Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model.

Background: Euonymus alatus (Thunb.) Siebold (EA) is a medicinal plant used in some Asian countries to treat various diseases, including cancer, hyperglycemia, diabetes, urticaria, dysmenorrhea, and arthritis. Owing to the wide range of pharmacological applications of EA, various roles of EA are being studied. Objective: We evaluated the immune-enhancing effect of EA treatment in a cyclophosphamide (Cy)-induced immunosuppressed rat model. Design: We analyzed the immune enhancement effect of EA on macrophages by western blotting. In addition, cell viability and natural killer (NK) cell activity were analyzed in splenocytes following EA treatment. For in vivo studies, analysis of weekly body weight, spleen weight, immune cell count, cytokine levels, and spleen histological findings was performed following EA administration in Cy-induced immunocompromised rats. Results: EA significantly increased cell viability and phospho-nuclear factor-kappa B and phospho-extracellular signal-regulated kinase protein levels in the macrophages. EA significantly increased NK cell activity in splenocytes compared with the control group. In Cy-induced immunosuppressed rats, EA administration increased spleen tissue weight and the contents of leukocytes, lymphocytes, granulocytes, intermediate cells, and plasma cytokines (tumor necrosis factor-α and interferon-γ). In addition, improvement in the damaged spleen tissue was observed. Conclusions: These findings confirm that EA exerts an immune-enhancing effect, thereby suggesting its potential as an immunostimulatory agent or functional food.

Assessment of a Therapeutic X-ray Radiation Dose Measurement System Based on a Flexible Copper Indium Gallium Selenide Solar Cell.

Several detectors have been developed to measure radiation doses during radiotherapy. However, most detectors are not flexible. Consequently, the airgaps between the patient surface and detector could reduce the measurement accuracy. Thus, this study proposes a dose measurement system based on a flexible copper indium gallium selenide (CIGS) solar cell. Our system comprises a customized CIGS solar cell (with a size 10 × 10 cm2 and thickness 0.33 mm), voltage amplifier, data acquisition module, and laptop with in-house software. In the study, the dosimetric characteristics, such as dose linearity, dose rate independence, energy independence, and field size output, of the dose measurement system in therapeutic X-ray radiation were quantified. For dose linearity, the slope of the linear fitted curve and the R-square value were 1.00 and 0.9999, respectively. The differences in the measured signals according to changes in the dose rates and photon energies were <2% and <3%, respectively. The field size output measured using our system exhibited a substantial increase as the field size increased, contrary to that measured using the ion chamber/film. Our findings demonstrate that our system has good dosimetric characteristics as a flexible in vivo dosimeter. Furthermore, the size and shape of the solar cell can be easily customized, which is an advantage over other flexible dosimeters based on an a-Si solar cell.

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial.

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30-40 years, who were randomly assigned to two groups-a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.

Immuno-enhancement effects of Platycodon grandiflorum extracts in splenocytes and a cyclophosphamide-induced immunosuppressed rat model.

BACKGROUND: Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats. METHODS: For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen. RESULTS: PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage. CONCLUSIONS: Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.

Rice Porridge Containing Welsh Onion Root Water Extract Alleviates Osteoarthritis-Related Pain Behaviors, Glucose Levels, and Bone Metabolism in Osteoarthritis-Induced Ovariectomized Rats.

Rice porridge containing Allium fistulosum (Welsh onion) root water extract (RAFR) has anti-inflammatory bioactive compounds. We examined whether the long-term administration of rice porridge with RAFR would prevent or delay the progression of osteoarthritis and menopausal symptoms in estrogen-deficient animals by ovariectomy. The rats consumed 40% fat energy diets containing 250 mg RAFR (rice: Allium fistulosum root = 13:1)/kg body weight (bw) (OVX-OA-RAFR-Low), 750 mg RAFR/kg bw (OVX-OA-RAFR-High) and 750 mg starch and protein/kg bw(OVX), respectively. After consuming the assigned diets for eight weeks, monoiodoacetate (OVX-OA) or saline (OVX) were injected into the knee joints of the rats for an additional three weeks. Sham rats were administered saline injections (normal-control). OVX-OA-RAFR improved oral glucose tolerance and also protected against decreases in bone mineral density and lean body mass in the legs and increases in fat mass in the abdomen, compared to the OVX and OVX-OA. OVX-OA-RAFR improved swelling and limping scores, normalized weight distribution between the osteoarthritic and normal limbs, and increased maximum running speeds compared to the OVX-OA. The OVX-OA deteriorated the articular cartilage by reducing the articular matrix and bone loss in the knee joint and it prevented knee joint deterioration when compared to the OVX. The improvement in osteoarthritis symptoms in OVX-OA-RAFR decreased the mRNA expression of matrix metallo-proteinase-1 and matrix metalloproteinase-13, tumor necrosis factor-α, and interleukin-1ß and interleukin-6 in the articular cartilage compared to OVX-OA rats. In conclusions, RAFR is effective in treating osteoarthritis symptoms and it may be used for a therapeutic agent in osteoarthritis-induced menopausal women.

