Abstract
BackgroundAndrographolide 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.MethodsThe effects of andrographolide on lipopolysaccharide (LPS)-induced chemokine up-regulation both in mouse cortex and in cultured primary astrocytes were measured, including cytokine profiling, gene expression, and, in cultured astrocytes, activation of putative signaling regulators.ResultsOrally 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)-α in astrocytes. In astrocytes, the inhibitory actions of andrographolide on chemokine and TNF-α up-regulation appeared to be mediated by nuclear factor-κB (NF-κB) or c-Jun N-terminal kinase (JNK) activation.ConclusionsThese results suggest that andrographolide may be useful as a therapeutic for neuroinflammatory diseases, especially those characterized by chemokine dysregulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0498-6) contains supplementary material, which is available to authorized users.
Highlights
Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti-inflammatory properties
We have shown that andrographolide attenuated IL-1β-stimulated up-regulation of the C-C motif ligand 5 (CCL5) chemokine via nuclear factor-κB (NF-κB) inhibition in vitro [24]
In the case of CCL2, CXCL1, and CXCL2, reductions only reached statistical significance with the higher andrographolide dose. These results indicate that oral andrographolide administered soon after peripheral LPS is efficacious in attenuating a range of LPS-induced chemokines in the cortex
Summary
Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti-inflammatory properties. In the central nervous system (CNS), chemokines mediate innate and adaptive immune responses, signaling for leukocyte recruitment as well as glial cell activation during neuroinflammation [1]. They are known to play important roles in interneuronal communication, neuronal progenitor cell migration, and oligodendrocyte maturation [2,3,4]. While cytokines/chemokines help clear harmful stimuli by initiating inflammatory responses and recruiting peripheral immune cells, dysregulation of chemokines has been implicated in various neurological diseases characterized by neuroinflammation, including neurodegenerative dementias such as Alzheimer’s disease, multiple sclerosis, traumatic brain injury, and specific types of meningitis [8,9,10,11]. There is an unmet need for safe and potent antineuroinflammatory therapeutics
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