Extraction, structures, biological effects and potential mechanisms of Momordica charantia polysaccharides: A review.

Momordica charantia L. is a kind of vegetable with medicinal value. As the main component of the vegetable, Momordica charantia polysaccharides (MCPs) mainly consist of galactose, galacturonic acid, xylose, rhamnose, mannose and the molecular weight range is 4.33 × 103-1.16 × 106 Da. MCPs have been found to have various biological activities in recent years, such as anti-oxidation, anti-diabetes, anti-brain injury, anti-obesity, immunomodulatory and anti-inflammation. In this review, we systematically summarized the extraction methods, structural characteristics and physicochemical properties of MCPs. Especially MCPs modulate gut microbiota and cause the alterations of metabolic products, which can regulate different signaling pathways and target gene expressions to exert various functions. Meanwhile, the potential structure-activity relationships of MCPs were analyzed to provide a scientific basis for better development or modification of MCPs. Future researches on MCPs should focus on industrial extraction and molecular mechanisms. In East Asia, Momordica charantia L. is used as both food and medicine. It is not clear whether MCP has its unique biological effects. Further study on the difference between MCPs and other food-derived polysaccharides will be helpful to the development and potential application of Momordica charantia L.

Cyanidin-3-O-Glucoside Alleviates Alcoholic Liver Injury via Modulating Gut Microbiota and Metabolites in Mice.

Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with multiple biological activities. This study aims to investigate the effects of C3G isolated from black rice on ALD and explore the potential mechanism. C57BL/6J mice (male) were fed with standard diet (CON) and Lieber-DeCarli liquid-fed (Eth) or supplemented with a 100 mg/kg/d C3G Diet (Eth-C3G), respectively. Our results showed that C3G could effectively ameliorate the pathological structure and liver function, and also inhibited the accumulation of liver lipids. C3G supplementation could partially alleviate the injury of intestinal barrier in the alcohol-induced mice. C3G supplementation could increase the abundance of Norank_f_Muribaculaceae, meanwhile, the abundances of Bacteroides, Blautia, Collinsella, Escherichia-Shigella, Enterococcus, Prevotella, [Ruminococcus]_gnavus_group, Methylobacterium-Methylorubrum, Romboutsia, Streptococcus, Bilophila, were decreased. Spearman's correlation analysis showed that 12 distinct genera were correlated with blood lipid levels. Non-targeted metabolic analyses of cecal contents showed that C3G supplementation could affect the composition of intestinal metabolites, particularly bile acids. In conclusion, C3G can attenuate alcohol-induced liver injury by modulating the gut microbiota and metabolites, suggesting its potential as a functional food ingredient against alcoholic liver disease.

The Potential Role of Vitamin E and the Mechanism in the Prevention and Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, and it is a multifactorial disease of the intestinal mucosa. Oxidative stress damage and inflammation are major risk factors for IBD. Vitamin E has powerful antioxidant and anti-inflammatory effects. Our previous work and other investigations have shown that vitamin E has a positive effect on the prevention and treatment of IBD. In this paper, the source and structure of vitamin E and the potential mechanism of vitamin E's role in IBD were summarized, and we also analyzed the status of vitamin E deficiency in patients with IBD and the effect of vitamin E supplementation on IBD. The potential mechanisms by which vitamin E plays a role in the prevention and treatment of IBD include improvement of oxidative damage, enhancement of immunity, maintenance of intestinal barrier integrity, and suppression of inflammatory cytokines, modulating the gut microbiota and other relevant factors. The review will improve our understanding of the complex mechanism by which vitamin E inhibits IBD, and it also provides references for doctors in clinical practice and researchers in this field.

Whole grain germinated brown rice intake modulates the gut microbiota and alleviates hypertriglyceridemia and hypercholesterolemia in high fat diet-fed mice.

Hyperlipidemia is a common clinical disorder of lipid metabolism in modern society and is considered to be one of the major risk factors leading to cardiovascular-related diseases. Germinated brown rice (GBR) is a typical whole grain food. The lipid-lowering effect of GBR has received increasing attention, but its mechanism of action is not fully understood. The gut microbiota has been proposed as a novel target for the treatment of hyperlipidemia. The aim of this study was to investigate the effects of GBR on the gut microbiota and lipid metabolism in high-fat diet (HFD)-fed C57BL/6J mice. The effect of GBR on hyperlipidemia was evaluated by measuring blood lipid levels and by pathological examination. The gut microbiota was detected by 16S rRNA sequencing, and the protein and mRNA expression levels involved in cholesterol metabolism were detected by western blotting and RT-qPCR to find potential correlations. The results showed that GBR supplementation could effectively reduce the levels of TC, TG, LDL-C and HDL-C in the serum and alleviate the excessive accumulation of fat droplets caused by HFD. Moreover, GBR intervention improved HFD-fed gut microbiota disorder via increasing the diversity of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio, and improving gut barrier damage. In addition, GBR could inhibit endogenous cholesterol synthesis and promote cholesterol transport and excretion. These findings suggest that GBR may be a competitive candidate for the development of functional foods to prevent abnormal lipid metabolism.