Lactobacillus intestinalis efficiently produces equol from daidzein and chungkookjang, short-term fermented soybeans.

Equol improves menopausal symptoms and it is synthesized from daidzein, one of the isoflavonoids in soybeans, by the bacteria in the large intestines of some people. The purpose of this study was to isolate equol-producing bacteria using daidzein from the intestinal microflora and to produce equol-containing chungkookjang (short-term fermented soybean). Equol-producing bacteria from the feces of Sprague-Dawley female rats were isolated using media containing daidzein. The isolated bacteria were cultured in thioglycollate media and equol production was identified through thin-layer chromatography and ultraperformance liquid chromatography-mass spectrometry. The bacteria were identified by 16S rRNA sequencing. The rate of equol production in different concentrations of daidzein was assessed. The expression of genes that code for enzymes associated with the production of equol from daidzein was detected through reverse transcription quantitative PCR. The bacterium we isolated was Lactobacillus intestinalis (LC096206.1, 99%). L. intestinalis was found to express daidzein reductase, dihydrodaidzein reductase, and tetrahydrodaidzein reductase, the enzymes involved in producing equol from daidzein. The conversion rate of equol from daidzein was highest (29.5%) using 200 µM daidzein for 48 h of incubation. When chungkookjang fermented with Bacillus amyloquencies SRCM100001 was incubated with L. intestinalis, 0.32 ± 0.04 mg equol/g chungkookjang was produced. In conclusion, L. intestinalis efficiently produces equol from not only daidzein but also in chungkookjang.

Metabolomics Associated with Genome-Wide Association Study Related to the Basal Metabolic Rate in Overweight/Obese Korean Women.

A previous genome-wide association study (GWAS) on obese/overweight Korean women reported five new genetic loci associated with the basal metabolic rate (BMR) and body mass index (BMI), NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17. This metabolite GWAS (mGWAS) aimed to identify the key metabolites and metabolic pathways regulated by these genes. Potential metabolic pathways associated with leanness and obesity were identified by detecting metabolites in association with GWAS. Waist circumference, lean body mass, and body fat mass were strongly associated with BMI rather than BMR. However, plasma triglyceride and total cholesterol were significantly higher in obese individuals with low BMR than in lean individuals with high BMR. Upon analyzing NRG3, BCL2L2-PABPN1, and SLC22A17, uric acid, succinic acid, arginine, uridine, and aspartic acid were the metabolites positively associated with obesity. Uric acid and arginine were both identified through general metabolomics targeting of obesity genes classified on the basis of BMI or BMR. Metabolites associated with disruption in beta-oxidation, lipid metabolism, branched-chain amino acid and aromatic amino acid catabolism, the urea cycle, and purine/pyrimidine metabolism play important roles in obesity classified on the basis of either BMI or BMR in middle-aged Korean women. These results further the current understanding of obesity and the predictability of obesity-related risks using mGWAS.

Orostachys japonicus A. Berger Extracts Induce Immunity-Enhancing Effects on Cyclophosphamide-Treated Immunosuppressed Rats.

