Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Bitter taste receptors (T2Rs), a subfamily of G protein-coupled receptors, are expressed not only in oral tissues but also in extraoral sites, playing key roles in physiological processes such as the gut-brain axis. However, structural information on T2Rs is limited, with only two human T2Rs, T2R14 and T2R46, experimentally determined to date. This study explores the potential of AlphaFold3 (AF3), an advanced AI-based protein structure prediction tool, to predict the structures of 25 human T2Rs and compares them with those of the earlier AlphaFold2 (AF2). The accuracy of AF3 was evaluated by comparing the predicted structures of T2R14 and T2R46 with known experimental structures. Our results show that AF3 provides more accurate structural predictions than AF2 for these receptors, though the predicted local distance difference test scores for AF3 were unexpectedly lower across all T2R subtypes. Subsequent analysis indicated that significant structural variations were observed in the receptor's extracellular region, in contrast to a higher degree of structural consistency in the intracellular region. Clustering based on sequence identity and root mean square deviation highlighted distinct groupings among the receptors. The structural properties of these T2Rs may be related to their ability to recognize thousands of diverse bitter substances through interaction with the taste receptor-specific G protein, α-gustducin. The present study provides evidence that AF3 can advance our understanding of T2R structure and research into the biological activity of T2R-ligand interactions in health-related processes, including risk reduction of obesity and diabetes.

DOI： 10.1016/j.crfs.2025.101146

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Several epidemiological studies and intervention trials have demonstrated that grapes and blueberries, which are rich in flavanols, can lower the risk of cardiovascular disease. However, the mechanisms of action of these compounds remain unclear due to their low bioavailability. OBJECTIVE: This study aimed to characterize the sensory properties, blood flow velocity, and oxidative stress of a polyphenol rich grape and blueberry extract (PEGB) containing approximately 16% flavanols (11% monomers and 4% dimers). METHOD: A sensory property of PEGB was compared with quercetin at uniform concentration using healthy young subjects. In addition, the reactivity of PEGB with O2•- was also compared with quercetin utilizing a luminescence method. Furthermore, the effect of a single administration of PEGB on the blood flow velocity of skeletal muscle arterioles was investigated using a laser Doppler method in rats. RESULTS: At a concentration where quercetin was barely tasteful, flavanol in PEGB exhibited a robust astringent taste. Furthermore, under pH conditions mimicking the oral cavity and intestinal tract, PEGB promoted O2•- production at low concentrations and scavenging O2•- at high concentrations. In contrast, quercetin demonstrated antioxidant activity. A single oral administration of PEGB significantly increased the blood flow velocity of skeletal muscle arterioles. CONCLUSION: The results demonstrate that PEGB exhibited a pronounced astringent taste, O2•- production at low concentrations in neutral pH environments, and significantly enhanced blood flow to skeletal muscle following a single administration to rats. These findings highlight the necessity for further investigation into the causal relationships between oral perception, redox properties, and bioactivity of polyphenols.

DOI： 10.1080/19390211.2024.2446186

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Abstract

Background

Flavanols (FLs), a group of polyphenols abundant in cocoa and red wine, have been associated with improved cognitive function, particularly hippocampus-dependent memory in older adults. However, their poor bioavailability has limited understanding of the mechanisms underlying their effects on the brain. This study aimed to investigate the cognitive and molecular responses following acute FLs administration in mice.

Methods

Male C57BL/6J mice were orally administered FLs (25 mg/kg) or distilled water (DW) and subjected to a novel object recognition test. In one experiment, FLs were administered before training, in another, after training. Exploratory behavior and the discrimination index (DI) were analyzed. Hippocampal tissues were collected at 15 min to 4 h post-administration to assess levels of brain-derived neurotrophic factor (BDNF) and phosphorylated extracellular signal-regulated kinase, cAMP response element-binding protein (CREB), and tyrosine kinase receptor type 2 by western blotting.

Results

Mice treated with FLs before training exhibited significantly longer exploration of the novel object and higher DI, whereas no enhancement was observed when FLs were administered after training. CREB phosphorylation increased at 30 min post-administration, and BDNF levels were elevated at 2 and 4 h.