Exploration on anti-hypoxia properties of peptides: a review.

Peptides are important components of human nutrition and health, and considered as safe, nontoxic, and easily absorbed potential drugs. Anti-hypoxia peptides are a kind of peptides that can prevent hypoxia or hypoxia damage. In this paper, the sources, preparations, and molecular mechanisms of anti-hypoxia peptides were systemically reviewed. The combination of bioinformatics, chemical synthesis, enzymatic hydrolysis, and microbial fermentation are recommended for efficient productions of anti-hypoxic peptides. The mechanisms of anti-hypoxic peptides include interference with glycolytic process and HIF-1α pathway, mitochondrial apoptosis, and inflammatory response. In addition, bioinformatics analysis, including virtual screening and molecular docking, provides an alternative or auxiliary method for exploring the potential anti-hypoxic activities and mechanisms of peptides. The potential challenges and prospects of anti-hypoxic peptides are also discussed. This paper can provide references for researchers in this field and promote further research and clinical applications of anti-hypoxic peptides in the future.

Targeting gut-liver axis by dietary lignans ameliorate obesity: evidences and mechanisms.

An imbalance between energy consumption and energy expenditure causes obesity. It is characterized by increased adipose accumulation and accompanied by chronic low-grade inflammation. Many studies have suggested that the gut microbiota of the host mediates the relationship between high-fat diet consumption and the development of obesity. Diet and nutrition of the body are heavily influenced by gut microbiota. The alterations in the microbiota in the gut may have effects on the homeostasis of the host's energy levels, systemic inflammation, lipid metabolism, and insulin sensitivity. The liver is an important organ for fat metabolism and gut-liver axis play important role in the fat metabolism. Gut-liver axis is a bidirectional relationship between the gut and its microbiota and the liver. As essential plant components, lignans have been shown to have different biological functions. Accumulating evidences have suggested that lignans may have lipid-lowering properties. Lignans can regulate the level of the gut microbiota and their metabolites in the host, thereby affecting signaling pathways related to fat synthesis and metabolism. These signaling pathways can make a difference in inhibiting fat accumulation, accelerating energy metabolism, affecting appetite, and inhibiting chronic inflammation. It will provide the groundwork for future studies on the lipid-lowering impact of lignans and the creation of functional meals based on those findings.

Alpha-Glucosidase Inhibitory Peptides: Sources, Preparations, Identifications, and Action Mechanisms.

With the change in people's lifestyle, diabetes has emerged as a chronic disease that poses a serious threat to human health, alongside tumor, cardiovascular, and cerebrovascular diseases. α-glucosidase inhibitors, which are oral drugs, have proven effective in preventing and managing this disease. Studies have suggested that bioactive peptides could serve as a potential source of α-glucosidase inhibitors. These peptides possess certain hypoglycemic activity and can effectively regulate postprandial blood glucose levels by inhibiting α-glucosidase activity, thus intervening and regulating diabetes. This paper provides a systematic summary of the sources, isolation, purification, bioavailability, and possible mechanisms of α-glucosidase inhibitory peptides. The sources of the α-glucosidase inhibitory peptides were introduced with emphasis on animals, plants, and microorganisms. This paper also points out the problems in the research process of α-glucosidase inhibitory peptide, with a view to providing certain theoretical support for the further study of this peptide.

Functional Perspective of Leeks: Active Components, Health Benefits and Action Mechanisms.

Leek (Allium fistulosum L.), a common and widely used food ingredient, is a traditional medicine used in Asia to treat a variety of diseases. Leeks contain a variety of bioactive substances, including sulfur compounds, dietary fiber, steroid compounds and flavonoid compounds. Many studies have shown that these active ingredients produce the following effects: promotion of blood circulation, lowering of cholesterol, relief of fatigue, anti-inflammation, anti-bacteria, regulation of cell metabolism, anti-cancer, anti-oxidation, and the lowering of fat and blood sugar levels. In this paper, the main bioactive components and biological functions of leeks were systemically reviewed, and the action mechanisms of bioactive components were discussed. As a common food, the health benefits of leeks are not well known, and there is no systematic summary of leek investigations. In light of this, it is valuable to review the recent progress and provide reference to investigators in the field, which will promote future applications and investigations of leeks.

Polysaccharides from Phellinus linteus: A systematic review of their extractions, purifications, structures and functions.

