Chan SJ, Wong WS, Wong PT, Bian JS.
Department of Pharmacology, Yong Loo Lin School of Medicine, National
University of Singapore, Singapore.
BACKGROUND AND PURPOSE 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). EXPERIMENTAL APPROACH 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. KEY
RESULTS 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. CONCLUSIONS
AND IMPLICATIONS 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.
PMID: 20880404 [PubMed - in process]
Posts
