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Increasing evidence has shown that β-amyloid (Aβ) induces hyperphosphorylation of tau and contributes to Aβ toxicity. Recently, tau hyperphosphorylation by glycogen synthase kinase-3β (GSK-3β) activation has been emphasized as one of the pathogenic mechanisms of Alzheimer's disease (AD). The phosphoinositide 3 kinase (PI3K)/Akt pathway is known as an upstream element of GSK-3β. The inhibitory control of GSK-3β, via the PI3K/Akt pathway, is an important mechanism of cell survival. In the present study, we investigated the neuroprotective effects of Angelica sinensis (AS), a traditional Chinese herbal medicine, against Aβ(1-42) toxicity in cultured cortical neurons and also the potential involvement of PI3K/Akt/GSK-3β signal pathway. We revealed that AS extract significantly attenuated Aβ(1-42) -induced neurotoxicity and tau hyperphosphorylation at multiple AD-related sites in a dose-dependent manner. Simultaneously, it increased the levels of phospho-Ser(473) -Akt and down-regulated GSK-3β activity by PI3K activation. The neuroprotective effects of AS extract against Aβ(1-42) -induced neurotoxicity and tau hyperphosphorylation were blocked by LY294002 (10 μM), a PI3K inhibitor. In addition, AS extract reversed the Aβ(1-42) -induced decrease in phosphorylation cyclic AMP response element binding protein (CREB), which could be blocked by the PI3K inhibitor. These results suggest that AS-mediated neuroprotection against Aβ toxicity is likely mediated by the PI3K/Akt/GSK-3β signal pathway.

Background: Although several studies have reported that C-reactive protein (CRP) is associated with physical performance, few studies have evaluated the relationships between CRP and physical performance among subjects who had a very low range of CRP. Therefore, it is still unclear whether a lower CRP is favorably associated with physical performance even within a very low range. Objective: The aim of this study was to investigate the relationships between CRP and physical performance among a Japanese population with a low serum CRP concentration (CRP <1.0 mg/l). Methods: We designed a cross-sectional survey for 775 persons aged 70 years and older living in Japan. High-sensitivity CRP was measured using a nephelometric method. The subjects whose serum CRP concentrations were higher than 10.0 mg/l were excluded. Physical performance was assessed using a 10-meter maximum walk test, leg extension power, and a timed ‘up and go’ test. Results: The median value (interquartile range) of CRP was 0.55 (0.29–1.20) mg/l. After adjustment for potential confounding factors, an inverse relation of CRP with the 10-meter maximum walk test and leg power was observed in all subjects (p for trend = 0.10 and 0.04, respectively). For subjects who had a CRP <1.0 mg/l, these inverse relations were unchanged (p for trend = 0.03 and 0.02, respectively). Conclusions: Serum CRP concentration is favorably related to physical performance, even within a very low range in a community-based elderly population aged 70 years and over. The findings suggest that maintaining as low CRP levels as possible may potentially maintain better physical performance.