Phellinus linteus (P. linteus) is a famous Chinese medicine and has a long history in China. In recent years, P. linteus polysaccharides (PLPs) have attracted extensive attention because of their biological activities such as anti-bacteria, anti-aging, anti-oxidation, anti-inflammation, anti-tumor, hepatoprotective effect and hypoglycemic effect. In this review, we systemically summarized the advances in extractions, purifications and structural characterizations of PLPs, and also analyzed their biological functions and molecular mechanisms. Meanwhile, the structure-activity relationships of PLPs are closely related to their anti-oxidation and anti-tumor activities. So far, the applications of PLPs are still very limited, further exploring structure-activity relationships, biological functions and their mechanisms of PLPs will promote to develop functional foods.

Targeting mTOR Signaling by Dietary Polysaccharides in Cancer Prevention: Advances and Challenges.

Cancer is the most serious problem for public health. Traditional treatments often come with unavoidable side effects. Therefore, the therapeutic effects of natural products with wide sources and low toxicity are attracting more and more attention. Polysaccharides have been shown to have cancer-fighting potential, but the molecular mechanisms remain unclear. The mammalian target of rapamycin (mTOR) pathway has become an attractive target of antitumor therapy research in recent years. The regulation of mTOR pathway not only affects cell proliferation and growth but also has an important effect in tumor metabolism. Recent studies indicate that dietary polysaccharides play a vital role in cancer prevention and treatment by regulating mTOR pathway. Here, the progress in targeting mTOR signaling by dietary polysaccharides in cancer prevention and their molecular mechanisms are systemically summarized. It will promote the understanding of the anticancer effects of polysaccharides and provide reference to investigators of this cutting edge field.

Laminarin ameliorates alcohol-induced liver damage and its molecular mechanism in mice.

Alcoholic liver disease (ALD) has become a health issue globally. Laminarin, a low molecular weight marine-derived ß-glucan, has been identified with multiple biological activities. In this study, the ameliorative effect on ALD of laminarin isolated from brown algae was investigated. Phenotypic, pathological alterations and biochemical characteristics indicated that laminarin administration (100 mg/kg/day) significantly alleviated liver injury and improved liver function in the alcohol-induced mice. Gene chip results indicated that laminarin treatment caused 52 up-regulated and 13 down-regulated genes in the hepatic tissues of alcohol-induced damage mice, and most of these genes are associated with regulation of oxidative stress (such as CYP450/glutathione-dependent antioxidation), Wnt signaling pathway, retinol metabolism, and cAMP pathway based on GO and KEGG analysis. PPI network analysis indicated that the downstream target genes lied in the hub of the net. Our experiments also confirmed the changed expressions of some target genes. Taken together, these results suggest that laminarin can ameliorate alcohol-induced damage in mice and its molecular mechanism lies in modulating anti-oxidation pathway, WNT pathway, and cAMP pathway, which regulate the expressions of downstream target genes and alleviate alcohol-induced damage. Our study provides new clue to prevent alcohol-induced damage and will be benefit to develop functional foods. PRACTICAL APPLICATIONS: This study verified the positive effect on alcoholic liver disease (ALD) of laminarin, a water-soluble brown algae-derived ß-glucan, linked by ß-(1,3) glycosidic bonds with ß-(1,6) branches. Laminarin significantly alleviated liver injury and improved liver function of ALD mice. Moreover, transcriptomics and bioinformatics analysis further revealed the gene expression patterns, hub targets, and signalings including CYP450/glutathione, Wnt, retinol metabolism, cAMP pathways regulated by laminarin. This research is the first evidence for hepatoprotective effect of laminarin against ALD and its molecular mechanism, which will be advantage to develop functional foods or adjuvant therapy of ALD.

Octacosanol Modifies Obesity, Expression Profile and Inflammation Response of Hepatic Tissues in High-Fat Diet Mice.

The incidence of obesity has increased significantly on account of the alterations of living habits, especially changes in eating habits. In this study, we investigated the effect of octacosanol on lipid lowering and its molecular mechanism. High-fat diet (HFD)-induced obesity mouse model was used in the study. Thirty C57BL/6J mice were divided into control, HFD, and HFD+Oct groups randomly, and every group included ten mice. The mice of HFD+Oct group were intragastrically administrated 100 mg/kg/day of octacosanol. After 10 weeks for treatment, our results indicated that octacosanol supplementation decreased the body, liver, and adipose tissues weight of HFD mice; levels of TC, TG, and LDL-c were reduced in the plasma of HFD mice; and level of HDL-c were increased. H&E staining indicated that octacosanol supplementation reduces the size of fat droplets of hepatic tissues and adipose cells comparing with the HFD group. Gene chip analysis found that octacosanol regulated 72 genes involved in lipid metabolism in the tissues of liver comparing to the HFD group. IPA pathway network analysis indicated that PPAR and AMPK may play a pivotal role in the lipid-lowering function of octacosanol. Real-time quantitative PCR and Western blot showed that the octacosanol supplementation caused change of expression levels of AMPK, PPARs, FASN, ACC, SREBP-1c, and SIRT1, which were closely related to lipid metabolism. Taken together, our results suggest that octacosanol supplementation exerts a lipid-decreasing effect in the HFD-fed mice through modulating the lipid metabolism-related signal pathway.

Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.

Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.

Oryzanol alleviates high fat and cholesterol diet-induced hypercholesterolemia associated with the modulation of the gut microbiota in hamsters.

A high fat and cholesterol diet (HFCD) can modulate the gut microbiota, which is closely related with hypercholesterolemia. This study aimed to explore the anti-hypercholesterolemia effect of oryzanol, and investigate whether the function of oryzanol is associated with the gut microbiota and related metabolites. 16S rRNA and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry were applied for the gut microbiota and untargeted metabolomics, respectively. The results showed that HFCD significantly upregulated body fat accumulation and serum lipids, including triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), and ratio of LDL-c/HDL-c, which induced hypercholesterolemia. Oryzanol supplementation decreased body fat accumulation and serum lipids, especially the LDL-c concentration and LDL-c/HDL-c ratio. In addition, the abundances of Desulfovibrio, Colidextribacter, norank_f__Oscillospiraceae, unclassified_f__Erysipelotrichaceae, unclassified_f__Oscillospiraceae, norank_f__Peptococcaceae, Oscillibacter, Bilophila and Harryflintia were increased and the abundance of norank_f__Muribaculaceae was decreased in HFCD-induced hyperlipidemia hamsters. Metabolites were changed after HFCD treatment and 9 differential metabolites belonged to bile acids and 8 differential metabolites belonged to amino acids. Those genera and metabolites were significantly associated with serum lipids. HFCD also disrupted the intestinal barrier. Oryzanol supplementation reversed the changes of the gut microbiota and metabolites, and intestinal barrier injury was also partly relieved. This suggests that oryzanol supplementation modulating the gut microbiota contributes to its anti-hyperlipidemia function, especially anti-hypercholesterolemia.

Targeting AMPK Signaling by Dietary Polyphenols in Cancer Prevention.

Cancer is a serious public health problem in the world and a major disease affecting human health. Dietary polyphenols have shown good potential in the treatment of various cancers. It is worth noting that cancer cells usually exhibit metabolic abnormalities of high glucose intake and inefficient utilization. AMPK is the key molecule in the regulation of energy metabolism and is closely related with obesity and diabetes. Recent studies indicate that AMPK also plays an important role in cancer prevention and regulating cancer-related genes and pathways, and dietary polyphenols can significantly regulate AMPK activity. In this review, the progress of dietary polyphenols preventing carcinogenesis via AMPK pathway is systemically summarized. From the viewpoint of interfering energy metabolism, the anti-cancer effects of dietary polyphenols are explained. AMPK pathway modulated by different dietary polyphenols affects pathways and target genes are summarized. Dietary polyphenols exert anti-cancer effect through the target molecules regulated by AMPK, which broadens the understanding of polyphenols anti-cancer mechanisms and provides value reference for the investigators of the novel field.

Dietary Supplementation of Octacosanol Improves Exercise-Induced Fatigue and Its Molecular Mechanism.

Several publications report that octacosanol (OCT) has different biological functions. This study was designed to evaluate the antifatigue effect and molecular mechanism of octacosanol (200 mg/(kg day)) in forced exercise-induced fatigue models of trained male C57BL/6 mice. Results showed that octacosanol ameliorated the mice's autonomic activities, forelimb grip strength, and swimming endurance, and the levels of liver glycogen (LG), muscle glycogen (MG), blood lactic acid (BLA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also regulated. Gene analysis results showed that treatment with OCT upregulated 29 genes, while 38 genes were downregulated in gastrocnemius tissue. Gene ontology (GO) analyses indicated that these genes enriched functions in relation to myofibril, contractile fiber, and calcium-dependent adenosinetriphosphatase (ATPase) activity. Octacosanol supplementation significantly adjusted the messenger RNA (mRNA) and protein expression levels related to fatigue performance. Octacosanol has an observably mitigating effect in exercise-induced fatigue models, and its molecular mechanism may be related to the regulation of tripartite motif-containing 63 (Trim63), periaxin (Prx), calcium voltage-gated channel subunit α1 H (Cacna1h), and myosin-binding protein C (Mybpc3) expression.