Andrographolide attenuates LPS-stimulated up-regulation of C-C and C-X-C motif chemokines in rodent cortex and primary astrocytes

Abstract

Background: Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti-inflammatory properties. In this study, we aimed to assess andrographolide's potential utility as an anti-neuroinflammatory therapeutic. Methods: The effects of andrographolide on lipopolysaccharide (LPS)-induced chemokine up-regulation both in mouse cortex and in cultured primary astrocyteswere measured, including cytokine profiling, gene expression, and, in cultured astrocytes, activation of putative signaling regulators. Results: Orally administered andrographolide significantly attenuated mouse cortical chemokine levels from the C-C and C-X-C subfamilies. Similarly, andrographolide abrogated a range of LPS-induced chemokines as well as tumor necrosis factor (TNF)-aα in astrocytes. In astrocytes, the inhibitory actions of andrographolide on chemokine and TNF-aα up-regulation appeared to be mediated by nuclear factor-ΚB (NF-ΚB) or c-Jun N-terminal kinase (JNK) activation. Conclusions: These results suggest that andrographolide may be useful as a therapeutic for neuroinflammatory diseases, especially those characterized by chemokine dysregulation.