Nutrients

Research

Jump to: Review

8 pages, 1452 KiB

Open AccessArticle

Identification and Functional Evaluation of Polyphenols That Induce Regulatory T Cells

by Tsukasa Fujiki, Ryosuke Shinozaki, Miyako Udono and Yoshinori Katakura

Nutrients 2022, 14(14), 2862; https://doi.org/10.3390/nu14142862 - 13 Jul 2022

Cited by 5 | Viewed by 2254

Abstract

Regulatory T cells (Tregs) and CD4⁺/CD25⁺ T cells play an important role in the suppression of excessive immune responses, homeostasis of immune function, and oral tolerance. In this study, we screened for food-derived polyphenols that induce Tregs in response to [...] Read more.

Regulatory T cells (Tregs) and CD4⁺/CD25⁺ T cells play an important role in the suppression of excessive immune responses, homeostasis of immune function, and oral tolerance. In this study, we screened for food-derived polyphenols that induce Tregs in response to retinaldehyde dehydrogenase (RALDH2) activation using macrophage-like THP-1 cells. THP-1 cells were transfected with an EGFP reporter vector whose expression is regulated under the control of mouse Raldh2 promoter and named THP-1 (Raldh2p-EGFP) cells. The THP-1 (Raldh2p-EGFP) cells were treated with 33 polyphenols after inducing their differentiation into macrophage-like cells using phorbol 12-myristate 13-acetate. Of the 33 polyphenols, five (kaempferol, quercetin, morin, luteolin and fisetin) activated Raldh2 promoter activity, and both quercetin and luteolin activated the endogenous Raldh2 mRNA expression and enzymatic activity. Furthermore, these two polyphenols increased transforming growth factor beta 1 and forkhead box P3 mRNA expression, suggesting that they have Treg-inducing ability. Finally, we verified that these polyphenols could induce Tregs in vivo and consequently induce IgA production. Oral administration of quercetin and luteolin increased IgA production in feces of mice. Therefore, quercetin and luteolin can induce Tregs via RALDH2 activation and consequently increase IgA production, suggesting that they can enhance intestinal barrier function. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

21 pages, 3592 KiB

Open AccessArticle

Hepatocyte-Specific Phgdh-Deficient Mice Culminate in Mild Obesity, Insulin Resistance, and Enhanced Vulnerability to Protein Starvation

by Momoko Hamano, Kayoko Esaki, Kazuki Moriyasu, Tokio Yasuda, Sinya Mohri, Kosuke Tashiro, Yoshio Hirabayashi and Shigeki Furuya

Nutrients 2021, 13(10), 3468; https://doi.org/10.3390/nu13103468 - 29 Sep 2021

Cited by 3 | Viewed by 3203

Abstract

l-Serine (Ser) is synthesized de novo from 3-phosphoglycerate via the phosphorylated pathway committed by phosphoglycerate dehydrogenase (Phgdh). A previous study reported that feeding a protein-free diet increased the enzymatic activity of Phgdh in the liver and enhanced Ser synthesis in [...] Read more.

l-Serine (Ser) is synthesized de novo from 3-phosphoglycerate via the phosphorylated pathway committed by phosphoglycerate dehydrogenase (Phgdh). A previous study reported that feeding a protein-free diet increased the enzymatic activity of Phgdh in the liver and enhanced Ser synthesis in the rat liver. However, the nutritional and physiological functions of Ser synthesis in the liver remain unclear. To clarify the physiological significance of de novo Ser synthesis in the liver, we generated liver hepatocyte-specific Phgdh KO (LKO) mice using an albumin-Cre driver. The LKO mice exhibited a significant gain in body weight compared to Floxed controls at 23 weeks of age and impaired systemic glucose metabolism, which was accompanied by diminished insulin/IGF signaling. Although LKO mice had no apparent defects in steatosis, the molecular signatures of inflammation and stress responses were evident in the liver of LKO mice. Moreover, LKO mice were more vulnerable to protein starvation than the Floxed mice. These observations demonstrate that Phgdh-dependent de novo Ser synthesis in liver hepatocytes contributes to the maintenance of systemic glucose tolerance, suppression of inflammatory response, and resistance to protein starvation. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

15 pages, 3708 KiB

Open AccessArticle

Inhibitory Effect of Tangeretin and Cardamonin on Human Intestinal SGLT1 Activity In Vitro and Blood Glucose Levels in Mice In Vivo

by Hideo Satsu, Ryosuke Shibata, Hiroto Suzuki, Shimon Kimura and Makoto Shimizu

Nutrients 2021, 13(10), 3382; https://doi.org/10.3390/nu13103382 - 26 Sep 2021

Cited by 7 | Viewed by 4698

Abstract

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this [...] Read more.

