1. ¹Department of Medicinal Chemistry and Natural Products, Medical Faculty, Hebrew University, Jerusalem, Israel
2. ²Department of Pharmacology, School of Pharmacy, Hebrew University, Jerusalem, Israel
3. ³Rehabilitation Center, Hadassah Medical Center, Hebrew University, Jerusalem, Israel
4. ⁴Laboratory of Experimental Neurology, AHEPA University Hospital, Thessaloniki, Greece
5. ⁵Laboratory of Physiology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
6. ⁶The Lautenberg Center for Immunology, Hadassah Medical School, Hebrew University, Jerusalem, Israel
7. ⁷Institute of Biochemistry, Medical Faculty, Justus-Liebig-University, Giessen, Germany
8. ⁸Department of Psychiatry, University of Freiburg Medical School, Freiburg, Germany
9. ⁹Departamento Biologia Celular, Fisiologia e Inmunologia, Facultad de Medicina, Universidad de Cordoba, Cordoba, Spain

Correspondence: Professor E Shohami, Department of Pharmacology, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. E-mail: esty@cc.huji.ac.il

Received 2 October 2007; Revised 10 March 2008; Accepted 13 March 2008; Published online 16 April 2008.

Abstract

Boswellia resin has been used as a major anti-inflammatory agent and for the healing of wounds for centuries. Incensole acetate (IA), isolated from this resin, was shown to inhibit the activation of nuclear factor-B, a key transcription factor in the inflammatory response. We now show that IA inhibits the production of inflammatory mediators in an in vitro model system of C6 glioma and human peripheral monocytes. Given the involvement of postinjury inflammation in the pathophysiology and outcome of traumatic brain injury, we examined the effect of IA on the inflammatory process and on the recovery of neurobehavioral and cognitive functions in a mouse model of closed head injury (CHI). In the brains of post-CHI mice, IA reduced glial activation, inhibited the expression of interleukin-1, and tumor necrosis factor- mRNAs, and induced cell death in macrophages at the area of trauma. A mild hypothermic effect was also noted. Subsequently, IA inhibited hippocampal neurodegeneration and exerted a beneficial effect on functional outcome after CHI, indicated by reduced neurological severity scores and improved cognitive ability in an object recognition test. This study attributes the anti-inflammatory activity of Boswellia resin to IA and related cembranoid diterpenes and suggests that they may serve as novel neuroprotective agents.