Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway.

Natural polysaccharides (NPs) possess numerous health-promoting effects, such as liver protection, kidney protection, lung protection, neuroprotection, cardioprotection, gastrointestinal protection, anti-oxidation, anti-diabetic, and anti-aging. Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway is an important endogenous antioxidant pathway, which plays crucial roles in maintaining human health as its protection against oxidative stress. Accumulating evidence suggested that Nrf2 antioxidant pathway might be one of key regulatory targets for the health-promoting effects of NPs. However, the information concerning regulation of NPs on Nrf2 antioxidant pathway is scattered, and NPs show different regulatory behaviors in their different health-promoting processes. Therefore, in this article, structural features of NPs having regulation on Nrf2 antioxidant pathway are overviewed. Moreover, regulatory effects of NPs on this pathway for health-promoting effects are summarized. Furthermore, structure-activity relationship of NPs for health-promoting effects by regulating the pathway is preliminarily discussed. Otherwise, the prospects on future work for regulation of NPs on this pathway are proposed. This review is beneficial to well-understanding of underlying mechanisms for health-promoting effects of NPs from the view angle of Nrf2 antioxidant pathway, and provides a theoretical basis for the development and utilization of NPs in promoting human health.

Nano-encapsulation of polyphenols in starch nanoparticles: fabrication, characterization and evaluation.

Nanoparticles are more promising than microcapsules as drug carriers because they can be absorbed directly by intestinal epithelial cells, significantly increasing the uptake and bioaccessibility of polyphenols. Our study aimed to use catechin (CC), epicatechin (EC) and proanthocyanidin (PAC) adsorption onto tapioca starch nanoparticles (TSNs), which were prepared by a physical method. These TSN loaded-polyphenols were subjected to adsorption kinetic, adsorption isotherm, adsorption capacity, antioxidant activity, and in vitro release analyses. The maximum adsorption capacities of TSNs for CC, EC and PACs were 179.39 mg g-1, 109.29 mg g-1 and 287.19 mg g-1, respectively. The adsorption dynamics and isotherms of polyphenols on TSNs conformed well to the pseudo-second-order kinetics and the Freundlich isotherms. Moreover, TSN loaded-polyphenols have low cytotoxicity and can continuously be released under stimulated gastric and intestinal conditions. Antioxidant activity tests showed that TSN loaded-polyphenols can remarkably scavenge DPPH free radicals; the IC50 of TSNs-CC, TSNs-EC and TSNs-PAC were 16.11, 16.59 and 16.93 µg mL-1, respectively.

Comparative study on physicochemical characteristics, α-glucosidase inhibitory effect, and hypoglycemic activity of pectins from normal and Huanglongbing-infected navel orange peels.

This study aimed at comparing the physicochemical characteristics, α-glucosidase inhibitory effect, and hypoglycemic activity of pectins (N-NOP and H-NOP) from peels of normal and Huanglongbing (HLB)-infected Navel oranges. Results indicated the pectins were high methoxy pectins mainly composed of homogalacturonan and rhamnogalacturonan-I. The pectins exhibited similar functional groups, surface morphology, and particle size, and had no triple-helical conformation in solution. They exerted fat and glucose absorption capacities and were mixed-type noncompetitive α-glucosidase inhibitors with IC50 values of 1.182 and 2.524 mg/ml, respectively. Both N-NOP and H-NOP showed hypoglycemic activity in alloxan-induced diabetic mice. Administration of them could promote the synthesis of hepatic glycogen and/or serum insulin to lower blood glucose levels and enhance antioxidant status to alleviate oxidative stress injury in diabetic mice. Moreover, N-NOP had higher yield, molecular weight, ζ-potential, oil holding capacity, α-glucosidase inhibitory effect and in vivo hypoglycemic activity, whereas H-NOP possessed higher uronic acid, degree of esterification, thermal stability, water holding capacity, swelling capacity, and fat absorption capacity. It could be concluded that some similarities and differences existed between N-NOP and H-NOP in physicochemical characteristics, functional properties, α-glucosidase inhibitory effects, and hypoglycemic activity. This study provides references for the basic research and application of pectins from peels of normal and HLB-infected Navel oranges. PRACTICAL APPLICATIONS: Pectin has been widely used in the food and pharmaceutical industries for several decades due to its health benefit, gelling, thickening, and emulsification performances. Diabetes mellitus is a worldwide concern in recent years. Pectins (N-NOP and H-NOP) from peels of normal and Huanglongbing (HLB)-infected Navel oranges possessed in vitro and in vivo hypoglycemic activities, indicating they were potential anti-antidiabetic substitutes of chemical drugs. Moreover, comparative understanding on the physicochemical characteristic, α-glucosidase inhibitory effect and hypoglycemic activity of pectins from peels of normal and Huanglongbing-infected Navel oranges was conducive to the recycling and utilization of Navel orange peels. Recently, the biological activity of pectin from peels of normal Navel oranges has been rarely reported, and the information on pectin from peels of Huanglongbing-infected Navel orange is rare. This study provides references for the basic research and application of pectins from peels of normal and HLB-infected Navel oranges.

