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Article ; Online: Antihypertensive and Vasorelaxant Effects of Citric Acid and Lemon Juice in Spontaneously Hypertensive Rats: In Vivo and Ex Vivo Studies.

Nakamura, Kozo / Suzuki, Yumiko / Goto, Kazuma / Yamaguchi, Shohei / Hiramitsu, Masanori

2023 Volume 15, Issue 17

Abstract: Hypertension is a key risk factor for heart, brain, and kidney disease development. Fruit consumption has been associated with a decrease in blood pressure. Lemon juice, which contains antihypertensive compounds, may exert antihypertensive effects. ... ...

Abstract	Hypertension is a key risk factor for heart, brain, and kidney disease development. Fruit consumption has been associated with a decrease in blood pressure. Lemon juice, which contains antihypertensive compounds, may exert antihypertensive effects. However, no research has verified the antihypertensive effects of citric acid, the most abundant ingredient in lemon juice. In the present study, we demonstrated the antihypertensive effects of citric acid and lemon juice by performing single oral administration tests and the aortic ring assay using spontaneously hypertensive rats (SHRs). Single oral doses of both agents markedly reduced the systolic and diastolic blood pressures in the SHRs. In addition, both these agents relaxed the thoracic aorta from the SHRs; however, these effects were notably attenuated by the removal of the aortic endothelium. Orally administered citric acid was rapidly absorbed and metabolized in vivo. Among the functional compounds in lemon juice, citric acid was identified as the primary antihypertensive component. Although more detailed studies are required to validate our findings, the novel functional attributes of citric acid can achieve the normalization of blood pressure when it is consumed via diet.
MeSH term(s)	Animals ; Rats ; Antihypertensive Agents/pharmacology ; Vasodilator Agents ; Rats, Inbred SHR ; Citric Acid/pharmacology ; Blood Pressure
Chemical Substances	Antihypertensive Agents ; Vasodilator Agents ; Citric Acid (2968PHW8QP)
Language	English
Publishing date	2023-09-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15173849
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Partial Characterization and Immunomodulatory Effects of Exopolysaccharides from

Nakata, Hajime / Imamura, Yoshiya / Saha, Sudeb / Lobo, René Emanuel / Kitahara, Shugo / Araki, Shota / Tomokiyo, Mikado / Namai, Fu / Hiramitsu, Masanori / Inoue, Takashi / Nishiyama, Keita / Villena, Julio / Kitazawa, Haruki

Foods (Basel, Switzerland)

2023 Volume 12, Issue 12

Abstract: The immunomodulatory properties of exopolysaccharides (EPSs) produced ... ...

Abstract	The immunomodulatory properties of exopolysaccharides (EPSs) produced by
Language	English
Publishing date	2023-06-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704223-6
ISSN	2304-8158
ISSN	2304-8158
DOI	10.3390/foods12122374
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Article: Effects of Lemon Beverage Containing Citric Acid with Calcium Supplementation on Bone Metabolism and Mineral Density in Postmenopausal Women: Double-Blind 11-Month Intervention Study.

Ikeda, Hiromi / Iida, Tadayuki / Hiramitsu, Masanori / Inoue, Takashi / Aoi, Satomi / Kanazashi, Miho / Ishizaki, Fumiko / Harada, Toshihide

Journal of nutrition and metabolism

2021 Volume 2021, Page(s) 8824753

Abstract: A critical factor for preventing osteoporosis after menopause is attenuation of the accelerated turnover rate of bone metabolism. The present randomized controlled study was conducted to clarify the effects of a lemon beverage with calcium (Ca) ... ...

