title: 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 astrocytes were 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)-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.
  
  
  CONCLUSIONS
  These results suggest that andrographolide may be useful as a therapeutic for neuroinflammatory diseases, especially those characterized by chemokine dysregulation.
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Kent Ridge, 117600, Singapore. a0030682@u.nus.edu.
authors: Siew Ying
authors: SY
authors: Wong
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Kent Ridge, 117600, Singapore. michelle.tan.g.k@sgh.com.sg.|Department of Clinical Research, Singapore General Hospital, Outram, Singapore. michelle.tan.g.k@sgh.com.sg.
authors: Michelle G K
authors: MG
authors: Tan
authors: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA. wabanks1@u.washington.edu.|Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA. wabanks1@u.washington.edu.
authors: William A
authors: WA
authors: Banks
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Kent Ridge, 117600, Singapore. fred_wong@nuhs.edu.sg.|Immunology Program, Life Science Institute, National University of Singapore, Kent Ridge, Singapore. fred_wong@nuhs.edu.sg.
authors: W S Fred
authors: WS
authors: Wong
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Kent Ridge, 117600, Singapore. peter_wong@nuhs.edu.sg.
authors: Peter T-H
authors: PT
authors: Wong
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Kent Ridge, 117600, Singapore. mitchell.lai@dementia-research.org.
authors: Mitchell K P
authors: MK
authors: Lai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D019743:Chemokines, CXC; D004224:Diterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; C030419:andrographolide; D048670:MAP Kinase Kinase 4