Conclusion

These findings suggest that FLs enhance short-term memory via hippocampal CREB activation and BDNF upregulation. Despite low systemic absorption, the rapid effects observed may involve sensory signaling pathways, potentially triggered by the astringent properties of FLs. This study provides mechanistic insight into the cognitive benefits of dietary FLs.

DOI： 10.1515/med-2025-1270

PubMed

Other URL： https://www.degruyterbrill.com/document/doi/10.1515/med-2025-1270/pdf

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Flavan-3-ols (FL) are poorly bioavailable astringent polyphenols that induce hyperactivation of the sympathetic nervous system. The aim of this study was to investigate the effects of repeated oral administration of FL on mice hindlimb skeletal muscle using immunohistochemical techniques. C57BL/6J male mice were orally administered 50 mg/kg of FL for a period of 2 weeks, and bromideoxyuridine (BrdU) was administered intraperitoneally 3 days prior to the dissection. The soleus and extensor digitorum longus (EDL) were excised and prepared for frozen sections. Myosin heavy chain (MHC) antibodies were used to classify muscle types, in addition, muscle cross-sectional areas (CSA) were measured. We observed a shift in the peak of CSA in the soleus muscle and to a larger extent in the EDL. In addition, a distinct shift toward fast muscle was detected, documented by a reduction in type I and an increase in type IIb in the soleus muscle, whereas in the EDL, we observed a decline in type IIa and an expansion in type IIb. Incorporation of BrdU into cells was significantly increased in all skeletal muscles, with a significant increase in cells co-expressing pair box 7 (Pax7), a marker of differentiation, as observed in the EDL. Given the evidence that β2-adrenergic receptors in skeletal muscles regulate differentiation and size, we measured plasma catecholamine (CA) concentrations following a single differentiation of FL. A single oral dose of FL was observed to significantly increase plasma CA. These findings indicate that catecholamines secreted into the bloodstream from the adrenal gland following oral administration of FL may influence skeletal muscle size and type via β2-receptors.

DOI： 10.1096/fj.202401865R

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.fbio.2024.104550

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Long-term intake of procyanidins has been suggested to reduce the risk of cardiovascular disease, dementia, and sensory function decline associated with aging. However, most of the ingested procyanidins are not absorbed and are excreted in the feces, so the mechanism of their beneficial impact is unknown. Procyanidins are the components of astringency in plant foods and their stimulation appears to be directly transmitted to the central nervous system via sensory nerves. Recent attention has been focused on the taste receptors expressed in the extra-oral gastrointestinal tract may regulate homeostasis via the neuroendocrine system. In this paper, we have reviewed recent findings on the relationship between the astringency of procyanidins and their bioregulatory effects.

DOI： 10.1093/bbb/zbad154

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential.

DOI： 10.3390/biom14020234

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Recent studies have indicated that the activation of bitter taste receptors (T2R) expressed in gastrointestinal secretory cells has a regulatory effect on the secretion of gastrointestinal hormones. Polyphenols are known to be ingested at a daily intake of 5 g or more and commonly have a bitter taste. Consequently, the interaction between the bitter taste receptor T2R46 and 490 polyphenols was investigated using in silico simulation techniques. It was demonstrated that W883.32 and E2657.39 play a pivotal role in the recognition of polyphenols and known ligands by T2R46, with frequent interactions observed, particularly with flavonoids. The results of the quantitative structure-activity relationship (QSAR) analysis demonstrated a high degree of correlation (R2 = 0.9359) between polyphenols and T2R46 in a model that incorporated molecular interaction field regions and branching scales. Furthermore, known ligands were also found to fit this model (R2 = 0.9155). These findings suggest that polyphenols may act as T2R46 ligands.

