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Characterization of thrombin/factor Xa inhibitors in Rhizoma Chuanxiong through UPLC-MS-based multivariate statistical analysis
Yang,Yi Yao1; Wu,Zhao Yu1; Xia,Fang Bo2; Zhang,Hao1; Wang,Xu1; Gao,Jian Li3; Yang,Feng Qing1; Wan,Jian Bo2,4
Source PublicationChinese Medicine (United Kingdom)

Background: The dry root and rhizome of Ligusticum chuanxiong Hort., or Chuanxiong, has been used as a blood-activating and stasis-removing traditional Chinese medicine for 1000 years. Our previous studies have shown the inhibitory activity on platelet and thrombin (THR) of Chuanxiong. THR and factor Xa (FXa) play significant roles in the coagulation cascade and their inhibitors are of valuable in the treatment of thromboembolic diseases. The aim of the present study is to screen THR and FXa inhibitors from Chuanxiong. Methods: Four extracts [ethyl acetate (EA), butanol (BA) and remained extract (RE) from 75% ethanol extract, and water extract (WE)] of Chuanxiong were prepared, and their THR/FXa inhibitory activities were assessed in vitro. Following silica-gel column chromatography (SC), the active EA extract and BA extract was further partitioned, respectively. Their active fractions (EA-SC1 to EA-SC5; BA-SC1 to BA-SC5) were obtained and analyzed by LC-MS. After modeling by the principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA), the specific marker compounds were predicted and identified. Their enzyme inhibitory was assessed in vitro and interactions with THR/FXa were investigated by molecular docking analysis. Results: Chuanxiong EA extract showed strong activity against THR and BA extract was more effective in inhibiting FXa activity, and their fractions exhibited obvious difference in enzyme inhibitory activity. Furthermore, marker compounds a-h were predicted by PCA and OPLS-DA, and their chemical structures were identified. Among them, senkyunolide A, Z-ligustilide, ferulic acid and senkyunolide I (IC50 was determined as 0.77 mM) with potential THR inhibitory activity, as well as isochlorogenic acid A with FXa inhibitory activity were screened out. It was found that the four components could interact with the active site of THR, and the binding energy was lower than - 5 kcal/mol. Isochlorogenic acid A were bound to the active site of FXa, and the binding energy was - 9.39 kcal/mol. The IC50 was determined as 0.56 mM. Conclusions: THR/FXa inhibitory components in different extracts of Chuanxiong were successfully characterized by the method of enzyme inhibition activity assays with ultra performance liquid chromatography-quadrupole time of flight mass spectrometry-based multivariate statistical analysis.

KeywordChuanxiong Enzyme Inhibitor Factor Xa Molecular Docking Multivariate Statistical Analysis Thrombin
URLView the original
Indexed BySCIE
WOS Research AreaIntegrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS SubjectIntegrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000567916700002
Scopus ID2-s2.0-85090857758
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Cited Times [WOS]:10   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorYang,Feng Qing; Wan,Jian Bo
Affiliation1.School of Chemistry and Chemical Engineering,Chongqing University,Chongqing,401331,China
2.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Taipa,Macao
3.Academy of Chinese Medical Sciences,Zhejiang Chinese Medical University,Hangzhou, Zhejiang,310053,China
4.College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu, Sichuan,China
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yang,Yi Yao,Wu,Zhao Yu,Xia,Fang Bo,et al. Characterization of thrombin/factor Xa inhibitors in Rhizoma Chuanxiong through UPLC-MS-based multivariate statistical analysis[J]. Chinese Medicine (United Kingdom),2020,15(1).
APA Yang,Yi Yao,Wu,Zhao Yu,Xia,Fang Bo,Zhang,Hao,Wang,Xu,Gao,Jian Li,Yang,Feng Qing,&Wan,Jian Bo.(2020).Characterization of thrombin/factor Xa inhibitors in Rhizoma Chuanxiong through UPLC-MS-based multivariate statistical analysis.Chinese Medicine (United Kingdom),15(1).
MLA Yang,Yi Yao,et al."Characterization of thrombin/factor Xa inhibitors in Rhizoma Chuanxiong through UPLC-MS-based multivariate statistical analysis".Chinese Medicine (United Kingdom) 15.1(2020).
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