Dataset Information

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

ABSTRACT:

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-?B (NF-?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·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)-?, interleukin (IL)-1? 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-?B activation.

Conclusions and implications

Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF-?B and microglial activation, and reduction in the production of cytokines including TNF-? and IL-1?, and pro-inflammatory factors such as PGE(2). Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke.

SUBMITTER: Chan SJ

PROVIDER: S-EPMC2990163 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Chan Su Jing SJ Wong W S Fred WS Wong Peter T H PT Bian Jin-Song JS

British journal of pharmacology 20101001 3

<h4>Background and purpose</h4>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).<h4>Experimental approach</h4>The MCA in rats was permanently occluded (by cautery), and 24 h later neurological effects were assessed with ...[more]

PMID: 20880404

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Project description:Ischemic stroke is one of the most common causes of mortality worldwide and is a primary cause of disability and mortality in adults. There is an unmet need for drugs that can effectively treat ischemic stroke. Hence, the present study explored the neuroprotective effects of andrographolide (Andro) in a mouse model of bilateral common carotid artery occlusion, and systematically evaluated the potential mechanisms underlying its effects. The effects of Andro on mouse brain tissue following cerebral ischemia‑reperfusion injury (CIRI) were evaluated by histopathological (H&E and Nissl) and immunofluorescence [glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN)] staining. A traditional Chinese medicine‑based network pharmacology method was performed to establish and analyze compound‑target‑disease and function‑pathway networks in order to elucidate the possible mechanisms responsible for the protective role of Andrographis paniculata in CIRI. In addition, western blot analysis and RT‑qPCR was performed to evaluate the expression and activation of signaling proteins predicted to be involved in this mechanism. The amelioration of histopathological alterations was observed in mice pre‑treated with Andro. Immunofluorescence staining revealed that Andro decreased the expression of GFAP and increased the expression of NeuN, and significantly decreased the levels of pro‑inflammatory cytokines (IL‑1β, IL‑6 and TNF‑α). Network pharmacology analysis revealed that neuroinflammatory response and apoptosis were associated with the effects of Andrographis paniculata on CIRI. Western blot analysis revealed that the mice pre‑treated with Andro exhibited an upregulated protein expression of tropomyosin receptor kinase B (TrkB), p‑PI3K and p‑Akt, as well as a decrease in the expression of GFAP and an increase in the expression of NeuN. In addition, the data of RT‑qPCR indicated that the mice pre‑treated with Andro exhibited a significantly decreased expression of encoding IL‑1β mRNA, IL‑6 mRNA and TNF‑α mRNA in the brain compared to the untreated mice following CIRI. On the whole, the findings of the present study suggest that pre‑treatment with Andro exerts a protective effect against CIRI, which may be partly related to its potential to reduce neuroinflammatory response and apoptosis in patients with stroke.

Dataset Information

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

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

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

Similar Datasets

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