Xi Yujie, Miao Yan, Zhou Rui, Wang Maolin, Zhang Fangbo, Li Yu, Zhang Yi, Yang Hongjun, Guo Feifei
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Chinese Medicine Research Institute, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Pharmacol. 2022 Mar 25;13:826535. doi: 10.3389/fphar.2022.826535. eCollection 2022.
Retinal degenerative diseases are related to retinal injury because of the activation of the complement cascade, oxidative stress-induced cell death mechanisms, dysfunctional mitochondria, chronic neuroinflammation, and production of the vascular endothelial growth factor. Anti-VEGF therapy demonstrates remarkable clinical effects and benefits in retinal degenerative disease patients. Hence, new drug development is necessary to treat patients with severe visual loss. He xue ming mu (HXMM) tablet is a CFDA-approved traditional Chinese medicine (TCM) for retinal degenerative diseases, which can alleviate the symptoms of age-related macular degeneration (AMD) and diabetic retinopathy (DR) alone or in combination with anti-VEGF agents. To elucidate the mechanisms of HXMM, a quantitative evaluation algorithm for the prediction of the effect of multi-target drugs on the disturbance of the disease network has been used for exploring the specific pathology of HXMM and TCM precision positioning. Compared with anti-VEGF agents, the drug disturbance of HXMM on the functional subnetwork shows that HXMM reduces the network robustness on the oxidative stress subnetwork and inflammatory subnetwork to exhibit the anti-oxidation and anti-inflammation activity. HXMM provides better protection to ARPE-19 cells against retinal injury after HO treatment. HXMM can elevate GSH and reduce LDH levels to exhibit antioxidant activity and suppress the expression of IL-6 and TNF-α for anti-inflammatory activity, which is different from the anti-VEGF agent with strong anti-VEGF activity. The experimental result confirmed the accuracy of the computational prediction. The combination of bioinformatics prediction based on the drug attack on network robustness and experimental validation provides a new strategy for precision application of TCM.
视网膜退行性疾病与视网膜损伤有关，这是由于补体级联反应的激活、氧化应激诱导的细胞死亡机制、线粒体功能障碍、慢性神经炎症以及血管内皮生长因子的产生。抗血管内皮生长因子（VEGF）疗法在视网膜退行性疾病患者中显示出显著的临床效果和益处。因此，开发新药来治疗严重视力丧失的患者很有必要。和血明目片是一种经中国国家食品药品监督管理总局（CFDA）批准用于治疗视网膜退行性疾病的传统中药，它可以单独或与抗VEGF药物联合使用，缓解年龄相关性黄斑变性（AMD）和糖尿病视网膜病变（DR）的症状。为了阐明和血明目片的作用机制，一种用于预测多靶点药物对疾病网络干扰影响的定量评估算法已被用于探索和血明目片的具体病理机制以及中药精准定位。与抗VEGF药物相比，和血明目片对功能子网的药物干扰表明，和血明目片降低了氧化应激子网和炎症子网上的网络稳健性，从而表现出抗氧化和抗炎活性。和血明目片能更好地保护视网膜色素上皮（ARPE）-19细胞免受过氧化氢（HO）处理后的视网膜损伤。和血明目片可以提高谷胱甘肽（GSH）水平并降低乳酸脱氢酶（LDH）水平，以表现出抗氧化活性，并抑制白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α的表达以发挥抗炎活性，这与具有强大抗VEGF活性的抗VEGF药物不同。实验结果证实了计算预测的准确性。基于药物对网络稳健性攻击的生物信息学预测与实验验证相结合，为中药的精准应用提供了一种新策略。
