BACKGROUND AND PURPOSEAndrographolide 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 APPROACHThe 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-kB (NF-kB), was measured by Western blot, and cytokines by immunoassay of brain extracts.
KEY RESULTSAndrographolide, 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)-a, interleukin (IL)-1b and prostaglandin (PG)E2 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-kB activation.
CONCLUSIONS AND IMPLICATIONSAndrographolide exhibited neuroprotective effects, with accompanying suppression of NF-kB and microglial activation, and reduction in the production of cytokines including TNF-a and IL-1b, and pro-inflammatory factors such as PGE2. Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke.
AbbreviationsICAM-1, intercellular adhesion molecule 1; IL-1b, interleukin-1b; iNOS, inducible NOS; NF-kB, nuclear factor-kappa B; PGE2, prostaglandin E2; pMCAO, permanent middle cerebral artery occlusion; ROS, reactive oxygen species; TNF-a, tumour necrosis factor-a; tPA, tissue-type plasminogen activator