The Japanese traditional therapy, honokiol, blocks key protein in inflammatory brain damage

March 19, 2012, BioMed Central

Microglia are the first line defence of the brain and are constantly looking for infections to fight off. Overactive microglia can cause uncontrolled inflammation within the brain, which can in turn lead to neuronal damage. New research published in BioMed Central's open access journal Journal of Neuroinflammation shows that, honokiol (HNK) is able to down-regulate the production of pro-inflammatory cytokines and inflammatory enzymes in activated microglia via Klf4, a protein known to regulate DNA.

Scientists from the National Brain Research Centre, Manesar, India, used lipopolysaccharide (LPS), a molecule present on the surface of bacteria, to stimulate an immune response from microglia cells. LPS mimics the effect of a bacterial infection and the microglia cells spring into action, releasing proinflammatory cytokines, such as TNFa.

Activation of microglia also stimulates the production of nitric oxide (NO) and Cox-2, which co-ordinate the immune response, leading to inflammation. However uncontrolled inflammation can lead to and permanent brain damage. Microglial inflammation is also observed in several including Alzheimer's disease, Parkinson's disease, and multiple sclerosis.

The team led by Dr Anirban Basu found that the inflammatory response was mediated by Klf4, a 'transcription' factor which binds directly to DNA to enhance or impede gene expression. Treating microglia with HNK reduced their activation and HNK treated cells secreted less cytokines in response to LPS. HNK also down regulated the activity of Klf4 (and pNF-kb - another regulator of inflammation).

Dr Basu suggested that HNK down regulates Klf4 which in turn down regulates NO and Cox-2 production. He said, "HNK can easily move across the and we found that HNK reduced levels of pNF-kb and Klf4 as well as the number of activated microglia in the brains of LPS treated mice."

He continued, "Our work with HNK has found that Klf4 is an important regulator of inflammation. Both HNK and Klf4 may be important not only in regulating inflammation due to infection, but may also have applications in other diseases which affect the brain and nervous system."

More information: Therapeutic targeting of Kruppel-like factor 4 abrogates microglial activation, Deepak K Kaushik, Rupanjan Mukhopadhyay, Kanhaiya L Kumawat, Malvika Gupta and Anirban Basu, Journal of Neuroinflammation (in press)

Related Stories

Recommended for you

Chronic inflammation causes loss of muscle mass during aging

January 12, 2018
People start losing muscle mass at the age of 40—about some 10 percent of the total muscle mass for each 10-year period, which may lead to fall-related injuries, slowing metabolism and reduced quality of life. Today, very ...

Breathing exercises help asthma patients with quality of life

December 13, 2017
A study led by the University of Southampton has found that people who continue to get problems from their asthma, despite receiving standard treatment, experience an improved quality of life when they are taught breathing ...

Study highlights the need for research into prevention of inflammatory bowel disease

December 7, 2017
Countries in Africa, Asia, the Middle East and South America have seen a rise in incidence of inflammatory bowel disease as they have become increasingly industrialised and westernised, a new study has found.

Air pollution can increase asthma risk in adults, even at low levels

November 24, 2017
Living close to a busy road can be bad for your respiratory health if you are middle aged, new Australian research has found.

Evidence found of oral bacteria contributing to bowel disorders

October 20, 2017
(Medical Xpress)—An international team of researchers has found evidence that suggests certain types of oral bacteria may cause or exacerbate bowel disorders. In their paper published in the journal Science, the group describes ...

New compound discovered in fight against inflammatory disease

September 22, 2017
A 10-year study by University of Manchester scientists for a new chemical compound that is able to block a key component in inflammatory illness has ended in success.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.