Network Pharmacology Reveals the Mechanism of Activity of Tongqiao Huoxue Decoction Extract Against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia-Reperfusion Injury
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作者:
Wu, Si-peng
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机构:
Anhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China
Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Peoples R ChinaAnhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China
Wu, Si-peng
[1
,2
]
Wang, Ning
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Anhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China
Anhui Acad Chinese Med, Inst Pharmacodynam & Safety Evaluat Chinese Med, Hefei, Peoples R China
Minist Educ, Key Lab Xinan Med, Hefei, Peoples R ChinaAnhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China
Wang, Ning
[1
,3
,4
]
Zhao, Li
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Anhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China
Anhui Acad Chinese Med, Inst Pharmacodynam & Safety Evaluat Chinese Med, Hefei, Peoples R China
Minist Educ, Key Lab Xinan Med, Hefei, Peoples R ChinaAnhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China
Zhao, Li
[1
,3
,4
]
机构:
[1] Anhui Univ Chinese Med, Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China
[2] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Peoples R China
[3] Anhui Acad Chinese Med, Inst Pharmacodynam & Safety Evaluat Chinese Med, Hefei, Peoples R China
[4] Minist Educ, Key Lab Xinan Med, Hefei, Peoples R China
Several clinical therapies such as tissue repair by replacing injured tissues with functional ones have been reported; however, there is great potential for exploring traditional herbal-induced regeneration with good safety. Tongqiao Huoxue Decoction (TQHXD), a well-known classical traditional Chinese medicinal formula, has been widely used for clinical treatment of stroke. However, biological activity and mechanisms of action of its constituents toward conferring protection against cerebral ischemia-reperfusion (I/R) injury remain unclear. In this present study, we evaluated TQHXD quality using HPLC; then, it was screened for its potential active ingredients using a series of indices, such as their drug-likeness and oral bioavailability. Subsequently, we analyzed the potential mechanisms of TQHXD anti-I/R using gene ontology functional enrichment analyses. The network pharmacological approach enabled us to screen 265 common targets associated with I/R, indicating that TQHXD had remarkable protective effects on infarction volume, neurological function scores, and blood-brain barrier (BBB) injury. In addition, TQHXD significantly promoted the recovery of regional cerebral blood flow (rCBF) 7 days after reperfusion compared to rats in the vehicle group. Immunofluorescence results revealed a significantly higher CD34 expression in TQHXD-treated rats 7 days after reperfusion. TQHXD is not merely effective but eventually develops a secretory profile composed of VEGF and cerebral blood flow, a typical signature termed the angiogenesis-associated phenotype. Mechanistically, our data revealed that TQHXD (6 g/kg) treatment resulted in a marked increase in expression of p-focal adhesion kinase (FAK) and p-Paxillin proteins. However, Ki8751-mediated inhibition of VEGFR2 activity repealed its angiogenesis and protective effects and decreased both p-FAK and p-Paxillin protein levels. Taken together, these findings affirmed the potential of TQHXD as a drug for the management of stroke, which might be exerted by increasing the angiogenesis via the VEGF pathway. Therefore, these results provide proof-of-concept evidence that angiogenesis is a major contributor to TQHXD-treated I/R and that TQHXD is a promising traditional ethnic medicine for the management of this condition.
机构:
Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Ou, Zhijie
Deng, Yanting
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Nanjing Univ Chinese Med, Sch Integrated Chinese & Western Med, 138 Xianlin Rd, Nanjing 210023, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Deng, Yanting
Wu, Yan
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Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Wu, Yan
Wang, Yuanqi
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Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Wang, Yuanqi
Zhao, Yijing
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Nanjing Univ Chinese Med, Sch Integrated Chinese & Western Med, 138 Xianlin Rd, Nanjing 210023, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Zhao, Yijing
Liu, Chang
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Nanjing Univ Chinese Med, Sch Integrated Chinese & Western Med, 138 Xianlin Rd, Nanjing 210023, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Liu, Chang
Wang, Zhuoyu
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Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Wang, Zhuoyu
Liu, Manhua
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Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Liu, Manhua
Hu, Xin
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Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Hu, Xin
Fang, Li
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Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
Fang, Li
Chen, Juping
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Changshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R ChinaChangshu Hosp Tradit Chinese Med, 162 Huanghe Rd, Suzhou 215516, Jiangsu, Peoples R China
机构:
Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China
Beijing Geriatr Med Res Ctr, Beijing, Peoples R China
Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Zheng, Yangmin
Hu, Yue
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Hu, Yue
Han, Ziping
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China
Beijing Geriatr Med Res Ctr, Beijing, Peoples R China
Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Han, Ziping
Yan, Feng
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China
Beijing Geriatr Med Res Ctr, Beijing, Peoples R China
Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Yan, Feng
Zhang, Sijia
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Zhang, Sijia
Yang, Zhenhong
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Yang, Zhenhong
Zhao, Fangfang
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Zhao, Fangfang
Li, Lingzhi
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Li, Lingzhi
Fan, Junfen
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China
Beijing Geriatr Med Res Ctr, Beijing, Peoples R China
Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Fan, Junfen
Wang, Rongliang
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China
Beijing Geriatr Med Res Ctr, Beijing, Peoples R China
Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Wang, Rongliang
Luo, Yumin
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Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
Capital Med Univ, Xuanwu Hosp, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China
Beijing Geriatr Med Res Ctr, Beijing, Peoples R China
Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, 45 Changchun St, Beijing 100053, Peoples R China
机构:
Univ Karachi, Dept Physiol, Pathophysiol Res Unit, Karachi 75270, PakistanUniv Karachi, Dept Physiol, Pathophysiol Res Unit, Karachi 75270, Pakistan
Shamim, Mufzala
Khan, Nazish Iqbal
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Univ Karachi, Dept Physiol, Pathophysiol Res Unit, Karachi 75270, PakistanUniv Karachi, Dept Physiol, Pathophysiol Res Unit, Karachi 75270, Pakistan
机构:
Jinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R ChinaJinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R China
Li, Na
Sun, Jie
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Sichuan Univ, West China Hosp, Dept Neurosurg, Chengdu, Peoples R ChinaJinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R China
Sun, Jie
Chen, Ji-Lin
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Jinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R ChinaJinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R China
Chen, Ji-Lin
Bai, Xue
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Southwest Med Univ, Affiliated Hosp Tradit Chinese Med, Dept Encephalopathy, Luzhou, Peoples R ChinaJinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R China
Bai, Xue
Wang, Ting-Hua
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Jinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R China
Sichuan Univ, West China Hosp, Dept Neurosurg, Chengdu, Peoples R ChinaJinzhou Med Univ, Liaoning Key Lab Diabet Cognit & Percept Dysfunct, Jinzhou, Peoples R China