Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover how natural drug fights inflammation

10.12.2010
Researchers at the Virginia Bioinformatics Institute at Virginia Tech have discovered how abscisic acid, a natural plant hormone with known beneficial properties for the treatment of disease, helps fight inflammation.

The results (http://www.ncbi.nlm.nih.gov/pubmed/210882970), which are published in the November 2010 Journal of Biological Chemistry, reveal important new drug targets for the development of treatments for inflammatory and immune-mediated diseases.

The scientists had reported some of the key molecular events in the immune system of mice that contribute to inflammation-related disease, including the involvement of a specific molecule found on the surface of immune cells involved in the body's fight against infection (http://www.ncbi.nlm.nih.gov/pubmed/21068720).

They have now gone one step further and revealed the mechanism by which the natural drug abscisic acid interacts with this protein, known as peroxisome proliferator-activated receptor-gamma, to block inflammation and the subsequent onset of disease.

"In previous work, our research group demonstrated that abscisic acid has beneficial effects on several conditions and diseases including obesity-related inflammation, diabetes, atherosclerosis, and inflammatory bowel disease," said Josep Bassaganya-Riera, associate professor of immunology at the Virginia Bioinformatics Institute, leader of the Nutritional Immunology and Molecular Medicine Group in the institute's CyberInfrastructure Division, and principal investigator of the study. "One idea for how abscisic acid reduces inflammation in these instances is that it binds to a special region of peroxisome proliferator-activated receptor-gamma, a binding site known as the ligand-binding domain where the drug would be expected to latch on to and exert its effect. Our results show that this is not the case and, for the first time, we have demonstrated that abscisic acid works independently of this ligand-binding domain of the receptor."

"This information is significant because it suggests the existence of new therapeutic targets or alternative modes of action that account for the effects of abscisic acid in the immune system," added Bassaganya-Riera. "Drugs that bind to the ligand-binding domain of peroxisome proliferator-activated receptor-gamma such as Avandia are associated with severe cardiovascular side effects. In contrast, the newly discovered alternative mechanism of peroxisome proliferator-activated receptor-gamma activation by abscisic acid does not appear to be linked to any known adverse side effects, thereby representing a promising new therapeutic avenue."

"The outcomes of this research illustrate the synergism that can result from combining computational and experimental approaches to characterize therapeutic targets", said David Bevan, associate professor of biochemistry at Virginia Tech. "By using molecular modeling approaches we were able to identify a potential binding site for abscisic acid on the lanthionine synthetase C-like 2 protein, a protein required for the beneficial health effects of abscisic acid. We were also able, again using docking studies, to reveal reasons for the lack of direct association of abscisic acid with peroxisome proliferator-activated receptor-gamma, which was experimentally validated by ligand-binding assays."

"Lanthionine synthetase C-like 2 represents the first step in a pathway leading to activation of peroxisome proliferator-activated receptor-gamma in immune cells by abscisic acid," said Raquel Hontecillas, assistant professor of immunology at the Virginia Bioinformatics Institute and one of the lead investigators of the study. "We have also shown that abscisic acid affects the expression of several genes involved in inflammation, metabolism and cell signaling, which provides further clues for possible intervention points in the treatment of inflammatory and immune-mediated diseases."

The researchers hope to more closely pinpoint some of the new drug targets in the molecular network of the immune response as they continue to dissect the way that the naturally occurring drug abscisic acid reduces damage due to inflammation. In addition, the novel understanding on how abscisic acid works will be used to develop new classes of drugs that target the same alternative pathway of peroxisome proliferator-activated receptor-gamma activation, a potentially safer approach than the use of drugs that target direct binding to the receptor.

The research was funded by award number 5R01AT004308 from the National Center for Complementary and Alternative Medicine at the National Institutes of Health, European Commission grant number 224836, the Ramon y Cajal Program, National Institute of Allergy and Infectious Diseases Contract No. HHSN272200900040C, National Institute of Allergy and Infectious Diseases Contract No. HHSN272201000056C, and funds from the Nutritional Immunology and Molecular Medicine Laboratory.

About the Nutritional Immunology and Molecular Medicine Group

The Nutritional Immunology and Molecular Medicine Group conducts translational research aimed at developing novel therapeutic and prophylactic approaches for modulating immune and inflammatory responses. The group combines computational modeling, bioinformatics approaches, pre-clinical experimentation and human clinical studies to better understand the mechanisms of immune regulation at mucosal surfaces and ultimately accelerate the development of novel treatments for infectious and immune-mediated diseases. Learn more at: www.vbi.vt.edu/nimm

Learn more about Josep Bassaganya-Riera at https://www.vbi.vt.edu/vbi_faculty/vbi_persons/dev_vbi_faculty?personId=177

Related links

Immune system changes linked to inflammatory bowel disease revealed
http://www.eurekalert.org/pub_releases/2010-12/vt-isc120910.php

Barry Whyte | EurekAlert!
Further information:
http://www.vt.edu

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>