Verification of In Vitro Anticancer Activity and Bioactive Compounds in Cordyceps Militaris-Infused Sweet Potato Shochu Spirits.

Many liqueurs, including spirits infused with botanicals, are crafted not only for their taste and flavor but also for potential medicinal benefits. However, the scientific evidence supporting their medicinal effects remains limited. This study aims to verify in vitro anticancer activity and bioactive compounds in shochu spirits infused with Cordyceps militaris, a Chinese medicine. The results revealed that a bioactive fraction was eluted from the spirit extract with 40% ethanol. The infusion time impacted the inhibitory effect of the spirit extract on the proliferation of colon cancer-derived cell line HCT-116 cells, and a 21-day infusion showed the strongest inhibitory effect. Furthermore, the spirit extract was separated into four fractions, A-D, by high-performance liquid chromatography (HPLC), and Fractions B, C, and D, but not A, exerted the effects of proliferation inhibition and apoptotic induction of HCT-116 cells and HL-60 cells. Furthermore, Fractions B, C, and D were, respectively, identified as adenosine, cordycepin, and N6-(2-hydroxyethyl)-adenosine (HEA) by comprehensive chemical analyses, including proton nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectroscopy (FT-IR), and electrospray ionization mass spectrometry (ESI-MS). To better understand the bioactivity mechanisms of cordycepin and HEA, the agonist and antagonist tests of the A3 adenosine receptor (A3AR) were performed. Cell viability was suppressed by cordycepin, and HEA was restored by the A3AR antagonist MR1523, suggesting that cordycepin and HEA possibly acted as agonists to activate A3ARs to inhibit cell proliferation. Molecular docking simulations revealed that both adenosine and cordycepin bound to the same pocket site of A3ARs, while HEA exhibited a different binding pattern, supporting a possible explanation for the difference in their bioactivity. Taken together, the present study demonstrated that cordycepin and HEA were major bioactive ingredients in Cordyceps militaries-infused sweet potato shochu spirits, which contributed to the in vitro anticancer activity.

Anticancer Activity and Molecular Mechanisms of Acetylated and Methylated Quercetin in Human Breast Cancer Cells.

Quercetin, a flavonoid polyphenol found in many plants, has garnered significant attention due to its potential cancer chemoprevention. Our previous studies have shown that acetyl modification of the hydroxyl group of quercetin altered its antitumor effects in HepG2 cells. However, the antitumor effect in other cancer cells with different gene mutants remains unknown. In this study, we investigated the antitumor effect of quercetin and its methylated derivative 3,3',4',7-O-tetramethylquercetin (4Me-Q) and acetylated derivative 3,3',4',7-O-tetraacetylquercetin (4Ac-Q) on two human breast cancer cells, MCF-7 (wt-p53, caspase-3-ve) and MDA-MB-231 (mt-p53, caspase-3+ve). The results demonstrated that 4Ac-Q exhibited significant cell proliferation inhibition and apoptosis induction in both MCF-7 and MDA-MB-231 cells. Conversely, methylation of quercetin was found to lose the activity. The human apoptosis antibody array revealed that 4Ac-Q might induce apoptosis in MCF-7 cells via a p53-dependent pathway, while in MDA-MB-231 cells, it was induced via a caspase-3-dependent pathway. Furthermore, an evaluation using a superoxide inhibitor, MnTBAP, revealed 4Ac-Q-induced apoptosis in MCF-7 cells in a superoxide-independent manner. These findings provide valuable insights into the potential of acetylated quercetin as a new approach in cancer chemoprevention and offer new avenues for health product development.

Effects of Cooking Methods on Caffeoylquinic Acids and Radical Scavenging Activity of Sweet Potato.

The effects of cooking methods, including steaming, deep-frying, and baking, on the phenolic content, 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, and isomerization of caffeoylquinic acids in sweet potato were investigated. A high correlation was observed between antioxidant capacity and total phenolic content. Deep-frying treatment resulted in higher antioxidant capacity with increasing heating time. The major phenolic components of raw sweet potat were 5-caffeoylquinic acid (CQA) and 3,5-dicaffeoylquinic acid (diCQA), which were reduced by heat treatment due to the isomerization of 5-CAQ to 3- and 4-CQA, and 3,5-diCQA to 3,4- and 4,5-diCQA. Moreover, 5-CQA was more stable than 3,5-diCQA even at 100 °C. Our results demonstrated that by controlling the cooking temperature and time, new bioactive compounds such as mono- and diCQA derivatives can be produced from sweet potato. These data indicate a potential approach for the development of new functional foods from sweet potato by controlling cooking temperature and time.

