TLR4/NF-κB-Mediated Anti-Inflammatory and Cognitive Protective Actions of Curcuma longa and Ar-turmerone in Alzheimer’s Disease Models
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In our previous study, we systematically compared various extraction methods and identified the 80% ethanolic extract of Curcuma longa L. (CL-80) as the most effective in protecting neurons from stress-induced damage in both in vitro and in vivo models. Although curcumin, a major constituent of C. longa, has demonstrated neuroprotective effects, the role of ar-turmerone, a bioactive sesquiterpenoid also derived from C. longa, remains underexplored in Alzheimer’s disease (AD) models. In this study, we evaluated the anti-inflammatory and cognitive-protective effects of CL-80 and ar-turmerone in both in vitro and in vivo models of amyloid-β (Aβ)-induced neurotoxicity. Primary cultured rat hippocampal neurons exposed to Aβ25−35 showed significantly increased expression of TNF-α, IFN-β, and iNOS, all of which were dose-dependently attenuated by CL-80 or arturmerone. Furthermore, both compounds suppressed Aβ-induced activation of the TLR4/NF-κB signaling axis at mRNA and protein levels. In an Aβ1−42-injected mouse model, oral administration of CL-80 or ar-turmerone significantly improved learning and memory performance in the Morris water maze and passive avoidance tests. Biochemical analyses of hippocampal tissues revealed reduced TLR4 expression and NF-κB activation, decreased acetylcholinesterase (AChE) activity, and restoration of acetylcholine (ACh) levels following treatment. Collectively, these findings suggest that both CL-80 and ar-turmerone exert neuroprotective effects by inhibiting TLR4/NF-κB-mediated neuroinflammation and preserving cholinergic function in an AD animal model. This study offers novel insight into the therapeutic potential of C. longa constituents for the treatment of AD.
Abstract
In our previous study, we systematically compared various extraction methods and identified the 80% ethanolic extract of Curcuma longa L. (CL-80) as the most effective in protecting neurons from stress-induced damage in both in vitro and in vivo models. Although curcumin, a major constituent of C. longa, has demonstrated neuroprotective effects, the role of ar-turmerone, a bioactive sesquiterpenoid also derived from C. longa, remains underexplored in Alzheimer’s disease (AD) models. In this study, we evaluated the anti-inflammatory and cognitive-protective effects of CL-80 and ar-turmerone in both in vitro and in vivo models of amyloid-β (Aβ)-induced neurotoxicity. Primary cultured rat hippocampal neurons exposed to Aβ25−35 showed significantly increased expression of TNF-α, IFN-β, and iNOS, all of which were dose-dependently attenuated by CL-80 or arturmerone. Furthermore, both compounds suppressed Aβ-induced activation of the TLR4/NF-κB signaling axis at mRNA and protein levels. In an Aβ1−42-injected mouse model, oral administration of CL-80 or ar-turmerone significantly improved learning and memory performance in the Morris water maze and passive avoidance tests. Biochemical analyses of hippocampal tissues revealed reduced TLR4 expression and NF-κB activation, decreased acetylcholinesterase (AChE) activity, and restoration of acetylcholine (ACh) levels following treatment. Collectively, these findings suggest that both CL-80 and ar-turmerone exert neuroprotective effects by inhibiting TLR4/NF-κB-mediated neuroinflammation and preserving cholinergic function in an AD animal model. This study offers novel insight into the therapeutic potential of C. longa constituents for the treatment of AD.