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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>