Antcin A contributs to anti-inflammatory effect of Niuchangchih (Antrodia camphorata)

Abstract

Inflammation is the responses of body to harmful stimuli in many pathological conditions. Prevention and treatment of inflammation are the main indication of a variety of natural products. Recently, Niuchangchih (Antrodia camphorata), a medicinal mushroom in Taiwan, has received considerable attention from the public due to its potent bioactivities, such as anti-inflammation, anti-cancer, immuno-modulatory and anti-hepatitis activities1. Till now, researchers have identified a total of 26 compounds from Niuchangchih, including 11 succinic/maleic acid derivatives, 8 triterpenoids, 1 benzenoids, 1 benzoquinone derivative, 5 miscellaneous compounds and polysaccharides, that possess anti-inflammatory effect2, 3. However, the mechanisms underlying their anti-inflammatory actions remain elusive. A recent study by Chen et al elucidated the molecular mechanisms of anti-inflammation of Niuchangchih. The authors isolated and purified 5 major antcins (A, B, C, H, and K) from fruiting bodies of Niuchangchih. They found that antcin A was most similar to glucocorticoids among the 5 compounds in the chemical structure. Furthermore, they demonstrated in human lung cancer cell A549 that antcin A was the active ingredient responsible for the anti-inflammatory effect of Niuchangchih, which might act via the same molecular mechanism triggered by glucocorticoids4. Finally, they showed the docking of antcin A to glucocorticoid receptor (GR) in a molecular modeling study. Thus, via mimicking glucocorticoids, antcin A may diffuse across the cell membrane and bind to the cytosolic GR that forms a dimmer after dissociated from the heat-shock protein (HSP) and then translocates into the nucleus to initiate the suppression of inflammation at the gene regulation level. Molecular docking showed that C-7 of antcin A was attached to the hydrophobic side of the steroidal backbone of GR, while C-7 of the other antcins was attached to the hydrophilic group, thus being expelled when docking to the binding cavity of GR. Chen's work is an important landmark in research of anti-inflammatory compounds in Niuchangchih. Hsien et al recently showed that the anti-inflammatory activity of antrocamphin A, another anti-inflammatory compound from Niuchangchih, resulted from suppressing pro-inflammatory molecule release via down-regulation of iNOS and COX-2 expression through NF-κB pathway5. Both the studies provide solid evidence for the potential of Niuchangchih to treat inflammation. To elucidate the mechanisms of action of antcin A and antrocamphin A in vivo, more animal experiments and randomized controlled clinical trials should be carried out. Since more than 20 compounds in Niuchangchih have been shown to possess anti-inflammatory activity6, 7, 8, further studies are needed to elucidate their mechanisms. It is also of interest to figure out whether these compounds act synergistically or independently. Notably, most anti-inflammatory compounds in Niuchangchih have been derived from the fruiting bodies so far. Further research is needed to uncover whether they can also be produced in fermented mycelia. Besides antcin A and antrocamphin A, many unknown ingredients responsible for the anti-infammatory effects of Niuchangchih remain to be discovered.