Effects of Prevotella copri on insulin, gut microbiota and bile acids.

Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1ß (IL-1ß) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.

The role of uterus mitochondrial function in high-fat diet-related adverse pregnancy outcomes and protection by resveratrol.

This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.

Hydroxyl Group Acetylation of Quercetin Enhances Intracellular Absorption and Persistence to Upregulate Anticancer Activity in HepG2 Cells.

Quercetin, a flavonoid compound widely distributed in many plants, is known to have potent antitumor effects on several cancer cells. Our previous study revealed that the acetylation of quercetin enhanced its antitumor effect. However, the mechanisms remain unknown. This study aimed to elucidate the bioavailability of acylated quercetin in the HepG2 cell model based on its antitumor effect. The positions of quercetin 3,7,3',4'-OH were acetylated as 3,7,3',4'-O-tetraacetylquercetin (4Ac-Q). The inhibitory effect of 4Ac-Q on HepG2 cell proliferation was assessed by measuring cell viability. The apoptosis was characterized by apoptotic proteins and mitochondrial membrane potential shifts, as well as mitochondrial reactive oxygen species (ROS) levels. The bioavailability of 4Ac-Q was analyzed by measuring the uptake and metabolites in HepG2 cells with high performance liquid chromatography (HPLC)-photodiode array detector (PDA) and-ultraviolet/visible detector (UV/Vis). The results revealed that 4Ac-Q enhanced the inhibitory effect on HepG2 cell proliferation and induced its apoptosis significantly higher than quercetin. Protein array analysis of apoptosis-related protein indicated that 4Ac-Q increased the activation or expression of pro-apoptotic proteins, including caspase-3, -9, as well as second mitochondria-derived activator of caspases (SMAC), and suppressed the expression of apoptosis inhibiting proteins such as cellular inhibitor of apoptosis (cIAP)-1, -2, Livin, Survivin, and X-linked inhibitor of apoptosis (XIAP). Furthermore, 4Ac-Q stimulated mitochondrial cytochrome c release into the cytosol by enhancing ROS level and depolarizing the mitochondrial membrane. Finally, the analysis of uptake and metabolites of 4Ac-Q in HpG2 cells with HPLC-PDA and -UV/Vis revealed that 4Ac-Q was metabolized to quercetin and several different acetylated quercetins which caused 2.5-fold higher quercetin present in HepG2 cells than parent quercetin. These data demonstrated that acetylation of the quercetin hydroxyl group significantly increased its intracellular absorption. Taken together, our findings provide the first evidence that acetyl modification of quercetin not only substantially augments the intracellular absorption of quercetin but also bolsters its metabolic stability to elongate its intracellular persistence. Therefore, acetylation could serve as a strategic approach to enhance the ability of quercetin and analogous flavonoids to suppress cancer cell proliferation.

Apoptosis Induction in HepG2 and HCT116 Cells by a Novel Quercetin-Zinc (II) Complex: Enhanced Absorption of Quercetin and Zinc (II).

