Impact of flavonol extracts derived from green tea or targeted flavonols as secondary ingredients on intestinal glucose transport.

The purpose of the current study was to examine the effect of adding secondary ingredients such as green tea derived water-soluble polysaccharides (GTP) and flavonol aglycone rich fractions derived from cellulase treated green tea extract (FVN) into catechin rich green tea extracts (GTE) on wheat starch digestion and intestinal glucose transport using in vitro digestion with Caco-2 cells. Co-digestion of wheat starch with GTE (16.88 g L-1) or GTE + GTP + FVN (16.69 g L-1) appeared to promote starch hydrolysis compared to control (15.49 g L-1). In case of major flavonoids, addition of epigallocatechin gallate (EGCG), EGCG + myricetin (M) into wheat starch significantly increased the digestion of starch into glucose. Glucose transport rate decreased by 22.35% in wheat starch + GTE + GTP + FVN (1.39%), while the least amount of glucose (1.70%) was transported in EGCG mixed with M (1% of EGCG) as secondary ingredients among individual flavonoids formulation. It indicated that inhibitory effect on glucose transport was higher in addition of GTE, GTP, and FVN as excipients ingredients rather than targeted major flavonoids. Results from the current study suggest that whole green tea including flavonoid rich fractions could enhance hypoglycemic potential of GTE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05140-2.

Characterized Polysaccharides from Green Tea Inhibited Starch Hydrolysis and Glucose Intestinal Uptake by Inducing Microstructural Changes of Wheat Starch.

The purpose of the current study was to investigate the effect of green tea ethanol extract (GTE) and polysaccharide fractions from green tea (PFGs) on the hydrolysis of wheat starch, microstructural changes, and intestinal transport of glucose. The amount of resistant starch (RS) was significantly lowered in the water-soluble polysaccharide (WSP), water-soluble polysaccharide-pectinase (WSP-P), and water-insoluble polysaccharide-alkali soluble (WISP-Alk-Soluble; p < 0.05). The microstructures of gelatinized wheat starch granules with WSP, WSP-P, and WISP-Alk-Soluble were spherical with small cracks. The amount of intestinal transported glucose from digested wheat starch was 2.12-3.50 times lower than the control group. The results from the current study suggest that water- and alkali-soluble PFGs could be potential ingredients to lower starch hydrolysis as well as to control the postprandial blood glucose level when foods that contain starch are consumed.

Profiling of In Vitro Bioaccessibility and Intestinal Uptake of Flavonoids after Consumption of Commonly Available Green Tea Types.

The aim of this study was to profile the bioaccessibility and intestinal absorption of epicatechins and flavonols in different forms of green tea and its formulation: loose leaf tea, powdered tea, 35% catechins containing GTE, and GTE formulated with green tea-derived polysaccharide and flavonols (CATEPLUS™). The bioaccessibillity and intestinal absorption of epicatechins and flavonols was investigated by using an in vitro digestion model system with Caco-2 cells. The bioaccessibility of total epicatechins in loose leaf tea, powdered tea, GTE, and CATEPLUS™ was 1.27%, 2.30%, 22.05%, and 18.72%, respectively, showing that GTE and CATEPLUS™ had significantly higher bioaccessibility than powdered tea and loose leaf tea. None of the flavonols were detected in powdered tea and loose leaf tea, but the bioaccessibility of the total flavonols in GTE and CATEPLUS™ was 85.74% and 66.98%, respectively. The highest intestinal absorption of epicatechins was found in CATEPLUS™ (171.39 ± 5.39 ng/mg protein) followed by GTE (57.38 ± 9.31), powdered tea (3.60 ± 0.67), and loose leaf tea (2.94 ± 1.03). The results from the study suggest that formulating green tea extracts rich in catechins with second components obtained from green tea processing could enhance the bioavailability of epicatechins.

Agrimonia pilosa Ledeb. Ameliorates Hyperglycemia and Hepatic Steatosis in Ovariectomized Rats Fed a High-Fat Diet.

