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Recent epidemiological and intervention studies have suggested that polyphenol-rich plant food consumption reduced the risk of cognitive decline. However, the findings were tentative and by no means definitive. In the present study, we examined the impact of short-term oral administration of cinnamtannin A2 (A2), an (−)-epicatechin tetramer, on adult hippocampal neurogenesis and cognitive function in mice. Mice received supplementation with vehicle (20% glycerol) or 100 μg/kg A2 for 10 days. Then, we conducted the open field test, the object location test, and the novel object test. In the open field test, the A2-treated group tended to spend more time in the center of the arena, compared to the vehicle-treated group. The A2-treated group spent significantly more time exploring objects placed in different locations, compared to the vehicle-treated group. There were no significant differences between groups in the object preference index or in the novel object test. In addition, A2 administration significantly increased the number of hippocampal bromodeoxyuridine-labeled cells in the dentate gyrus, but not in the CA1 or CA3 regions. These results suggested that short-term administration of A2 may impact spatial memory by enhancing neurogenesis in the dentate gyrus of adult mice. [Display omitted] • Ten daily gavage doses of cinnamtannin A2 (A2) increased exploration behavior in mice. • A2 enhanced mouse spatial memory detected with the object location test. • A2 increased BrdU-positive cells in hippocampal dentate gyrus, but not CA1 or CA3. [ABSTRACT FROM AUTHOR]

Abstract Present investigation determines the protective effect of Cinnamtannin A2 against chronic renal failure (CRF). 5/6 nephrectomized rat model was used to induced CRF by removing the kidneys and rats were treated with Cinnamtannin A2 10 mg/kg, i.p. for the period 30 days. Nephroprotective effect Cinnamtannin A2 was assessed by estimating the biochemical parameters of renal function test and cytokines in the serum of nephractomized rats. Oxidative stress parameters were estimated in the kidney tissue and western blot assay and qRT-PCR assay was performed to determine the expression of protein in renal tissue of nephractomized rats. Moreover histopathology study was done to observe the tubular injury. Data of the report reveals that treatment with Cinnamtannin A2 ameliorates the altered level of creatinine, blood urea nitrogen (BUN), Neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1) and cytokines in the serum and microalbuminurea in the urine of 5/6 nephrectomized rat. Oxidative stress level was reduced in Cinnamtannin A2 treated group than CRF group. Moreover treatment with Cinnamtannin A2 attenuates the altered expression of proteins involved in Nrf2-Keap1 pathway in the kidney tissue of 5/6 nephrectomized rat. Result of histopathology reveals that tubular injury score was reduced in the kidney tissue of Cinnamtannin A2 treated group than CRF group. In conclusion, data of the report suggest that treatment with Cinnamtannin A2 ameliorates the level of KIM1 and NAGL in 5/6 nephractomized rats by regulating Nrf2- Keap1 pathway.

Present investigation determines the protective effect of Cinnamtannin A2 against chronic renal failure (CRF). 5/6 nephrectomized rat model was used to induced CRF by removing the kidneys and rats were treated with Cinnamtannin A2 10 mg/kg, i.p. for the period 30 days. Nephroprotective effect Cinnamtannin A2 was assessed by estimating the biochemical parameters of renal function test and cytokines in the serum of nephractomized rats. Oxidative stress parameters were estimated in the kidney tissue and western blot assay and qRT-PCR assay was performed to determine the expression of protein in renal tissue of nephractomized rats. Moreover histopathology study was done to observe the tubular injury. Data of the report reveals that treatment with Cinnamtannin A2 ameliorates the altered level of creatinine, blood urea nitrogen (BUN), Neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1) and cytokines in the serum and microalbuminurea in the urine of 5/6 nephrectomized rat. Oxidative stress level was reduced in Cinnamtannin A2 treated group than CRF group. Moreover treatment with Cinnamtannin A2 attenuates the altered expression of proteins involved in Nrf2-Keap1 pathway in the kidney tissue of 5/6 nephrectomized rat. Result of histopathology reveals that tubular injury score was reduced in the kidney tissue of Cinnamtannin A2 treated group than CRF group. In conclusion, data of the report suggest that treatment with Cinnamtannin A2 ameliorates the level of KIM1 and NAGL in 5/6 nephractomized rats by regulating Nrf2- Keap1 pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] 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 O 2 · - scavenging ability, but they promoted O 2 · - 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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2023 JCBN.)

Certain nutrients stimulate glucagon-like peptide-1 (GLP-1) secretion from the intestinal enteroendocrine L-cells, but due to rapid degradation by the DPP-4 enzyme, >90% is converted to inactive metabolite before reaching the target organs via circulation. Plants are a source of potent bioactive compounds that promote endogenous secretion of GLP-1 from L-cells. To search for the effective bioactive compound from a vast library of natural compounds, a reliable and low-cost assay is required considering the high cost of commercial assays. We developed a low-cost sandwich enzyme-linked immunosorbent assays (s-ELISAs) for detecting 'total', 'sensitive active', and 'wide-range active' GLP-1. The s-ELISAs exhibited high sensitivity with measurement ranges between 0.94~240, 0.98~62.5, and 4.8~4,480 pmol/L, respectively. High precision was observed; i.e., CVs within 5% and 20% for intra- and inter-assay variations, respectively, and excellent recovery of exogenous GLP-1 from assay buffer. The developed s-ELISAs had the same performance as the commercial kits and approximately 80% cheaper cost. For their application, cinnamtannin A2-induced GLP-1 secretion was confirmed in STC-1 cells consistent with our previous findings. The s-ELISAs were further validated by measuring plasma GLP-1 level in mice after oral administration of black soy bean seed coat extract containing cinnamtannin A2., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2023 JCBN.)

The article focuses on a study conducted on dimeric, trimeric and tetrameric purified and isolated units of procyanidins. These were isolated form cacao liquor and their influence on incretin effect in mice is studied. The results showed that cinnamtannin A2, which increased the glucagon-like peptide-1 (GLP-1) and insulin secretion levels in the plasma, has potential to improve hyperglycemia.

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 in situ 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., Competing Interests: No potential conflicts of interest were disclosed.