LC–MS-based multivariate statistical analysis for the screening of potential thrombin/factor Xa inhibitors from Radix Salvia Miltiorrhiza

Abstract

Background: The dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known traditional Chinese medicine with anticoagulant activity. Taking into account that thrombin (THR) and factor Xa (FXa) play crucial roles in the coagulation cascade, it is reasonable and meaningful to screening THR and/or FXa inhibitors from Danshen. Methods: Four extracts [butanol (BA), ethyl acetate (EA) and remained extract (RE) from 75% ethanol extract, and water extract (WE)] of Danshen were prepared, and their THR/FXa inhibitory activities were assessed in vitro. Then, the active EA extract was further separated by silica-gel column chromatography (SC), and its fractions (SC1-SC5) were analyzed by LC-MS. The principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were employed for predicting the specific marker compounds. The chemical structures of targeted compounds were identified by LC-MS/MS and their interactions with THR/FXa were analyzed by the molecular docking analysis. Results: Danshen EA extract showed strong activity against THR and FXa, and its fractions (SC1-SC5) exhibited obvious difference in inhibitory activity against these two enzymes. Furthermore, four marker compounds with potential THR/FXa inhibitory activity were screened by PCA and OPLS-DA, and were identified as cryptotanshinone, tanshinone I, dihydrotanshinone I and tanshinone IIA. The molecular docking study showed that all these four tanshinones can interact with some key amino acid residues of the THR/FXa active cavities, such as HIS57 and SER195, which were considered to be promising candidates targeting THR and/or FXa with low binding energy (< − 7 kcal mol −1). Conclusions: LC-MS combined with multivariate statistical analysis can effectively screen potential THR/FXa inhibitory components in Danshen.

Characterization of α-Glucosidase Inhibitors from Psychotria malayana Jack Leaves Extract Using LC-MS-Based Multivariate Data Analysis and In-Silico Molecular Docking

“…Similar technology has been applied to evaluate the activity of Clinacanthus nutans leaves against cisplatin toxicity [19]. In addition, potential thrombin/factor Xa inhibitors were reported from Salvia miltiorrhiza Bunge and Ligusticum chuanxiong Hort using the LC-MS-based multivariate data analysis technique [20,21]. Chromatographic technique-based metabolomics was also applied to compare and reveal the chemical profiles of raw and fermented Chinese Ge-Gen-Qin-Lian decoction (a traditional chinese medicine formula) during investigation of its anti-diabetic effects on high-fat diet and streptozotocin-induced rats [22].…”

In Silico Approach of Potential Phytochemical Inhibitor from Moringa oleifera, Cocos nucifera, Allium cepa, Psidium guajava, and Eucalyptus globulus for the treatment of COVID-19 by Molecular Docking

“…Auto Dock 4.2 (Scripps Research Institute, La Jolla, CA, USA) was used to validate the compound's binding energy to the protein receptor. The 2D interactions diagram were retrieved from Discovery Studio 4.5 (Dassault Systemes BIOVIA, San Diego, CA, USA 17 . The bioactive compounds from ve medicinal plants were obtained in the format .sdf from Pubchem compound database.…”

Multivariate Analysis on The Determinants of Work Fatigue Factors for Nurses Inpatient Care at RSUD Arifin Achmad Hospital Pekanbaru

“…This type of analytic cross-sectional cross-sectional study design in which the independent variables and dependent variables are expressed at the same time to respondents who aim to find out certain factors and problems. Respondents in this study were nurses inpatient installation Arifin Achmad Regional Hospital of Riau Province, amounting to 431 people [18][19][20][21][22].…”