Selected coffee (Coffea arabica L.) extracts inhibit intestinal α-glucosidases activities in-vitro and postprandial hyperglycemia in SD Rats.

One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes, α-amylase, and α-glucosidases, in the digestive organs. Coffee consumption has been reported to beneficial effects for controlling calorie and cardiovascular diseases, however, the clear efficacy and mode of action are yet to be proved well. Therefore, in this study we evaluated in- vitro rat intestinal α-glucosidases and porcine α-amylase inhibitory activities as well as in vivo (Sprague-Dawley rat model) blood glucose lowering effects of selected coffee extracts. The water extracted Sumatra coffee (SWE) showed strong α-glucosidase inhibitory activity (IC50, 4.39 mg/mL) in a dose-dependent manner followed by Ethiopian water extract (EWE) (IC50, 4.97) and Guatemala water extract (GWE) (IC50, 5.19). Excepted for GWE all the coffee types significantly reduced the plasma glucose level at 0.5 h after oral intake (0.5 g/kg-body weight) in sucrose and starch-loaded SD rats. In sucrose loading test SWE (p < 0.001) and EWE (p < 0.05) had significantly postprandial blood glucose reduction effect, when compared to control. The maximum blood glucose levels (Cmax) of EWE administration group were decreased by about 18% (from 222.3 ± 16.0 to 182.5 ± 15.4, p < 0.01) and 19% (from 236.2 ± 25.1 to 191.3 ± 13.2 h·mg/dL, p < 0.01) in sucrose and starch loading tests, respectively. These results indicate that selected coffee extract may improve exaggerated postprandial spikes in blood glucose via inhibition of intestinal sucrase and thus delays carbohydrate absorption. These in vitro and in vivo studies therefore could provide the biochemical rationale for the benefit of coffee-based dietary supplement and the basis for further clinical study.

Anti-Obesity and Anti-Adipogenic Effects of Administration of Arginyl-Fructose-Enriched Jeju Barley (Hordeum vulgare L.) Extract in C57BL/6 Mice and in 3T3-L1 Preadipocytes Models.

In our previous study, we reported that arginyl-fructose (AF), one of the Amadori rearrangement compounds (ARCs) produced by the heat processing of Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. This reduced absorption of carbohydrate might be helpful to control body weight gain due to excessive carbohydrate consumption and support induced calorie restriction. However, the weight management effect, except for the effect due to anti-hyperglycemic action, along with the potential mechanism of action have not yet been determined. Therefore, the efforts of this study are to investigate and understand the possible weight management effect and mechanism action of AF-enriched barley extracts (BEE). More specifically, the effect of BEE on lipid accumulation and adipogenic gene expression, body weight gain, body weight, plasma lipids, body fat mass, and lipid deposition were evaluated using C57BL/6 mice and 3T3-L1 preadipocytes models. The formation of lipid droplets in the 3T3-L1 treated with BEE (500 and 750 µg/mL) was significantly blocked (p < 0.05 and p < 0.01, respectively). Male C57BL/6 mice were fed a high-fat diet (30% fat) for 8 weeks with BEE (0.3 g/kg-body weight). Compared to the high fat diet control (HFD) group, the cells treated with BEE significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (CEBP/α), the mRNA expression of downstream lipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), and sterol regulatory element-binding protein 1c (SREBP-1c). Supplementation of BEE effectively lowered the body weight gain, visceral fat accumulation, and plasma lipid concentrations. Compared to the HFD group, BEE significantly suppressed body weight gain (16.06 ± 2.44 g vs. 9.40 ± 1.39 g, p < 0.01) and increased serum adiponectin levels, significantly, 1.6-folder higher than the control group. These results indicate that AF-enriched barley extracts may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

Immune Modulatory Activities of Arginyl-Fructose (AF) and AF-Enriched Natural Products in In-Vitro and In-Vivo Animal Models.

The immune system plays an important role in maintaining body homeostasis. Recent studies on the immune-enhancing effects of ginseng saponins have revealed more diverse mechanisms of action. Maillard reaction that occurs during the manufacturing processes of red ginseng produces a large amount of Amadori rearrangement compounds (ARCs), such as arginyl-fructose (AF). The antioxidant and anti-hyperglycemic effects of AF have been reported. However, the possible immune enhancing effects of non-saponin ginseng compounds, such as AF, have not been investigated. In this study the effects of AF and AF-enriched natural product (Ginofos, GF) on proliferation of normal mouse splenocytes were evaluated in vitro and male BALB/c mice models. The proliferation of splenocytes treated with mitogens (concanavalin A, lipopolysaccharide) were further increased by addition of AF (p < 0.01) or GF (p < 0.01), in a dose dependent manner. After the 10 days of oral administration of compounds, changes in weights of spleen and thymus, serum immunoglobulin, and expression of cytokines were measured as biomarkers of immune-enhancing potential in male BALB/c mice model. The AF or GF treated groups had higher weights of the thymus (0.94 ± 0.25 and 0.86 ± 0.18, p < 0.05, respectively) than that of cyclophosphamide treated group (0.59 ± 0.18). This result indicates that AF or AF-enriched extract (GF) increased humoral immunity against CY-induced immunosuppression. In addition, immunoglobulin contents and expression of cytokines including IgM (p < 0.01), IgG (p < 0.05), IL-2 (p < 0.01), IL-4 (p < 0.01), IL-6 (p < 0.01), and IFN-γ (p < 0.05) were also significantly increased by supplementation of AF or GF. These results indicate that AF has immune enhancing effects by activation of adaptive immunity via increase of expression of immunoglobulins and cytokines such as IgM, IgG, IL-2, IL-4, IL-6 and thereby proliferating the weight of thymus. Our findings provide a pharmacological rationale for AF-enriched natural products such as ginseng and red ginseng that can possibly have immune-enhancement potential and should be further evaluated.

