PMID- 32908557 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240329 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2020 DP - 2020 TI - Network Pharmacology-Based Approach to Revealing Biological Mechanisms of Qingkailing Injection against IschemicStroke: Focusing on Blood-Brain Barrier. PG - 2914579 LID - 10.1155/2020/2914579 [doi] LID - 2914579 AB - Ischemic stroke is the most common type of cerebrovascular accident worldwide. It causes long-term disability and death. Qingkailing (QKL) injection is a traditional Chinese patent medicine which has been clinically applied in the treatment of ischemic stroke for nearly thirty years. In the present study, network pharmacology combined with experimentation was used to elucidate the mechanisms of QKL. ADME screening and target prediction identified 62 active compounds and 275 targets for QKL. Topological screening of the protein-protein interaction (PPI) network was used to build a core PPI network consisting of 408 nodes and 17,830 edges. KEGG enrichment indicated that the main signaling pathway implicated in ischemic stroke involved hypoxia-inducible factor-1 (HIF-1). Experimentation showed that QKL alleviated neurological deficits, brain infraction, blood-brain barrier (BBB) leakage, and tight junction degeneration in a mouse ischemic stroke model. Two-photon laser scanning microscopy was used to evaluate BBB permeability and cerebral microvessel structure in living mice. HIF-1alpha, matrix metalloproteinase-9 (MMP-9), and tight junction proteins such as occludin, zonula occludins-1 (ZO-1), claudin-5, and VE-Cadherin were measured by western blotting. QKL upregulated ZO-1 and downregulated HIF-1alpha and MMP-9. QKL has a multiapproach, multitarget, and synergistic effect against ischemic stroke. CI - Copyright (c) 2020 Shuang Zhang et al. FAU - Zhang, Shuang AU - Zhang S AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. FAU - Wang, Xueqian AU - Wang X AUID- ORCID: 0000-0001-9138-1491 AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. FAU - Cheng, Fafeng AU - Cheng F AUID- ORCID: 0000-0002-3409-1196 AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. FAU - Ma, Chongyang AU - Ma C AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. AD - School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China. FAU - Fan, Shuning AU - Fan S AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. FAU - Xu, Wenxiu AU - Xu W AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. FAU - Jin, Na AU - Jin N AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. FAU - Liu, Shuling AU - Liu S AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. FAU - Lv, Kai AU - Lv K AUID- ORCID: 0000-0002-8579-4342 AD - The Third Affiliated Hospital of Beijing University of Chinese Medicine, 51 An Wai Xiaoguan Street, Chaoyang District, Beijing 100029, China. FAU - Wang, Qingguo AU - Wang Q AUID- ORCID: 0000-0002-2865-903X AD - Beijing Key Laboratory, School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China. LA - eng PT - Journal Article DEP - 20200827 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC7474352 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. EDAT- 2020/09/11 06:00 MHDA- 2020/09/11 06:01 PMCR- 2020/08/27 CRDT- 2020/09/10 05:35 PHST- 2020/03/02 00:00 [received] PHST- 2020/06/18 00:00 [revised] PHST- 2020/07/30 00:00 [accepted] PHST- 2020/09/10 05:35 [entrez] PHST- 2020/09/11 06:00 [pubmed] PHST- 2020/09/11 06:01 [medline] PHST- 2020/08/27 00:00 [pmc-release] AID - 10.1155/2020/2914579 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2020 Aug 27;2020:2914579. doi: 10.1155/2020/2914579. eCollection 2020.