Comparison of phytochemical profiles, antioxidant and antiproliferative activities in Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruits.

Here, we examined the phytochemical profiles, antioxidant activity (AA), and antiproliferative activity (APA) of four Chinese bayberry (Myrica rubra Sieb. et Zucc.) pulp extracts. They were found to be rich in total phenolics content (TPC; 186.45 ± 5.42 to 498.94 ± 8.25 mg of gallic acid equiv./100 g FW) and total flavonoids content (TFC; 126.28 ± 4.18 to 194.35 ± 12.03 mg of catechin equiv./100 g FW). For all varieties, the free flavonoid/phenolic/anthocyanin contents were higher than that the bound fractions. Wild pink bayberry (WPB) displayed the highest values of TPC and TFC, and also showed the highest total antioxidant activity (TAA) as revealed by peroxyl radical scavenging capacity (PSC) (451.47 ± 8.01 µmol Vit. C equiv./100 g FW), and free cellular antioxidant activity (CAA) (184.99 ± 6.11 µmol quercetin equiv./100 g FW, no PBS wash; 117.78 ± 2.34 µmol quercetin equiv./100 g FW, PBS wash) assays. Bayberry extracts had a marked reduction in the APA of HepG2 cells, and WPB exhibited the lowest EC50 (8.50 ± 0.83 mg/ml) value, which was probably associated with cell cycle arrest and apoptosis induction. PRACTICAL APPLICATION: Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit is rich in natural phenolic compounds, which might be a functional ingredient in food and nutraceutical products. Our findings would provide a logical strategy to promote the comprehensive utilization of phenolics in bayberry fruit with both health and economy benefits.

Wild pink bayberry fruit: the effect of in vitro gastrointestinal digestion on phytochemical profiles, and antioxidant and antiproliferative activities.

The regular consumption of polyphenol-rich foods is essential to prevent the onset of diseases. Wild fruits are known to possess higher levels of bioactive components than the domesticated fruits because of the severe environmental conditions they are grown in. The aim of this study was to evaluate the phytochemical profiles, and antioxidant and antiproliferative activities of a wild pink bayberry fruit after in vitro digestion and to compare them with results obtained with a chemical extraction method. A low release of total phenolics and anthocyanins was observed after digestion compared with chemical extraction, while more flavonol contents were found by HPLC analysis. The digesta samples demonstrated low levels of extracellular antioxidant activity (EAA) and cellular antioxidant activity (CAA). However, the cellular uptake rate was increased during the in vitro digestion, and the largest value of 75.35% was obtained in the colon step. Notably, the antiproliferative activity in the colon digesta (10.14 ± 0.13 mg mL-1) was close to that of extracts (7.6 ± 0.63 mg mL-1). Pearson correlation analysis revealed that EAA and CAA were significantly correlated with TPC, while the antiproliferative activity was significantly correlated with the total contents of three flavonol compounds (quercetin, kaempferol, and myricetin). Our observations provide new insights into the bioactivity variation of whole fruits as affected by simulated digestion.

Effects of α-casein and ß-casein on the stability, antioxidant activity and bioaccessibility of blueberry anthocyanins with an in vitro simulated digestion.

Blueberry anthocyanins are well-known for their diverse biological functions. However, the instability during digestion results in their weak bioavailability. The current study aimed to investigate the alteration in the stability, antioxidant capacity and bioaccessibility of blueberry anthocyanins with the addition of α-casein and ß-casein in a simulated digestion system using pH differential method, HPLC-MS analysis, peroxyl scavenging capacity (PSC) assay, cellular antioxidant activity (CAA) and penetration test. The results showed that both α-casein and ß-casein could increase the stability of blueberry anthocyanins during intestinal digestion and protect their antioxidant capacity. Moreover, the addition of α-casein or ß-casein would enhance the bioaccessibility of blueberry anthocyanins. In conclusion, our study highlights that the interaction between α-casein or ß-casein with blueberry anthocyanins can protect the compounds against influences associated with the simulated digestion.

