Frailty-Preventing Effect of an Intervention Program Using a Novel Complete Nutritional "COMB-FP Meal": A Pilot Randomized Control Trial.

Frailty is a huge concern for the aging population, and dietary nutrition is considered a key factor in the prevention of aging. To solve the problem of frailty in the aging population, we developed a novel dietary intervention program using a novel COMpletely Balanced for Frailty Prevention (COMB-FP) meal, based on the Dietary Reference Intake for Japanese; in addition, we conducted a pilot randomized control trial comparing an exercise program only (control group) with exercise plus the COMB-FP meal program (test group). We included 110 male and female healthy volunteers with pre-frailty or frailty; the trial lasted for 12 weeks. Two daily meals were replaced with the COMB-FP meals during the trial in the test group. Walking speed and cognitive function were significantly improved in the test group compared with the control group. We observed a similar pattern in other frailty-related outcomes, such as occupancy of the microbiome, World Health Organization well-being index (WHO-5), and oxidative stress. Our study might indicate the importance of a well-balanced intake of nutrients for frailty prevention.

Rice-memolin, a novel peptide derived from rice bran, improves cognitive function after oral administration in mice.

Many people eat polished rice, while rice bran, a by-product known to be rich in protein and expected to have potential functions for health benefits, has not been effectively utilized. In this study, we determined that orally administered Val-Tyr-Thr-Pro-Gly (VYTPG) derived from rice bran protein improved cognitive decline in mice fed a high-fat diet (HFD). It was demonstrated that VYTPG was released from model peptides corresponding to fragment sequences of original rice proteins (Os01g0941500, Os01g0872700, and allergenic protein) after treatment with thermolysin, a microorganism-derived enzyme often used in industrial scale processes. The thermolysin digest also improved cognitive decline after oral administration in mice. Because VYTPG (1.0 mg/kg) potently improved cognitive decline and is enzymatically produced from the rice bran, we named it rice-memolin. Next, we investigated the mechanisms underlying the cognitive decline improvement associated with rice-memolin. Methyllycaconitine, an antagonist for α7 nicotinic acetylcholine receptor, suppressed the rice-memolin-induced effect, suggesting that rice-memolin improved cognitive decline coupled to the acetylcholine system. Rice-memolin increased the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells and promoted the mRNA expression of EGF and FGF-2 in the hippocampus, implying that these neurotropic factors play a role in hippocampal neurogenesis after rice-memolin administration. Epidemiologic studies demonstrated that diabetes is a risk factor for dementia; therefore, we also examined the effect of rice-memolin on glucose metabolism. Rice-memolin improved glucose intolerance. In conclusion, we identified a novel rice-derived peptide that can improve cognitive decline. The mechanisms are associated with acetylcholine and hippocampal neurogenesis. Rice-memolin is the first rice-brain-derived peptide able to improve cognitive decline.

Lessons from the health policies for children during the pandemic in Japan.

It is everyone's desire to seek the sound growth of children through food education and there is a critical need for fostering an environment for this purpose. Health policies are important for this support. To the present, the Japanese society has been greatly disrupted by COVID-19 pandemic. "Stay at home", "mokusyoku (silent eating)", and mask wearing were encouraged in nationwide campaigns as public health measures to combat COVID-19. There are some papers reporting negative effects of "stay at home" and lockdowns such as weight gain, decrease in physical activities and change in eating habits. In Japan, while benefits and advantages of food education during mealtime were previously well studied, the "mokusyoku" rule may directly run counter to this food education. Moreover, there are several reports showing that nutrients might contribute to prevention of infectious diseases. Japanese children were also encouraged to wear masks all day long. The results of the clinical research, especially randomized control trials, show limited protective effect of masks. On the other hand, negative outcomes of the masks were reported in various scenes. This review focuses on these topics and arousing reconsideration for a better environment for children.

Hypotensive peptides derived from plant proteins.

Hypertension is a risk factor for arteriosclerosis development and is recognized as a silent killer. Certain processed food materials, digested by protease or through the use of fermentation, have shown exertion of hypotensive effects in human clinical or animal studies, and hypotensive peptides were isolated from them. This review discusses the hypotensive peptides derived from plant proteins, such as grain, soy, vegetables, and seaweeds, and their hypotensive mechanisms. Although angiotensin I-converting enzyme (ACE) inhibition is often noted as one of the mechanisms that may exert antihypertensive effects, ACE inhibitory activity measured by in vitro studies is not associated with the actual hypotensive effect. Thus, this review only highlights the peptide hypotensive effect determined by in vivo studies. This review also discusses the tendency of the amino acid sequence of ACE-inhibitory hypotensive peptides and the possible additional effects of hypotensive peptides independent of ACE inhibition.

