Hydroxytyrosol Alleviates Obesity-Induced Cognitive Decline by Modulating the Expression Levels of Brain-Derived Neurotrophic Factors and Inflammatory Factors in Mice.

Hydroxytyrosol (HT; 3,4-dihydroxyphenyl ethanol) is an important functional polyphenol in olive oil. Our study sought to evaluate the protective effects and underlying mechanisms of HT on obesity-induced cognitive impairment. A high-fat and high-fructose-diet-induced obese mice model was treated with HT for 14 weeks. The results show that HT improved the learning and memory abilities and enhanced the expressions of brain-derived neurotrophic factors (BDNFs) and postsynaptic density proteins, protecting neuronal and synaptic functions in obese mice. Transcriptomic results further confirmed that HT improved cognitive impairment by regulating gene expression in neural system development and synaptic function-related pathways. Moreover, HT treatment alleviated neuroinflammation in the brain of obese mice. To sum up, our results indicated that HT can alleviate obesity-induced cognitive dysfunction by enhancing BDNF expression and alleviating neuroinflammation in the brain, which also means that HT may become a potentially useful nutritional supplement to alleviate obesity-induced cognitive decline.

Quantitative analyses for several nutrients and volatile components during fermentation of soybean by Bacillus subtilis natto.

This study is to reveal the variation of five pivotal substances, including polysaccharides, proteins, isoflavones, fatty acids and volatile components during the soybean fermentation process by Bacillus subtilis natto. After 96 h of soybean fermentation, the polysaccharide contents were significantly decreased, and the glucose and galactose contents showed the greatest decline in all the monosaccharide components. Moreover, isoflavone glycoside levels were decreased, while the isoflavone aglycone levels were increased following the fermentation. In addition, the SCFAs contents were also significantly increased in comparison with the unfermented soybean. Furthermore, 16 amino acids and 36 volatile components were detected in the fermented soybean. Finally, 21 key compounds were identified through PCA and OPLS-DA analysis of total compounds in the fermentation process. These findings demonstrated that Bacillus subtilis natto had a significant influence on the biochemical profiles of soybean fermentation and consequently contributed to its unique quality.

Water extract of shepherd's purse prevents high-fructose induced-liver injury by regulating glucolipid metabolism and gut microbiota.

Shepherd's purse as a wild vegetable is getting more and more attention on health benefits. Water extract of shepherd's purse (WESP) was prepared and analyzed for the chemical constituents. The mice were fed high-fructose (HF) diet and treated with WESP at 50, 100 and 200 mg/kg·bw for 8 weeks. The HF-fed mice receiving WESP exhibited the inhibitions against abnormal weight gain, hepatic fat accumulation and lipid metabolic by down-regulating FAS and ACC expressions. WESP also significantly alleviated hyperglycemia, oxidative stress, and inflammatory response by regulating of NF-κB pathway. Moreover, WESP dose-dependently increased the acetic, propionic, and butyric acids levels in HF-fed mice. Furthermore, WESP significantly alleviated the HF-induced gut dysbiosis by reducing the ratio of Firmicutes to Bacteroidetes and increasing the abundance of potential beneficial bacteria. Our findings indicate that WESP may be an effective dietary supplement for preventing the liver damage.

Non-digestive stachyose enhances bioavailability of isoflavones for improving hyperlipidemia and hyperglycemia in mice fed with high fat diet.

This study examined the efficacy of non-digestive stachyose on enhancing the absorption of soy isoflavones to improve metabolic syndrome in C57/BL6 mice. UPLC-q/TOF-MS was employed to analyze the content of isoflavones in urine and faeces. Stachyose significantly increased urinary contents of total isoflavones, genistein, daidzein and glycitein in mice. Supplementation of stachyose, soybean isoflavones or a combination prevented high fat diet (HFD)-induced body weight gain, accumulated adipose, dyslipidemia and hyperglycemia in obese mice. Interestingly, co-supplementation of stachyose and isoflavones improved all the mentioned parameters more effectively than administration of stachyose or isoflavones alone. Histological observation of hepatic tissues also confirmed the beneficial effects of co-supplementation of stachyose and isoflavones. These findings suggest that co-ingestion of non-digestible oligosaccharides and polyphenols as normal diet is a promising potential strategy for managing or reducing the risk of metabolic syndrome, which will lead to new knowledge on whole soybean and have extensive application in development of healthy food.

