Medical School of Ophthalmology & Optometry, Shandong University of Traditional Chinese Medicine, Jinan, 250002, China.
Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
Biomed Pharmacother. 2019 Dec;120:109381. doi: 10.1016/j.biopha.2019.109381. Epub 2019 Sep 19.
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.
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.
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.
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.
清火柔肝方(QHRGF)是一种中药方剂,已广泛应用于治疗葡萄膜炎数十年。然而,QHRGF 在葡萄膜炎中的抑制机制仍不清楚。
利用中药药理学数据与分析平台,对 QHRGF 复方注射液的有效成分进行搜索和筛选,并基于网络拓扑分析可能的治疗靶点。此外,还纳入了各种已知的疾病靶点数据库,筛选出葡萄膜炎的治疗靶点蛋白,并构建蛋白质-蛋白质相互作用(PPI)网络。对关键节点进行富集分析。最后,通过实验验证 QHRGF 对葡萄膜炎的抑制作用。
我们鉴定了 259 个 QHRGF 的主要候选靶点,并成功构建了“QHRGF-化合物-靶点-葡萄膜炎”网络。基因富集分析显示,上述靶点在细胞周期、自身免疫性疾病、细胞凋亡及相关信号通路中发挥着重要作用。我们证实,QHRGF 通过调节自然杀伤 T(NKT)细胞并抑制 MAPK 信号通路,减轻实验性自身免疫性葡萄膜炎(EAU)大鼠的局部炎症。
QHRGF 可能主要通过 MAPK 信号通路调节局部免疫反应和炎症因子。对于自身免疫性葡萄膜炎,QHRGF 可能是一种有前途的、持久的治疗策略。