略。