Abstract	A critical factor for preventing osteoporosis after menopause is attenuation of the accelerated turnover rate of bone metabolism. The present randomized controlled study was conducted to clarify the effects of a lemon beverage with calcium (Ca) supplementation that makes use of the chelating action of citric acid. Comprehensive evaluations of bone were performed by assessments of bone mineral density (BMD) and biomarkers related to bone turnover. Seventy-nine postmenopausal women were enrolled and asked to participate in an 11-month continuous intake of the test beverages. The subjects were divided into three groups: those who consumed a lemon beverage containing citric acid with Ca supplementation (LECA group), those who consumed a lemon beverage containing citric acid without Ca supplementation (LE group), and those who consumed no test beverage (control group). Using a double-blind protocol, subjects in the LECA and LE groups consumed one bottle containing 290 mL of the test beverage each day. The ratio of change in BMD after 11 months was significantly higher in the LECA group as compared to the control and LE groups. The LECA group also showed significant decreases in concentrations of tartrate-resistant acid phosphatase 5b (TRACP-5b), a bone resorption marker, and bone alkaline phosphatase (BAP) as compared to the other groups, as well as a significant decrease in concentration of osteocalcin (OC), a bone formation marker, as compared to the LE group. Based on our findings, we speculated that bone resorption and bone formation in postmenopausal women might be suppressed along with an increase in Ca resorption caused by chelation of citric acid in association with continuous ingestion of a Ca-supplemented lemon beverage containing citric acid, resulting in suppression of high bone metabolic turnover. In addition, the results provide information regarding BMD maintenance in the bones of the trunk, including the lumbar spine and proximal femur.
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573563-9
ISSN	2090-0732 ; 2090-0724
ISSN (online)	2090-0732
ISSN	2090-0724
DOI	10.1155/2021/8824753
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Article ; Online: Partial Characterization and Immunomodulatory Effects of Exopolysaccharides from Streptococcus thermophilus SBC8781 during Soy Milk and Cow Milk Fermentation

Foods. 2023 June 15, v. 12, no. 12

2023

Abstract: The immunomodulatory properties of exopolysaccharides (EPSs) produced by Streptococcus thermophilus have not been explored in depth. In addition, there are no comparative studies of the functional properties of EPSs produced by streptococci in different ... ...

Abstract	The immunomodulatory properties of exopolysaccharides (EPSs) produced by Streptococcus thermophilus have not been explored in depth. In addition, there are no comparative studies of the functional properties of EPSs produced by streptococci in different food matrices. In this work, EPSs from S. thermophilus SBC8781 were isolated after soy milk (EPS-s) or cow milk (EPS-m) fermentation, identified, and characterized in their abilities to modulate immunity in porcine intestinal epithelial cells. Fresh soy milk and cow milk were inoculated with S. thermophilus SBC8781 (7 log CFU/mL) and incubated at 37 °C for 24 h. The extraction of EPSs was performed by the ethanol precipitation method. Analytical techniques, including NMR, UV-vis spectroscopy, and chromatography, identified and characterized both biopolymer samples as polysaccharides with high purity levels and similar Mw. EPS-s and EPS-m had heteropolysaccharide structures formed by galactose, glucose, rhamnose, ribose, and mannose, although with different monomer proportions. On the other hand, EPS-s had higher quantities of acidic polymer than EPS-m. The biopolymer production of the SBC8781 strain from the vegetable culture broth was 200–240 mg/L, which was higher than that produced in milk, which reached concentrations of 50–70 mg/L. For immunomodulatory assays, intestinal epithelial cells were stimulated with 100 µg/mL of EPS-s or EPS-m for 48 h and then stimulated with the Toll-like receptor 3 agonist poly(I:C). EPS-s significantly reduced the expression of IL-6, IFN-β, IL-8, and MCP-1 and increased the negative regulator A20 in intestinal epithelial cells. Similarly, EPS-m induced a significant reduction of IL-6 and IL-8 expressions, but its effect was less remarkable than that caused by EPS-s. Results indicate that the structure and the immunomodulatory activity of EPSs produced by the SBC8781 strain vary according to the fermentation substrate. Soy milk fermented with S. thermophilus SBC8781 could be a new immunomodulatory functional food, which should be further evaluated in preclinical trials.
Keywords	Streptococcus thermophilus ; Toll-like receptor 3 ; agonists ; biopolymers ; chromatography ; culture media ; epithelium ; ethanol ; exopolysaccharides ; fermentation ; functional foods ; galactose ; glucose ; immunity ; immunomodulators ; interleukin-6 ; interleukin-8 ; intestines ; mannose ; milk ; rhamnose ; ribose ; soymilk ; swine ; ultraviolet-visible spectroscopy ; vegetable growing
Language	English
Dates of publication	2023-0615
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704223-6
ISSN	2304-8158
ISSN	2304-8158
DOI	10.3390/foods12122374
Database	NAL-Catalogue (AGRICOLA)

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Article: Isolation and extraction of antimicrobial substances against oral bacteria from lemon peel.