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in V_max and an increase in K_m, whereas suppression by cardamonin was associated with a reduction in V_max and no change in K_m. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Graphical abstract

12 pages, 2251 KiB

Open AccessArticle

Maslinic Acid Attenuates Denervation-Induced Loss of Skeletal Muscle Mass and Strength

by Yuki Yamauchi, Farhana Ferdousi, Satoshi Fukumitsu and Hiroko Isoda

Nutrients 2021, 13(9), 2950; https://doi.org/10.3390/nu13092950 - 25 Aug 2021

Cited by 14 | Viewed by 3567

Abstract

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength [...] Read more.

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-β signaling in MA-treated mice. In addition, qPCR data showed that MA induced Igf1 expression and suppressed the expressions of Atrogin-1, Murf1 and Tgfb. Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

13 pages, 1333 KiB

Open AccessArticle

Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

by Thouria Bourhim, Myra O. Villareal, Chemseddoha Gadhi and Hiroko Isoda

Nutrients 2021, 13(8), 2697; https://doi.org/10.3390/nu13082697 - 4 Aug 2021

Cited by 10 | Viewed by 3409

Abstract

The beneficial effect on health of argan oil is recognized worldwide. We have previously reported that the cake that remains after argan oil extraction (argan press-cake or APC) inhibits melanogenesis in B16 melanoma cells in a time-dependent manner without cytotoxicity. In this study, [...] Read more.

The beneficial effect on health of argan oil is recognized worldwide. We have previously reported that the cake that remains after argan oil extraction (argan press-cake or APC) inhibits melanogenesis in B16 melanoma cells in a time-dependent manner without cytotoxicity. In this study, the global gene expression profile of B16 melanoma cells treated with APC extract was determined in order to gain an understanding of the possible mechanisms of action of APC. The results suggest that APC extract inhibits melanin biosynthesis by down-regulating microphthalmia-associated transcription factor (Mitf) and its downstream signaling pathway through JNK signaling activation, and the inhibition of Wnt/β-catenin and cAMP/PKA signaling pathways. APC extract also prevented the transport of melanosomes by down-regulating Rab27a expression. These results suggest that APC may be an important natural skin whitening product and pharmacological agent used for clinical treatment of pigmentary disorders. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

14 pages, 1632 KiB

Open AccessArticle

Exosome-Mediated Activation of Neuronal Cells Triggered by γ-Aminobutyric Acid (GABA)

by Ryo Inotsuka, Miyako Udono, Atsushi Yamatsu, Mujo Kim and Yoshinori Katakura

Nutrients 2021, 13(8), 2544; https://doi.org/10.3390/nu13082544 - 25 Jul 2021

Cited by 18 | Viewed by 4255

Abstract

γ-Aminobutyric acid (GABA) is a potent bioactive amino acid, and several studies have shown that oral administration of GABA induces relaxation, improves sleep, and reduces psychological stress and fatigue. In a recent study, we reported that exosomes derived from GABA-treated intestinal cells serve [...] Read more.

γ-Aminobutyric acid (GABA) is a potent bioactive amino acid, and several studies have shown that oral administration of GABA induces relaxation, improves sleep, and reduces psychological stress and fatigue. In a recent study, we reported that exosomes derived from GABA-treated intestinal cells serve as signal transducers that mediate brain–gut interactions. Therefore, the purpose of this study was to verify the functionality of GABA-derived exosomes and to examine the possibility of improving memory function following GABA administration. The results showed that exosomes derived from GABA-treated intestinal cells (Caco-2) activated neuronal cells (SH-SY5Y) by regulating genes related to neuronal cell functions. Furthermore, we found that exosomes derived from the serum of GABA-treated mice also activated SH-SY5Y cells, indicating that exosomes, which are capable of activating neuronal cells, circulate in the blood of mice orally administered GABA. Finally, we performed a microarray analysis of mRNA isolated from the hippocampus of mice that were orally administered GABA. The results revealed changes in the expression of genes related to brain function. Gene Set Enrichment Analysis (GSEA) showed that oral administration of GABA affected the expression of genes related to memory function in the hippocampus. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

