Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Drug Des Devel Ther. 2022 May 5;16:1349-1363. doi: 10.2147/DDDT.S348985. eCollection 2022.
Proton pump inhibitors, as the first-line drugs for treating gastroesophageal reflux disease (GERD), are unable to completely relieve patients' symptoms and patients are prone to recurrence after prolonged drug withdrawal. Thus, it is crucial to find herbal medicines as a complementary and alternative treatment. Hewei Jiangni granule (HWJNG) is a classical Chinese medicinal formula with clinical therapeutic effects on GERD, but its pharmacological mechanism of action remains unclear. This study aimed to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy.
A network pharmacology approach was applied to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. The active ingredients of HWJNG, as well as therapeutic targets of GERD were acquired from specialized databases. The "herb-ingredient-gene-target" network for HWJNG in GERD treatment was built. The protein-protein interaction (PPI) network was constructed to screen the core coincident targets. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The core targets and signaling pathways associated with the anti-neurogenic inflammatory effect were partially verified via experiments in vivo at molecular level.
In total, 179 chemical ingredients in HWJNG and 298 intersection targets between GERD and HWJNG were selected from databases. A large proportion of core targets and top signaling pathways were involved in neurogenic inflammation. HWJNG significantly alleviated pathological injuries of esophagus and reversed dilated intracellular spaces. Additionally, HWJNG markedly inhibited the excessive release of inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor receptor (TNF-a), as well as regulated stimulation sensors including transient receptor potential vanilloid type 1 (TRPV1) and its related neuroinflammatory mediators in GERD mice.
HWJNG is a promising therapeutic strategy for GERD treatment via regulation of multiple targets and pathways, its effects in alleviating neurogenic inflammation are especially acknowledged.
质子泵抑制剂作为治疗胃食管反流病（GERD）的一线药物，无法完全缓解患者的症状，且停药后易复发。因此，寻找草药作为补充和替代治疗方法至关重要。和胃降逆颗粒（HWJNG）是一种治疗 GERD 的经典中药方剂，具有临床疗效，但作用机制尚不清楚。本研究旨在探讨和验证 HWJNG 治疗 GERD 的药理机制。
采用网络药理学方法探讨和验证 HWJNG 治疗 GERD 的药理机制。从专业数据库中获取 HWJNG 的活性成分和 GERD 的治疗靶点。构建 HWJNG 治疗 GERD 的“草药-成分-基因-靶点”网络。构建蛋白质-蛋白质相互作用（PPI）网络筛选核心共有靶点。然后进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。部分验证了与抗神经炎症作用相关的核心靶点和信号通路在体内分子水平的实验。
共从数据库中筛选出 HWJNG 的 179 种化学成分和 GERD 与 HWJNG 的 298 个交叉靶点。大量核心靶点和顶级信号通路涉及神经炎症。HWJNG 显著减轻食管病理损伤，逆转扩张的细胞内间隙。此外，HWJNG 显著抑制了炎症细胞因子（如白细胞介素-1β、白细胞介素-6、肿瘤坏死因子受体-α）和 TRPV1 及其相关神经炎症介质的过度释放。
HWJNG 通过调节多个靶点和通路是 GERD 治疗的一种有前途的治疗策略，其缓解神经炎症的作用尤其值得关注。