In Vitro and in Vivo Anti-Hyperglycemic Activities of Taxifolin and Its Derivatives Isolated from Pigmented Rice (Oryzae sativa L. cv. Superhongmi).

Superhongmi is a new rice variety, which was developed for the enrichment of bioactive compounds through cross-breeding three varieties of rice breeds in Korea. The high-performance liquid chromatography coupled with a photodiode array detector quadrupole and tandem time-of-flight mass spectrometry (HPLC/PDA/QTOF-MS) analysis has revealed that superhongmi bran extract contained four taxifolin derivatives as well as cyanidin 3-glucoside. The high-performance countercurrent chromatography (CCC) and reversed-phase HPLC led to the isolation of aforementioned five compounds, and spectroscopic analysis identified cyanidin 3-glucoside (1), along with (2R,3R)-taxifolin 3-O-ß-d-glucopyranoside (2), (2R,3R)-4'-O-methyltaxifolin 3-O-ß-d-glucopyranoside (a novel compound) (3), (2R,3R)-taxifolin (4), and (2R,3R)-4'-O-methyltaxifolin (5). Compound 2 had the highest rat small intestinal sucrase inhibitory activity (0.54 mM) relevant for potentially managing postprandial hyperglycemia, followed by compound 1 (0.97 mM) and compound 4 (1.74 mM, IC50). The anti-hyperglycemic effect of compound 4 (taxifolin), a main peak in HPLC analysis was investigated using a Sprague-Dawley (SD) rat model. Compared to a control, taxifolin treatment (p < 0.001) reduced significantly after sucrose loading the observed postprandial blood glucose and the maximum blood glucose (Cmax) by 15% (203.60 ± 15.86 to 172.30 ± 12.74). These results indicate that taxifolin derivatives that inhibit the activity of carbohydrate-hydrolyzing enzymes resulting in reduced dietary carbohydrate absorption can potentially be used as a strategy to manage diabetes.

Active compound chrysophanol of Cassia tora seeds suppresses heat-induced lipogenesis via inactivation of JNK/p38 MAPK signaling in human sebocytes.

BACKGROUND: Heat induced by infrared (IR) radiation from sun exposure increases skin temperature and can lead to thermal and photo-aging. However, little is known about the relationship between heat induced by IR radiation and lipid biosynthesis in human sebocytes. This study investigated the expression of factors involved in lipid biosynthesis in human sebocytes exposed to heat. The effect of Cassia tora extract and chrysophanol, which is widely used as anti-inflammatory agent, on the heat shock effect in sebocytes was then examined. METHODS: For the treatment, cells were maintained in culture medium without FBS (i.e., serum starved) for 6 h and then moved for 30 min to incubators at 37 °C (control), 41 °C, or 44 °C (heat shock). Culture media were replaced with fresh media without FBS. To investigate expression of gene and signaling pathway, we performed western blotting. Lipid levels were assessed by Nile red staining. The cytokine levels were measured by cytokine array and ELISA kit. RESULTS: We found that peroxisome proliferator-activated receptor (PPAR)γ and fatty acid synthase (FAS) were upregulated and the c-Jun N-terminal kinase (JNK)/p38 signaling pathways were activated in human sebocytes following heat exposure. Treatment with Cassia tora seed extract and chrysophanol suppressed this up-regulation of PPARγ and FAS and also suppressed the increase in IL-1ß levels. CONCLUSION: These findings provide evidence that IR radiation can stimulate sebum production; Cassia tora seed extract and chrysophanol can reverse lipid stimulated inflammatory mediation, and may therefore be useful for treating skin disorders such as acne vulgaris.

Inhibition of Osteoarthritis-Related Molecules by Isomucronulatol 7-O-ß-d-glucoside and Ecliptasaponin A in IL-1ß-Stimulated Chondrosarcoma Cell Model.

Osteoarthritis (OA) is the common form of arthritis and is characterized by disability and cartilage degradation. Although natural product extracts have been reported to have anti-osteoarthritic effects, the potential bioactivity of Ryupunghwan (RPH), a traditional Korean medicinal botanical formula that contains Astragalus membranaceus, Turnera diffusa, Achyranthes bidentata, Angelica gigas, Eclipta prostrata, Eucommia ulmoides, and Ilex paraguariensis, is not known well. Therefore, the inhibitory effects of single compounds isolated from RPH on the OA-related molecules were investigated using IL-1ß-stimulated chondrosarcoma SW1353 (SW1353) cell model. Two bioactive compounds, isomucronulatol 7-O-ß-d-glucoside (IMG) and ecliptasaponin A (ES) were isolated and purified from RPH using column chromatography, and then the structures were analyzed using ESI-MS, ¹H-NMR, and 13C-NMR spectrum. The expression or amount of matrix metalloproteinase 13 (MMP13), COX1/2, TNF-α, IL-1ß or p65 was determined by RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA). RPH pretreatment reduced the expression and amounts of MMP13, and the expression of collagen II, COX1/2, TNF-α, IL-1ß or p65, which were increased in IL-1ß-stimulated SW1353 cells. IMG reduced the expression of all OA-related molecules, but the observed inhibitory effect was less than that of RPH extract. The other single compound ES showed the reduced expression of all OA-related molecules, and the effect was stronger than that in IMG (approximately 100 fold). Combination pretreatment of both single components remarkably reduced the expression of MMP13, compared to each single component. These synergic effects may provide potential molecular modes of action for the anti-osteoarthritic effects of RPH observed in clinical and animal studies.