scholarly journals Screening of Potential Thrombin and Factor Xa Inhibitors from the Danshen–Chuanxiong Herbal Pair through a Spectrum–Effect Relationship Analysis

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7293
Author(s):  
Xu Wang ◽  
Dai-Yan Zhang ◽  
Shi-Jun Yin ◽  
Hui Jiang ◽  
Min Lu ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Inhibitory Activity ◽  
Factor Xa ◽  
Binding Energies ◽  
Tanshinone Iia ◽  
Effect Relationship ◽  
Tanshinone I ◽  
Relationship Analysis ◽  
Ms Analysis ◽  
Spectrum Effect

In this study; a spectrum–effect relationship analysis combined with a high-performance liquid chromatography–mass spectrometry (LC–MS) analysis was established to screen and identify active components that can inhibit thrombin and factor Xa (THR and FXa) in Salviae Miltiorrhizae Radix et Rhizoma–Chuanxiong Rhizoma (Danshen–Chuanxiong) herbal pair. Ten potential active compounds were predicted through a canonical correlation analysis (CCA), and eight of them were tentatively identified through an LC–MS analysis. Furthermore; the enzyme inhibitory activity of six available compounds; chlorogenic acid; Z-ligustilide; caffeic acid; ferulic acid; tanshinone I and tanshinone IIA; were tested to verify the feasibility of the method. Among them; chlorogenic acid was validated to possess a good THR inhibitory activity with IC50 of 185.08 µM. Tanshinone I and tanshinone IIA are potential FXa inhibitors with IC50 of 112.59 µM and 138.19 µM; respectively. Meanwhile; molecular docking results show that tanshinone I and tanshinone IIA; which both have binding energies of less than −7.0 kcal·mol−1; can interact with FXa by forming H-bonds with residues of SER214; GLY219 and GLN192. In short; the THR and FXa inhibitors in the Danshen–Chuanxiong herbal pair have been successfully characterized through a spectrum–effect relationship analysis and an LC–MS analysis.

scholarly journals Screening and Characterizing Tyrosinase Inhibitors from Salvia miltiorrhiza and Carthamus tinctorius by Spectrum-Effect Relationship Analysis and Molecular Docking

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ya-Li Wang ◽  
Guang Hu ◽  
Qian Zhang ◽  
Yu-Xiu Yang ◽  
Qiao-Qiao Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Salvia Miltiorrhiza ◽  
Carthamus Tinctorius ◽  
Amino Acid Residues ◽  
Analysis Method ◽  
Effect Relationship ◽  
Relationship Analysis ◽  
Ms Analysis ◽  
Spectrum Effect

Tyrosinase (TYR) is a rate-limiting enzyme in the synthesis of melanin, while direct TYR inhibitors are a class of important clinical antimelanoma drugs. This study established a spectrum-effect relationship analysis method and high-performance liquid chromatography-mass spectrometry (LC-MS) analysis method to screen and identify the active ingredients that inhibited TYR in Salvia miltiorrhiza–Carthamus tinctorius (Danshen–Honghua, DH) herbal pair. Seventeen potential active compounds (peaks) in the extract of DH herbal pair were predicted, and thirteen of them were tentatively identified by LC-MS analysis. Furthermore, TYR inhibitory activities of five pure compounds obtained from the DH herbal pair were validated in the test in which kojic acid served as a positive control drug. Among them, three compounds including protocatechuic aldehyde, hydroxysafflor yellow A, and tanshinone IIA were verified to have high TYR inhibitory activity (IC50 value of 455, 498, and 1214 μM, resp.) and bind to the same amino acid residues in TYR catalytic pocket according to the results of the molecular docking test. However, the other two compounds lithospermic acid and salvianolic acid A had a weak effect on TYR, as they do not combine with the active amino acid residues or act on the active center of TYR. Therefore, the developed methods (spectrum-effect relationship analysis and molecular docking) could be used to effectively screen TYR inhibitors in complex mixtures such as natural products.

