It has been reported that the ingestion of food-derived peptides exerts beneficial effect on human health and, these several types of peptides are on the market as functional foods components. So far, to elucidate the mechanisms for the beneficial effects, food-derived peptides have been detected from human blood after ingestion of collagen and elastin peptides. Ingestion of collagen peptides increases di- and tri-peptides which contain hydroxyproline (Hyp), and the maximum concentration reached to nmol/mL level in human plasma. Among these food-derived collagen peptide, prolyl-hydroxyproline (Pro-Hyp) was a major component and approximately 20 types of Hyp containing peptides were identified as minor components. Ingestion of elastin peptides similarly increased prolyl-glycine to nmol/mL level in human plasma. In addition, it has been recently demonstrated the increase of Hyp containing cyclic peptides in human plasma after ingestion of collagen peptides. These findings indicate that the ingestions of polypeptides can increase di- and tri- peptides in human blood, which are composed of several amino acid sequences, and those may be candidates for active components of functional foods with the beneficial effects. Especially, since the food-derived cyclic peptides does not exist in the test food, the digestion and absorption of the peptides should be precisely investigated to elucidate the mechanisms for the production of cyclic peptides.

Aging is an inevitable part of life for human and is associated with a decline in the physical and functional capacity of tissues and organs. Recently, some bioactive food components have been demonstrated to potentially exhibit the anti-aging effects in different animal models. Senescence-accelerated mouse (SAM) strains were established as a model of accelerated aging. Nine major SAM-prone (SAMP) strains and three major SAMresistant (SAMR) strains have been established. The SAMP strains grow normally, but they show early signs of aging, including greatly reduced physical activity and loss of hair glossiness, coarseness of the skin, hair loss, periophthalmic lesions, and increased lordokyphosis of the spine. Their life spans are markedly shorter than normal. All SAMP strains exhibit accelerated senescence compared to the SAMR strains and each SAMP strain exhibits characteristic disorders. For example, SAM prone 8 (SAMP8) spontaneously exhibits agerelated cognitive impairment as well as shortened life span. This review focuses on the effects of dietary food components on appearance aging and age-related cognitive decline in an animal model of accelerated senescence such as SAMP1 and SAMP8, respectively.

A cognitive dysfunction is growing up year by year as a serious social issue. However, appropriate therapeutic drugs and preventive foods have not been developed yet. Thus far, it has been reported that polyphenols and peptides could improve a cognitive decline, whereas no evidence on their intact transport across the blood-brain barrier and accumulation in the brain parenchyma has been claimed. The signs of the Alzheimer's disease might be initiated 10 to 20 years before clinical definitive diagnosis, by impaired glutamate signaling at the astrocyte as well as amyloid-β accumulation in the brain. Thus, in this review we discuss the possibility of prevention of initial Alzheimer's disease by food factors.

Capsaicin, a pungent component in capsicum, is a ligand for TRPV1 (transient receptor potential vanilloid 1)which regulates nerve-related pein-sensitive signal and inflammation. However, the effects of capsaicin on bone metabolism are not elucidated. We have showed that capsaicin inhibited LPS-induced osteoclast differentiation and bone resorbing activity. The receptor of capsaicin, TRPV1 was only expressed in osteoblasts but not in macrophages and osteoclast precursor cells. In osteoblasts, capsaicin suppressed PG (prostaglandin) E₂ production through the downregulation of COX (cyclooxygenase)-2 and mPGES (membrane-bound PGE synthase)-1 expression, resulting in suppression of RANKL (receptor activator of NF-κB ligand) expression. In vivo study, intraperitoneally injection of LPS resulted in severe bone loss in the femur and treatment of capsaicin attenuated its bone loss. Current reports showed that capsaicin has a protective effect on periodontal bone resorption through a nerve system-mediated mechanism, and other report suggested capsaicin has abilities to direct inhibition of periodontal pathogens. Controversially, TRPV1 knockout mice have shown resistance to periodontal disease. In this review, we described the effects of capsaicin on inflammatory bone diseases. We suggest functional food capsaicin is one of a candidate for maintaining bone health.

Beta-cryptoxanthin is a typical carotenoid as the natural compound derived from citrus. Beta-cryptoxanthin possesses various biological activities including anti-oxidative effects, however, the effects of beta-cryptoxanthin on bone metabolism was still unclear. We reported that beta-cryptoxanthin showed bone protective effects through the inhibition of bone-resorbing cells such as osteoclasts. Beta-cryptoxanthin inhibited osteoclast differentiation and bone resorption that was induced by lipopolysaccharide (LPS), a major pathogenic factor of periodontitis. In osteoblasts, beta-cryptoxanthin suppressed mPGES (membrane-bound PGE synthase)-1 expression that was resulted in down-regulation of PGE₂ production and following RANKL (receptor activator of NF-κB ligand) expression. In osteoclasts, beta-cryptoxanthin inhibited RANKL-induced osteoclast differentiation and induced apoptosis of mature osteoclasts. We further demonstrated that beta-cryptoxanthin directly suppressed IKK (inhibitor of NF-κB kinase) activity by competing for ATP in vitro assay. In silico molecular docking analysis showed that beta-cryptoxanthin binds to the ATP binding pocket of IKK protein. These data suggest that beta-cryptoxanthin blocks IKKNF-κB signaling via the direct suppression of IKK activity, followed by inhibiting PGE₂-mediated osteoclast differentiation and function. In this review, we described the function of beta-cryptoxanthin on bone-related diseases. In conclusion, beta-cryptoxanthin is a candidate for a functional food for maintaining bone health in an aging society.