Salted and Unsalted Zhàcài (Brassica juncea var. tumida) Alleviated High-Fat Diet-Induced Dyslipidemia by Regulating Gut Microbiota: A Multiomics Study.

SCOPE: Zhàcài (ZC), a salting-processed Brassica juncea var. tumida vegetable, is widely consumed as a pickle, but little is known about the health benefits of both salted and unsalted ZC as a whole food. METHODS AND RESULTS: The preventive effects of salted and unsalted ZC against dyslipidemia are assessed in high-fat (HF) diet-fed mice. HF intake for 12 continuous weeks cause dyslipidemia in mice, as evidenced by the elevations in serum total triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels by 30%, 66%, and 117%, respectively. Metabolomics analysis and the 16S rRNA genes sequencing suggest that dietary administration of salted and unsalted ZC (2.5% w/w) alleviates HF-induced dyslipidemia, metabolic disorders of short-chain fatty acids, and disturbance of intestinal flora in mice. These positive effects of unsalted ZC are stronger than those of salted ZC. Moreover, fecal bacteria transplantation confirms the antidyslipidemia of ZC. CONCLUSION: These results suggest that consumption of ZC may prevent HF-induced dyslipidemia by regulating gut microbiota.

Citric acid-enhanced dissolution of polyphenols during soaking of different teas.

This study examined the dissolution kinetics and antioxidant activity of tea polyphenols during the soaking of white, yellow, green, oolong, black, and dark teas. All these teas were, respectively, soaked with either freshly boiled distilled water (DW) or 10 mmol/L citric acid-water solution. The residue obtained from one extraction was used for the next extraction and this process was performed consecutively 10 times, soaking for 30 s each time. UHPLC-QqQ-MS measurement identified epigallocatechin gallate as the major polyphenol in white, yellow, green, oolong, and black tea infusions. As soaking times increased, the polyphenol concentrations rose initially and then dropped. Antioxidant activity was noted to decrease as soaking times increased in all tea infusions except for the DW-soaked oolong and dark teas. These findings suggested that citric acid could increase the polyphenol content in tea infusions. Specifically, the cumulative contents of epigallocatechin gallate was noted to increase 2.1-5.1 times. PRACTICAL APPLICATIONS: After water, tea is one of the most consumed beverages in the world. Drinking tea has been linked to the reduced risk of various diseases, including cancer, cardiovascular system disease, obesity, and neurodegenerative diseases, largely due to its rich polyphenol content. Moreover, the addition of citrus to a tea infusion provides an interesting and feasible method for increasing the dissolution of tea polyphenols, a finding that offers extensive potential for applications in the development of compound tea drinks.

Supplementation of okra seed oil ameliorates ethanol-induced liver injury and modulates gut microbiota dysbiosis in mice.

This aim of this study is to assess the possible effects of dietary okra seed oil (OSO) consumption on attenuation of alcohol-induced liver damage and gut microbiota dysbiosis, and associated mechanisms in mice. Mice were orally administered alcohol alone or in combination with OSO at 400 and 800 mg per kg bw for 8 weeks. OSO caused a strong inhibition of abnormal weight loss and liver fat accumulation in alcohol-administered mice. Malonaldehyde production was also effectively antagonized, and glutathione peroxidase and superoxide dismutase activities were elevated by OSO treatment in ethanol-based mice (p < 0.05). Concentrations of hepatic TNF-α, IL-1 and IL-6 were decreased after OSO treatment when compared with alcohol-treated mice, respectively (p < 0.05). As revealed by 16S rDNA gene sequence analysis, OSO notably reduced the Proteobacteria proportion and enhanced the Bacteroidetes population of alcohol-treated mice, and a significant reduction in Clostridium XlVa and Staphylococcus was observed, revealing that OSO attenuated the alcohol-induced gut dysbiosis. OSO also attenuated lipid metabolic disorder by modulating metabolism of serum free fatty acids in ethanol-based mice, but had no significant difference in cecum total short-chain fatty acids among the tested mice. Amelioration of these parameters and liver injury via H&E staining examination demonstrated that OSO consumption could effectively protect against liver damage and maintain intestinal eubiosis in mice.

