Abstract
Natural products from plants are an excellent source of Human pancreatic α-amylase (HPA) inhibitors which have therapeutic application as oral agents to control blood glucose levels. The mechanism of action by Bisdemethoxycurcumin (BDMC) has been reported, isolated from Curcuma longa rhizomes, which inactivates HPA, a target for type-2 diabetes. This study validates its mode of action and its target which has to date remained largely unknown. The cytotoxicity and bioactivity of crude extract and BDMC on the pancreatic acinar AR42J secretory model cell line were evaluated with LD50 value of 16.25 μg ml-1 and 63.53 μM, and secretory α-amylase inhibition of 41% and 30%, respectively. BDMC uncompetitively inhibits HPA (Ki' of 10.1μM) and a binding affinity (Ka) of 8.5 x 104 M-1 with the involvement of surface exposed aromatic residues. The thermodynamic parameters suggest that binding is both enthalpically and entropically driven with ΔGº of - 28.13 kJ mol-1. Computational ligand docking showed that inactivation depends on hydrogen bonding and π-π interactions. Thus, BDMC, a natural product could be lowering post-prandial glycemia via a novel mode of binding and inactivation of HPA and may proved to be a good drug candidate to reduce/control post-prandial hyperglycemia.
Keywords: Human pancreatic α-amylase, bisdemethoxycurcumin, ligand binding, AR42J cell line, docking
The Natural Products Journal
Title:Deciphering the Inactivation of Human Pancreatic α-Amylase, an Antidiabetic Target, by Bisdemethoxycurcumin, a Small Molecule Inhibitor, Isolated from Curcuma longa
Volume: 3 Issue: 1
Author(s): Sudha Ponnusamy, Smita Zinjarde, Shobha Bhargava, Urmila Kulkarni-Kale, Sangeeta Sawant and Ameeta Ravikumar
Affiliation:
Keywords: Human pancreatic α-amylase, bisdemethoxycurcumin, ligand binding, AR42J cell line, docking
Abstract: Natural products from plants are an excellent source of Human pancreatic α-amylase (HPA) inhibitors which have therapeutic application as oral agents to control blood glucose levels. The mechanism of action by Bisdemethoxycurcumin (BDMC) has been reported, isolated from Curcuma longa rhizomes, which inactivates HPA, a target for type-2 diabetes. This study validates its mode of action and its target which has to date remained largely unknown. The cytotoxicity and bioactivity of crude extract and BDMC on the pancreatic acinar AR42J secretory model cell line were evaluated with LD50 value of 16.25 μg ml-1 and 63.53 μM, and secretory α-amylase inhibition of 41% and 30%, respectively. BDMC uncompetitively inhibits HPA (Ki' of 10.1μM) and a binding affinity (Ka) of 8.5 x 104 M-1 with the involvement of surface exposed aromatic residues. The thermodynamic parameters suggest that binding is both enthalpically and entropically driven with ΔGº of - 28.13 kJ mol-1. Computational ligand docking showed that inactivation depends on hydrogen bonding and π-π interactions. Thus, BDMC, a natural product could be lowering post-prandial glycemia via a novel mode of binding and inactivation of HPA and may proved to be a good drug candidate to reduce/control post-prandial hyperglycemia.
Export Options
About this article
Cite this article as:
Ponnusamy Sudha, Zinjarde Smita, Bhargava Shobha, Kulkarni-Kale Urmila, Sawant Sangeeta and Ravikumar Ameeta, Deciphering the Inactivation of Human Pancreatic α-Amylase, an Antidiabetic Target, by Bisdemethoxycurcumin, a Small Molecule Inhibitor, Isolated from Curcuma longa, The Natural Products Journal 2013; 3 (1) . https://dx.doi.org/10.2174/2210315511303010005
DOI https://dx.doi.org/10.2174/2210315511303010005 |
Print ISSN 2210-3155 |
Publisher Name Bentham Science Publisher |
Online ISSN 2210-3163 |
Call for Papers in Thematic Issues
Ayurvedic medicinal therapeutic approaches for inflammatory and neurodegenerative disorders
Usually, in our elderly population, neurodegenerative disorders occur due to neuron death. Alzheimer?s disease (AD) is an irreversible and progressive neurodegenerative disease. Dementia is the leading cause of AD, which affects about 30 million people worldwide. According to the World Alzheimer report 2018, a new case of dementia develops every ...read more
Recent Advances in Biotransformation of Bioactive Terpenoids using Aspergillus niger
Biotransformation is the reaction catalyzed by biological catalysts of either isolated enzymes or whole cell cultures of microorganisms. This process has been extensively applied in the conversion of bioactive terpenoids with high regio- and stereospecifity. This process has been also applied in the lead discovery and development. Aspergillus niger has ...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
Related Articles
-
Editorial [ Diseases of the Kidney: Molecular Mechanisms and Current Therapy Executive Editor: Stephen I-Hong Hsu ]
Current Molecular Medicine In Silico Approach to Finding New Active Compounds from Histone Deacetylase (HDAC) Family
Current Pharmaceutical Design Exploring the Management of Statin Intolerant Patients: 2016 and Beyond
Current Vascular Pharmacology Teratological Consequences of Nitric Oxide Synthesis Inhibition
Current Pharmaceutical Design Allele Frequencies of Two Main Metformin Transporter Genes: SLC22A1 rs628031 A>G and SLC47A1 rs2289669 G>A among the Javanese Population in Indonesia
Current Pharmacogenomics and Personalized Medicine The Multidomain Mobility Lab in Older Persons: From Bench to Bedside. The Assessment of Body Composition in Older Persons at Risk of Mobility Limitations
Current Pharmaceutical Design Dietary Patterns and Prevention of Type 2 Diabetes: From Research to Clinical Practice; A Systematic Review
Current Diabetes Reviews Nicotine Replacement Therapy During Pregnancy and Lactation Induce Structural and Functional Changes in the Lungs of the Progeny
Current Women`s Health Reviews Pulse Wave Velocity Assessment for Cardiovascular Risk Prognostication in ESKD: Weighting Recent Evidence
Current Vascular Pharmacology EDITORIAL [Hot Topic: Diabetes Cardiovascular Complications (Guest Editor: Costanza Emanueli)]
Endocrine, Metabolic & Immune Disorders - Drug Targets The Functional Logic of Cytosolic 5’-Nucleotidases.
Current Medicinal Chemistry Vascular Endothelial Dysfunction and Nutritional Compounds in Early Type 1 Diabetes
Current Diabetes Reviews Risk of Vertical HIV Transmission Combines the ‘B35-Cw4 Disadvantage’ and the ‘Pattern of Inheritance’ Theories of Progression
Current HIV Research Syntheses, Transformations and Pharmaceutical Applications of Kynurenic Acid Derivatives
Current Medicinal Chemistry Subject Index To Volume 5
Anti-Infective Agents in Medicinal Chemistry Mucoadhesivity Characterization of Isabgol Husk Mucilage Microspheres Crosslinked by Glutaraldehyde
Current Drug Delivery Current HIV Treatment Guidelines - An Overview
Current Pharmaceutical Design Air Pollution Exposure and Blood Pressure: An Updated Review of the Literature
Current Pharmaceutical Design Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy
Current Diabetes Reviews Nanotechnology and Atherosclerosis Imaging: Emerging Diagnostic and Therapeutic Applications
Recent Patents on Cardiovascular Drug Discovery