DOI： 10.1016/j.crfs.2024.100914

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Intervention trials confirmed that blood flow-mediated dilatation increases significantly after intake of astringent (-)-epicatechin (EC) oligomers (procyanidins)-rich foods, but the mechanism remains unclear. We have previously found that procyanidins can activate the sympathetic nervous and subsequently increase blood flow. Here, we examined whether procyanidin-derived reactive oxygen species (ROS) activate transient receptor potential (TRP) channels in gastrointestinal sensory nerves and consequently induce sympathoexcitation. We evaluated the redox properties of EC and its tetramer cinntamtannin A2 (A2) at pH 5 or 7, mimicking plant vacuole or oral cavity/small intestine using a luminescent probe. At pH 5, A2 or EC showed O2·- scavenging ability, but they promoted O2·- generation at pH 7. We observed blood flow in rat cremaster arterioles using laser Doppler, a single oral dose of 10 µg/kg A2 markedly increased blood flow, while EC showed little activity. This change with A2 was significantly dampened by co-administration of adrenaline blocker, ROS scavenger N-acetyl-L-cysteine (NAC), TRP vanilloid 1, or ankyrin 1 antagonist. We also performed a docking simulation of EC or A2 with the binding site of a typical ligand for each TRP channel and calculated the respective binding affinities. The binding energies were notably higher for A2 than typical ligands, suggesting that A2 is less likely to bind to these sites. ROS produced at neutral pH following the orally administered A2 to the gastrointestinal tract could activate TRP channels, triggering sympathetic hyperactivation and causing hemodynamic changes.

DOI： 10.1016/j.bcp.2023.115682

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Metabolic cage housing which is exposed to a number of environmental stressors is often used in pharmacokinetic studies. In this study, we compared the difference in stress response between single- and paired-housing in metabolic cages by evaluating the alteration of urinary stress hormones and behavior. Mice were randomly divided into single- or paired-housing groups and placed in a metabolic cage with wire mesh. Their urine was collected every 24 h for consecutive 4 days to determine excreted catecholamine and corticosterone. The change in body weight was significantly decreased at 3 and 4 days in the single-housing group compared with that before the experiment, but not paired-housing group. The level of urinary catecholamines, such as noradrenaline, adrenaline, and their metabolite vanillylmandelic acid, was significantly increased in the single-housing compared with paired housing group and urinary corticosterone increased as well. Next, for the two similarly housed groups, we observed spontaneous behavior on the fourth day and conducted an elevated plus-maze test on the fifth day. Spontaneous behavior was not different between experimental groups. In the elevated plus-maze test, the proportion of time spent in the open arms was significantly prolonged in the paired-housing group compared to that of the single-housing group. Short-term social isolation stress loading in metabolic cages was suggested to exhibit endocrinological and behavioral changes in mice. To reduce such interference due to stress exposure, it was suggested to keep two mice in a metabolic cage.

DOI： 10.1016/j.neulet.2023.137246

PubMed

Authorship：Lead author,　Last author,　Corresponding author  

<p></p>

DOI： 10.1271/kagakutoseibutsu.61.246

CiNii Research

Authorship：Lead author,　Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>Cyanidin 3-<i>O</i>-glucoside (C3G), an antioxidant, is one of the most abundant anthocyanin in plant foods. Intervention trials and subsequent meta-analyses have suggested that anthocyanins could reduce the risks of cardiovascular diseases. This study investigated hemodynamic alterations following a single intra­gastric dose of C3G by measuring blood flow in rat cremaster muscle arteriole for 60 min. Next, in excised aortas, we performed western blotting to measure the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). A single oral dose of C3G significantly increased blood flow soon after ingestion, and it was maintained throughout the experimental period. In addition, aortic Akt phosphorylation increased. Then, we examined the impact of repeated oral administrations of C3G for 14 days. The mean blood pressure was significantly reduced at 7 and 14 days after treatment, with a slight increase in aortic eNOS expression. Immunohistochemical analyses of the soleus showed that the level of CD31, an angiogenesis-marker protein, was significantly increased with C3G. These results suggested that an oral dose of C3G increased blood flow, which promoted angiogenesis within skeletal muscle, and consequently, blood pressure was reduced.</p>

