The research, published today in the academic journal RNA, was led by Dr Cornelia de Moor in the School of Pharmacy. It shows that cordycepin reduces inflammatory gene products in airway smooth muscle cells – the cells that contract during an asthma attack.
Several studies have suggested that cordycepin could be an effective drug for a variety of conditions, including cancer, stroke, kidney damage and inflammatory lung disease but until now it was unclear how cordycepin could bring about so many different beneficial effects at the cellular level.
Dr de Moor said: “We have shown that cordycepin reduces the expression of inflammatory genes in airway smooth muscle cells by acting on the final step in the synthesis of their messenger RNAs (mRNAs) which carry the chemical blueprint for the synthesis of proteins. This process is called polyadenylation. Commonly used anti-inflammatory drugs either work much earlier in the activation of inflammatory genes, such as prednisone, or work on one of the final products of the inflammatory reaction (e.g. ibuprofen).These findings indicate that cordycepin acts by a completely different mechanism than currently used anti-inflammatory drugs, making it a potential drug for patients in which these drugs don’t work well.
“However, it is a surprise that cordycepin does not affect the synthesis of mRNAs from other genes, because nearly all mRNAs require polyadenylation.”
Dr de Moor’s research suggests that this is because inflammatory genes can be very rapidly induced and that cordycepin has its many and varied effects by altering the synthesis of other classes of rapidly induced genes as well. If this is true if could be said that cordycepin slows down the rapid cellular responses to tissue damage and may work by preventing the over-activation of these responses which are associated with conditions such as asthma, rheumatoid arthritis, renal failure, cancer and stroke damage.
However, it also indicates that cordycepin could have adverse effects on normal wound healing and on the natural defences against infectious diseases.
Dr de Moor said: “We are hoping to further investigate which genes are more dependent on polyadenylation than others and why this is the case, as well as test the effect of cordycepin on animal models of disease. Clinical testing of cordycepin is not in our immediate plans, as we think we first have to understand this drug in more detail before we can risk treating patients with it.”
Additional funding has been awarded by the Biotechnology and Biological Sciences Research Council to continue this vital work.
A copy of the paper is available online at http://rnajournal.cshlp.org/content/early/2012/10/29/rna.032391.112.full.pdf+html
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More than 90 per cent of research at The University of Nottingham is of international quality, according to the most recent Research Assessment Exercise. The University’s vision is to be recognised around the world for its signature contributions, especially in global food security, energy & sustainability, and health. The University won a Queen’s Anniversary Prize for Higher and Further Education in 2011, for its research into global food security.
More information is available from Dr Cornelia de Moor, at The University of Nottingham, on +44 (0)115 9515041, Cornelia.De_Moor@nottingham.ac.uk
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