Quercetin forms complexes with various metals due to its structural attributes. It predominantly exhibits chelating activity at the 3-hydroxy/4-carbonyl group. Previously, coordination in synthetically obtained quercetin-zinc (II) complexes has been limited to this group. However, the expanded coordination observed in quercetin-iron complexes has opened avenues for diverse applications. Thus, synthesizing novel quercetin-zinc complexes with different coordination positions is a significant advance. In our study, we not only synthesized and comprehensively characterized a new quercetin-zinc (II) complex, Zn-Q, but also evaluated the structure and bioactivity of chelate complexes (Q+Zn) derived from co-treatment in cell culture mediums. The structure of the new compound Zn-Q was comprehensively characterized using 1D 1H and 2D correlation spectroscopy (COSY), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), electrospray ionization mass spectrometer (ESI-MS), and X-ray diffraction analysis (XRD) analysis. Subcellular localization and absorption of these zinc (II) complexes were determined using the ZnAF-2 DA zinc ion fluorescence probe. Throughout the experiments, both Zn-Q and Q+Zn exhibited significant antioxidant, cell growth inhibitory, and anticancer effects in HepG2 and HCT116 cells, with Zn-Q showing the highest potential for inducing apoptosis via the caspase pathway. Tracking intracellular zinc complex absorption using zinc fluorescent probes revealed zinc (II) localization around the cell nucleus. Interestingly, there was a proportional increase in intracellular quercetin absorption in conjunction with zinc (II) uptake. Our research highlights the advantages of quercetin complexation with zinc (II): enhanced anticancer efficacy compared to the parent compound and improved bioavailability of both quercetin and zinc (II). Notably, our findings, which include enhanced intracellular uptake of both quercetin and zinc (II) upon complex formation and its implications in apoptosis, contribute significantly to the understanding of metal-polyphenol complexes. Moving forward, comprehensive functional assessments and insights into its mechanism of action, supported by animal studies, are anticipated.

Effects of glyphosate exposure on western diet-induced non-alcoholic fatty liver disease in mice.

We evaluated whether glyphosate promotes western diet (WD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed WD and received intragastrical glyphosate (0.05, 5 or 50 mg/kg) for 6 months. Glyphosate did not promote WD-induced obesity, hypercholesterolemia, glucose intolerance, hepatic steatosis, and fibrosis. Nonetheless, the higher dose (50 mg) enhanced hepatic CD68+ macrophage density, p65, TNF-α, and IL-6 protein levels. Furthermore, this dose decreased hepatic Nrf2 levels, while enhancing lipid peroxidation in the liver and adipose tissue. Hepatic transcriptome revealed that glyphosate at 50 mg upregulated 212 genes and downregulated 731 genes. Genes associated with oxidative stress and inflammation were upregulated, while key cell cycle-related genes were downregulated. Our results indicate that glyphosate exposure - in a dose within the toxicological limits - impairs hepatic inflammation/redox dynamics in a NAFLD microenvironment.

Ameliorative Effects of Anthocyanin Metabolites on Western Diet-Induced NAFLD by Modulating Co-Occurrence Networks of Gut Microbiome.

Anthocyanins (Acn) have been reported to have preventive effects on Western diet (WD)-induced non-alcoholic fatty liver disease (NAFLD). However, the amount of Acn that reached the bloodstream were less than 1%, suggesting that anthocyanin metabolites (Acn-M) in the gut may contribute to their in vivo effects. This study is focused on a gut microbiota investigation to elucidate the effect of two major Acn-M, protocatechuic acid (PC) and phloroglucinol carboxaldehyde (PG), on NAFLD prevention. C57BL/6N male mice were divided into five groups and fed with a normal diet (ND), WD, WD + 0.5% PC, WD + 0.5% PG and WD + a mixture of 0.25% PC + 0.25% PG (CG) for 12 weeks. The results revealed that WD-fed mice showed a significant increase in final body weight, epididymis fat weight, liver weight and fat accumulation rate, serum total cholesterol, alanine aminotransferase, monocyte chemoattractant protein 1, and 2-thiobarbituric acid reactive substances. At the same time, these indices were significantly decreased by Acn-M in the order of PG, CG > PC. In particular, PG significantly decreased serum glucose and insulin resistance. Gut microbiome analysis revealed that PG significantly increased the relative abundance of Parabacteroides, Prevotella, Prevotella/Bacteroides ratio, and upregulated glucose degradation pathway. Interestingly, the co-occurrence networks of Lachnospiraceae and Desulfovibrionaceae in the PC and PG groups were similar to the ND group and different to WD group. These data suggest that PC and PG were able to recover the gut microbiome networks and functions from dysbiosis caused by WD. Therefore, PG might act as a master metabolite for anthocyanins and prevent WD-induced NAFLD and gut dysbiosis.

Re-Evaluation of the Cross-Reactions of the Antibody against the Causative Agent for Paracoccidioidomycosis Ceti; Paracoccidioides ceti and the Related Fungal Species.

