Drug Design, Development and Therapy (May 2022)
Network Pharmacology Analysis of Hewei Jiangni Granule for Gastroesophageal Reflux Disease and Experimental Verification of Its Anti-Neurogenic Inflammation Mechanism
Abstract
Yuan Cheng,1,2,* Fushun Kou,1,2,* Xiaosi Zhang,1,2 Yi Dai,3 Lei Shi,2 Chune Xie,2 Xiaohong Li,2 Junxiang Li2 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Pharmacotherapy and Oriental Medicine, School of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan*These authors contributed equally to this workCorrespondence: Junxiang Li; Xiaohong Li, Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, 1st Section Fangxingyuan, Fangzhuang, Fengtai District, Beijing, 100078, People’s Republic of China, Email [email protected]; [email protected]: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: Hewei Jiangni granule, gastroesophageal reflux disease, network pharmacology, neurogenic inflammation