Estrogen deficiency is associated with obesity, dyslipidemia, and increased insulin resistance in postmenopausal women. An efficient therapeutic agent prevents or improves postmenopausal conditions induced by estrogen deficiency. Here, we investigated the effects of aqueous Agrimonia pilosa Ledeb. extract on glucose and lipid metabolism in ovariectomized rats fed a high-fat diet (HFD). Female Sprague-Dawley rats were sham-operated or ovariectomized, and 3 weeks later were assigned to the following groups: sham-operated + HFD (S); ovariectomized + HFD (OVX); and ovariectomized + HFD with 0.5% A. pilosa aqueous extract (OVX + 0.5A) groups. Ovariectomy significantly increased body weight and dietary intake relative to the S group. However, A. pilosa treatment did not significantly affect weight gain or dietary intake. Blood triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol levels tended to decrease in the A. pilosa-supplemented group. Blood glucose levels were significantly lower in the OVX + 0.5A group than those in the OVX group. Blood adiponectin and insulin concentrations increased significantly after A. pilosa treatment in the ovariectomized group. A. pilosa supplementation tended to decrease liver weights and prevented lipid accumulation. These effects correlated with reduced hepatic expression of lipogenesis-related genes (fatty acid synthase, acetyl-coenzyme A carboxylase alpha, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase). Therefore, A. pilosa may improve metabolic disorders in ovariectomized rats.

Hypoglycemic effect of soluble polysaccharide and catechins from green tea on inhibiting intestinal transport of glucose.

BACKGROUND: Water soluble polysaccharide derived from green tea (WSP) is produced as byproducts when catechins were extracted from green tea. Although inhibitory effect of green tea catechins on the glucose transport in small intestine has been studied, the hypoglycemic efficacy of the WSP or its combinational effect has not been studied. In order to investigate hypoglycemic efficacy of the WSP or its combinational effect with green tea extract (GTE), co-consumption of GTE and WSP with wheat starch was investigated using in vitro digestion coupled with Caco-2 cells. The mechanism of the intestinal glucose transport was elucidated throughout the gene expression of the intestinal glucose transporters, which included sodium dependent glucose transporter (SGLT1) and glucose transporter 2 (GLUT2), using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The co-digestion of wheat starch with GTE during the small intestinal phase was the most rapidly digested into reducing sugar (73.96 g L-1 ) compared to itself (48.44 g L-1 ), WSP (60.35 g L-1 ), and GTE + WSP (61.81 g L-1 ). Intestinal glucose transport was 11.82, 7.59, 4.49, and 2.40% for wheat starch, wheat starch with GTE, WSP, and GTE + WSP, respectively. The highest decreased expression pattern in SGLT1 was observed when cells treated with wheat starch + GTE + WSP (0.66-fold) compared to GTE or WSP treatment. CONCLUSION: The results suggested that co-consumption of green tea derived products with wheat starch could delay the intestinal absorption of glucose. Results from the current study suggested that GTE and WSP could be the useful supplements of dietary therapy for hyperglycemia to delay glucose absorption. © 2020 Society of Chemical Industry.

Addition of flavonols and polysaccharides as excipient ingredients into epicatechin rich green tea extract inhibited free radical formation and glucose uptake.

It was revealed that excipient ingredients such as flavonols (FVN) or polysaccharides (GTP) which could be derived from green tea enhanced catechin absorption. We hypothesized that the addition of FVN or GTP as excipient ingredients into epicatechin rich green tea extracts (GTE) may improve the health benefits that accompany its consumption. When FVN8.7 (8.7% of GTE, w/w) was added to the GTE (20 mg) as an excipient ingredient, the bioaccessibility and intestinal absorption of total epicatechins was 1.2 and 1.5 times higher than that of only GTE, respectively. This was due to the free radical scavenging capacity of flavonols, showing 114.23 ± 3.07 µmol TE per g for GTE 100 + FVN8.7 and 113.64 ± 1.61 µmol TE per g for GTE 100 + FVN2, respectively. This was significantly higher than the GTE or GTE 100 + OW2 (onion peel and whangchil extracts, 2% of GTE, w/w) which have the same amount of total flavonols. Regarding potential hypoglycemic effects, co-digestion of GTE (20 mg) + green tea polysaccharides (2 mg) + FVN (5 mg) with wheat starch significantly reduced glucose intestinal absorption by 41.85 ± 1.75% compared to only the wheat starch. The results from the current study suggest that whole green tea components rich in flavonols and polysaccharides could be potential hypoglycemic excipient ingredients for green tea catechins.