Bioactive flavonoids from Rubus corchorifolius inhibit α-glucosidase and α-amylase to improve postprandial hyperglycemia.

This research established an optimized method for the extraction and enrichment of flavonoids from R. corchorifolius fruit. Under the optimized extraction conditions, 12 flavonoids (1-12) were isolated, of which six (2-4, 9-10, 12) were obtained from R. corchorifolius for the first time. Compound 4 showed significant α-glucosidase (4.96 µM) and α-amylase (8.04 µM) inhibitory effects. Molecular modeling revealed that compound 4 exhibits strong binding with the active sites of α-glucosidase and α-amylase. Lineweaver-Burk plot analysis and surface plasmon resonance revealed the possible dynamic binding mechanism of the flavonoids with α-glucosidase and α-amylase. The enriched flavonoids and compound 4 showed significant hypoglycemic effects in mice administered a high dose of glucose. In this study, a variety of flavonoids with hypoglycemic activity were found for the first time, revealing the rich chemical composition of R. corchorifolius fruit and highlighting the potential value of R. corchorifolius fruit flavonoids as dietary supplements.

Serum Ceramide Reduction by Blueberry Anthocyanin-Rich Extract Alleviates Insulin Resistance in Hyperlipidemia Mice.

Blueberry anthocyanin-rich extract (BAE) was supplemented to high-fat diet (HFD)-fed mice to investigate sphingolipid metabolism modulating factors involved in the attenuated hyperinsulinemia and hyperlipidemia. A BAE-containing diet effectively controlled food intake and liver weight and significantly attenuated insulin resistance triggered by a HFD. Higher BAE (200 mg/kg of body weight) administration performed more efficiently in the improvement of hepatic steatosis and adipocyte hypertrophy, together with distinct suppressions in serum triacylglycerol and cholesterol in total and species. Serum lipid compositions revealed 200 mg/kg of BAE supplementation remarkably suppressed ceramide accumulation. Consistently, genes encoding enzymes associated with sphingomyelin conversion and ceramide de novo synthesis were modulated toward a healthy direction for restrained sphingolipid accumulation. Further, the inhibited mRNA expressions of protein phosphatase 2A and protein kinase Cζ involved in blocking Akt phosphorylation connected the controlled ceramides with the restored insulin sensitivity.

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress-Induced Intestinal Environment Imbalance and Lipopolysaccharide-Induced Liver Injury in HFD-Fed Rats by Regulating the Nrf2/HO-1/NQO1 and MAPK Pathways.

SCOPE: This study investigates the modulatory effects of Lonicera caerulea L. polyphenols (LCPs) on the intestinal environment and lipopolysaccharide (LPS)-induced liver injury via the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (HO-1)/NQO1 and mitogen-activated protein kinase (MAPK) pathways in a rat model of oxidative stress damage (OSD). METHODS AND RESULTS: To examine the prebiotic properties of LCP, a model of high-fat-diet-induced OSD is established using Sprague Dawley rats. In the colon, treatment with LCP for 8 weeks ameliorates enhanced intestinal permeability (glucagon-like peptide-2 content and occludin protein increase, whereas claudin-2 protein decreases), intestinal inflammation (levels of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nuclear factor kappa-B p65 (NF-κB p65), decrease), and intestinal OSD (through regulation of the Nrf2/HO-1/NQO1 pathway). Moreover, LCP alleviates LPS-induced liver injury by suppressing the nuclear translocation of NF-κB p65 and activation of the MAPK signaling pathway. Additionally, Bacilli, Lactobacillales, Lactobacillaceae, Lactobacillus, Akkermansia, Actinobacteria, Proteobacteria, Rothia, and Blautia are found to be the key intestinal microbial taxa related to intestinal OSD and LPS-induced liver injury in rats. CONCLUSION: LCP treatment potentially modulates the intestinal environment and alleviates liver injury by suppressing oxidative-stress-related pathways and altering the composition of the intestinal microbiota.

Blueberry Malvidin-3-galactoside Suppresses Hepatocellular Carcinoma by Regulating Apoptosis, Proliferation, and Metastasis Pathways In Vivo and In Vitro.