DOI： 10.3164/jcbn.22-50

PubMed

CiNii Research

Authorship：Lead author,　Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>The impact of repeated administration of cinntamtannin A2 (A2, 25 μg/kg) on skeletal muscle disuse atrophy model mice induced by hindlimb suspension for 14 days was examined. In soleus, weight loss and a reduction in the average myofibre size with shifting to the smaller side of the peak were observed in the suspension-vehicle group, but A2 reduced these changes. Average myofibre size significantly increased in ground-A2 compared to ground-vehicle. A marked increase in the dephosphorylation of forkhead box O (FoxO) 3a by the suspension was reduced by A2. The phosphorylation of protein kinase B (Akt) and eukaryotic translation initiation factor 4E-binding protein (4EBP)-1 were significantly increased by the treatment of A2. In addition, a single dose of A2 increased dramatically in the 24-h excretion of catecholamines in urine. These results suggest that A2 admin­istration results in sympa­thetic nerve activation and promotes hypertrophy while inhibiting the progress of disuse muscle atrophy.</p>

DOI： 10.3164/jcbn.23-12

PubMed

CiNii Research

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

B-type procyanidins, a series of catechin oligomers, are among the most ingested polyphenols in the human diet. Results of meta-analyses have suggested that intake of B-type procyanidins reduces cardiovascular disease risk. Another recent focus has been on the effects of B-type procyanidins on central nervous system (CNS) function. Although long-term B-type procyanidin ingestion is linked to health benefits, a single oral intake has been reported to cause physiological alterations in circulation, metabolism, and the CNS. Comprehensive analyses of previous reports indicate an optimal mid-range dose for the hemodynamic effects of B-type procyanidins, with null responses at lower or higher doses, suggesting hormesis. Indeed, polyphenols, including B-type procyanidins, elicit hormetic responses in vitro, but animal and clinical studies are limited. Hormesis of hemodynamic and metabolic responses to B-type procyanidins was recently confirmed in animal studies, however, and our work has linked these effects to the CNS. Here, we evaluate the hormetic response elicited by B-type procyanidins, recontextualizing the results of intervention trials. In addition, we discuss the possibility that this hormetic response to B-type procyanidins arises via CNS neurotransmitter receptors. We have verified the direction of future research for B-type procyanidins in this review.

DOI： 10.3389/fnut.2022.969823

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FLs. In addition, we examined the impact of the repeated administration of 50 mg/kg FLs for 14 days on adipose tissues in mice. In BAT, FLs tended to increase the level of Ucp-1 along with significant increase of thermogenic transcriptome factors expressions, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Expression of browning markers, CD137 and transmembrane protein (TMEM) 26, in addition to PGC-1α were increased in epididymal adipose (eWAT) by FLs. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 by FLs. These results exert that FLs induce browning in adipose, and this change is possibly produced by the activation of the SNS.

DOI： 10.3390/nu13124214

PubMed

Authorship：Lead author,　Last author,　Corresponding author  

DOI： 10.34433/j00697.2021296006

CiNii Research

J-GLOBAL

Authorship：Lead author,　Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>We previously found that a single dose of theaflavins induced skeletal muscle metabolic changes. In this study, we examined the effect of theaflavins on disuse muscle atrophy model mice by hindlimb suspension. Mice were assigned to 4 groups; ground-vehicle, ground-theaflavins, suspension-vehicle, and suspension-theaflavins, dosed with theaflavins (250 mg/kg/day) for 2 weeks. The peak of myotube size of cross sectional area was significantly moved to the smaller side in the suspension-vehicle group compared with the ground-vehicle group, and these shifts were significantly reduced by the treatment with theaflavins in both soleus and extensor digitorum longus. The level of phosphorylated eukaryotic translation initiation factor 4E-binding protein (4EBP)-1, located downstream of the Akt/mTOR pathway, was significantly different between suspension-vehicle and suspension-theaflavins in soleus. The ratio of forkhead box O (FoxO) 3a to phosphorylated FoxO3a significantly increased in soleus or tended to rise in extensor digitorum longus of suspension-vehicle group compared with ground-vehicle. In contrast, these changes were not observed in suspension-theaflavins group. These results suggested that theaflavins inhibited the progress of disuse muscle atrophy through modulation of protein metabolism.</p>