Miyake, Yoshiaki / Hiramitsu, Masanori

Journal of food science and technology

2011 Volume 48, Issue 5, Page(s) 635–639

Abstract: We have isolated 4 antibacterial substances that were active against the oral bacteria that cause dental caries and periodontitis, such as Streptococcus mutans, Prevotella intermedia, and Porphyromonas gingivalis, from lemon peel, a waste product in the ... ...

Abstract	We have isolated 4 antibacterial substances that were active against the oral bacteria that cause dental caries and periodontitis, such as Streptococcus mutans, Prevotella intermedia, and Porphyromonas gingivalis, from lemon peel, a waste product in the citrus industry. The isolated substances were identified as 8-geranyloxypsolaren, 5-geranyloxypsolaren, 5-geranyloxy-7-methoxycoumarin, and phloroglucinol 1-β-D-glucopyranoside (phlorin) upon structural analyses. Among these, 8-Geranyloxypsolaren, 5-geranyloxypsolaren, and 5-geranyloxy-7-methoxycoumarin exhibited high antibacterial activity. These 3 compounds were effectively extracted using ethanol and n-hexane, whereas phlorin was extracted with water. Further, the above 3 compounds were present in lemon essential oil and abundantly present in the residue produced upon the cooling treatment of concentrated lemon essential oil.
Language	English
Publishing date	2011-03-03
Publishing country	India
Document type	Journal Article
ZDB-ID	242498-8
ISSN	0975-8402 ; 0022-1155
ISSN (online)	0975-8402
ISSN	0022-1155
DOI	10.1007/s13197-011-0330-3
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Article ; Online: Effects of lifelong intake of lemon polyphenols on aging and intestinal microbiome in the senescence-accelerated mouse prone 1 (SAMP1).

Shimizu, Chikako / Wakita, Yoshihisa / Inoue, Takashi / Hiramitsu, Masanori / Okada, Miki / Mitani, Yutaka / Segawa, Shuichi / Tsuchiya, Youichi / Nabeshima, Toshitaka

Scientific reports

2019 Volume 9, Issue 1, Page(s) 3671

Abstract: Polyphenols have been examined for their beneficial effects on health, particularly in rodents, but their lifelong effects are unclear. Lemons (Citrus limon), containing lemon polyphenols (LPP), are widely consumed but the effects of LPP on aging are ... ...

Abstract	Polyphenols have been examined for their beneficial effects on health, particularly in rodents, but their lifelong effects are unclear. Lemons (Citrus limon), containing lemon polyphenols (LPP), are widely consumed but the effects of LPP on aging are unknown. Therefore, we examined the effects of LPP on aging such as aging-related scores, locomotor activity, cognitive functions, and intestinal microbiome using senescence-accelerated mouse prone 1 (SAMP1) and senescence-accelerated resistant mouse 1 (SAMR1). All mice had ad libitum access to water (P1_water group, SAMR1) or 0.1% LPP (P1_LPP group). In the P1_LPP group, LPP intake prolonged the lifespan by approximately 3 weeks and delayed increases in aging-related scores (e.g., periophthalmic lesions) and locomotor atrophy. The P1_water group showed large changes in the intestinal microbiome structure, while the R1 and P1_LPP groups did not. The phylum Bacteroidetes/Firmicutes, which is associated with obesity, in the P1_water group was significantly lower and higher than that in the P1_LPP and R1 groups, respectively. Although the relative abundance of Lactobacillus significantly increased in both P1 groups with aging, the P1_LPP group showed a significantly lower increase than the P1_water group. Thus, lifelong intake of LPP may have anti-aging effects on both phenotypes and the intestinal environment.
MeSH term(s)	Aging/drug effects ; Animals ; Antioxidants/pharmacology ; Body Weight/drug effects ; Citrus/chemistry ; Cognition/drug effects ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/physiology ; Male ; Membrane Proteins/genetics ; Memory, Long-Term/drug effects ; Mice, Mutant Strains ; Motor Activity/drug effects ; Nuclear Proteins/genetics ; Polyphenols/pharmacology
Chemical Substances	Antioxidants ; Membrane Proteins ; Nuclear Proteins ; Polyphenols ; Samp1 protein, mouse
Language	English
Publishing date	2019-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-40253-x
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Article ; Online: Coffee Ingestion Suppresses Hyperglycemia in Streptozotocin-Induced Diabetic Mice.