Paracoccidioidomycosis ceti (PCM-C) is a chronic granulomatous keloidal dermatitis in cetaceans that has been reported worldwide and is caused by Paracoccidioides ceti. Serological cross-reactions among highly pathogenic fungal infections and related diseases have been reported. However, the true cross-reaction of antibodies against P. ceti has remained unknown due to the use of positive control sera from infected dolphins. This study aimed to re-evaluate antibodies from mechanically dislodged fungal cells in the infected tissue of a PCM-C case and demonstrate the actual cross-reaction. The results revealed a limited cross-reaction between PCM-C and paracoccidioidomycosis, while the antibodies did not react with other pathogens such as Coccidioides posadasii, Histoplasama capsulatum, and Arthrographis kalrae. Thus, the method for evaluation of the antibody against PCM-C is reliable, and there is potential for epidemiological study.

Effects of Amazake Produced with Different Aspergillus on Gut Barrier and Microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. To explore the preventive effects of dietary foods on IBD, we evaluated the effects of the traditional Japanese fermented beverage "Amazake" on gut barrier function in this study. Black koji Amazake (BA) derived from Aspergillus luchuensis MEM-C strain and yellow koji Amazake (YA) derived from Aspergillus oryzae were made in this study, and their nutrients were analyzed. Mice with mild gut barrier dysfunction induced by Western diet were administered with 10% of each Amazake for two months. Mice gut microbiota were analyzed by 16S rRNA gene sequencing. BA contained a higher amount of isomaltooligosaccharides, citric acid, and ferulic acid than YA. The animal data revealed that BA significantly induced the expressions of antioxidant factors and enzymes such as NF-E2-related factor 2 (Nfr2), heme oxygenase 1 (HO1), and superoxide dismutase-2 (SOD-2). The gut barrier protein, occludin, and fecal immunoglobulin A (IgA) were also significantly enhanced by BA. Furthermore, the levels of serum endotoxin and hepatic monocyte chemotactic protein-1 (MCP-1) were decreased in both the BA and YA groups. In gut microbiota, Lachnospiraceae was increased by BA while Akkermansia muciniphilia was increased by YA. Black koji Amazake contained a higher amount of isomaltooligosaccharides, citric acid, and ferulic acid than yellow koji Amazake and contributed to protecting gut barrier function to reduce endotoxin intrusion and inflammation.

Extraction Efficiency and Alpha-Glucosidase Inhibitory Activities of Green Tea Catechins by Different Infusion Methods.

Alpha-glucosidase is an important target for glycemic control with the aim of reducing the risk of type 2 diabetes (T2D). Green tea catechins have been reported to inhibit alpha-glucosidase activity as a potential beverage to control blood glucose levels. However, the effects of the daily infusion style of green tea on tea catechins and their activity remain unclear. In this study, the extraction efficiency of catechins was investigated for 12 green tea extracts (GTEs) infused with 70% ethanol (70% EtOH for 24 h, a favored solvent for catechin extraction), room temperature water infusion (RT H2O for 24 h, an easy way to drink tea), and hot water infusion (Hot H2O for 90 s, a standard way to drink tea). Eight catechins were quantified by HPLC, and the inhibitory effect of GTEs and their catechins on alpha-glucosidase was measured with both rat intestinal enzymes and human Caco-2 cells. The inhibitory mechanism was further analyzed in silico by docking catechins to human alpha-glucosidase using Molecular Operating Environment software. The results showed that total catechins and gallate catechins were efficiently extracted in the order of 70% EtOH, RT H2O, and Hot H2O, and the inhibitory activity against alpha-glucosidase also followed a similar order. Pearson correlation analysis indicated that the alpha-glucosidase inhibitory activity of GTEs was significantly positively correlated with the contents of total catechins, especially gallate catechins. Gallate catechins, such as EGCg and ECg, showed lower IC50 values than free catechins for the enzyme in both rats and humans. In silico simulation revealed that gallate catechins were bound to the different sites with free catechins, and the docking energy of gallate catechins was lower than that of free catechins. Taken together, our data indicated that the daily infusion style of green tea significantly impacted the extraction efficiency and alpha-glucosidase inhibitory activities of catechins, which will give us insight into the use of green tea catechins for glycemic control through efficient infusion.

Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid.

Gut microbiota-diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-α & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus, which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1α), which can be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1, which can be prevented by dietary supplementation of PCA.

Assessment of Areca Nut Bioactivities in Western Diet-Induced Mice NAFLD Model.