In this study, we evaluated the immunity-enhancing effects of Orostachys japonicus A. Berger (OJ). To examine the immune protective effect in vitro, primary mouse splenocytes were treated with water or ethanol extracts of OJ in the absence or presence of cyclophosphamide (CY), which is a cytotoxic, immunosuppressive agent. The extracts increased the propagation of splenocytes and inhibited CY-induced cytotoxicity. Further, to examine the immunostimulatory effects in vivo, adult Wistar rats were orally administered OJ extracts with or without CY treatment. With the administration of OJ extracts, CY-treated immunosuppressed rats showed improved physical endurance, as assessed by the forced swim test. In addition, extract administration increased not only the number of immunity-related cells but also the levels of plasma cytokines. OJ extracts also recovered splenic histology in CY-treated rats. These findings suggest that an OJ regimen can enhance immunity by increasing immune cell propagation and specific plasma cytokine levels.

Immunostimulatory Effect of Zanthoxylum schinifolium-Based Complex Oil Prepared by Supercritical Fluid Extraction in Splenocytes and Cyclophosphamide-Induced Immunosuppressed Rats.

Complex oil of Zanthoxylum schinifolium and Perilla frutescens seed (ZPCO) is used as a traditional medicine due to its pharmacological activities. The aim of this study was to investigate the immunostimulatory effect of ZPCO in isolated splenocytes as well as in an immunosuppressed rat model, which was generated via oral administration of cyclophosphamide. Notably, our results showed that ZPCO exerted an immunity-enhancing effect both in vitro and in vivo. Specifically, ZPCO treatment enhanced the viability and inflammatory cytokine production of splenocytes and NK cell activity in vitro. Moreover, this product improved host defense under immunosuppressive conditions by increasing the number of immune cells and promoting the expression of cytokines involved in immune responses. Our results suggest that complex oil including Z. schinifolium should be explored as a novel immunostimulatory agent that could potentially be used for therapeutic purposes or as an ingredient in functional foods.

Combination of Aronia, Red Ginseng, Shiitake Mushroom and Nattokinase Potentiated Insulin Secretion and Reduced Insulin Resistance with Improving Gut Microbiome Dysbiosis in Insulin Deficient Type 2 Diabetic Rats.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and nattokinase (AGM; 3.4:4.1:2.4:0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and the gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either (1) 0.5 g AGM (AGM-L), (2) 1 g AGM (AGM-H), (3) 1 g dextrin (control), or (4) 1 g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 244 mg ß-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller with AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance deteriorated in the control group and was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of the gut microbiome and AGM prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

Red mulberry fruit aqueous extract and silk proteins accelerate acute ethanol metabolism and promote the anti­oxidant enzyme systems in rats.

Red mulberry (Morus alba) fruit is rich in anthocyanins, and mulberry leaves are used by silk worms to make silk protein. We determined that the water and ethanol extract of mulberry fruit and silk amino acids accelerated ethanol degradation and suppressed temporal cognitive dysfunction in acute alcohol administered rats. The mechanism was explored in rats with acute oral administration of silk protein and mulberry fruit extracts. Rats were given 0.3 g of dextrin (control) and water extract (WMB) and ethanol extract of mulberry (EMB), silk protein hydrolysates (SKA), and a commercial product (positive­control) based on body weight. After 30 min, rats were administered 3 g ethanol/kg body weight and serum ethanol and acetaldehyde levels were measured. After 3 h movements were measured with a video tracking system and at 5 h cognitive function was measured by Y maze test. WMB contain much higher rutin, luteolin and quercetins than EMB. In SKA rats, serum alcohol concentrations slowly increased until 60 min, but were markedly elevated until 120 min. However, WMB rats exhibited rapidly increased serum alcohol levels until 60 min and showed the lowest peak of serum alcohol levels, indicating the highest degradation of alcohol. The patterns of serum acetaldehyde levels were similar to those of serum ethanol levels but WMB was more effective for reducing serum acetaldehyde levels than serum ethanol levels. WMB was most effective for increasing mRNA expression of alcohol dehydrogenase and acetaldehyde dehydrogenase. WMB and SKA decreased lipid peroxides by increasing activities of SOD and GSH­Px in the liver and they also reduced pro­inflammatory cytokines such as tumor necrosis factor­α and interleukin­6. WMB and SKA exerted better anti­oxidant effects than the positive­control. WMB containing higher flavonoids reduced pro­inflammatory cytokines better than SKA. In conclusions, both WMB and SKA might reduce acute alcohol­induced hangover and liver and brain damage by lowering serum alcohol and acetaldehyde levels.