scholarly journals Identification of Antitumor Constituents in Toad Venom by Spectrum-Effect Relationship Analysis and Investigation on Its Pharmacologic Mechanism

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4269
Author(s):  
Ji-Heng Wu ◽  
Yue-Ting Cao ◽  
Hong-Ye Pan ◽  
Long-Hu Wang
Keyword(s):  
Flow Cytometry ◽  
Susceptibility Gene ◽  
In Vitro Assays ◽  
Breast Cancer Susceptibility Gene ◽  
Effect Relationship ◽  
Relationship Analysis ◽  
Effect Model ◽  
Toad Venom ◽  
Spectrum Effect

(1) Background: Toad venom (Bufonis Venenum, known as ‘Chansu’ in Chinese), the secretion of the ear-side gland and skin gland of Bufo gargarizans cantor or Duttaphrynus melanostictus Schneider, has been utilized to treat several diseases in China for thousands of years. However, due to the chemical variability of the components, systematic chemical composition and the key pharmacophores in toad venom have not yet fully understood. Besides, it contains a variety of effective compounds with different physiological activity and chemotypes, mainly including alkaloids, bufogenins, bufotoxins, and so on. The recent pharmacological researches have demonstrated that several bufogenins have remarkable pharmacological effects, such as anti-inflammatory, analgesic effects, and anti-tumor effects. Aim of the study: To identify the bioactive compounds and pharmacophores originating from toad venom based on analyzing spectrum-effect relationship by chemometrics and to explore the anti-cancer mechanism primarily. (2) Materials and methods: Fingerprint of the 21 batches of samples was established using HPLC (High Performance Liquid Chromatography). The anti-tumor activity of extracts were determined by in-vitro assays. Chemometric analysis was used to establish the spectrum-effect model and screen for active ingredients. Pharmacodynamic tests for the screened active compound monomers were conducted with in-vitro assays. Further anti-tumor mechanisms were investigated using western blot and flow cytometry. (3) Results: The established spectrum-effect model has satisfactory fitting effect and predicting accuracy. The inhibitory effect of major screened compounds on lung carcinoma cells A549 were validated in vitro, demonstrating that arenobufagin, telocinobufogenin, and cinobufotalin had significant anti-tumor effects. Through further investigation of the mechanism by western blotting and flow cytometry, we elucidated that arenobufagin induces apoptosis in A549 cells with the enhanced expression of cleaved PARP (poly (ADP-ribose) polymerase). These results may provide valuable information for further structural modification of bufadienolides to treat lung cancer and a method for discovery of anti-tumor active compounds. Conclusions: Our research offers a more scientific method for screening the principal ingredients dominating the pharmacodynamic function. These screened compounds (arenobufagin, etc.) were proven to induce apoptosis by overactivation of the PARP-pathway, which may be utilized to make BRCA (breast cancer susceptibility gene) mutant cancer cells more vulnerable to DNA damaging agents and kill them.

UPLC-MS/MS analysis for antioxidant components of Lycii Fructus based on spectrum-effect relationship

Talanta ◽  
2018 ◽  
Vol 180 ◽  
pp. 389-395 ◽  
Author(s):  
Xian-Fei Zhang ◽  
Juan Chen ◽  
Jun-Li Yang ◽  
Yan-Ping Shi
Keyword(s):  
Effect Relationship ◽  
Ms Analysis ◽  
Spectrum Effect

Potential hypoglycemic metabolites in dark tea fermented by Eurotium cristatum based on UPLC-QTOF-MS/MS combining global metabolomic and spectrum-effect relationship analysis

2021 ◽  
Author(s):  
Xingliang Xiang ◽  
Chao Sao ◽  
Qingxin Shi ◽  
Jiani Wu ◽  
Zhaoxiang Zeng ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Glucose Metabolism ◽  
Therapeutic Effects ◽  
Effect Relationship ◽  
Relationship Analysis ◽  
Spectrum Effect

The preventive and therapeutic effects of dark tea fermented by Eurotium cristatum (DTE) in glucose metabolism have been demonstrated. However, few studies have investigated comprehensive changes of chemical composition and...

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