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result(s) for
"UTSUNOMIYA Hirotoshi"
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Infused juice concentrate of Japanese plum Prunus mume attenuates inflammatory vascular remodeling in a mouse model of hypertension induced by angiotensin II
by
Utsunomiya, Hirotoshi
,
Cicalese, Stephanie M.
,
Eguchi, Satoru
in
Antihypertensives
,
Blood pressure
,
Coronary vessels
2023
Fruit from the Prunus mume tree is a traditional food in Japan. Recently, bainiku-ekisu, an infused juice concentrate of Japanese Prunus mume, is attracting attention as a health promoting supplement. Angiotensin II (Ang II) plays a central role in development of hypertension. It has been reported that bainiku-ekisu treatment attenuates the growth-promoting signaling induced by Ang II in vascular smooth muscle cells. However, whether bainiku-ekisu has any effect on an animal model of hypertension remains unknown. Therefore, this study was designed to explore the potential anti-hypertensive benefit of bainiku-ekisu utilizing a mouse model of hypertension with Ang II infusion. Male C57BL/6 mice were infused with Ang II for 2 weeks and given 0.1% bainiku-ekisu containing water or normal water for 2 weeks with blood pressure evaluation. After 2 weeks, mice were euthanized, and the aortas were collected for evaluation of remodeling. Aortic medial hypertrophy was observed in control mice after Ang II infusion, which was attenuated in bainiku-ekisu group with Ang II infusion. Bainiku-ekisu further attenuated aortic induction of collagen producing cells and immune cell infiltration. Development of hypertension induced by Ang II was also prevented by bainiku-ekisu. Echocardiograph indicated protection of Ang II-induced cardiac hypertrophy by bainiku-ekisu. In vascular fibroblasts, bainiku-ekisu attenuated vascular cell adhesion molecule-1 induction, an endoplasmic reticulum stress marker, inositol requiring enzyme-1α phosphorylation, and enhancement in glucose consumption in response to Ang II. In conclusion, Bainiku-ekisu prevented Ang II-induced hypertension and inflammatory vascular remodeling. Potential cardiovascular health benefit to taking bainiku-ekisu should be further studied.
Journal Article
Deletion of Nrf2 leads to rapid progression of steatohepatitis in mice fed atherogenic plus high-fat diet
2013
Background
The transcription factor nuclear factor-E2-related factor-2 (Nrf2) inhibits lipid accumulation and oxidative stress in the liver by interfering with lipogenic pathways and inducing antioxidative stress genes.
Methods
The involvement of Nrf2 in defense against the development of steatohepatitis was studied in an experimental model induced by an atherogenic plus high-fat (Ath + HF) diet. Wild-type (WT) and
Nrf2
-null mice were fed the diet. Their specimens were analyzed for pathology as well as for the expression levels of genes involved in fatty acid metabolism and those involved via the Nrf2 transcriptional pathway.
Results
In
Nrf2
-null mice fed the diet, steatohepatitis developed rapidly, leading to precirrhosis. The Ath + HF diet increased hepatic triglyceride levels and changed fatty acid composition in both mouse groups. However, oleic acid (C18:1 n-9) predominated in the livers of
Nrf2
-null mice. Correlating well with the pathology, the mRNA levels of the factors involved in fatty acid metabolism (
Lxr
,
Srebp
-
1a
,
1c
,
Acc
-
1
,
Fas
,
Scd
-
1
, and
Fatty acid transporting peptides 1
,
3
,
4
), the inflammatory cytokine genes (
Tnf
-
α
and
IL
-
1β
), and the fibrogenesis-related genes (
Tgf
-
β1
and
α
-
Sma
) were significantly increased in the livers of
Nrf2
-null mice fed the diet, compared with the levels of these factors in matched WT mice. Oxidative stress was significantly increased in the livers of
Nrf2
-null mice fed the diet. This change was closely associated with the decreased levels of antioxidative stress genes.
Conclusions
Nrf2 deletion leads to the rapid onset and progression of steatohepatitis induced by an Ath + HF diet, through both up-regulation of co-regulators of fatty acid metabolism and down-regulation of oxidative metabolism regulators in the liver.
Journal Article
Association between subjective oral dysfunction and locomotive syndrome in community-dwelling older adults
2021
The need for support and care is a major problem facing societies around the world. Locomotive syndrome (LS) refers to a condition in which people require healthcare services because of problems associated with locomotion. Oral dysfunction is also associated with various long-term care factors including activities of daily living. The purpose of this study was to determine the association between oral dysfunction and LS. The study participants were 407 elderly people living in a rural area in Japan. Evaluation of oral dysfunction was based on subjective judgment by each participant. LS was assessed using Locomo-25, which is a self-administered questionnaire and was defined by a Locomo-25 score ≥ 7 points. Those with a “decline in masticatory function” and “difficulty swallowing” had higher odds of LS than those without these dysfunctions (odds ratio (OR) = 2.134, 2.007, respectively). Furthermore, participants with a Locomo-25 score ≥ 11 had higher odds of a “decline in masticatory function” (OR = 2.657) than those with a Locomo-25 score < 11, and those with a Locomo-25 score ≥ 9 had higher odds of “difficulty swallowing” (OR = 2.411) than those with a Locomo-25 score < 9. These findings suggest that a strong relationship exists between oral dysfunction and LS.