Gastroprotective actions of Taraxacum coreanum Nakai water extracts in ethanol-induced rat models of acute and chronic gastritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum coreanum Nakai has been traditionally used for treating inflammatory diseases including gastrointestinal diseases. AIM OF THE STUDY: We studied whether water extracts of Taraxacum coreanum Nakai (TCN) had a protective effect on acute and chronic gastritis induced by ethanol/HCl in an animal model of gastritis and its mechanism was also explored. MATERIALS AND METHODS: In the acute study, rats were orally administered 0.15g/mL dextrin (normal-control), 0.15g/mL dextrin (control), 0.05g/mL TCN (TCN-L), 0.15g/mL TCN (TCN-H), or 0.01g/mL omeprazole (orally; positive-control), followed by oral administration of 1mL of 60% ethanol plus 150mM HCl (inducer). In the chronic study, rats were administered 10% diluted inducer in drinking water, and 0.6% dextrin, 0.2% or 0.6% TCN, and 0.05% omeprazole were administered in chow for 4 weeks. Acid content, gastric structure, oxidative stress, and markers of inflammation in the stomach tissue were measured at the end of experiment. RESULTS: Acute and chronic ethanol/HCl administration caused the inner layer of the stomach to redden, hemorrhage, and edema in the control group; TCN-H reduced these symptoms more effectively than did the omeprazole positive-control. Acid production and total acidity in the stomach increased in the control group, which was markedly suppressed by omeprazole. TCN also reduced the acid production and acidity, but not to the same degree as omeprazole. H-E and PAS staining revealed that in the inner layer of the stomach, cellular structure was disrupted, with an increased nuclear size and thickness, disarrangement, and decreased mucin in the control group. TCN prevented the cellular disruption in the inner layer, and TCN-H was more effective than the positive-control. This was associated with oxidative stress and inflammation. TCN dose-dependently reduced the infiltration of mast cells and TNF-α expression in the inner layer of the stomach, and decreased lipid peroxides by increasing superoxide dismutase and glutathione peroxidase expression. CONCLUSIONS: TCN-H acutely and chronically protected against gastritis and gastric ulcer by reducing oxidative stress and inflammation, not by completely suppressing gastric acid production.

Gastrodia elata Blume Rhizome Aqueous Extract Improves Arterial Thrombosis, Dyslipidemia, and Insulin Response in Testosterone-Deficient Rats.

Testosterone deficiency deteriorates glucose and lipid metabolism with reducing muscle mass. We investigated whether the consumption of water extracts of Gastrodia elata Blume rhizome (GEB) rich in gastrodin would reduce the symptoms of testosterone deficiency and improve blood flow in orchidectomized (ORX) rats. ORX rats were given high-fat diets supplemented with either 1% cellulose (ORX-control), 0.3% GEB (GEB-L), or 1% GEB (GEB-H) for 8 weeks. Sham-operated rats were fed the same diet as OVX-control rats (normal-control). ORX-control rats had reduced serum testosterone levels by one-fifth, compared to normal-control rats. ORX-control rats exhibited decreased lean body mass, attenuated blood flow, and impaired cholesterol metabolism and glucose control due to decreased insulin secretory response. GEB increased serum insulin levels dose-dependently and GEB-H mostly enhanced dyslipidemia in ORX rats. GEB completely normalized arterial thrombosis time and blood flow in ORX rats. Interestingly, ORX-control rats showed attenuated hepatic insulin signaling but greater AMPK and CREB activities, which reduced triglyceride accumulation, compared to normal-control. GEB-H improved hepatic insulin signaling but maintained the AMPK and CREB activities in ORX rats. In conclusions, GEB ameliorated the impairment of cholesterol and glucose metabolism and blood flow in ORX rats. GEB may be a potential preventive measure for reducing the risk of cardiovascular diseases associated with testosterone deficiency.

Supplementation of fermented Maillard-reactive whey protein enhances immunity by increasing NK cell activity.