Dietary Factors and Eating Behaviors Affecting Diet-Induced Thermogenesis in Obese Individuals: A Systematic Review.

Obese individuals are considered to have lower energy expenditure (EE) rates than non-obese individuals. We aimed to investigate the effects of various factors related to food intake on diet-induced thermogenesis (DIT) in the EE of obese individuals. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed relevant literature from PubMed, Embase, and Medline databases from study inception till the end of July 2019. Studies on dietary factors affecting DIT in obese individuals were included. Fifteen studies were included; these studies assessed macronutrient, single-nutrient, or supplement meal compositions, as well as dietary patterns and behaviors. The effect of obesity on DIT was not constant in each study. Differences in DIT pertained to the protein ratio being higher than the fat ratio or the carbohydrate ratio being higher than the fat ratio. High intake of calcium and vitamin D as well as high-oleic peanut supplements increased DIT in obese people. In addition, ascorbic acid intake, fatty acid saturation, and the chain length of various fatty acids had no effects on DIT. In conclusion, the findings suggest that in obese individuals, DIT is associated with various factors related to meal, nutrient, and dietary habits. However, because of the complexity of the relationship between DIT and obesity, it is difficult to determine the critical element underlying this association.

Carnosic acid attenuates obesity-induced glucose intolerance and hepatic fat accumulation by modulating genes of lipid metabolism in C57BL/6J-ob/ob mice.

BACKGROUND: Carnosic acid (CA), a major bioactive component of rosemary (Rosmarinus officinalis) leaves, is known to possess antioxidant and anti-adipogenic activities. In this study it was hypothesized that CA would ameliorate obesity-induced glucose intolerence and hepatic fat accumulation, and possible mechanisms are suggested. RESULTS: It was observed that a 0.02% (w/w) CA diet effectively decreased body weight, liver weight and blood triglyceride (TG) and total cholesterol levels (P < 0.05) compared with the control diet. CA at 0.02% significantly improved glucose tolerance, and hepatic TG accumulation was reduced in a dose-dependent manner. Hepatic lipogenic-related gene (L-FABP, SCD1 and FAS) expression decreased whereas lipolysis-related gene (CPT1) expression increased in animals fed the 0.02% CA diet (P < 0.05). Long-chain fatty acid content and the ratio of C18:1/C18:0 fatty acids were decreased in adipose tissue of animals fed the 0.02% CA diet (P < 0.05). Serum inflammatory mediators were also decreased significantly in animals fed the 0.02% CA diet compared with those of the obese control group (P < 0.05). CONCLUSION: These results suggest that CA is an effective anti-obesity agent that regulates fatty acid metabolism in C57BL/6J-ob/ob mice.

Nutritional modulators of ulcerative colitis: clinical efficacies and mechanistic view.