Soybean soluble polysaccharides enhance bioavailability of genistein and its prevention against obesity and metabolic syndrome of mice with chronic high fat consumption.

This study aimed to explore a novel strategy for the simultaneous consumption of soluble soybean polysaccharides (SSPS) and insoluble genistein to improve the bioavailability of genistein and its prevention against obesity and metabolic syndrome in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed a normal diet and HFD supplemented or not (n = 8) with SSPS (2.5%), genistein (0.5%) and their mixture (S + G) for 12 weeks. The UPLC-qTOP/MS assay showed that SSPS observably enhanced the urinary concentration of genistein and its metabolites compared to that of single genistein in mice. Supplementation of SSPS, genistein or their combination prevented HFD-induced gain weight, dyslipidemia, oxidative stress and inflammation in obese mice. Interestingly, the combined S + G ingestion exhibited more effective alleviation of dyslipidemia by modulating hepatic FAS, ACC, SREBP-1C and ADRP expressions relative to that of individual SSPS or genistein. Furthermore, S + G activated the energy metabolism pathway AMPK in the liver, and the hepatic PPAR-α/PPAR-γ pathways were doubly activated to alleviate lipogenesis, inflammation, obesity and metabolic syndrome. Moreover, S + G supplementation dramatically modified the gut microbial species at the phylum level with a decrease in Firmicutes and increase in Bacteroidetes. These findings support that the combined supplementation of SSPS and genistein is a novel couple to prevent obesity and metabolic syndrome.

Correction: Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells.

Correction for 'Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells' by Qiu Wu et al., Food Funct., 2018, 9, 1736-1746.

Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells.

This study was designed to investigate the tumor-inhibitory effects of quercetin (Que) and its water-soluble metabolites, quercetin-3'-sulfate (Q3'S) and quercetin-3-glucuronide (Q3G), as well as to make the molecular mechanism and structure-antitumor relationship clear. It was found that Que, Q3'S, and Q3G could inhibit the growth of human breast cancer MCF-7 cells in a dose-dependent manner, with the IC50 values of 23.1, 27.6, and 73.2 µM, respectively, and their anticancer effect was ranked as Que > Q3'S > Q3G. Furthermore, flow cytometric assay revealed that Que, Q3'S, and Q3G mediated the cell-cycle arrest principally at the S phase and decreased the number of G0/G1 and G2/M after a 48 h treatment with human breast MCF-7 cells. Moreover, it was found that 70.8%, 58.2%, and 48.0% of MCF-7 cancer cells entered the early phase of apoptosis when treated with 100 µM Que, Q3'S, and Q3G for 48 h, respectively. In addition, induction of apoptosis by Que, Q3'S, and Q3G was accompanied by marginal generation of intracellular reactive oxygen species (ROS) in the MCF-7 cancer cells. Overall, these results demonstrate that Que, Q3'S, and Q3G possess strong antitumor effects through induction of an ROS-dependent apoptosis pathway in MCF-7 cells.

Soybean soluble polysaccharide enhances absorption of soybean genistein in mice.