Kobayashi, Misato / Kurata, Takao / Hamana, Yoshiki / Hiramitsu, Masanori / Inoue, Takashi / Murai, Atsushi / Horio, Fumihiko

Journal of nutritional science and vitaminology

2017 Volume 63, Issue 3, Page(s) 200–207

Abstract: Coffee consumption reduces the risk of type 2 diabetes in humans, but the mechanism remains unclear. In this study, we investigated the effect of coffee on pancreatic β-cells in the induction of diabetes by streptozotocin (STZ) treatment in mice. We ... ...

Abstract	Coffee consumption reduces the risk of type 2 diabetes in humans, but the mechanism remains unclear. In this study, we investigated the effect of coffee on pancreatic β-cells in the induction of diabetes by streptozotocin (STZ) treatment in mice. We examined the effect of coffee, caffeine, or decaffeinated coffee ingestion on STZ-induced hyperglycemia. After STZ injection in Exp. 1 and 2, serum glucose concentration and water intake in coffee ingestion (Coffee group) tended to be lowered or was significantly lowered compared to those in water ingestion (Water group) instead of coffee. In Exp. 1, the values for water intake and serum glucose concentration in caffeine ingestion (Caffeine group) were similar to those in the Water group. In Exp. 2, serum glucose concentrations in the decaffeinated coffee ingestion (Decaf group) tended to be lower than those in the Water group. Pancreatic insulin contents tended to be higher in the Coffee and Decaf groups than in the Water group (Exp. 1 and 2). In Exp. 3, subsequently, we showed that coffee ingestion also suppressed the deterioration of hyperglycemia in diabetic mice which had been already injected with STZ. This study showed that coffee ingestion prevented the development of STZ-induced diabetes and suppressed hyperglycemia in STZ-diabetic mice. Caffeine or decaffeinated coffee ingestion did not significantly suppress STZ-induced hyperglycemia. These results suggest that the combination of caffeine and other components of decaffeinated coffee are needed for the preventive effect on pancreatic β-cell destruction. Coffee ingestion may contribute to the maintenance of pancreatic insulin contents.
Language	English
Publishing date	2017
Publishing country	Japan
Document type	Journal Article
ZDB-ID	191366-9
ISSN	1881-7742 ; 0301-4800
ISSN (online)	1881-7742
ISSN	0301-4800
DOI	10.3177/jnsv.63.200
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Article ; Online: Effects of lifelong intake of lemon polyphenols on aging and intestinal microbiome in the senescence-accelerated mouse prone 1 (SAMP1)

Chikako Shimizu / Yoshihisa Wakita / Takashi Inoue / Masanori Hiramitsu / Miki Okada / Yutaka Mitani / Shuichi Segawa / Youichi Tsuchiya / Toshitaka Nabeshima

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 11

Abstract: Abstract Polyphenols have been examined for their beneficial effects on health, particularly in rodents, but their lifelong effects are unclear. Lemons (Citrus limon), containing lemon polyphenols (LPP), are widely consumed but the effects of LPP on ... ...