18 pages, 2250 KiB

Open AccessArticle

Long-Term Caffeine Intake Exerts Protective Effects on Intestinal Aging by Regulating Vitellogenesis and Mitochondrial Function in an Aged Caenorhabditis Elegans Model

by Hyemin Min, Esther Youn and Yhong-Hee Shim

Nutrients 2021, 13(8), 2517; https://doi.org/10.3390/nu13082517 - 23 Jul 2021

Cited by 9 | Viewed by 4235

Abstract

Caffeine, a methylxanthine derived from plants, is the most widely consumed ingredient in daily life. Therefore, it is necessary to investigate the effects of caffeine intake on essential biological activities. In this study, we attempted to determine the possible anti-aging effects of long-term [...] Read more.

Caffeine, a methylxanthine derived from plants, is the most widely consumed ingredient in daily life. Therefore, it is necessary to investigate the effects of caffeine intake on essential biological activities. In this study, we attempted to determine the possible anti-aging effects of long-term caffeine intake in the intestine of an aged Caenorhabditis elegans model. We examined changes in intestinal integrity, production of vitellogenin (VIT), and mitochondrial function after caffeine intake. To evaluate intestinal aging, actin-5 (ACT-5) mislocalization, lumenal expansion, and intestinal colonization were examined after caffeine intake, and the levels of vitellogenesis as well as the mitochondrial activity were measured. We found that the long-term caffeine intake (10 mM) in the L4-stage worms at 25 °C for 3 days suppressed ACT-5 mislocalization. Furthermore, the level of autophagy, which is normally increased in aging animals, was significantly reduced in these animals, and their mitochondrial functions improved after caffeine intake. In addition, the caffeine-ingesting aging animals showed high resistance to oxidative stress and increased the expression of antioxidant proteins. Taken together, these findings reveal that caffeine may be a potential anti-aging agent that can suppress intestinal atrophy during the progression of intestinal aging. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

10 pages, 4514 KiB

Open AccessArticle

Exosomes Derived from Fisetin-Treated Keratinocytes Mediate Hair Growth Promotion

by Mizuki Ogawa, Miyako Udono, Kiichiro Teruya, Norihisa Uehara and Yoshinori Katakura

Nutrients 2021, 13(6), 2087; https://doi.org/10.3390/nu13062087 - 18 Jun 2021

Cited by 24 | Viewed by 15119

Abstract

Enhanced telomerase reverse transcriptase (TERT) levels in dermal keratinocytes can serve as a novel target for hair growth promotion. Previously, we identified fisetin using a system for screening food components that can activate the TERT promoter in HaCaT cells (keratinocytes). In the present [...] Read more.

Enhanced telomerase reverse transcriptase (TERT) levels in dermal keratinocytes can serve as a novel target for hair growth promotion. Previously, we identified fisetin using a system for screening food components that can activate the TERT promoter in HaCaT cells (keratinocytes). In the present study, we aimed to clarify the molecular basis of fisetin-induced hair growth promotion in mice. To this end, the dorsal skin of mice was treated with fisetin, and hair growth was evaluated 12 days after treatment. Histochemical analyses of fisetin-treated skin samples and HaCaT cells were performed to observe the effects of fisetin. The results showed that fisetin activated HaCaT cells by regulating the expression of various genes related to epidermogenesis, cell proliferation, hair follicle regulation, and hair cycle regulation. In addition, fisetin induced the secretion of exosomes from HaCaT cells, which activated β-catenin and mitochondria in hair follicle stem cells (HFSCs) and induced their proliferation. Moreover, these results revealed the existence of exosomes as the molecular basis of keratinocyte-HFSC interaction and showed that fisetin, along with its effects on keratinocytes, caused exosome secretion, thereby activating HFSCs. This is the first study to show that keratinocyte-derived exosomes can activate HFSCs and consequently induce hair growth. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