OBJECTIVE: The objective of this study was to investigate the impact of supplementation with fermented Maillard-reactive whey protein (F-MRP) on natural killer (NK) cell activity, circulating cytokines, and serum protein levels. METHODS: A randomized, double-blind, placebo-controlled study was conducted on a sample of 80 participants without diabetes or obesity. Over an 8-week study period, the F-MRP group consumed 6 g of powder containing 4.2 g of F-MRP each day, whereas the placebo group consumed the same amount of maltodextrin. For each participant, NK cell activity was evaluated based on the ratio of effector cells (E; peripheral blood mononuclear cells, PBMCs) to target cells (T; K562 cells) at E : T ratios of 10 : 1, 5 : 1, 2.5 : 1, and 1.25 : 1. RESULTS: Body mass index (BMI) and NK cell activity under all assay conditions were significantly increased in the F-MRP group at the 8-week follow-up visit compared with the values at the baseline, whereas the placebo group showed significant reductions in NK cell activity (at an E : T ratio of 5 : 1), serum albumin, and pre-albumin at the 8-week follow-up visit compared with the values at the baseline. When comparing the changes between the placebo and F-MRP groups, the increases in NK cell activity under all assay conditions and serum interleukin (IL)-12 in the F-MRP group were greater than those in the placebo group after adjusting for baseline values. There were also significant differences in pre-albumin and insulin-like growth factor (IGF)-1 between the two groups; the change in (Δ) IL-12 was positively correlated with both Δpre-albumin (r = 0.435, P = 0.006) and ΔNK cell activity at an E : T ratio of 10 : 1 (r = 0.571, P < 0.001) in the F-MRP group. CONCLUSION: Daily consumption of F-MRP enhanced NK cell function, which was positively associated with ΔIL-12. Moreover, ΔIL-12 was positively correlated with Δpre-albumin.

Topical treatments of Saussurea costus root and Thuja orientalis L. synergistically alleviate atopic dermatitis-like skin lesions by inhibiting protease-activated receptor-2 and NF-κB signaling in HaCaT cells and Nc/Nga mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD. MATERIALS AND METHODS: HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)-4, IL-13, and IFN-γ in the dorsal skin and HaCaT cells were measured. RESULTS: Chlorogenic acid (129.6±10.2µg/g) for SC and catechin and apigenin (93.4±13.2 and 16.9±1.3µg/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-α and IL-6 in HaCaT cells activated by 3µg/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-γ, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice. CONCLUSION: SC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD.

Randomized, double-blind, placebo-controlled trial of Ficus carica paste for the management of functional constipation.

BACKGROUND AND OBJECTIVES: Constipation affects up to 20% of the world's population. The aim of this study was to investigate whether supplementation with Ficus carica paste could be used to treat constipation in Korean subjects with functional constipation. METHODS AND STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled trial. Subjects with functional constipation were orally supplemented with either F. carica paste (n=40) or placebo (n=40) for 8 weeks. We measured the efficacy and safety of F. carica paste. Primary outcomes (colon transit time) and secondary outcomes (questionnaire related to defecation) were compared before and after the 8-week intervention period. RESULTS: F. carica paste supplementation was associated with a significant reduction in colon transit time and a significant improvement in stool type and abdominal discomfort compared with the placebo. Blood parameters and clinical findings for organ toxicity remained within normal ranges. CONCLUSION: These results suggest that F. carica paste may have beneficial effects in subjects suffering from constipation.

The combination of Artemisia princeps Pamp, Leonurus japonicas Houtt, and Gardenia jasminoides Ellis fruit attenuates the exacerbation of energy, lipid, and glucose by increasing hepatic PGC-1α expression in estrogen-deficient rats.