The pandemic of COVID-19 by the SARS-CoV-2 infection has caused a great impact on socio-economic activities worldwide. It is essential to take measures to reduce exposure to the SARS-CoV-2 virus as well as to increase the resistance to infection in the human host as for prophylaxis and treatment of COVID-19. Functional food ingredients have antiviral, immunomodulatory, and anti-inflammatory effects. Numerous studies showed the efficacy of dietary supplements containing these food components to prevent and reduce the severity of viral respiratory infections including COVID-19. A significant correlation between COVID-19 morbidity/severity and low levels of vitamin C/vitamin D has been reported. Zinc, probiotics, turmeric (curcumin), coenzyme Q10, and lactoferrin showed efficacy for COVID-19. This is a narrative review of the clinical evidence of functional food ingredients for prophylaxis and adjunct treatment of COVID-19.

This study examined the changes in concentration of cyclic prolyl-hydroxyproline (cyclo(Pro-Hyp)) in human plasma after ingestion of gelatin, gelatin hydrolysate (collagen peptide; CP) and low-molecular weight CP. This human study showed that gelatin ingestion significantly increased cyclo (Pro-Hyp) levels in plasma from 1 hour after ingestion as well as CP and low-molecular weight CP. Furthermore, the ratio of cyclic Pro-Hyp to the total content of cyclic and liner Pro-Hyp in plasma after gelatin ingestion was highest among other CP ingestions. These results suggested that gelatin can be candidate for active components of the health benefits by gelatin and CP ingestion. In addition, in case of gelatin, large individual differences in cyclo (Pro-Hyp) concentration was observed in plasma at each time point after ingestion. It might indicates that cyclo (Pro-Hyp) concentration into plasma is affected not only molecular size of gelatin products, but also cyclization ability in each subjects. A further study for elucidating the mechanism of peptide cyclization in gastrointestinal tract is now in progress.

Olive leaf extract (OLE) is an important source of hydroxytyrosol. Its beneficial properties such as antioxidant and anti-inflammatory have been reported. However, the effect of OLE on skeletal muscle has not been clarified. Here we aimed to investigate the muscle changes with OLE in disuse-induced muscle atrophy model.

Male Wistar rats were divided into three groups, Non-casted, Casted, and OLE group. In the immobilized group, unilateral ankle joint was immobilized in full plantar flexion by a cast (Casted). During the experiment period, OLE was orally administrated at the dose of 100 mg/kg body weight to OLE group. After 2 weeks of hindlimb immobilization, soleus, plantar, gastrocnemius muscles were dissected. The level of muscle atrophy was assessed by muscle weight and cross-sectional area (CSA) of muscle fiber. No significant differences were observed between Casted group and OLE group in muscle weight, but the decrease of CSA of plantar muscle suppressed in OLE group.

The effect of OLE on muscle cells were studied in LPS-induced C2C12 myotubes. Treatment with OLE prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Our findings indicate that OLE may be involved in the improvement of disuse muscle atrophy.

Urolithin (U) is a group of metabolites of ellagic acid (EA) and has antioxidant activity. In this study, we investigated the effect of U analogs (UA, UB, UC, UD, and UH) and EA on type1 hypersensitivity in vitro and in vivo. UA, UB, UC, and UH inhibited the release of β-hexosaminidase, an indicator of degranulation, from sensitized RBL-2H3 cells stimulated with DNP-albumin. Next, we evaluated the effect of UA on allergic symptoms in a mouse model of Japanese cedar pollinosis. BALB/c female mice were intraperitoneally injected with Japanese cedar pollen antigen as primary sensitization 3 times for 3 weeks. Further antigen was administered intranasally as secondary sensitization with or without UA for 19 days. Dexamethasone (Dex) was used as a positive control. The number of sneezes and eosinophils in the UA and Dex administration groups decreased significantly compared to the control group. Serum IgE levels were not different among the three groups. In conclusion, oral intake of UA suppresses sneezing and eosinophil migration. These suppressions might be caused by inhibition of mast cell degranulation.

Acai (Euterpe oleracea Mart. Palmae, Arecaceae) is a palm plant native to the Brazilian Amazon and is eaten locally for the purpose of improving health. Acai is known as a kind of superfood in Japan, and is taken especially for the purpose of improving anemia. In this study, we investigated the hematopoiesis of acai pulp solution and its mechanism. The erythropoiesis inducer roxadustat upregulated both the erythropoietin (EPO) contents in plasma and the Epo transcript level in kidney two hours after administration. According to this protocol, acai pulp solution was orally administered once to wild-type mice, and blood EPO level and renal Epo gene expression were measured two hours later. Two hours after administration, acai and roxadustat significantly increased blood EPO levels by about 2.5-fold and 6-fold, respectively. Acai and roxadustat also upregulated the Epo transcript level in the kidney by about 10-fold and 20-fold, respectively. Then, renal oxygen levels were histologically analyzed with a hypoxic probe, pimonidazole, that binds to reduced thiol groups. Acai significantly induced renal hypoxia, as indicated by increased pimonidazole staining. Furthermore, to investigate erythropoiesis effect of acai, we orally administered acai pulp solution to wild-type mice for four days and measured hematological parameters. Acai administration for four days significantly increased red blood cells count, hemoglobin level, and hematocrit level. These results demonstrated that acai increases the EPO expression via hypoxic action in the kidney. Acai is expected as a functional food for improving anemia.