DOI： 10.3164/jcbn.20-68

PubMed

CiNii Research

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

We previously found that a single dose of B-type procyanidin mixture increase in skeletal muscle blood flow (BF). We compared BF changes following administration of (-)-epicatechin (EC, monomer) and the B-type procyanidins procyanidin B2 (B2, dimer), procyanidin C1 (C1, trimer), and cinnamtannin A2 (A2, tetramer). Each chemical was administered orally to rats, followed by BF measurement in cremaster arteriole for 60 min. About 10 and 100 µg/kg of B2 and C1 elicited BF increase, the effect was potent at 100 µg/kg. BF also increased significantly after administration of 10 µg/kg A2, but not with the administration at 100 µg/kg. EC yielded no BF changes. Co-treatment with the nonselective adrenaline blocker carvedilol attenuated the BF increase seen with 10 µg/kg A2 treatment. This outcome suggested the involvement of sympathetic nerve activation in the BF increase by this dose of A2. Co-treatment of 100 µg/kg A2 with the α2 blocker yohimbine exhibited an increase of BF significantly. The α2 adrenaline receptor in the vasomotor centre is an inhibitory receptor and it regulates hemodynamics. This result suggested that high doses of A2 did not alter BF because of activating the α2 adrenergic receptor. Phosphorylation of aortic endothelial nitric oxide synthase (eNOS) increased with 10 µg/kg A2 alone or co-treatment with 100 µg/kg A2 and yohimbine, but not with co-treatment of 10 µg/kg A2 and carvedilol or 100 µg/kg A2 alone. These results imply that A2 does not directly activate eNOS, but that shear stress from the increased BF might be associated with eNOS phosphorylation.

DOI： 10.1080/10715762.2020.1759805

PubMed

Authorship：Lead author,　Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p> It is known that administering a gavage to rodents evokes a cardiac reflex, due to gastrointestinal stimulation. Consequently, it is difficult to evaluate changes in hemodynamics after a single oral dose of a pungent or astringent, which alters the circulation by increasing sympathetic activity. In the present study, we developed a method for administering a gavage without significantly affecting hemodynamics measurements. We marked a gastric tube at 10 cm from the tip, to mark the distance from the oral cavity to the stomach body of Wistar male rats. Rats were intubated under urethane anesthesia.After 10–15 min of stabilization, we measured the mean blood pressure (MBP), heart rate (HR), and blood flow (BF) in the cremaster arteriole under two different conditions; condition 1: a pointed gastric tube, room temperature distilled water, and injected at normal speed (approximately 3 ml/min); condition 2: a rounded gastric tube, 37°C distilled water, and injection at 1.0 ml/min. Under condition 1, we observed striking hemodynamic alterations, due to the somatic afferent reflex. In contrast, under condition 2, these hemodynamic changes were nearly eliminated. In addition, we could clearly detect hemodynamic changes in rats after a single gavage treatment of pungent (capsaicin) or astringent (cinnamtannin A2). We observed transient increases in the HR and MBP soon after treatment with capsaicin. Moreover, cremasteric BF was elevated with cinnamtannin A2. These results confirmed the utility of the gavage method developed in this study.</p>

DOI： 10.1538/expanim.20-0200

PubMed

CiNii Research

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Flavan-3-ols (FLs), specifically catechin and its oligomer B-type procyanidins, are suggested to potently bind to bovine serum albumin (BSA). We examined the interaction between BSA and FLs by fluorescence quenching and found the following order of binding activities to BSA: cinnamtannin A2 (A2; tetramer) > procyanidin C1 (C1; trimer) ≈ procyanidin B2 (B2, dimer) > (-)epicatechin (EC, monomer). Docking simulations between BSA and each compound at the binding site showed that the calculated binding energies were consistent with the results of our experimental assay. FLs exerted cytotoxicity at 1000 μg/mL in F11 cell culture with fetal bovine serum containing BSA. In culture containing serum-free medium, FLs exhibited significant cell proliferation at 10-4 μg/mL and cytotoxicity was observed at concentrations greater than 10 μg/mL. Results of this study suggest that interactions between polyphenols and BSA should be taken into account when evaluating procyanidin in an in vitro cell culture system.