Anti-Hypertensive Effects of Peptides Derived from Rice Bran Protein.

Hypertension is one of the major risk factors for arteriosclerosis. Anti-hypertensive peptides derived from animal proteins, such as milk, eggs and fish, are well studied. Anti-hypertensive peptides have also been identified from plant proteins such as soybeans. Rice bran, a byproduct of white rice polishing, is rich in protein and its high protein efficiency ratio is well known. This review discusses the anti-hypertensive peptides identified from rice bran protein and their mechanisms. In addition, we describe protease-digested rice bran from which functional peptides have not been isolated.

Rice Bran Supplement Containing A Functional Substance, the Novel Peptide Leu-Arg-Ala, has Anti-Hypertensive Effects: A Double-Blind, Randomized, Placebo-Controlled Study.

The anti-hypertensive effect of processed rice bran (PRB) was recently reported, for which the novel peptide Leu-Arg-Ala (LRA) was identified as the functional substance. The purpose of this study was to assess the anti-hypertensive effects of a rice bran supplement containing PRB in individuals with high-normal blood pressure (systolic blood pressure (SBP): 130⁻139 mmHg and/or diastolic blood pressure (DBP): 85⁻89 mmHg) or grade 1 hypertension (SBP: 140⁻159 mmHg and/or DBP: 90⁻99 mmHg). One hundred individuals with high-normal blood pressure or grade 1 hypertension were recruited to participate in this double-blind, randomized, placebo-controlled study. Participants were randomly allocated to the placebo group (n = 50) or the test group (n = 50). Each group took four test tablets (43 µg LRA/day) or four placebo tablets daily. The decrease in blood pressure in the test group compared with the placebo group was the primary outcome. Adverse events were recorded and hematological/urinary parameters measured to determine the safety of the supplement, which was the secondary outcome. In total, 87 participants completed the study. The SBP of the test group at 12 weeks was significantly lower than that of the placebo group (p = 0.0497). No serious adverse events were observed. Daily consumption of a rice bran supplement containing PRB can safely improve mildly elevated blood pressure.

Vasorelaxant and Antihypertensive Effects That Are Dependent on the Endothelial NO System Exhibited by Rice Bran-Derived Tripeptide.

We recently identified a novel, potent antihypertensive peptide, Leu-Arg-Ala (LRA; minimum effective dose = 0.25 mg/kg), from rice bran protein. In this study, we found that LRA potently relaxed mesenteric arteries isolated from spontaneously hypertensive rats (SHRs) (EC50 = 0.1 µM). In contrast, the vasorelaxant activity of each amino acid that constitutes the LRA tripeptide was remarkably attenuated. The LRA-induced vasorelaxant activity was inhibited by N(G)-nitro-l-arginine methyl ester (L-NAME; NO synthase [NOS] inhibitor) but not by an antagonist of bradykinin B2 and Mas receptors or by a phosphoinositide 3-kinase inhibitor. The antihypertensive effect induced after the oral administration of LRA was inhibited by L-NAME. LRA also induced the phosphorylation of endothelial NOS in human umbilical vein endothelial cells. Taken together, LRA may exhibit antihypertensive effects via NO-mediated vasorelaxation. LRA is the first example of a NO-dependent vasorelaxant peptide identified from rice bran protein.

A Novel Antihypertensive Peptide Identified in Thermolysin-Digested Rice Bran.

SCOPE: Hypertension is a risk factor for arteriosclerosis. In this study, we investigate the antihypertensive effect of protease-digested rice bran in a spontaneously hypertension rat (SHR) model. We also purify a novel antihypertensive peptide from the digest. METHODS AND RESULTS: Thermolysin-digested rice bran (TRB) is administered to SHRs for 4 weeks, and systolic blood pressure (SBP) was measured weekly using the tail-cuff method. TRB shows an antihypertensive effect in a dose-dependent manner. TRB also reduces angiotensin I-converting enzyme (ACE) activity in lung tissue and serum troponin I levels. TRB is fractionated by HPLC and ACE-inhibitory activity in the HPLC fractions is measured. Peptides LRA and YY are identified from the two fractions with the strongest ACE-inhibitory activity. Amino acid sequence of these peptides are found in a vicilin-like seed storage protein, and identified in rice bran protein using the peptide mass fingerprint method. We confirm that LRA and YY are cleaved by thermolysin digestion of a model synthetic peptide. Orally administered LRA (0.25 mg kg-1 ) or YY (0.5 mg kg-1 ) lowers the SBP of SHRs at 4 h after administration. CONCLUSION: We identify a novel, orally active antihypertensive peptide, LRA from the digest of rice bran protein.