Journal Article
Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis
by
WARABI Eiji
,
HORIE Masaki
,
TAGUCHI Keiko
in
Abdominal Surgery
,
Adaptor Proteins, Signal Transducing - genetics
,
Animals
2012
Background
The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is a key regulator for induction of hepatic antioxidative stress systems. We aimed to investigate whether activation of Nrf2 protects against steatohepatitis.
Method
Wild-type mice (WT),
Nrf2
gene-null mice (
Nrf2
-null) and
Keap1
gene-knockdown mice (
Keap1
-kd), which represent the sustained activation of Nrf2, were fed a methionine- and choline-deficient diet (MCDD) for 13 weeks and analyzed.
Results
In
Keap1
-kd fed an MCDD, steatohepatitis did not develop over the observation periods; however, in
Nrf2
-null fed an MCDD, the pathological state of the steatohepatitis was aggravated in terms of fatty change, inflammation, fibrosis and iron accumulation. In WT mice fed an MCDD, Nrf2 and antioxidative stress genes regulated by Nrf2 were potently activated in the livers, and in
Keap1
-kd, their basal levels were potently activated. Oxidative stress was significantly increased in the livers of the
Nrf2
-null and suppressed in the livers of the
Keap1
-kd compared to that of WT, based on the levels of 4-hydroxy-2-nonenal and malondialdehyde. Iron accumulation was greater in the livers of the
Nrf2
-null mice compared to those of the WT mice, and it was not observed in
Keap1
-kd. Further, the iron release from the isolated hepatocyte of
Nrf2
-null mice was significantly decreased. Sulforaphane, an activator of Nrf2, suppressed the pathological states and oxidative stress in the livers.
Conclusions
Nrf2 has protective roles against nutritional steatohepatitis through inhibition of hepatic iron accumulation and counteraction against oxidative stress-induced liver injury. Nrf2 activation by pharmaceutical intervention could be a new option for the prevention and treatment of steatohepatitis.
Journal Article
Correction: Tokusanai et al. Prunus mume Extract Inhibits SARS-CoV-2 and Influenza Virus Infection In Vitro by Directly Targeting Viral Particles. Int. J. Mol. Sci. 2025, 26, 8487
by
Utsunomiya, Hirotoshi
,
Tateishi, Koichiro
,
Kato, Chikara
in
Influenza
,
Severe acute respiratory syndrome coronavirus 2
2026
In the original publication [...]
Journal Article
Prunus mume Extract Inhibits SARS-CoV-2 and Influenza Virus Infection In Vitro by Directly Targeting Viral Particles
by
Utsunomiya, Hirotoshi
,
Tateishi, Koichiro
,
Kato, Chikara
in
Analysis
,
Animals
,
Antiviral Agents - pharmacology
2025
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are major respiratory pathogens associated with substantial morbidity and a risk of severe disease. However, the effectiveness of current vaccines and antiviral drugs is limited by viral mutations. Umeboshi, a traditional Japanese food prepared from pickled Prunus mume, is known for its health benefits; certain components of P. mume have exhibited antimicrobial properties. However, the efficacy of P. mume against SARS-CoV-2 and influenza virus remains unknown. We aimed to examine the antiviral activity of P. mume extracts against SARS-CoV-2 and influenza virus. Cytopathic effect (CPE) assays and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) analyses with full-time treatment demonstrated that four extracts (PM2, PM3, PM4, and PM6) among eight tested inhibited the replication of both viruses. Subsequent time-of-addition assays, plaque assays, and transmission electron microscopy (TEM) confirmed that PM2 directly inactivated viral particles of both viruses by disrupting their structural integrity. Additional evaluations of virion integrity and infectivity suggested that the antiviral activity of PM2 may also involve mechanisms other than direct virion disruption. These findings suggest that P. mume-derived components exhibit direct antiviral activities against SARS-CoV-2 and influenza virus, supporting their potential development as antiviral agents or infection-preventive dietary products.
