Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia.
OBJECTIVE
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).


METHODS
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.


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
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.
Chan
Su Jing
SJ
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wong
W S Fred
WS
Wong
Peter T H
PT
Bian
Jin-Song
JS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004224:Diterpenes; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; C030419:andrographolide; D015232:Dinoprostone