Abstract	Abstract Polyphenols have been examined for their beneficial effects on health, particularly in rodents, but their lifelong effects are unclear. Lemons (Citrus limon), containing lemon polyphenols (LPP), are widely consumed but the effects of LPP on aging are unknown. Therefore, we examined the effects of LPP on aging such as aging-related scores, locomotor activity, cognitive functions, and intestinal microbiome using senescence-accelerated mouse prone 1 (SAMP1) and senescence-accelerated resistant mouse 1 (SAMR1). All mice had ad libitum access to water (P1_water group, SAMR1) or 0.1% LPP (P1_LPP group). In the P1_LPP group, LPP intake prolonged the lifespan by approximately 3 weeks and delayed increases in aging-related scores (e.g., periophthalmic lesions) and locomotor atrophy. The P1_water group showed large changes in the intestinal microbiome structure, while the R1 and P1_LPP groups did not. The phylum Bacteroidetes/Firmicutes, which is associated with obesity, in the P1_water group was significantly lower and higher than that in the P1_LPP and R1 groups, respectively. Although the relative abundance of Lactobacillus significantly increased in both P1 groups with aging, the P1_LPP group showed a significantly lower increase than the P1_water group. Thus, lifelong intake of LPP may have anti-aging effects on both phenotypes and the intestinal environment.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial.

Ito, Shin / Takahama, Hiroyuki / Asakura, Masanori / Abe, Yukio / Ajioka, Masayoshi / Anzai, Toshihisa / Arikawa, Takuo / Hayashi, Takaharu / Higashino, Yorihiko / Hiramitsu, Shinya / Iwahashi, Noriaki / Izumi, Chisato / Kimura, Kazuo / Kinugawa, Koichiro / Kioka, Hidetaka / Lim, Young-Jae / Matsuoka, Ken / Matsuoka, Satoshi / Motoki, Hirohiko /

Nakamura, Sunao / Nakayama, Takafumi / Nomura, Akihiro / Sasaoka, Taishi / Takiuchi, Shin / Toyoda, Shigeru / Ueda, Tomoya / Watanabe, Tetsuya / Yamada, Akira / Yamamoto, Masayoshi / Sozu, Takashi / Kitakaze, Masafumi

Scientific reports

2023 Volume 13, Issue 1, Page(s) 12517

Abstract: Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, ... ...

Abstract	Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m
MeSH term(s)	Humans ; Heart Failure ; Stroke Volume/physiology ; Taste ; Ventricular Dysfunction, Left/drug therapy ; Ventricular Function, Left/physiology ; Hypertension/drug therapy
Chemical Substances	candesartan (S8Q36MD2XX) ; azilsartan (F9NUX55P23)
Language	English
Publishing date	2023-08-02
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-39779-y
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Article ; Online: Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.

Hiramitsu, Masanori / Shimada, Yasuhito / Kuroyanagi, Junya / Inoue, Takashi / Katagiri, Takao / Zang, Liqing / Nishimura, Yuhei / Nishimura, Norihiro / Tanaka, Toshio

Scientific reports

2014 Volume 4, Page(s) 3708

Abstract: Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a ... ...

Abstract	Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32 mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Cell Line, Tumor ; Citrus/chemistry ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Diet, High-Fat/adverse effects ; Fatty Liver/drug therapy ; Fatty Liver/genetics ; Fatty Liver/metabolism ; Flavanones/pharmacology ; Flavonoids/pharmacology ; Hep G2 Cells ; Humans ; Lipids/physiology ; Liver/drug effects ; Mitochondria/drug effects ; Mitochondria/genetics ; Mitochondria/metabolism ; Obesity/genetics ; Obesity/metabolism ; Organelle Biogenesis ; RNA, Messenger/genetics ; Rats ; Zebrafish
Chemical Substances	DNA, Mitochondrial ; Flavanones ; Flavonoids ; Lipids ; RNA, Messenger ; Adenosine Triphosphate (8L70Q75FXE) ; eriocitrin (AS293HR5XQ)
Language	English
Publishing date	2014-01-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep03708
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