Ulcerative colitis (UC) is an inflammation-associated disease of the colon and rectum. The onset and progress of the disease are directly influenced by the nature of the intestinal microflora, the intestinal barrier function, and the immunological responses of the host. The epithelial invasion of pathogenic bacteria due to excess contact and/or barrier dysfunction is related to inflammation mediated by intestinal immune responses. Although the etiology of UC is not clearly understood, recent studies have shown a rising incidence of UC worldwide, and this phenomenon is more prominent in Asian countries and in Asian immigrants in Western countries. The increased prevalence of UC also contributes to an increased risk of developing colorectal cancer. Environmental factors, including changes in dietary habits, have been suggested as major risk factors of UC. A systematic review showed a negative association between UC risk and vegetable intake, whereas total fat, omega-6 fatty acids and meat intake were positively associated with an increased risk of UC. Individual dietary factors and energy balance have been suggested as having important roles in inducing changes in the microbial population and intestinal barrier integrity and in regulating inflammatory immune responses, directly or indirectly. Excess energy intake is now known to increase pathogenic microbial populations. Likewise, the application of appropriate probiotics may reverse the pathogenic progression of the disease. In the meantime, dietary anti-inflammatory compounds, including omega-3 fatty acids and other phytochemicals, may directly suppress inflammatory responses in the course of UC development. In this review, the increased prevalence of UC and its management are interpreted from the standpoint of nutritional modulation to regulate the intestinal microflora population, intestinal epithelium permeability, and inflammatory responses.

Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma.

BACKGROUND: Antioxidants have been suggested to alleviate the pathophysiological features of asthma, and grape seed proanthocyanidin extract (GSPE) has been reported to have powerful antioxidant activity. PURPOSE: This study was performed to determine whether GSPE has a therapeutic effect on allergic airway inflammation in both acute and chronic murine model of asthma. METHODS: Acute asthma model was generated by intraperitoneal sensitization of ovalbumin (OVA) with alum followed by aerosolized OVA challenges, whereas chronic asthma model was induced by repeated intranasal challenges of OVA with fungal protease twice a week for 8 weeks. GSPE was administered by either intraperitoneal injection or oral gavage before OVA challenges. Airway hyperresponsiveness (AHR) was measured, and airway inflammation was evaluated by bronchoalveolar lavage (BAL) fluid analysis and histopathological examination of lung tissue. Lung tissue levels of various cytokines, chemokines, and growth factors were analyzed by quantitative polymerase chain reaction and ELISA. Glutathione assay was done to measure oxidative burden in lung tissue. RESULTS: Compared to untreated asthmatic mice, mice treated with GSPE showed significantly reduced AHR, decreased inflammatory cells in the BAL fluid, reduced lung inflammation, and decreased IL-4, IL-5, IL-13, and eotaxin-1 expression in both acute and chronic asthma models. Moreover, airway subepithelial fibrosis was reduced in the lung tissue of GSPE-treated chronic asthmatic mice compared to untreated asthmatic mice. Reduced to oxidized glutathione (GSH/GSSG) ratio was increased after GSPE treatment in acute asthmatic lung tissue. CONCLUSION: GSPE effectively suppressed inflammation in both acute and chronic mouse models of asthma, suggesting a potential role of GSPE as a therapeutic agent for asthma.

Dietary aloin, aloesin, or aloe-gel exerts anti-inflammatory activity in a rat colitis model.

AIMS: Aloe has been a very popular folk remedy for inflammation-related pathological conditions despite the lack of studies reporting its efficacy in vivo. The present study evaluated the anti-inflammatory effects of aloe components (aloin, aloesin and aloe-gel) known to be biologically active in the rat model of colitis. MAIN METHODS: Male Sprague Dawley rats were fed experimental diets for 2 weeks before and during the induction of colitis. Drinking water containing 3% dextran sulfate sodium (DSS) was provided for 1 week to induce colitis. At the end of the experimental period, clinical and biochemical markers were compared. KEY FINDINGS: Plasma leukotriene B(4) (LTB(4)) and tumor necrosis factor-α (TNF-α) concentrations were significantly decreased in all groups supplemented with aloe components compared to the colitis control group (p<0.05). Animals fed both a 0.1% and 0.5% aloesin supplemented diet showed colonic myeloperoxidase (MPO) activities which were decreased by 32.2% and 40.1%, respectively (p<0.05). Colonic mucosa TNF-α and interleukin-1ß (IL-1ß) mRNA expressions were significantly reduced in all animals fed aloin, aloesin, or aloe-gel (p<0.05). SIGNIFICANCE: Dietary supplementation of aloe components ameliorates intestinal inflammatory responses in a DSS-induced ulcerative colitis rat model. In particular, aloesin was the most potent inhibitor. Further studies are required for a more complete understanding of the specific mechanism of the action of these supplements.

Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase.

In an effort to find chemicals inhibiting the enzymatic activity of the hepatitis C virus (HCV) NS5B polymerase, a series of thiobarbituric acid derivatives were selected from a library provided by Korea Research Institute of Chemical Technology and characterized. The selected compounds exhibited IC50 values ranging from 1.7 to 3.8 µM, and EC50 values ranging from 12.3 to 20.7 µM against NS5B polymerase of type 1b strain. They showed little effect against type 2a polymerase. One of the compounds, G05, was selected and further characterized. It inhibited the synthesis of RNA by recombinant HCV NS5B polymerase in a dose dependent manner. The CC50 value was 77 µM. The inhibition was in a noncompetitive manner with the substrate UTP. The compound did not inhibit the elongation step of RNA synthesis in a single-cycle processive polymerization assay. It inhibited the binding of NS5B polymerase to the template RNA in a dose-dependent manner.

HMCO5, herbal extract, inhibits NF-kappaB expression in lipopolysaccharide treated macrophages and reduces atherosclerotic lesions in cholesterol fed mice.

HMCO5 is a herbal extract which comprises of eight different herbs. We studied whether this extract has anti-atherosclerotic effects. In lipopolysaccharide (LPS) stimulated RAW264.7 cells, HMCO5 inhibited NF-kappaB activation as well as iNOS promoter activity, inhibited the secretion of TNF-alpha and IL-1beta, and directly inhibited the intracellular accumulation of reactive oxygen species. ApoE knock-out mice fed a high-fat high-cholesterol diet with HMCO5 for 10 weeks showed a significant reduction in atherosclerotic lesions. A notable finding was the preservation of the smooth muscle cell layer in the media of aorta in the HMCO5 co-treated mice. HMCO5 treated mice did not show significant decrease in serum level of cholesterol. These results suggest that HMCO5 has anti-atherosclerotic effects which in part may be attributable to the inhibition of production of NF-kappaB dependent pro-inflammatory cytokines.

Effects of dietary mulberry, Korean red ginseng, and banaba on glucose homeostasis in relation to PPAR-alpha, PPAR-gamma, and LPL mRNA expressions.

Despite lack of scientific evidences to support its therapeutic efficacy, the use of herbal supplements has significantly increased. The purpose of this study was to evaluate the effects of traditional anti-diabetic herbs on the progress of diabetes in db/db mice, a typical non-insulin-dependent model. Five different experimental diets were as follows: control diet, 0.5% mulberry leaf water extract diet, 0.5% Korean red ginseng diet, 0.5% banaba leaf water extract diet, and 0.5% combination diet (mulberry leaf water extract/Korean red ginseng/banaba leaf water extract, 1:1:1). Blood levels of glucose, insulin, HbA1c, and triglyceride were measured every 2 weeks. At 12 weeks of age, animals were sacrificed, and tissue mRNA levels of PPAR-alpha, PPAR-gamma, and LPL were determined. Results indicated that mulberry leaf water extract, Korean red ginseng, banaba leaf water extract, and the combination of above herbs effectively reduced blood glucose, insulin, TG, and percent HbA1c in study animals (p<0.05). We also observed that the increased expressions of liver PPAR-alpha mRNA and adipose tissue PPAR-gamma mRNA in animals fed diets supplemented with test herbs. The expression of liver LPL mRNA was also increased with experimental diets containing herbs. The efficacy was highest in animals fed the combination diet for all of the markers used. These results suggest that mulberry leaf water extract, Korean red ginseng, banaba leaf water extract, and the combination of these herbs fed at the level of 0.5% of the diet significantly increase insulin sensitivity, and improve hyperglycemia possibly through regulating PPAR-mediated lipid metabolism.