Journal Article
Inhibition by caffeic acid of the influenza A virus multiplication in vitro
2014
Caffeic acid has been shown to inhibit the multiplication of influenza A virus in vitro, whereas caffeine, quinic acid and chlorogenic acid do not. Caffeic acid has also been shown to have antiviral activity against herpes simplex virus (DNA virus) and polio virus (RNA virus). In the present study, a comparison of the one-step growth curve of the influenza virus in the presence of caffeic acid with that in the absence of the reagent showed that an eclipse period of the virus multiplication in the infected cells was not affected by the reagent, while the progeny virus yield was markedly decreased in the presence of caffeic acid. In additional experiments, it was found that the addition of caffeic acid at an early time point post-infection (within 3 h post-infection) was mandatory for extensive antiviral activity, suggesting that a major target of the reagent exists in the early stages of infection. Simultaneously with the decrease in the progeny virus yield, both the virus-induced cytopathic effects and apoptotic nuclear fragmentation were markedly suppressed by the reagent, suggesting that caffeic acid suppresses, at least temporally, the degeneration of the virus-infected cells and that the observed antiviral activity is likely not the secondary result of the cytotoxic effects of the reagent. These results suggest the potential pharmacological use of caffeic acid or its derivatives as an antiviral drug against influenza A virus.
Journal Article
Endogenous calcitonin regulates lipid and glucose metabolism in diet-induced obesity mice
2018
Calcitonin (CT) plays an important role in calcium homeostasis, and its precursor, proCT, is positively associated with the body mass index in the general human population. However, the physiological role of endogenous CT in the regulation of metabolism remains unclear. Knockout mice with gene-targeted deletion of exon 4 of
Calca
(CT KO) were generated by targeted modification in embryonic stem cells. Male mice were used in all experiments and were fed a slightly higher fat diet than the standard diet. The CT KO mice did not exhibit any abnormal findings in appearance, but exhibited weight loss from 15 months old, i.e., significantly decreased liver, adipose tissue, and kidney weights, compared with wild-type control mice. Furthermore, CT KO mice exhibited significantly decreased fat contents in the liver, lipid droplets in adipose tissues, serum glucose, and lipid levels, and significantly increased insulin sensitivity and serum adiponectin levels. CT significantly promoted 3T3-L1 adipocyte differentiation and suppressed adiponectin release. These results suggested that CT gene deletion prevents obesity, hyperglycemia, and hyperlipidemia in aged male mice. This is the first definitive evidence that CT may contribute to glucose and lipid metabolism in aged male mice, possibly via decreased adiponectin secretion from adipocytes.
Journal Article
Biological and epidemiological evidence of anti-allergic effects of traditional Japanese food ume (Prunus mume)
2018
Japanese apricot (
Prunus mume
;
ume
) is a traditional food in Japan that has been shown to have various beneficial health effects. There is some evidence to suggest that
ume
is also effective against allergic disease. Here, we conducted a cross-sectional epidemiological pilot study to examine the association between
ume
intake frequency and allergic symptoms including rhinitis in 563 adults (288 men and 275 women) who resided in Wakayama, Japan. After adjusting for age, present illness and medication, women with high
ume
intake had significantly lower odds ratio (OR) for the presence of symptoms of allergy [OR: 0.49 with 95% confidence interval (CI): 0.25–0.97]. Therefore, we investigated the anti-allergic effect of
ume
on passive cutaneous anaphylaxis (PCA) reaction in immunoglobulin E (IgE)-sensitized mice. The animal study demonstrated that oral administration of
ume
extract attenuated the PCA reaction and mast cell degranulation. Furthermore, RBL-2H3 mast cells were used to identify anti-allergic
ume
compounds. The following
ume
compounds inhibited IgE-mediated mast cell degranulation: vanillin, syringic acid, protocatechuic aldehyde, lyoniresinol and
p
-coumaric acid. These results suggested that
ume
has the potential to inhibit mast cell degranulation and may be associated with reduced risk of allergic symptoms in women.
Journal Article
The Relationship between Locomotive Syndrome and Depression in Community-Dwelling Elderly People
by
Utsunomiya, Hirotoshi
,
Kono, Ryohei
,
Nomura, Sachiko
in
Activities of daily living
,
Aging
,
Analysis
2017
Locomotive syndrome (LS) is a concept that refers to the condition of people requiring healthcare services because of problems associated with locomotion. Depression is a major psychiatric disease among the elderly, in addition to dementia. The purpose of this study was to determine the association between LS and depression. The study participants were 224 healthy elderly volunteers living in a rural area in Japan. LS was defined as scores ≥ 16 on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Depression was defined as scores ≥ 5 on the 15-item Geriatric Depression Scale (GDS-15). Height and body weight were measured. The prevalence of LS and depression was 13.9% and 24.2%, respectively. Compared with the non-LS group, the LS group was older, was shorter, had a higher BMI, and had higher GDS-15 scores. Logistic regression analysis showed that participants with GDS-15 scores ≥ 6 had higher odds for LS than those with GDS-15 scores < 6 (odds ratio [OR] = 4.22). Conversely, the depression group had higher GLFS-25 scores than the nondepression group. Participants with GLFS-25 scores ≥ 5 had higher odds for depression than those with GLFS-25 scores < 5 (OR = 4.53). These findings suggest that there is a close relationship between LS and depression.
Journal Article