We previously reported that the dried peel powder of Citrus kawachiensis, one of the citrus products of Ehime, Japan, exerted anti-inflammatory effects in the brain of a lipopolysaccharide-injected systemic inflammation animal model. Inflammation is one of the main mechanisms underlying aging in the brain; therefore, we herein evaluated the anti-inflammatory and other effects of the dried peel powder of C. kawachiensis in the senescence-accelerated mouse-prone 8 (SAMP8) model. The C. kawachiensis treatment inhibited microglial activation in the hippocampus, the hyper-phosphorylation of tau at 231 of threonine in hippocampal neurons, and ameliorated the suppression of neurogenesis in the dentate gyrus of the hippocampus. These results suggest that the dried peel powder of C. kawachiensis exert anti-inflammatory and neuroprotective effects.

Our previous study showed that the subcutaneous administration of auraptene (AUR) suppresses inflammatory responses including the hyperactivation of microglia in the substantia nigra (SN) of the midbrain of lipopolysaccharide-induced Parkinson's disease (PD)-like mice, as well as inhibits dopaminergic neuronal cell death in this region. We also showed that the oral administration of the dried peel powder of Citrus kawachiensis, which contains relatively high amounts of AUR, suppresses inflammatory responses including the hyperactivation of microglia in the systemically inflamed brain.In the present study we showed that the oral administration of this dried peel powder successfully suppressed microglial activation and protected against dopaminergic neuronal cell death in the SN, suggesting its potential as a neuroprotective agent for the treatment of patients with PD.

Cerebral ischemia/reperfusion leads to delayed neuronal cell death, resulting in brain damage. Auraptene (AUR) and naringin (NGIN), which exert neuroprotective effects in ischemic brain, are abundant in the peel of Citrus kawachiensis. Although parts of AUR/NGIN are transited from the peel to the juice during the squeezing of this fruit, these amounts in juice might be too low to exert effects. We thus prepared the AUR/NGIN-rich fruit juice of C. kawachiensis by addition of peel paste to the raw juice. The present study revealed that orally administration of the dried powder of this AUR/NGIN-rich fruit juice (2.5 g/kg/d) for 7 d to ischemic mice significantly suppressed the ischemia-induced neuronal cell death in the hippocampus, which was coincidently with the reduction of hyperactivation of microglia and astrocytes. These results suggest that AUR/NGIN-rich juice of C. kawachiensis may possess therapeutic potential for the prevention of neurodegenerative diseases via inhibition of inflammatory processes.