Abstract
The potential role of polyphenolic acetate (PA) in causing diverse biological and pharmacological actions has been well studied in our laboratory. Our investigations, for the first time, established the role of calreticulin transacetylase (CRTAase) in catalyzing the acetylation of nitric oxide synthase (NOS) by Pas leading to robust activation of NOS. 7, 8- Diacetoxy-4-methylcoumarin (DAMC) and other acetoxycoumarins augmented the expression of thioredoxin (TRX) and vascular endothelial growth factor (VEGF) in human peripheral blood mononuclear cells (PBMCs). These findings substantiated our earlier observations that DAMC was a superb inducer of angiogenesis. The enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to increased expression and activity of TRX in PBMCs due to the action of DAMC was revealed by real time RT-PCR analysis. The possible activation of TRX due to acetylation was confirmed by the fact that TRX activity of PBMCs was enhanced by variousacetoxycoumarins in tune with their affinities to CRTAase as substrates. DAMC caused enhanced production of NO by way of acetylation of NOS as mentioned above and thereby acted as an inducer of VEGF. Real time RT-PCR and VEGF ELISA results also revealed the overexpression of TRX. DAMC and other PAs were found to reduce the oxidative stress in cells as proved by significant reduction of intracellular ROS levels. Thus, the crucial role of TRX in DAMCinduced angiogenesis with the involvement of VEGF was established.
Keywords: Calreticulin transacetylase, Vascular endothelial growth factor, Thioredoxin, Nitric oxide synthase.
Current Topics in Medicinal Chemistry
Title:The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis
Volume: 15 Issue: 2
Author(s): Bilikere S. Dwarakanath, Hanumantharao G. Raj, Virinder S. Parmar, Marc E. Bracke, Anthony L. DePass, Ekta Kohli, Luciano Saso, Ashok K. Prasad, Diwan S. Rawat, Daman Saluja, Rini Joshi, Suvro Chatterji, Prija Ponnan, Prabhjoth Singh, Nivedita Priya, Sanjay Goel, Ajit Kumar, Sushma Manral, Shvetambri Arora and Vishwajeet Rohil
Affiliation:
Keywords: Calreticulin transacetylase, Vascular endothelial growth factor, Thioredoxin, Nitric oxide synthase.
Abstract: The potential role of polyphenolic acetate (PA) in causing diverse biological and pharmacological actions has been well studied in our laboratory. Our investigations, for the first time, established the role of calreticulin transacetylase (CRTAase) in catalyzing the acetylation of nitric oxide synthase (NOS) by Pas leading to robust activation of NOS. 7, 8- Diacetoxy-4-methylcoumarin (DAMC) and other acetoxycoumarins augmented the expression of thioredoxin (TRX) and vascular endothelial growth factor (VEGF) in human peripheral blood mononuclear cells (PBMCs). These findings substantiated our earlier observations that DAMC was a superb inducer of angiogenesis. The enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to increased expression and activity of TRX in PBMCs due to the action of DAMC was revealed by real time RT-PCR analysis. The possible activation of TRX due to acetylation was confirmed by the fact that TRX activity of PBMCs was enhanced by variousacetoxycoumarins in tune with their affinities to CRTAase as substrates. DAMC caused enhanced production of NO by way of acetylation of NOS as mentioned above and thereby acted as an inducer of VEGF. Real time RT-PCR and VEGF ELISA results also revealed the overexpression of TRX. DAMC and other PAs were found to reduce the oxidative stress in cells as proved by significant reduction of intracellular ROS levels. Thus, the crucial role of TRX in DAMCinduced angiogenesis with the involvement of VEGF was established.
Export Options
About this article
Cite this article as:
Dwarakanath S. Bilikere, Raj G. Hanumantharao, Parmar S. Virinder, Bracke E. Marc, DePass L. Anthony, Kohli Ekta, Saso Luciano, Prasad K. Ashok, Rawat S. Diwan, Saluja Daman, Joshi Rini, Chatterji Suvro, Ponnan Prija, Singh Prabhjoth, Priya Nivedita, Goel Sanjay, Kumar Ajit, Manral Sushma, Arora Shvetambri and Rohil Vishwajeet, The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis, Current Topics in Medicinal Chemistry 2015; 15 (2) . https://dx.doi.org/10.2174/1568026615666141209162446
DOI https://dx.doi.org/10.2174/1568026615666141209162446 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pharmacotherapy and Prevention of Vascular Dementia
CNS & Neurological Disorders - Drug Targets The Role of Peroxidation of Mitochondrial Membrane Phospholipids in Pancreatic β -Cell Failure
Current Diabetes Reviews Effects of Oral L-Citrulline Supplementation on Lipoprotein Oxidation and Endothelial Dysfunction in Humans with Vasospastic Angina
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment
Current Pharmaceutical Design Radiolabeled Compounds in Diagnosis of Infectious and Inflammatory Disease
Current Pharmaceutical Design Barriers to Risk Stratification Accuracy in Ischemic Heart Disease in Women: The Role of Non-Obstructive Coronary Artery Disease
Current Pharmaceutical Design Biomarkers of Atrial Fibrillation in Hypertension
Current Medicinal Chemistry Novel Inflammatory Biomarkers in Cardiovascular Therapeutics
Current Medicinal Chemistry Passive Smoking and Coronary Heart Disease
Current Vascular Pharmacology Attenuation of Diabetes-induced Cardiac and Subcellular Defects by Sulphur-containing Amino Acids
Current Medicinal Chemistry Impact of Ivabradine on Health-Related Quality of Life of Patients with Ischaemic Chronic Heart Failure
Current Vascular Pharmacology Strategies to Avoid TAVI-related Acute Kidney Injury
Current Pharmaceutical Design Effect of Standardized Hydroalcoholic Extract of Saffron Stamen on High Blood Pressure and Baroreflex Sensitivity in Anesthetized Rats
Endocrine, Metabolic & Immune Disorders - Drug Targets Stem Cell Function, Self-Renewal, Heterogeneity, and Regenerative Potential in Skeletal Muscle Stem Cells
Recent Patents on Regenerative Medicine Non-Respiratory Manifestations of COVID-19 and Pathophysiological Evidences
New Emirates Medical Journal Clinical Applications of Cardiovascular Magnetic Resonance
Current Pharmaceutical Design Mononuclear Cell Recruitment and Inflammation in Atherosclerosis
Vascular Disease Prevention (Discontinued) A Review on Electrocardiographic Changes in Diabetic Patients
Current Diabetes Reviews Cardiovascular Complications in Inflammatory Bowel Disease
Current Drug Targets Targeting Myocardial Metabolism for the Treatment of Stable Angina
Current Pharmaceutical Design