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Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia.
- Source :
- British Journal of Pharmacology; Oct2010, Vol. 161 Issue 3, p668-679, 12p
- Publication Year :
- 2010
-
Abstract
- <bold>Background and Purpose: </bold>Andrographolide is a diterpenoid lactone isolated from a traditional medicinal herb, Andrographis paniculata. It possesses potent anti-inflammatory activity. The present study examined potential therapeutic effects of andrographolide on cerebral ischaemia using a rat model with permanent middle cerebral artery occlusion (pMCAO).<bold>Experimental Approach: </bold>The MCA in rats was permanently occluded (by cautery), and 24 h later neurological effects were assessed with behavioural scores. Infarct volume and microglial activation were determined histologically. The p65 form of the transcription factor, nuclear factor-κB (NF-κB), was measured by Western blot, and cytokines by immunoassay of brain extracts.<bold>Key Results: </bold>Andrographolide, given i.p. 1 h after pMCAO, reduced infarct volume with a maximum reduction of approximately 50% obtained at 0.1 mg·kg(-1). Neurological deficits were also reduced by andrographolide, reflecting a correlation between infarct volume and neurological deficits. pMCAO was found to induce activation of microglia and elevate tumour necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin (PG)E(2) in the ischaemic brain areas. Andrographolide (0.1 mg·kg(-1)) significantly attenuated or abolished these effects. In addition, andrographolide suppressed the translocation of p65 from cytosol to nucleus, indicating reduced NF-κB activation.<bold>Conclusions and Implications: </bold>Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF-κB and microglial activation, and reduction in the production of cytokines including TNF-α and IL-1β, and pro-inflammatory factors such as PGE(2). Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke. [ABSTRACT FROM AUTHOR]
- Subjects :
- NEUROPROTECTIVE agents
DITERPENES
LABORATORY rats
CEREBRAL ischemia
ANTI-inflammatory agents
ARTERIAL occlusions
MICROGLIA
HISTOLOGY
TRANSCRIPTION factors
NF-kappa B
IMMUNOASSAY
TUMOR necrosis factors
PROSTAGLANDINS
INTERLEUKINS
CELL metabolism
BIOLOGICAL models
BRAIN
RESEARCH
INFARCTION
ANIMAL experimentation
DINOPROSTONE
RESEARCH methodology
INTERLEUKIN-1
MEDICAL cooperation
EVALUATION research
HYDROCARBONS
RATS
COMPARATIVE studies
DNA-binding proteins
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 161
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 65012958
- Full Text :
- https://doi.org/10.1111/j.1476-5381.2010.00906.x