This study was designed to probe the promoting effects of soybean soluble polysaccharide (SSPS) on bioavailability of genistein in mice and the underlying molecular mechanism. Male Kunming mice (n=8) were administered intragastrically with either saline, SSPS (5mg/kgbw), genistein (100mg/kgbw), or SSPS (5 or 50mg/kgbw) together with genistein (100mg/kgbw) for consecutive 28days. UPLC-qTOF/MS analysis showed that co-administration of SSPS and genistein in mice caused significant elevation in the urinary levels of genistein and its metabolites (p<0.05). Furthermore, the fecal excretion of genistein was also enhanced by co-administration of SSPS. However, the feces level of dihydrogenistein, a characteristic metabolite of genistein degraded by gut microorganism, was dose-dependently decreased by the combined treatment of SSPS. Additionally, co-treatment of SSPS with genistein also decreased the small intestinal levels of uridinediphosphate-glucuronosyltransferase (UGT), sulfotransferase (SULT), P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP1), and multidrug resistance-associated protein-2 (MRP2) in mice. These findings suggest that the inhibition of SSPS against small intestinal first-pass metabolism of genistein is involved in the promoting effect of genistein bioavailability in mice.

Hepatoprotective Effects of Sophoricoside against Fructose-Induced Liver Injury via Regulating Lipid Metabolism, Oxidation, and Inflammation in Mice.

The dried fruit of Sophora japonica L. is a traditional Chinese herb tea rich in sophoricoside that is an isoflavone glycoside. The aim of current study was to investigate the hepatic protective effect of sophoricoside in high fructose (HF) diet fed mice. Healthy male mice were fed 30% fructose water and treated 80 and 160 mg/kg·bw sophoricoside continuously for 8 wk. Our data showed that administration of sophoricoside at 80 and 160 mg/kg·bw observably decreased the body weight and liver weight in HF-fed mice. It was found that the treatment of sophoricoside decreased the hepatic cholesterol and triglyceride levels, and serum low-density lipoprotein-cholesterol and apolipoprotein-B levels, and elevated the serum high-density lipoprotein-cholesterol and apolipoprotein-A1 levels. Moreover, the administration of sophoricoside decreased the HF-caused elevations of hepatic malonaldehyde, interleukin-1 and tumor necrosis factor-α levels, while increased the HF-induced decreases of hepatic superoxide dismutase and glutathione peroxidase activities. Meanwhile, serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities were reduced by treatment of sophoricoside in HF-fed mice. Histopathology of hematoxylin and eosin (H&E) and oil red O staining of liver tissues also confirmed the beneficial effects of sophoricoside against liver injury induced by HF-diet in mice. These findings indicated that sophoricoside may be a novel natural isoflavone for alleviating HF-induced liver injury. PRACTICAL APPLICATION: Fruit of Sophora japonica L. is a traditional herb tea and it recently becomes popular in China. Sophoricoside is an isoflavone glycoside (Genistein-4'-O-ß-d-glucopyranoside) isolated from S. japonical L, and it possessed differential effects on the body health. The ingestion of sophoricoside or sophora fruit tea may be a novel strategy to prevent non-alcoholic fatty liver disease.

Soluble soybean polysaccharides enhance the protective effects of genistein against hepatic injury in high l-carnitine-fed mice.

This study was to develop a novel strategy for the simultaneous consumption of soluble soybean polysaccharides (SSPS) to enhance the absorption of genistein and its protective effects against high l-carnitine-induced hepatic injury in mice. UPLC-qTOP/MS measurements showed that SSPS observably increased the urinary concentration of genistein and its metabolites in mice. The mice fed with 3% l-carnitine water for 12 weeks experienced a disturbance of the hepatic lipid metabolism, oxidative stress and inflammation, which was evidenced by abnormal TC, LDL, RAHFR and MDA levels, unusual AST, ALT, ALP, SOD and GSP-Px activities, and increased IF-1, IF-6 and TNF-α expressions. Interestingly, the co-supplementation of SSPS and genistein was capable of regulating these imbalances more effectively than the administration of SSPS or genistein alone, which was also confirmed by histological observations of the mouse liver. These findings suggest that the co-ingestion of SSPS and genistein is a feasible strategy for improving liver protection in mice.

Non-digestible stachyose promotes bioavailability of genistein through inhibiting intestinal degradation and first-pass metabolism of genistein in mice.