Anthocyanin, a natural antioxidant, is reported to have cytotoxicity against cancer cells; however, the mechanism remains unclear. The aim of the present study was to investigate the mechanism by which malvidin-3-galactoside (M3G), the prominent anthocyanin in blueberry, suppresses the development of hepatocellular carcinoma. In vitro, M3G suppressed the proliferation, polarization, migration, and invasion activities of HepG2 cells by regulating the protein expression of cyclin D1, cyclin B, cyclin E, caspase-3, cleaved caspase-3, Bax, p-JNK, and p-p38, activating phosphatase and tensin homologue deleted on chromosome 10 (PTEN), accompanied by a decrease in the p-AKT level, and lowering the protein expression levels of MMP-2 and MMP-9. In vivo, M3G promoted the apoptosis of liver tumor cells, as determined by immunohistochemistry (cleaved caspase-3, Ki-67, PTEN, and p-AKT), a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and hematoxylin-eosin staining. Overall, these results suggest that M3G, as an adjuvant ingredient or nutritional supplement, may be beneficial for liver cancer prevention and the modulatory mechanism seems to be associated with inhibition of proliferation, apoptosis, migration, and invasion-related pathways.

Hydrothermal stability of phenolic extracts of brown rice.

The phenolics were extracted and purified from brown rice and twenty-seven compounds were identified, including six phenolic acids, four phenolic acid glycosides, and eight flavonoid glycosides. Afterwards, the hydrothermal stability of phenolic extracts of brown rice was investigated after treatment at 60, 80, or 100 °C for 120 min. After hydrothermal treatment, ferulic acid, p-coumaric acid and free glucose were increased, while the phenolic glycosides were decreased. In addition, the total phenolic and total flavonoid content were decreased by 5.7%-9.2% and 3.5%-5.8% after initial 30 min, and then they were slightly recovered after treatment for 120 min. Consequently, there was a slight reduction (<10%) in the total antioxidant activity of the phenolic extracts after hydrothermal treatment. These results suggest that hydrothermal treatment of phenolic extracts of brown rice made some phenolic glycosides deglycosylated, but does not lead to a large reduction in their overall antioxidant activity.

Identification of Cyanidin-3-arabinoside Extracted from Blueberry as a Selective Protein Tyrosine Phosphatase 1B Inhibitor.

Protein tyrosine phosphatase 1B (PTP1B) is an important target for type 2 diabetes. PTP1B inhibitors can reduce blood glucose levels by increasing insulin sensitivity. Anthocyanins often play a hypoglycemic effect, but the research about them have mainly focused on glucosidase. At present, the research about protein tyrosine phosphatase 1B (PTP1B) target is less, and the corresponding molecular mechanism is still unclear. Therefore, in this present study, anthocyanins isolated from blueberry were used to study the inhibitory activity on PTP1B. The isolated cyanidin-3-arabinoside (Cya-3-Ara) exhibited a better inhibitory activity with IC50 = 8.91 ± 0.63 µM, which was higher than the positive control (oleanolic acid, IC50 = 13.9 ± 1.01 µM), and the mechanism of PTP1B inhibition was reversible mixed pattern. The structure-activity relationship (SAR) between anthocyanins and PTP1B inhibition was investigated. The enzyme activity inhibition and molecular docking showed that anthocyanins had high selectivity for PTP1B inhibition. Further study showed that Cya-3-Ara could promote glycogen synthesis through ameliorating PTP1B-involved IRS-1/PI3K/Akt/GSK3ß pathways. Cya-3-Ara could also be regarded as a synergistic inhibitor (CI ≤ 0.54) of oleanolic acid to obtain a better inhibitory effect on PTP1B. Taken together, our study clearly illustrates the SAR between anthocyanins and PTP1B inhibition and the mechanism of Cya-3-Ara in the insulin signaling pathway.

The Profile and Bioaccessibility of Phenolic Compounds in Cereals Influenced by Improved Extrusion Cooking Treatment.

The aim of this study was to investigate the effect of Improved Extrusion Cooking Treatment (IECT) on the phenolics and its bioaccessibility in cereals, represented by brown rice, wheat, and oat. Data showed that total phenolic content and total antioxidant activity in free form were significantly decreased, while the bound form was increased after IECT. After IECT, the total free phenolic acids of brown rice and wheat were significantly decreased by 5.88% and 45.66%, respectively, while the total bound phenolic acids of brown rice, wheat, and oat were significantly increased by 6.45%, 8.78%, and 9.10%, respectively. Brown rice provided the most bioaccessible phenolics and antioxidant compounds, followed by oat and wheat. IECT significantly decreased the bioaccessible phenolics of brown rice and oat by 31.09% and 30.95%, while it had minimal effect on the bioaccessible phenolics of wheat. These results showed that IECT greatly affected the phenolics and its bioaccessibiltiy of cereals, with the effect depending on cereal matrix and the sensitivity of free and bound phenolics. Furthermore, bioaccessible phenolic acids of raw and processed cereals were considerably low, and it slightly contributed to the bioaccessible phenolics.