Integrated Network Pharmacology and Antioxidant Activity-Guided Screen System to Exploring Antioxidants and Quality Markers of Shunaoxin Pills against Chronic Cerebral Ischemia

Nian-Wei Chang<sup>a</sup>; Dan-Dan Cheng<sup>a</sup>; Jia-Nan Ni<sup>a</sup>; Ying-Ying Guo<sup>a</sup>; Guang-Cui Chu <sup>a</sup>; Unchol Kim<sup>bc</sup>; Min Jiang<sup>b</sup>; Gang Bai<sup>b</sup>

Integrated Network Pharmacology and Antioxidant Activity-Guided Screen System to Exploring Antioxidants and Quality Markers of Shunaoxin Pills against Chronic Cerebral Ischemia

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DOI：10.4103/wjtcm.wjtcm_5_19

KeyWord:Antioxidant, chronic cerebral ischemia, network pharmacology, Q-markers, Shunaoxin pills

Author	Institution
Nian-Wei Chang^a	a.Graduate School, Tianjin University of Traditional Chinese Medicine
Dan-Dan Cheng^a	a.Graduate School, Tianjin University of Traditional Chinese Medicine
Jia-Nan Ni^a	a.Graduate School, Tianjin University of Traditional Chinese Medicine
Ying-Ying Guo^a	a.Graduate School, Tianjin University of Traditional Chinese Medicine
Guang-Cui Chu ^a	a.Graduate School, Tianjin University of Traditional Chinese Medicine
Unchol Kim^bc	b.College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology,Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People’s Republic of China;c.Department of Genetic Engineering,State Academy of Sciences, Pyongyang, Democratic People’s Republic of Korea
Min Jiang^b	b.College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology,Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People’s Republic of China
Gang Bai^b	b.College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology,Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People’s Republic of China

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Abstract:

Objective: The main objective of the study is to screen the quality markers (Q-markers) for relieving oxidative stress damage and against chronic cerebral ischemia in Shunaoxin pills (SNX). Methods: The benefit effect of SNX was evaluated by a rat chronic cerebral ischemia model. The main ingredients of SNX were identified by ultra-performance liquid chromatography-quadrupole time-of-flight, whereas its core targets and pathways around antioxidative stress were predicted by PharmMapper and kyoto encyclopedia of genes and genomes (KEGG) analysis. Moreover, the antioxidants were screened by high-performance liquid chromatography with postcolumn derivatization system and then representative ingredients were verified by cell experiments. Results: SNX could increase expression of catalase and superoxide dismutase (SOD) as well as antagonize oxidative damage in the brain. The effects may be related to three types of antioxidant pathways, including nitrogen metabolism, arachidonic acid metabolism, and the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway by multiple active components regulate targets. Among them, ferulic acid and ligustilide were shown the key scavenging ability for reactive oxygen free radicals and significantly increased the contents of nitric oxide (NO), NO synthase, and SOD as well as decreased malonaldehyde. Conclusion: The oxidation resistances of biological and chemical processes in SNX to protect against cerebral oxidative stress injury were preliminary revealed by an integrated network pharmacology and antioxidant activity-guided screen system. Ferulic acid and ligustilide played a major antioxidant role that could be used as Q-markers to control the quality of SNX.