Wei Liu1, Xiawei Zhang2, Bing Mao3, Hongli Jiang4. 1. Division of Respiratory Medicine, Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, 37 Guoxuexiang Lane, Chengdu, Sichuan, 610041, PR China; Department of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, 1 Keyuansilu Road, Chengdu, Sichuan, 610041, PR China. Electronic address: liu_wei0929@163.com. 2. Division of Respiratory Medicine, Department of Integrated Traditional and Western Medicine, West China School of Medicine, Sichuan University, 37 Guoxuexiang Lane, Chengdu, Sichuan, 610041, PR China. Electronic address: xwzhang0626@foxmail.com. 3. Division of Respiratory Medicine, Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, 37 Guoxuexiang Lane, Chengdu, Sichuan, 610041, PR China. Electronic address: maobing@medmail.com.cn. 4. Division of Respiratory Medicine, Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, 37 Guoxuexiang Lane, Chengdu, Sichuan, 610041, PR China. Electronic address: doc_jhl@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Mucus hypersecretion (MH) is recognized as a key pathophysiological and clinical feature of many airway inflammatory diseases. MUC5AC is a major component of airway mucus. Tanreqing injection (TRQ) is a widely used herbal formula for the treatment of respiratory inflammations for years in China. However, a holistic network pharmacology approach to understanding its therapeutic mechanisms against MH has not been pursued. AIM OF THE STUDY: This study aimed to explore the systems-level potential active compounds and therapeutic mechanisms of TRQ in the treatment of MH. MATERIALS AND METHODS: We established systems pharmacology-based strategies comprising compound screenings, target predictions, and pathway identifications to speculate the potential active compounds and therapeutic targets of TRQ. We also applied compound-target and target-disease network analyses to evaluate the possible action mechanisms of TRQ. Then, lipopolysaccharide (LPS)-induced Sprague-Dawley (SD) rat model was constructed to assess the effect of TRQ in the treatment of MH and to validate the possible molecular mechanisms as predicted in systems pharmacology approach. RESULTS: The comprehensive compound collection successfully generated 55 compound candidates from TRQ. Among them, 11 compounds with high relevance to the potential targets were defined as representative and potential active ingredients in TRQ formula. Target identification revealed 172 potential targets, including pro-inflammatory cytokines of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-8. Pathway analyses uncovered the possible action of TRQ in the regulation of IL-17 signaling pathway and its downstream protein MUC5AC. Then in vivo experiment indicated that TRQ could significantly inhibit LPS stimulated MUC5AC over-production as well as the expression of TNF-α, IL-6, IL-8, and IL-17A, in both protein and mRNA levels. CONCLUSIONS: Based on the systems pharmacology method and in vivo experiment, our work provided a general knowledge on the potential active compounds and possible therapeutic targets of TRQ formula in its anti-MH process. This work might suggest directions for further research on TRQ and provide more insight into better understanding the chemical and pharmacological mechanisms of complex herbal prescriptions in a network perspective.
ETHNOPHARMACOLOGICAL RELEVANCE: Mucus hypersecretion (MH) is recognized as a key pathophysiological and clinical feature of many airway inflammatory diseases. MUC5AC is a major component of airway mucus. Tanreqing injection (TRQ) is a widely used herbal formula for the treatment of respiratory inflammations for years in China. However, a holistic network pharmacology approach to understanding its therapeutic mechanisms against MH has not been pursued. AIM OF THE STUDY: This study aimed to explore the systems-level potential active compounds and therapeutic mechanisms of TRQ in the treatment of MH. MATERIALS AND METHODS: We established systems pharmacology-based strategies comprising compound screenings, target predictions, and pathway identifications to speculate the potential active compounds and therapeutic targets of TRQ. We also applied compound-target and target-disease network analyses to evaluate the possible action mechanisms of TRQ. Then, lipopolysaccharide (LPS)-induced Sprague-Dawley (SD) rat model was constructed to assess the effect of TRQ in the treatment of MH and to validate the possible molecular mechanisms as predicted in systems pharmacology approach. RESULTS: The comprehensive compound collection successfully generated 55 compound candidates from TRQ. Among them, 11 compounds with high relevance to the potential targets were defined as representative and potential active ingredients in TRQ formula. Target identification revealed 172 potential targets, including pro-inflammatory cytokines of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-8. Pathway analyses uncovered the possible action of TRQ in the regulation of IL-17 signaling pathway and its downstream protein MUC5AC. Then in vivo experiment indicated that TRQ could significantly inhibit LPS stimulated MUC5AC over-production as well as the expression of TNF-α, IL-6, IL-8, and IL-17A, in both protein and mRNA levels. CONCLUSIONS: Based on the systems pharmacology method and in vivo experiment, our work provided a general knowledge on the potential active compounds and possible therapeutic targets of TRQ formula in its anti-MH process. This work might suggest directions for further research on TRQ and provide more insight into better understanding the chemical and pharmacological mechanisms of complex herbal prescriptions in a network perspective.