Alpha-glycerylphosphorylcholine (αGPC) is a precursor of acetylcholine and can increase acetylcholine concentration in the brain. In addition, αGPC has a role in cholinergic function as well as monoaminergic transmission, including dopaminergic and serotonergic systems. These monoaminergic systems are related to feelings and emotions, including motivation, reward processing, anxiety, and depression. However, the precise effects of αGPC on human feelings and emotions remain to be elucidated. In this study, we investigated changes in the subjective feelings of healthy volunteers using the KOKORO scale before and after administering αGPC. Thirty-nine volunteers participated in a single-blind, placebo-controlled design. Participants completed a KOKORO scale test to quantify self-reported emotional states, three times each day for two weeks preceding treatment and then for a further two weeks while self-administering treatment. αGPC treatment show a tendency to increase motivation during the intervention period. Furthermore, motivation at night was significantly higher in the αGPC group than in the placebo group (p < 0.05). However, αGPC did not show any effects on anxiety. These data suggest that αGPC can be used to increase motivation in healthy individuals.

Administration of alpha-glycerophosphocholine (GPC), a choline compound in food, is expected to contribute to human health. In this study, we evaluated its effect on aging in senescence-accelerated mouse prone 8 (SAMP8) mice. Male SAMP8 mice had free access to a commercial stock diet and drinking water with or without GPC (0.07 mg/ml). Mice in the GPC group had significantly lower total senescence grading score than that of the control group at 36 weeks of age. Administration of GPC decreased the deposition of transthyretin (TTR), an amyloidogenic protein, in the brain. Aggregated TTR activated microglia and led to neuroinflammation. Thus, GPC would protect the brain by reducing TTR deposition and preventing neuroinflammation. In a histological study of knee joints, it was found that SAMP8 mice administered GPC showed decreased joint degeneration. These results suggest that GPC delays the aging process and may be a useful compound in anti-aging functional food development.

Carnosic acid (CA) is recognized as a unique neuroprotective compound in the herb rosemary, since it induces expression of antioxidant enzymes including heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), and glutathione S-transferase (GST) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a nuclear transcription factor. In this study, we examined the cytoprotective effects of CA against starvation. We found that CA protected starvation-induced SH-SY5Y cell death by activating Akt and extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, CA induced moderate autophagy and dephosphorylation of a transcriptional factor, the forkhead box protein O3a (FoxO3a). These effects of CA play an important role in cytoprotection.

Vitamins play essential roles in cellular reactions and maintain human health. Recent studies have revealed that some vitamins including D3, B6 and K2 and their derivatives have an anti-cancer effect. As a mechanism, their inhibitory effect on cancer-related angiogenesis has been demonstrated. Vitamin K2 (menaquinones) has an anti-cancer effect in particular for hepatic cancer and inhibits angiogenesis. In the current study, we demonstrated that sole vitamin K3 (menadione) selectively inhibits the in vitro activity of eukaryotic DNA polymerase γ, which is a mitochondrial DNA polymerase, and suppresses angiogenesis in a rat aortic ring model. The anti-angiogenic effect of vitamin K3 has been shown in angiogenesis models using human umbilical vein endothelial cells (HUVECs) with regard to HUVEC growth, tube formation on reconstituted basement membrane and chemotaxis. These results suggest that vitamin K3 may be a potential anti-cancer agent like vitamin K2.

We evaluated the effects of long-term glycerophosphocholine (GPC) intake on microglia, the blood-brain barrier (BBB), and neurogenesis in senescence-accelerated mice prone 8 (SAMP8). The GPC intake suppressed microglial activation and BBB disruption and sustained doublecortin-positive cells in the hippocampus. The results indicate that GPC intake exerts anti-inflammatory and neuroprotective effects in the brain of aged mice.

Pseudomonas fluorescens lectin (PFL), which belongs to the high mannose (HM)-binding OAAH (Oscillatoria agardhii agglutinin homologue) lectin family, induces cancer cell death. However, the detailed mechanisms underlying this process have not yet been elucidated. We found that PFL decreased various integrins as well as EGFR in cancer cells by promoting internalization and autophagic degradation of these molecules, subsequently inducing caspase-8 dependent cell apoptosis. As revealed by an ex vivo angiogenesis assay using the rat aortic model, PFL inhibited neovascularization in a dose-dependent manner, which was potentially mediated by down-regulation of endothelium integrins. Interestingly, PFL also down-regulated B7-H4 in cancer cells, which has been implicated as a negative regulator of T cell-mediated immunity. We found that B7-H4 co-localized with β3 integrin in MKN28 gastric cancer cells. siRNA silencing of B7-H4 in MKN28 cells decreased expression of β3 integrin, suggesting physical and functional association between these molecules. Direct interaction of PFL with integrin αvβ3 or B7-H4 was examined by surface plasmon resonance analysis, which detected high affinity glycan-dependent binding to PFL. These investigations suggest that PFL interaction with cell surface integrins is a key process for the anti-cancer activities of PFL.