Changying Jing1, Zhuolun Sun2, Xiaofeng Xie3, Xiuyan Zhang1, Shanshan Wu1, Keying Guo2, Hongsheng Bi4. 1. Medical School of Ophthalmology & Optometry, Shandong University of Traditional Chinese Medicine, Jinan, 250002, China. 2. Shandong Provincial Hospital affiliated to Shandong University, Jinan, China. 3. Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China. 4. Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China. Electronic address: hongshengbi1@163.com.
Abstract
BACKGROUND: Qinghuo Rougan Formula (QHRGF) is a traditional Chinese medicine (TCM) that has been widely apllied to treat uveitis for several decades. However, the inhibitory mechanism of QHRGF in uveitis has remained to be an enigma. METHODS: The Chinese herbal medicine pharmacology data and analysis platform wereused to search and screen for the effective components of the QHRGF compound injection and to analyse possible therapeutic targets based on network topology. In addition, various known disease target databases were enraolled, the therapeutic target proteins in uveitis were screened, and a protein-protein interaction (PPI) network was constructed. Enrichment analysis was performed on key nodes. Finally, the inhibitory effect of QHRGF on uveitis was verified by experiments. RESULTS: We identified 259 major candidate targets of QHRGF and successfully constructed a 'QHRGF-compound-target-uveitis' network. Above-mentioned targets revealed by Gene enrichment analysis have played an significant role in the cell cycle, autoimmune disease, apoptosis and related signal pathways. We demonstrated that QHRGF attenuates local inflammation in experimental autoimmune uveoretinitis (EAU) rats by regulating natural killer T (NKT) cells and inhibiting MAPK signal pathways. CONCLUSION: QHRGF may regulate the local immune response and inflammatory factors mainly through the MAPK signal pathway. For autoimmune uveitis, QHRGF may be a promising, long-lasting treatment strategy.
BACKGROUND: Qinghuo Rougan Formula (QHRGF) is a traditional Chinese medicine (TCM) that has been widely apllied to treat uveitis for several decades. However, the inhibitory mechanism of QHRGF in uveitis has remained to be an enigma. METHODS: The Chinese herbal medicine pharmacology data and analysis platform wereused to search and screen for the effective components of the QHRGF compound injection and to analyse possible therapeutic targets based on network topology. In addition, various known disease target databases were enraolled, the therapeutic target proteins in uveitis were screened, and a protein-protein interaction (PPI) network was constructed. Enrichment analysis was performed on key nodes. Finally, the inhibitory effect of QHRGF on uveitis was verified by experiments. RESULTS: We identified 259 major candidate targets of QHRGF and successfully constructed a 'QHRGF-compound-target-uveitis' network. Above-mentioned targets revealed by Gene enrichment analysis have played an significant role in the cell cycle, autoimmune disease, apoptosis and related signal pathways. We demonstrated that QHRGF attenuates local inflammation in experimental autoimmune uveoretinitis (EAU) rats by regulating natural killer T (NKT) cells and inhibiting MAPK signal pathways. CONCLUSION: QHRGF may regulate the local immune response and inflammatory factors mainly through the MAPK signal pathway. For autoimmune uveitis, QHRGF may be a promising, long-lasting treatment strategy.