The areca nut is often consumed as a chewing food in the Asian region. Our previous study revealed that the areca nut is rich in polyphenols with high antioxidant activity. In this study, we further assessed the effects and molecular mechanisms of the areca nut and its major ingredients on a Western diet-induced mice dyslipidemia model. Male C57BL/6N mice were divided into five groups and fed with a normal diet (ND), Western diet (WD), WD with areca nut extracts (ANE), areca nut polyphenols (ANP), and arecoline (ARE) for 12 weeks. The results revealed that ANP significantly reduced WD-induced body weight, liver weight, epididymal fat, and liver total lipid. Serum biomarkers showed that ANP ameliorated WD-enhanced total cholesterol and non-high-density lipoprotein (non-HDL). Moreover, analysis of cellular signaling pathways revealed that sterol regulatory element-binding protein 2 (SREBP2) and enzyme 3-hydroxy-3-methylglutaryld coenzyme A reductase (HMGCR) were significantly downregulated by ANP. The results of gut microbiota analysis revealed that ANP increased the abundance of beneficial bacterium Akkermansias and decreased the abundance of the pathogenic bacterium Ruminococcus while ARE shown the opposite result to ANP. In summary, our data indicated that areca nut polyphenol ameliorated WD-induced dyslipidemia by increasing the abundance of beneficial bacteria in the gut microbiota and reducing the expressions of SREBP2 and HMGCR while areca nut ARE inhibited this improvement potential.

The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway.

Redox balance is essential to maintain the body's normal metabolism. Once disrupted, it may lead to various chronic diseases, such as diabetes, neurodegenerative diseases, cardiovascular diseases, inflammatory diseases, cancer, aging, etc. Oxidative stress can cause or aggravate a series of pathological processes. Inhibition of oxidative stress and related pathological processes can help to ameliorate these chronic diseases, which have been found to be associated with Nrf2 activation. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damage, but also directly regulate genes related to the above-mentioned pathological processes to counter the corresponding changes. Therefore, targeting Nrf2 has great potential for the prevention or treatment of chronic diseases, and many natural phytochemicals have been reported as Nrf2 activators although the defined mechanisms remain to be elucidated. This review article focuses on the possible mechanism of Nrf2 activation by natural phytochemicals in the prevention or treatment of chronic diseases and the regulation of oxidative stress. Moreover, the current clinical trials of phytochemical-originated drug discovery by targeting the Nrf2-ARE pathway were also summarized; the outcomes or the relationship between phytochemicals and chronic diseases prevention are finally analyzed to propose the future research strategies and prospective.

Tissue-specific mechanisms of fat metabolism that focus on insulin actions.

BACKGROUND: The accumulation of ectopic fats is related to metabolic syndromes with insulin resistance, which is considered as the first hit in obesity-related diseases. However, systematic understanding of the occurrence of ectopic fats is limited, since organisms are capable of orchestrating complicated intracellular signaling pathways to ensure that the correct nutritional components reach the tissues where they are needed. Interestingly, tissue-specific mechanisms lead to different consequences of fat metabolism with different insulin sensitivities. AIM OF REVIEW: To summarize the mechanisms of fat deposition in different tissues including adipose tissue, subcutis, liver, muscle and intestines, in an attempt to elucidate interactive mechanisms involving insulin actions and establish a potential reference for the rational uptake of fat. KEY SCIENTIFIC CONCEPTS OF REVIEW: Tissue-specific fat metabolism serves as a trigger for developing abnormal fat metabolism or as a compensatory agent for regulating normal fat metabolism. Outcomes of de novo lipogenesis and adipogenesis differ in the subcutaneous adipose tissue (SAT), liver and muscle, with the participation of insulin actions. Overload of lipid metabolic capability results in SAT fat expansion, and ectopic fat accumulation implicates impaired lipo-/adipogenesis in SAT. Regulating insulin actions may be a key measure on fat deposition and metabolism in individuals.

Ameliorative effect of the oil components derived from sweet potato shochu on impaired short-term memory in mice after amyloid ß25-35 injection.

