Cao Jinyi, Lei Lu, Wang Kai, Sun Jing, Qiao Yi, Duan Jialin, Zhao Chao, Cui Jia, Feng Zhijun, Wang Jing-Wen, Wen Aidong, Yang Zhifu
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Evid Based Complement Alternat Med. 2021 Apr 14;2021:9834856. doi: 10.1155/2021/9834856. eCollection 2021.
Huangqi-Honghua herb pair is known for its medicinal value to treat Qi deficiency and blood stasis syndrome with a long history in clinical practice. To understand its possible mechanism in a systematic study, a network pharmacological method was addressed.
Detailed information on the HH compounds was obtained from two public databases, and oral bioavailability (OB) and drug-like (DL) of the compounds were evaluated. A correlation between HH compounds, its potential targets, and known targets was extrapolated, and the herb-compound-target-disease (H-C-T-D) network was established. Next, the pathway enrichment and essential genes were analyzed. Then, three key genes (VEGFA, VEGFR2, and eNOS), highly associated with angiogenesis, were screened and verified through western blot assay.
Out of 276 compounds, 21 HH compounds and 78 target genes regulating the major pathways associated with CI in the network are analyzed. The bioactive compounds in HH were active in various signal transduction pathways such as the toll-like receptor signaling pathway, VEGF signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway are important pathways that may regulate anti-inflammatory, antiapoptotic, immune correlation, and antioxidative effects. The core genes are PTGS2, TNF, NOS2, IL6, BCL2, IL1B, SOD2, NOS3, SOD1, MMP9, and VEGFA. The in vitro results suggested that HH treatment could significantly elevate the expression of proangiogenic genes such as VEGFA, VEGFR2, and eNOS compared with OGD groups.
Our results predict that HH may regulate the expression of VEGFA, VEGFR2, and eNOS via the VEGF and HIF-1 signaling pathway to promote angiogenesis and alleviate cerebral ischemia injury.
黄芪-红花药对治疗气虚血瘀证具有药用价值，在临床实践中有悠久历史。为在系统研究中了解其可能机制，采用了网络药理学方法。
从两个公共数据库获取黄芪-红花化合物的详细信息，并评估化合物的口服生物利用度（OB）和类药性（DL）。推断黄芪-红花化合物与其潜在靶点和已知靶点之间的相关性，并建立草药-化合物-靶点-疾病（H-C-T-D）网络。接下来，分析通路富集和关键基因。然后，筛选出与血管生成高度相关的三个关键基因（VEGFA、VEGFR2和eNOS），并通过蛋白质印迹分析进行验证。
在276种化合物中，分析了21种黄芪-红花化合物和78个调节网络中与脑缺血相关主要通路的靶基因。黄芪-红花中的生物活性化合物在多种信号转导通路中具有活性，如Toll样受体信号通路、VEGF信号通路、TNF信号通路和HIF-1信号通路，这些是可能调节抗炎、抗凋亡、免疫相关和抗氧化作用的重要通路。核心基因有PTGS2、TNF、NOS2、IL6、BCL2、IL1B、SOD2、NOS3、SOD1、MMP9和VEGFA。体外结果表明，与氧糖剥夺组相比，黄芪-红花处理可显著提高促血管生成基因如VEGFA、VEGFR2和eNOS的表达。
我们的结果预测，黄芪-红花可能通过VEGF和HIF-1信号通路调节VEGFA、VEGFR2和eNOS的表达，以促进血管生成并减轻脑缺血损伤。
