Incensole acetate: a novel neuroprotective agent isolated from Boswellia carterii.
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-kappaB, 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-1beta, and tumor necrosis factor-alpha 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.
Moussaieff
Arieh
A
Department of Medicinal Chemistry and Natural Products, Medical Faculty, Hebrew University, Jerusalem, Israel.
Shein
Na'ama A
NA
Tsenter
Jeanna
J
Grigoriadis
Savvas
S
Simeonidou
Constantina
C
Alexandrovich
Alexander G
AG
Trembovler
Victoria
V
Ben-Neriah
Yinon
Y
Schmitz
Michael L
ML
Fiebich
Bernd L
BL
Munoz
Eduardo
E
Mechoulam
Raphael
R
Shohami
Esther
E
D000818:Animals; D029743:Boswellia / Q000737:chemistry*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000473:pathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects
D016207:Cytokines; D004224:Diterpenes; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; C530368:incensole acetate