DOI： 10.3390/molecules24203667

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

DOI： 10.1039/C8FO02125B

PubMed

Authorship：Lead author,　Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>Cinnamtannin A2, an (−)-epicatechin tetramer, was reported to have potent physiological activity. Cinnamtannin A2 is rarely absorbed from the gastrointestinal tract into the blood and the mechanisms of its beneficial activities are unknown. Cinnamtannin A2 reported to increase sympathetic nervous activity, which was induced by various stressors. In present study, we examined the stress response in the mouse paraventricular nucleus following a single oral dose of cinnamtannin A2 by monitoring mRNA expression of corticotropin-releasing hormone (CRH) and c-fos using <i>in situ</i> hybridization. Corticotropin-releasing hormone mRNA showed a tendency to increase at 15 min and significantly increased at 60 min following a single oral administration of 100 µg/kg cinnamtannin A2. After a single dose of 10 µg/kg cinnamtannin A2, there was significant upregulation of CRH mRNA at 60 min. These results suggested that cinnamtannin A2 was recognized as a stressor in central nervous system and this may lead to its beneficial effects on circulation and metabolism.</p>

DOI： 10.3164/jcbn.19-19

PubMed

CiNii Research

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

We previously confirmed that postprandial alterations in the circulation and metabolism after a single oral dose of flavan 3-ols (mixture of catechin and catechin oligomers) were involved in an increase in sympathetic nervous activity. However, it is well known that, in response to various stresses, activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs together with sympathetic nerve activity, which is associated with activation of the sympathetic-adrenal-medullary (SAM) axis. In this study, we examined whether the HPA axis was activated after a single dose of flavan 3-ols. We administered an oral dose of 10 or 50 mg/kg flavan 3-ols to male ICR mice, removed the brains, and fixed them in paraformaldehyde-phosphate buffer. Other animals that were treated similarly were decapitated, and blood was collected. In the paraventricular nucleus (PVN), c-fos mRNA expression increased significantly at 15 min after administration of either 10 or 50 mg/kg flavan 3-ols. Corticotropin-releasing hormone (CRH) mRNA expression levels significantly increased at 240 min after administration of 10 mg/kg flavan 3-ols, and at 60 min after administration of 50 mg/kg flavan 3-ols. Plasma corticosterone levels were also significantly increased at 240 min after ingestion of 50 mg/kg flavan 3-ols. In this experiment, we confirmed that the ingestion of flavan 3-ols acted as a stressor in mammals with activation both the SAM and HPA axes.

DOI： 10.1016/j.neulet.2018.06.015

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVES: We previously found that elevated energy expenditure following a single oral dose of flavan 3-ols (FL), a mixture of catechins and B type procyanidins, is caused by sympathetic nerve activation. In the present study, we compared the activity of the FL components (-)-epicatechin (EC; monomer), procyanidin B2 (B2; dimer), procyanidin C1 (C1; trimer), cinnamtannin A2 (A2; tetramer), and more than pentamer fraction (P5). METHODS: Male ICR mice were treated with a single oral dose of FL, EC, B2, C1, A2, or P5. The animals were sacrificed and blood and brown adipose tissue (BAT) sampled. The plasma catecholamine (CA) levels and BAT uncoupling protein (UCP)-1 mRNA expression were determined. RESULTS: A single dose of 10 mg/kg FL significantly increased plasma CA and UCP-1 mRNA levels. B2, C1, and A2, but not EC and P5 (all at 1 mg/kg), significantly increased plasma adrenaline levels. Plasma noradrenaline was significantly elevated by B2 and A2, but not by EC, C1, or P5. UCP-1 mRNA levels were significantly increased by C1 and P5. In the dose response study of A2, 10-3 mg/kg A2 increased UCP-1 mRNA levels significantly, but not 10-2 and 10-1 mg/kg A2. In addition, combination treatment with 10-1 mg/kg A2 and yohimbine, an α2 adrenalin blocker, remarkably increased UCP-1 mRNA levels. CONCLUSION: These results suggest that FL and its components, except EC, increase UCP-1 mRNA and plasma CA with varying efficacy.

DOI： 10.1371/journal.pone.0201203

PubMed

J-GLOBAL