Method for Inhibiting TNF-Alpha to Control Inflammation

Caritas St. Elizabeth's Medical Center
posted on 02/13/2009

• request more info 
•   
•  LICENSE ONLINE

Description: Studies have shown that melatonin, and N-acetylserotonin (NAS) have anti-oxidant activity and anti-aging property. It has been discovered that NAS and N-acetyl dopamine (NAD) have a modulatory effect on TNF-alpha synthesis and superoxide production. TNF-alpha is a potent inducer of inflammation in many diseases. In order to determine TNF-alpha production in response to melatonin, NAS and NAD on LPS-stimulated cells, differentiated THP-1 cells were co-incubated with 10 ng/ml LPS and 50, 100, 200 and 400 µM melatonin, NAS or NAD. Melatonin, NAS and NAD inhibited 93 to 99% of TNF-alpha production (P = 0.03) compared with control. The maximum inhibition of superoxide production was determined with 100 µM melatonin, NAS and NAD. However, at 100 µM dose, NAS and NAD have more potent effect to reduce superoxide production compared with melatonin. Advantages: Melatonin, NAS and NAD attenuate LPS-stimulated TNF-alpha production, PMA- and fMLP-stimulated superoxide production. Further compound optimization could lead to an effective way of contolling TNF-alpha activity which could lead to several inflammation indications.