This study was designed to explore the molecular mechanism of stachyose in enhancing the gastrointestinal stability and absorption of soybean genistein in mice. Male Kunming mice in each group (n = 8) were administered by intragastric gavage with saline, stachyose (250 mg/kg·bw), genistein (100 mg/kg·bw), and stachyose (50, 250, and 500 mg/kg·bw) together with genistein (100 mg/kg·bw) for 4 consecutive weeks, respectively, and then their urine, feces, blood, gut, and liver were collected. UPLC-qTOF/MS analysis showed that levels of genistein and its metabolites (dihydrogenistein, genistein 7-sulfate sodium salt, genistein 4'-ß-D-glucuronide, and genistein 7-ß-D-glucuronide) in serum and urine were increased with an increase in stachyose dosages in mice. Furthermore, the feces level of genistein aglycone was also elevated by co-treatment of stachyose with genistein. However, the feces concentration of dihydrogenistein, a characteristic metabolite of genistein by gut microorganism, was decreased by stachyose administration in a dose-dependent manner. Additionally, the simultaneous administration with stachyose and genistein in mice could decrease intestinal SULT, UGT, P-gp, and MRP1 expression, relative to the treatment with individual stachyose or genistein. These results demonstrate that stachyose-mediated inhibition against the intestinal degradation of genistein and expression of phase II enzymes and efflux transporters can largely contribute to the elevated bioavailability of soybean genistein.

Effects of stachyose on absorption and transportation of tea catechins in mice: possible role of Phase II metabolic enzymes and efflux transporters inhibition by stachyose.

BACKGROUND: Nutritional and absorption-promoting properties of stachyose combined with tea catechins (TC) have been revealed. However, the mechanism involved in non-digestible oligosaccharides-mediated enhancement of flavonoid absorption has largely remained elusive. METHODS: This study was designed to investigate the molecular mechanism of stachyose in enhancing absorption and transportation of TC in mice. Mice were orally pre-treated with stachyose (50, 250, and 500 mg/kg·bw) for 0-8 weeks, and 1 h before sacrifice, mice were treated with TC (250 mg/kg·bw). RESULTS: Gas chromatography-mass spectrometry analysis showed that serum concentrations of epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate were dose- and time-dependently elevated with stachyose pre-treatment in mice. Furthermore, pre-treatment with stachyose in mice reduced intestinal sulfotransferase and uridine diphosphate-glucuronosyltransferase levels by 3.3-43.2% and 23.9-30.4%, relative to control mice, respectively. Moreover, intestinal P-glycoprotein and multidrug resistance-associated protein-1 contents were decreased in mice by pre-administration of stachyose in dose- and time-dependent manner. CONCLUSIONS: This is the first time to demonstrate that suppression of Phase II metabolic enzymes and efflux transporters of TC in the intestine can play a major role in increasing absorption of TC by stachyose feeding.

Enhancing the hepatic protective effect of genistein by oral administration with stachyose in mice with chronic high fructose diet consumption.

Dietary supplementation of soy stachyose or genistein is known to be of hepatoprotective health interest. This study showed that co-administration of genistein and stachyose caused stronger inhibition on abnormal weight gain and liver fat accumulation by decreasing fatty acid synthetase expression and balancing disorderly lipid metabolism than that of genistein or stachyose alone in high-fructose (HF) diet-fed mice. Furthermore, the production of malonaldehyde and carbonyl derivatives of proteins was also more effectively inhibited by co-treatment of genistein and stachyose, and thereby glutathione peroxidase and superoxide dismutase activities were elevated in HF-fed mice. Moreover, genistein in combination with stachyose was more effective to reduce the impact of HF on the serum markers of liver damage by inhibiting inflammatory cytokine release than stachyose or genistein alone in mice. The potential mechanism was that stachyose enhanced absorption of genistein in HF-fed mice by oral supplementation of genistein together with stachyose. These findings indicate that co-ingestion of stachyose and genistein may serve as a novel strategy for hepatic protection.