Background: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA for treating cardiovascular disorders. The roles of cytochrome P450 enzymes (CYPs) in the metabolism of STS have remained unclear. This study aims to screen the main CYPs for metabolism of STS and study their interactions in vitro.
Methods: Seven major CYPs were screened for metabolism of STS by human liver microsomes (HLMs) or recombinant CYP isoforms. Phenacetin (CYP1A2), coumarin (CYP2A6), tolbutamide (CYP2C9), metoprolol (CYP2D6), chlorzoxazone (CYP2E1), S-mephenytoin (CYP2C19), and midazolam (CYP3A4) were used as probe substrates to determine the potential of STS in affecting CYP-mediated phase I metabolism in humans. Enzyme kinetic studies were performed to investigate the modes of inhibition of the enzyme-substrate interactions by GraphPad Prism Enzyme Kinetic 5 Demo software.
Results: Sodium tanshinone IIA sulfonate inhibited the activity of CYP3A4 in a dose-dependent manner by the HLMs and CYP3A4 isoform. The K m and V max values of STS were 54.8 ± 14.6 µM and 0.9 ± 0.1 nmol/mg protein/min, respectively, for the HLMs and 7.5 ± 1.4 µM and 6.8 ± 0.3 nmol/nmol P450/min, respectively, for CYP3A4. CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP2C19 showed minimal or no effects on the metabolism of STS.
Conclusion: This in vitro study showed that STS mainly inhibited the activities of CYP3A4.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802617 | PMC |
| http://dx.doi.org/10.1186/s13020-016-0083-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells.
Viruses
December 2024
Department of Rehabilitation and Regenerative Medicine, College of Physicians and Surgeons, Columbia University, HHSC-1518, 701 W. 168th Street, New York, NY 10032, USA.
This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays.
View Article and Find Full Text PDFPreparation of pH-Responsive Tanshinone IIA-Loaded Calcium Alginate Nanoparticles and Their Anticancer Mechanisms.
Pharmaceutics
January 2025
State Key Laboratory for Macromolecule Drugs and Large-Scale Manufacturing, College of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China.
Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of (Danshen), a common Chinese medicinal herb. However, clinical applications of Tan IIA are limited due to its poor solubility in water. : To overcome this limitation, we developed a calcium alginate hydrogel (CA) as a hydrophilic carrier for Tan IIA, which significantly improved its solubility.
View Article and Find Full Text PDFProteins and DNA Sequences Interacting with Tanshinones and Tanshinone Derivatives.
Int J Mol Sci
January 2025
Department of Pharmacology and Therapeutics, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala P.O. Box 7062, Uganda.
Tanshinones, biologically active diterpene compounds derived from , interact with specific proteins and DNA sequences, influencing signaling pathways in animals and humans. This study highlights tanshinone-protein interactions observed at concentrations achievable in vivo, ensuring greater physiological relevance compared to in vitro studies that often employ supraphysiological ligand levels. Experimental data suggest that while tanshinones interact with multiple proteomic targets, only a few enzymes are significantly affected at biologically relevant concentrations.
View Article and Find Full Text PDFPeripheral Evolution of Tanshinone IIA and Cryptotanshinone for Discovery of a Potent and Specific NLRP3 Inflammasome Inhibitor.
J Med Chem
January 2025
College of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
Natural products (NPs) continue to serve as an invaluable source in drug discovery, and peripheral evolution of NPs is a highly efficient evolution strategy. Herein, we describe a unified "methyl to amide" peripheral evolution of Tanshinone IIA and Cryptotanshinone for discovery of NLRP3 inflammasome inhibitors. There were 54 compounds designed and prepared, while the chemoinformatic analysis revealed that these evolved NP analogues occupy a unique chemical space.
View Article and Find Full Text PDFBiomimetic metal-phenolic nanocarrier for co-delivery of multiple phytomedical bioactive components for anti-atherosclerotic therapy.
Int J Pharm
January 2025
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515 China. Electronic address:
Atherosclerosis, a major cause of cardiovascular diseases, involves complex pathophysiological processes. The co-delivery of multiple bioactive components derived from phytomedicine to atherosclerotic plaque is challenging, especially for those with varied solubilities. This study introduces a novel metal-phenolic network-based core-shell recombinant high-density lipoprotein nanocarrier (SSPH-MPN@rHDL) for co-delivering multiple bioactive components from Salvia miltiorrhiza and Carthamus tinctorius, including salvianic acid A (SAA), salvianolic acid B (SAB), protocatechuic aldehyde (PCA), hydroxysafflor yellow A (HSYA), and tanshinone IIA (TS-IIA).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!