26 pages, 4675 KiB

Open AccessArticle

A Mechanistic Study of the Antiaging Effect of Raw-Milk Cheese Extracts

by Guillaume Cardin, Cyril Poupet, Muriel Bonnet, Philippe Veisseire, Isabelle Ripoche, Pierre Chalard, Anne Chauder, Etienne Saunier, Julien Priam, Stéphanie Bornes and Laurent Rios

Nutrients 2021, 13(3), 897; https://doi.org/10.3390/nu13030897 - 10 Mar 2021

Cited by 3 | Viewed by 3925

Abstract

Many studies have highlighted the relationship between food and health status, with the aim of improving both disease prevention and life expectancy. Among the different food groups, fermented foods a have huge microbial biodiversity, making them an interesting source of metabolites that could [...] Read more.

Many studies have highlighted the relationship between food and health status, with the aim of improving both disease prevention and life expectancy. Among the different food groups, fermented foods a have huge microbial biodiversity, making them an interesting source of metabolites that could exhibit health benefits. Our previous study highlighted the capacity of raw goat milk cheese, and some of the extracts recovered by the means of chemical fractionation, to increase the longevity of the nematode Caenorhabditis elegans. In this article, we pursued the investigation with a view toward understanding the biological mechanisms involved in this phenomenon. Using mutant nematode strains, we evaluated the implication of the insulin-like DAF-2/DAF-16 and the p38 MAPK pathways in the phenomenon of increased longevity and oxidative-stress resistance mechanisms. Our results demonstrated that freeze-dried raw goat milk cheese, and its extracts, induced the activation of the DAF-2/DAF-16 pathway, increasing longevity. Concerning oxidative-stress resistance, all the extracts increased the survival of the worms, but no evidence of the implication of both of the pathways was highlighted, except for the cheese-lipid extract that did seem to require both pathways to improve the survival rate. Simultaneously, the cheese-lipid extract and the dried extract W70, obtained with water, were able to reduce the reactive oxygen species (ROS) production in human leukocytes. This result is in good correlation with the results obtained with the nematode. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 1448 KiB

Open AccessReview

Potential Nutrients from Natural and Synthetic Sources Targeting Inflammaging—A Review of Literature, Clinical Data and Patents

by Sushruta Koppula, Mahbuba Akther, Md Ezazul Haque and Spandana Rajendra Kopalli

Nutrients 2021, 13(11), 4058; https://doi.org/10.3390/nu13114058 - 13 Nov 2021

Cited by 11 | Viewed by 3941

Abstract

Inflammaging, the steady development of the inflammatory state over age is an attributable characteristic of aging that potentiates the initiation of pathogenesis in many age-related disorders (ARDs) including neurodegenerative diseases, arthritis, cancer, atherosclerosis, type 2 diabetes, and osteoporosis. Inflammaging is characterized by subclinical [...] Read more.

Inflammaging, the steady development of the inflammatory state over age is an attributable characteristic of aging that potentiates the initiation of pathogenesis in many age-related disorders (ARDs) including neurodegenerative diseases, arthritis, cancer, atherosclerosis, type 2 diabetes, and osteoporosis. Inflammaging is characterized by subclinical chronic, low grade, steady inflammatory states and is considered a crucial underlying cause behind the high mortality and morbidity rate associated with ARDs. Although a coherent set of studies detailed the underlying pathomechanisms of inflammaging, the potential benefits from non-toxic nutrients from natural and synthetic sources in modulating or delaying inflammaging processes was not discussed. In this review, the available literature and recent updates of natural and synthetic nutrients that help in controlling inflammaging process was explored. Also, we discussed the clinical trial reports and patent claims on potential nutrients demonstrating therapeutic benefits in controlling inflammaging and inflammation-associated ARDs. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

21 pages, 2170 KiB

Open AccessReview

Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials

by Risa Araki, Akira Yada, Hirotsugu Ueda, Kenichi Tominaga and Hiroko Isoda

Nutrients 2021, 13(6), 2003; https://doi.org/10.3390/nu13062003 - 10 Jun 2021

Cited by 18 | Viewed by 5385

Abstract

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs [...] Read more.

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): −0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: −0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins. Full article

(This article belongs to the Special Issue Anti-aging Nutrients with Health Beneficial Effects)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Anti-aging Nutrients with Health Beneficial Effects

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (11 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI