Yao Dai1, Xixi Chen2, Heng Yang1, Jiayue Yang1, Qichao Hu3, Xiaolin Xiao1, Xiaochuan Guo1, Jinhao Zeng4, Xiao Ma5. 1. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China. 2. Department of Clinical Medicine, Chengdu Medical College, Chengdu 610500, China. 3. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. 4. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China. Electronic address: zengjinhao@cdutcm.edu.cn. 5. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: tobymaxiao@cdutcm.edu.cn.
Abstract
BACKGROUND: Chronic glomerulonephritis (CGN) is a relatively common primary glomerular disease. Huangkui capsule (HKC) combined with angiotensin receptor blocker (ARB) for CGN is frequently used in clinical practice, however, there is still lack of high-quality evidence-based evidence and network pharmacology to clarify the therapeutic efficacy and pharmacological mechanisms. PURPOSE: Integrating evidence-based medicine and network pharmacology to explain the therapeutic efficacy and pharmacological mechanisms of ARB combined with HKC for CGN. METHODS: Studies matching the topic were searched from PubMed, Web of Science, Embase database, the Cochrane Library, Chinese National Knowledge Infrastructure, CBM databases, the VIP medicine information system and the Wanfang database and screened according to inclusion and exclusion criteria. The data of the included studies were meta-analyzed by blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urine protein (24hUP) and effective rate (ER). A meta-analysis of the data from the included studies was performed. Then, based on the network pharmacology, the chemical ingredients in HKC and their targets of action, disease targets, common targets and other relevant information were screened, and the key pathways were relevantly annotated based on bioinformatics technology to explore the potential mechanisms of HKC and ARB for CGN. RESULTS: The results showed that SCR index (p < 0.05), 24hUP index (p < 0.001) in the group treated with HKC and ARB were significantly lower than those in the control group. BUN index in the group treated with HKC and VAL were significantly lower than those in the control group (p < 0.001). Effective rate index in the group treated with HKC and ARB was significantly higher than those in the control group (p < 0.001). There was no significant difference in BUN treated with IRB, LOS, and TEL (p = 0.181; p = 0.811; p = 0.067). Based on network pharmacology, the results were as follows: The PPI network indicated that STAT3, AKT1, MAPK1, TP53 and JUN were key target proteins. The results of KEGG analysis suggested that the pharmacological mechanisms were mainly associated with AGE-RAGE signaling pathway in diabetic complications. CONCLUSION: The combination of ARB and HKC can achieve better therapeutic effects in the treatment of CGN, meanwhile, ARB and HKC have a significant improved effectiveness in the treatment of CGN compared with ARB or HKC alone. In addition, HKC and ARB synergistically treated CGN through a multi-pathway network.
BACKGROUND: Chronic glomerulonephritis (CGN) is a relatively common primary glomerular disease. Huangkui capsule (HKC) combined with angiotensin receptor blocker (ARB) for CGN is frequently used in clinical practice, however, there is still lack of high-quality evidence-based evidence and network pharmacology to clarify the therapeutic efficacy and pharmacological mechanisms. PURPOSE: Integrating evidence-based medicine and network pharmacology to explain the therapeutic efficacy and pharmacological mechanisms of ARB combined with HKC for CGN. METHODS: Studies matching the topic were searched from PubMed, Web of Science, Embase database, the Cochrane Library, Chinese National Knowledge Infrastructure, CBM databases, the VIP medicine information system and the Wanfang database and screened according to inclusion and exclusion criteria. The data of the included studies were meta-analyzed by blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urine protein (24hUP) and effective rate (ER). A meta-analysis of the data from the included studies was performed. Then, based on the network pharmacology, the chemical ingredients in HKC and their targets of action, disease targets, common targets and other relevant information were screened, and the key pathways were relevantly annotated based on bioinformatics technology to explore the potential mechanisms of HKC and ARB for CGN. RESULTS: The results showed that SCR index (p < 0.05), 24hUP index (p < 0.001) in the group treated with HKC and ARB were significantly lower than those in the control group. BUN index in the group treated with HKC and VAL were significantly lower than those in the control group (p < 0.001). Effective rate index in the group treated with HKC and ARB was significantly higher than those in the control group (p < 0.001). There was no significant difference in BUN treated with IRB, LOS, and TEL (p = 0.181; p = 0.811; p = 0.067). Based on network pharmacology, the results were as follows: The PPI network indicated that STAT3, AKT1, MAPK1, TP53 and JUN were key target proteins. The results of KEGG analysis suggested that the pharmacological mechanisms were mainly associated with AGE-RAGE signaling pathway in diabetic complications. CONCLUSION: The combination of ARB and HKC can achieve better therapeutic effects in the treatment of CGN, meanwhile, ARB and HKC have a significant improved effectiveness in the treatment of CGN compared with ARB or HKC alone. In addition, HKC and ARB synergistically treated CGN through a multi-pathway network.