Cinnamaldehyde inhibits inflammation and brain damage in a mouse model of permanent cerebral ischaemia.

Abstract

BACKGROUND AND PURPOSE:

Recent findings suggest the importance of inflammation in the pathogenesis of cerebral ischaemia and its potential as a therapeutic target. Cinnamaldehyde is a diterpene with a wide range of anti-inflammatory effects thus may be advantageous in the treatment of cerebral ischaemia. The present study examined the potential therapeutic effects of cinnamaldehyde on cerebral ischaemia using a mouse model with permanent middle cerebral artery occlusion.

EXPERIMENTAL APPROACH:

Male CD-1 mice, which had the middle cerebral artery occluded, were treated (i.p.) with cinnamaldehyde. Neuroprotection by cinnamaldehyde was analysed by evaluating neurological deficit scores, brain oedema and infarct volume. Expressions of signal transduction molecules and inflammatory mediators were measured by Western blotting, qRT-PCR and immunohistochemical staining. Activation of NF-κB was assessed by Western blotting, immunohistochemistry and immunofluorescence.

KEY RESULTS:

Cinnamaldehyde reduced the neurological deficit scores, brain oedema and infarct volume. Cinnamaldehyde suppressed the activation of signal transduction molecules including toll-like receptor 4, tumour necrosis receptor-associated factor 6 and NF-κB, attenuated the increased levels of TNF-α, IL-1β, CCL2 and endothelial-leukocyte adhesion molecule-1 and ultimately reduced leukocyte infiltration into the ischaemic brain areas after cerebral ischaemia.

CONCLUSIONS AND IMPLICATIONS:

Cinnamaldehyde protects against cerebral ischaemia injury by inhibiting inflammation, partly mediated by reducing the expression of toll-like receptor 4, tumour necrosis receptor-associated factor 6 and the nuclear translocation of NF-κB. Our findings suggest that cinnamaldehyde may serve as a new candidate for further development as a treatment for stroke.

• Authors: Jingru Zhao, Xiangjian Zhang, Lipeng Dong, Ya Wen, Xiufen Zheng, Cong Zhang, Rong Chen, Ye Zhang, Yaoru Li, Tingting He, Xingyuan Zhu, Litao Li
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 172 Issue 20 Pg. 5009-23 (Oct 2015) ISSN: 1476-5381 [Electronic] England
• PMID: 26234631 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The British Pharmacological Society.

Chemical References

• Anti-Inflammatory Agents
• Ccl2 protein, mouse
• Chemokine CCL2
• E-Selectin
• Interleukin-1beta
• NF-kappa B
• Neuroprotective Agents
• RNA, Messenger
• TNF Receptor-Associated Factor 6
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Water
• Acrolein
• cinnamaldehyde

Topics

• Acrolein (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Brain (drug effects, metabolism, pathology)
• Chemokine CCL2 (genetics)
• Disease Models, Animal
• E-Selectin (genetics)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, pathology)
• Interleukin-1beta (genetics)
• Male
• Mice
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• RNA, Messenger (metabolism)
• TNF Receptor-Associated Factor 6 (metabolism)
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (genetics)
• Water (metabolism)