Sweet potato shochu oil is a by-product of shochu production and usually discarded although some physiological functions are considered. In this study, we investigated the effects of shochu oil on short-term memory using a murine model of spontaneous alternating behavior induced by the intracerebroventricular (ICV) administration of amyloid ß25-35 (Aß25-35). Mice were orally administered shochu oil for 15 days. Experiments with a Y-maze model revealed that the Aß25-35 caused a significant decrease in spontaneous alternation behavior, and supplementation with shochu oil significantly improved this behavior. DNA microarray analysis revealed that the administration of shochu oil downregulated the expression of S100a9 and Ptgs2, which reportedly exacerbate amyloid ß deposition in Alzheimer's disease. The administration of shochu oil upregulated the expression of Dnaja1 and PP2A, which is typically downregulated in Alzheimer's disease. These data suggest that shochu oil possible ameliorates on impaired short-term memory in mice after amyloid ß25-35 injection, as indicated by its effects on improving spontaneous alternation behavior and modulating the expressions of related genes.

In Vitro Antioxidant Activity of Areca Nut Polyphenol Extracts on RAW264.7 Cells.

Chewing areca nuts is a popular hobby in the Asian region, and areca nuts are rich in polyphenols, although some alkaloids are included. In this study, we explored the antioxidant activity of areca nut polyphenols (ANP) in lipopolysaccharides (LPS)-stimulated RAW264.7 cells. The results revealed that ANP reduced the level of reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells and enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). RNA-seq analysis showed that ANP down-regulated the transcription of genes related to the cancer pathway at 160 µg/mL, and the inflammatory pathway as well as viral infection pathway at 320 µg/mL. The cellular signaling analysis further revealed that the expressions of these genes were regulated by the mitogen-activated protein kinase (MAPK) pathway, and ANP downregulated the activation of the MAPK signaling pathway stimulated by LPS. Collectively, our findings showed that ANP inhibited the MAPK pathway and activated the Nrf2/HO-1 antioxidant pathways to reduce ROS generation induced by LPS.

Potential Biomarkers for Chronic Seasonal Heat Stress in Kagoshima Berkshire Pigs Reared in the Subtropical Region.

Introduction: Potential biomarkers for chronic seasonal heat stress in Kagoshima Berkshire pigs reared in the subtropical region were investigated by comparing the biomarker changes in the summer (a period of chronic heat stress) and winter (a thermoneutral period) seasons. Material and Methods: Pigs were allocated to summer- and winter-finishing cohorts, 12 each. The evaluations included assessment of carcass traits and internal organs' normality carried out at the time of slaughter, and measurement of biomarkers in whole blood: derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential as markers of oxidative stress, and serum amyloid A and albumin/globulin (A/G) ratio as markers of acute and chronic inflammation, respectively. Results: The summer-finished pigs reared under subtropical field conditions showed lower carcass quality than the winter-finished pigs, indicating a potential adverse effect of summer temperatures on the swine industry. Marginal changes were observed in d-ROMs and the A/G ratio between the summer- and winter-finishing cohorts. Conclusion: The results demonstrate that d-ROMs and the A/G ratio could be used as sensitive markers for heat stress under field conditions.

Natural Garlic Organosulfur Compounds Prevent Metabolic Disorder of Lipid and Glucose by Increasing Gut Commensal Bacteroides acidifaciens.

A number of reports of the effects of garlic on gut microbiota revealed that the active garlic organosulfur compounds (OSCs) are destabilized by the action of alliinase during garlic preparation. In this study, garlic alliinase was deactivated to obtain stable garlic OSCs. Experiments with C57BL/6J mice fed with lipid and glucose metabolic disorder-inducing Western diet (WD) revealed that stable garlic OSCs prevented the disorder by increasing the relative abundance of gut Bacteroides acidifaciens. Molecular analysis indicated that garlic OSCs inhibited dyslipidemia and fatty liver by increasing taurine and subsequently promoting hepatic fatty acid ß-oxidation. In parallel, garlic OSCs could meliorate glucose homeostasis by inhibiting dipeptidyl peptidase-4 (DPP-4) and hepatic gluconeogenesis. In vitro bacterial culture experiments revealed that garlic OSCs directly increased the growth of gut Bacteroides acidifaciens. The results of this study demonstrate that the molecular mechanism of the preventive effect of garlic OSCs on the WD-induced metabolic disorder is attributed to the enhanced growth of Bacteroides acidifaciens and the consequent increase in taurine.