Exploration of the Specific Pathology of HXMM Tablet Against Retinal Injury Based on Drug Attack Model to Network Robustness

Yujie Xi; Yan Miao; Rui Zhou; Maolin Wang; Fangbo Zhang; Yu Li; Yi Zhang; Hongjun Yang; Feifei Guo

doi:10.3389/fphar.2022.826535

Exploration of the Specific Pathology of HXMM Tablet Against Retinal Injury Based on Drug Attack Model to Network Robustness

Front Pharmacol. 2022 Mar 25:13:826535. doi: 10.3389/fphar.2022.826535. eCollection 2022.

Authors

Yujie Xi^{1

2}, Yan Miao³, Rui Zhou^{1

4}, Maolin Wang¹, Fangbo Zhang¹, Yu Li^{1

2}, Yi Zhang¹, Hongjun Yang^{1

2

5}, Feifei Guo¹

Affiliations

¹ Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
² Chinese Medicine Research Institute, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
³ Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
⁴ College of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
⁵ Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.

Abstract

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 H₂O₂ 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.

Keywords: age-related macular degeneration; diabetic retinopathy; drug attack; he xue ming mu tablet; inflammation; network robustness; oxidative stress.