Effects of a single dose of tablets containing lactononadecapeptide on cognitive function in healthy adults: a randomized, double-blind, cross-over, placebo-controlled trial.

Lactononadecapeptide (LNDP; NIPPLTQTPVVVPPFLQPE) is a memory-improving peptide. The current study aimed to determine the effects of a single dose of tablets containing LNDP on cognitive function in healthy Japanese men aged 30-59 years. A randomized, double-blind, cross-over, placebo-controlled trial was conducted in participants randomly assigned to receive LNDP or placebo tablets. The Uchida-Kraepelin test was used to induce cognitive load in participants as a model of work load. Cognitive function was evaluated using the Japanese version of the CNS Vital Signs. Composite memory and verbal memory were significantly higher following consumption of LNDP than placebo tablets. Carryover effects were observed in attention and concentration domains so that period 1 data was analyzed. LNDP consumption led to higher processing speed, executive function, and cognitive flexibility than placebo. Thus, supplementation with a single dose of LNDP tablets may improve cognitive functions including memory, attention, concentration, and information processing in daily life.

Dietary apple polyphenols increase skeletal muscle capillaries in Wistar rats.

Dietary apple polyphenols (AP) have been shown to exhibit beneficial effects on muscle endurance. Fast-to-slow change in the composition of myosin heavy chains was known as one of the molecular mechanisms. Here, we examined the effects of dietary AP on the capillaries and mitochondria in the rat skeletal muscle to elucidate the mechanisms underlying muscular endurance enhancement. Twenty-four Wistar male rats were divided into three groups, namely, the control group, 0.5% AP group, and 5% AP group (n = 8 in each group). After a feeding period of 4 weeks, rats were dissected, gastrocnemius muscles were removed, and the density of capillaries and levels of mitochondrial proteins were analyzed. Capillary density of the gastrocnemius increased to 17.8% in rats fed with 5% AP as compared to the control rats. No significant change was observed in the mitochondrial content and dynamics (fusion/fission) of regulatory proteins. To investigate the mechanisms underlying the increase in the capillary density, positive (vascular endothelial cell growth factor, VEGF) and negative (thrombosponsin-1, TSP-1) factors of angiogenesis were analyzed. TSP-1 expression significantly decreased in rats fed with 0.5% AP and 5% AP by approximately 25% and 40%, respectively, as compared with the control rats. There were no significant differences in VEGF expression. Thus, dietary AP may increase the muscle capillary density by decreasing TSP-1 expression. We concluded that the increase in the capillary density and the fast-to-slow change in myosin heavy chains by AP feeding are the main causes for muscle endurance enhancement in Wistar rats.

Apple procyanidins promote mitochondrial biogenesis and proteoglycan biosynthesis in chondrocytes.

Apples are well known to have various benefits for the human body. Procyanidins are a class of polyphenols found in apples that have demonstrated effects on the circulatory system and skeletal organs. Osteoarthritis (OA) is a locomotive syndrome that is histologically characterized by cartilage degeneration associated with the impairment of proteoglycan homeostasis in chondrocytes. However, no useful therapy for cartilage degeneration has been developed to date. In the present study, we detected beneficial effects of apple polyphenols or their procyanidins on cartilage homeostasis. An in vitro assay revealed that apple polyphenols increased the activities of mitochondrial dehydrogenases associated with an increased copy number of mitochondrial DNA as well as the gene expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), suggesting the promotion of PGC-1α-mediated mitochondrial biogenesis. Apple  procyanidins also enhanced proteoglycan biosynthesis with aggrecan upregulation in primary chondrocytes. Of note, oral treatment with apple procyanidins prevented articular cartilage degradation in OA model mice induced by mitochondrial dysfunction in chondrocytes. Our findings suggest that apple procyanidins are promising food components that inhibit OA progression by promoting mitochondrial biogenesis and proteoglycan homeostasis in chondrocytes.