Study on effects of processing technology and storage on the composition of Ampelopsis grossedentata by untargeted metabolomics.

Ampelopsis grossedentata is a traditional medicinal and edible plant rich in bioactive compounds. This paper focus on the white powder on the surface of A. grossedentata, and the effects of processing technology and storage time on the composition of bioactive compounds in Ampelopsis grossedentata extracts (AMP). 33 compounds in AMP were identified and 30 compounds were reported for the first time compared with standards by UHPLC-Q-Orbitrap-MS. Organic acid, phenol, and flavonoids were detected in powder samples. Through comparing the mass spectrum data of three processing samples (traditional method, fermentation and drying-only), five compounds in fermentation samples were higher than other groups, and the content of most compounds of the traditional process was decreased compared with drying-only process. For the storage time research, the powder on the surface was found to be more unstable than leaf parts after 24 h, suggesting that sealing preservation is crucial in the process after powder precipitation.

Mulberry Ethanol Extract and Rutin Protect Alcohol-Damaged GES-1 Cells by Inhibiting the MAPK Pathway.

Mulberry extract has been proven to have the effect of resisting alcohol damage, but its mechanism is still unclear. In this study, the composition of mulberry ethanol extract (MBE) was identified by LC-MS/MS and the main components of MBE were ascertained by measuring. Gastric mucosal epithelial (GES-1) cells were used to elucidate the mechanism of MBE and rutin (the central part of MBE) helped protect against alcohol damage. The results revealed that phenolics accounted for the majority of MBE, accounting for 308.6 mg/g gallic acid equivalents and 108 substances were identified, including 37 flavonoids and 50 non-flavonoids. The treatment of 400 µg/mL MBE and 320 µM rutin reduced early cell apoptosis and the content of intracellular reactive oxygen species, malondialdehyde and increased glutathione. The qPCR results indicated that the MBE inhibits the expression of genes in the mitogen-activated protein kinase (MAPK) pathway, including p38, JNK, ERK and caspase-3; rutin inhibits the expression of p38 and caspase-3. Overall, MBE was able to reduce the oxidative stress of GES-1 cells and regulated apoptosis-related genes of the MAPK pathway. This study provides information for developing anti-ethanol injury drugs or functional foods.

Research progress on intervention effect and mechanism of protocatechuic acid on nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has become a surge burden worldwide due to its high prevalence, with complicated deterioration symptoms such as liver fibrosis and cancer. No effective drugs are available for NALFD so far. The rapid growth of clinical demand has prompted the treatment of NAFLD to become a research hotspot. Protocatechuic acid (PCA) is a natural secondary metabolite commonly found in fruits, vegetables, grains, and herbal medicine. It is also the major internal metabolites of anthocyanins and other polyphenols. In the present manuscript, food sources, metabolic absorption, and efficacy of PCA were summarized while analyzing its role in improving NAFLD, as well as the mechanism involved. The results indicated that PCA could ameliorate NAFLD by regulating glucose and lipid metabolism, oxidative stress and inflammation, gut microbiota and metabolites. It was proposed for the first time that PCA might reduce NAFLD by enhancing the energy consumption of brown adipose tissue (BAT). However, the PCA administration mode and dose for NAFLD remain inconclusive. Fresh insights into the specific molecular mechanisms are required, while clinical trials are essential in the future. This review provides new targets and reasoning for the clinical application of PCA in the prevention and treatment of NAFLD.

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid-induced HepG2 cells via the LKB1/AMPK signaling pathway.

Impaired lipid and glucose metabolism in the liver is a crucial characteristic of nonalcoholic fatty liver disease (NAFLD). Coniferaldehyde (CA), a kind of phenolic compound found in many edible plants, has multiple biological and pharmacological functions. However, since the effect and molecular mechanism of CA on hepatic lipid and glucose metabolism disorders in NAFLD remain unknown, this study investigated its impact on the lipid and glucose metabolism of palmitic acid (PA)-induced HepG2 cells. Compared with the HepG2 cells treated only with PA, supplementation with 25, 50, and 100 µM CA reduced the levels of intracellular triglyceride (by 7.11%, 19.62%, and 31.57%) and total cholesterol (by 8.46%, 23.32%, and 27.17%), and enhanced glucose uptake (by 40.91%, 57.49%, and 61.32%) and intracellular glycogen content (by 12.75%, 41.27%, and 53.77%). Moreover, CA supplementation downregulated the expression of sterol regulatory element-binding protein-1, fatty acid synthase, and stearoyl-CoA desaturase 1 related to lipogenesis while upregulating the expression of carnitine palmitoyltransferase 1α related to fatty acid oxidation. CA supplementation also upregulated the glucose transporter 2 protein expression and phosphorylation of glycogen synthase kinase 3ß while downregulating the phosphorylation of glycogen synthase. Most importantly, most of these effects of CA were reversed by pretreatment with AMP-activated protein kinase (AMPK) inhibitor and small interfering RNA-liver kinase B1 (LKB1). In conclusion, CA ameliorated the lipid and glucose metabolism in PA-induced HepG2 cells via the LKB1/AMPK signaling pathway. PRACTICAL APPLICATION: In this study, coniferaldehyde appeared to be effective in ameliorating hepatic lipid and glucose metabolism disorders in nonalcoholic fatty liver disease by reducing the levels of intracellular triglyceride and total cholesterol and enhancing glucose uptake and intracellular glycogen content via the LKB1/AMPK signaling pathway in vitro. Therefore, our findings provide new evidence in support of that supplementation with coniferaldehyde or food rich in coniferaldehyde might be considered as a viable dietary intervention strategy for preventing and treating nonalcoholic fatty liver disease.

