Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia

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-kappa B (NF-kappa B), 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 center dot 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)-alpha, interleukin (IL)-1 beta and prostaglandin (PG)E-2 in the ischaemic brain areas. Andrographolide (0.1 mg center dot kg(-1)) significantly attenuated or abolished these effects. In addition, andrographolide suppressed the translocation of p65 from cytosol to nucleus, indicating reduced NF-kappa B activation. CONCLUSIONS AND IMPLICATIONS Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF-kappa B and microglial activation, and reduction in the production of cytokines including TNF-alpha and IL-1 beta, and pro-inflammatory factors such as PGE(2). Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke.