Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk

Abstract

Although Astragali Radix (Astragalus, AR), the root of Astragalus membranaceus (Fisch) Bunge, is widely used in oriental medicine for tonifying the immune response and improving circulation, the underlying mechanism(s) by which these effects are induced remains unclear. Here, we report that AR displays anti-inflammatory effects in zymosan air-pouch mice by reducing the expression of iNOS, COX-2, IL-6, IL-1beta and TNF-alpha and by decreasing the production of nitric oxide (NO). In a similar manner, AR reduces the expression of IL-6, iNOS, and COX-2 in lipopolysaccharide (LPS)-treated Raw 264.7 cells. We further demonstrate that AR attenuates the activity of p38 and Erk1/2 and stimulates mitogen-activated protein kinase phosphatase-1 (MKP-1) in LPS-treated Raw 264.7 cells. Additionally, AR interferes with the translocation of NFkappaB to the nucleus, subsequently resulting in NFkappaB-dependent transcriptional repression. Taken together, these data reveal that AR has an anti-inflammatory effect that is mediated by the MKP-1-dependent inactivation of p38 and Erk1/2 and inhibition of NFkappaB-mediated transcription. These results imply that the AR herb has a potential anti-inflammatory activity.