The influence of oxygen on the metabolites of phenolic blueberry extract and the mouse microflora during in vitro fermentation.

The elevated intestinal oxygen in certain unhealthy conditions (e.g., mucosa injury) enhances the expansion of aerobic/facultative anaerobic bacteria (mainly Proteobacteria) in gut microbiota (GM) and is strongly linked to various diseases. The alteration of GM, influenced by oxygen, may affect the bioavailability of dietary polyphenols. In vitro digestion, dialysis and fermentation of phenolic blueberry extract (BE) were performed here using the GM of mice under different oxygen conditions. Oxygen delayed the degradation of the main phenolic components, including quercetin, kaempferol and their rutinose-conjugates, in BE during in vitro fermentation. In addition, the metabolites of BE were also influenced by oxygen. Oxygen skewed the production of 3-hydroxyphenylacetatic acid to 4-hydroxyphenylacetatic acid. Moreover, oxygen also blunted hippuric, 3-phenylpropionic, and 3-hydroxycinnamic acids production. Furthermore, oxygen enhanced the expansion of Salmonella and Escherichia belonging to phylum Proteobacteria and suppressed the proliferation of the anaerobic bacteria Clostridium and Bacteroides belonging to phyla Firmicutes and Bacteroidetes, respectively, which was reversed by BE supplementation.

Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet-Fed Mice through Increased Thermogenesis.

BACKGROUND: Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. OBJECTIVES: In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)-fed obese mice. METHODS: The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. RESULTS: After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. CONCLUSIONS: Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid.

SCOPE: Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM). METHODS AND RESULTS: Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of TαMCA, TßMCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro. CONCLUSION: GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM.

Chlorogenic Acid Stimulates the Thermogenesis of Brown Adipocytes by Promoting the Uptake of Glucose and the Function of Mitochondria.

Brown adipose tissue (BAT) prevents obesity and related diseases by uncoupling oxidative phosphorylation with adenosine triphosphate. Previous studies have demonstrated that polyphenols can promote the thermogenesis of BAT in mice. Chlorogenic acid (CGA) is a common phenolic acid found in fruits and vegetables, as well as traditional Chinese medicine, which is responsible for a variety of physiological activities. However, it is still unclear whether CGA has positive effects on the thermogenesis of BAT. In this study, CGA enhances the thermogenesis and proton leak of brown adipocytes, however, no changes are evident regarding the differentiation of C3 H10 T1/2 into brown adipocytes. Surprisingly, CGA promotes the uptake of glucose by upregulating the glucose transporter 2 and phosphofructokinase. Moreover, CGA increases the number and the function of mitochondrial. Taken together, CGA stimulates thermogenesis of brown adipocytes by promoting the uptake of glucose and the function of mitochondria. PRACTICAL APPLICATION: Chlorogenic acid (CGA) is widely found in fruits, vegetables, and traditional Chinese medicines, which has been considered to have antibacterial and anti-inflammatory function. However, whether it has the function of resisting obesity and promoting thermogenesis is still unclear. In this study, brown adipocyte was used to explore the function and mechanism of CGA on thermogenesis. It provides new ideas for the utilization of foods rich in CGA and traditional Chinese medicine.

Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function.

SCOPE: Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue (BAT) formation and function increases energy expenditure and may protect against obesity. Cyanidin-3-glucoside (C3G) is an anthocyanin compound that occurs naturally in many fruits and vegetables. In this study, we investigated the effect and mechanism of C3G on the prevention of obesity. METHODS AND RESULTS: Db/db mice received C3G dissolved in drinking water for 16 wk; drinking water served as the vehicle treatment. The total body weight, energy intake, metabolic rate, and physical activity were measured. The lipid droplets, gene expression and protein expression were evaluated by histochemical staining, real-time PCR, and western blots. We found that C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown-like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function. CONCLUSION: Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity.

Mulberry and mulberry wine extract increase the number of mitochondria during brown adipogenesis.

Mulberry extract (ME) has been shown to possess beneficial effects towards obesity, but its mechanism is still unclear. In small mammals, mitochondria enriched brown adipose tissue (BAT) is known to convert protein's electrochemical energy to heat and maintain a constant body temperature. Improving the mitochondrial function or increasing the number of mitochondria could promote the metabolism of carbohydrate and fat. Thus, this study was designed to investigate the mitochondrial function regulated by ME and mulberry wine extract (MWE) during the brown adipogenesis. The C3H10T1/2 mesenchymal stem cell was treated with ME and MWE, both of which significantly (p < 0.05) increased the expression levels of fatty acid oxidation related genes such as peroxisome proliferator-activated receptor-γ coactivator-1α, PR domain-containing 16 and carnitine palmitoyltransferase 1α during brown adipogenesis. These changes were accompanied with increases in mitochondrial oxidative complex proteins upon ME and/or MWE exposure. Notably, ME and/or MWE also significantly (p < 0.05) increased the expression of the transcription factor A and the nuclear respiratory factor-1, which are the key transcription factors of mitochondrial biogenesis. In parallel, the mitochondrial copy number and brown adipose tissue specific gene-uncoupling protein-1 expression were dramatically (p < 0.05) elevated after ME or MWE treatment. Cyanidin-3-glucoside (Cy-3-glu) was found to be one of the most abundant anthocyanins in ME and MWE. Therefore, the BAT regulatory activity of ME and MWE might be, at least in part, due to the effect of Cy-3-glu. These results suggested that ME and MWE could ameliorate metabolic disease through an improvement in mitochondrial functions.