BACKGROUND: Artemisia princeps Pamp (APP), Leonurus japonicas Houtt (LJH), and Gardenia jasminoides Ellis fruit (GJE) have been traditionally used in East Asia to treat women's diseases related to reproductive system. They may attenuate the deterioration of energy, lipid, glucose and bone metabolism by estrogen deficiency. The present study explored the combination of APP, LJH, and GJE to overcome the symptoms of estrogen deficiency and the mechanism was explored. METHODS: Ovariectomized (OVX) rats were divided into five groups and fed high-fat diets supplemented with 2 % dextrin (control), 2 % APP, 2 % APP + LJH (15:5), APP + LJH + GJE (10:5:5) or 17ß-estradiol (30 µg/kg bw/day) for 8 weeks. After 8 weeks of their consumption, energy, lipid, glucose and bone metabolisms were investigated and hepatic insulin signaling and fatty acid metabolism were determined. RESULTS: APP + LJH + GJE, but not APP itself, improved energy metabolism and attenuated a decrease in energy expenditure by the same amount as estrogen. Moreover, APP + LJH + GJE reduced visceral fat and intramuscular fat and increased lean body mass measured by DEXA by as much as the positive-control. APP itself suppressed increased LDL cholesterol and triglyceride levels in OVX rats and APP + LJH + GJE alleviated dyslipidemia in OVX rats. Overnight-fasted serum insulin levels and HOMA-IR were reduced in the descending order of APP, APP + LJH, APP + LJH + GJE, positive-control in OVX rats. APP and APP + LJH elevated insulin secretion in the 1st part of OGTT to decrease serum glucose levels while APP + LJH + GJE reduced serum glucose levels without increasing serum insulin levels during OGTT. APP + LJH + GJE decreased insulin resistance during ITT in OVX rats more than the positive-control. The APP + LJH + GJE group exhibited increased hepatic peroxisomal proliferator-activated receptor-γ coactivator-1α expression, which increased the number of genes involved in fatty acid oxidation and decreased fatty acid synthesis. Hepatic insulin signaling (pAkt and pGSK-1ß) was also potentiated to reduce phosphoenolpyruvate carboxykinase proteins. CONCLUSION: The combination of APP + LJH + GJE attenuated various menopausal symptoms in OVX rats. Thus, it may have potential as a therapeutic agent for the treatment of postmenopausal symptoms.

Anti-Diabetic Activities of Gastrodia elata Blume Water Extracts Are Mediated Mainly by Potentiating Glucose-Stimulated Insulin Secretion and Increasing ß-Cell Mass in Non-Obese Type 2 Diabetic Animals.

The brain is an important modulator of glucose metabolism, and is known to respond Gastrodia elata Blume water extract (GEB). Therefore, we examined whether long-term administration of GEB has hypoglycemic activity, and its action mechanism was explored in partially-pancreatectomized rats that exhibit similar characteristics as Asian type 2 diabetes, non-obese insulin-insufficient diabetes. The rats were provided high-fat diets supplemented with either of (1) 0.5% GEB (GEB-L), (2) 2% GEB (GEB-H), (3) 2% dextrin (control), or (4) 2% dextrin with rosiglitazone (20 mg/kg body weight; positive-control) for eight weeks. GEB dose-dependently improved hypothalamic insulin signaling, enhanced whole-body insulin sensitivity during hyperinsulinemic euglycemic clamp, and reduced hepatic glucose output in a hyperinsulinemic state. GEB dose-dependently increased the area under the curve of the serum insulin levels at the first and second phases during hyperglycemic clamp compared to the control, whereas the positive control had no effect. Insulin sensitivity during the hyperglycemic state also improved, dose-dependently, in response to GEB compared with that of the control, but was less than the positive control. GEB-H increased the mass of ß-cells by potentiating proliferation and decreasing apoptosis. In conclusion, GEB could be a therapeutic agent for treating Asian type 2 diabetes.

Methyl jasmolate treated buckwheat sprout powder enhances glucose metabolism by potentiating hepatic insulin signaling in estrogen-deficient rats.

OBJECTIVES: Methyl jasmolate (MeJA)-treated vegetables produce higher concentrations of various bioactive compounds. We investigated whether long-term oral consumption of MeJA-treated and untreated buckwheat sprout powder improves energy, glucose, lipid, and bone metabolism induced by estrogen deficiency in ovariectomized (OVX) rats fed high-fat diets, and explored the mechanisms involved. METHODS: OVX rats were divided into four groups and fed high-fat diets supplemented with 3% dextrin (OVX-control), buckwheat sprout powder (BWS), or MeJA-treated buckwheat sprout powder (MJ-BWS) for 12 wk. Sham rats without estrogen deficiency had a control diet as a normal-control. RESULTS: MeJA-treatment increased total polyphenols and flavonoids by about 1.6 fold and isoorientin, orientin, rutin, and vitexin were elevated by about 18% in buckwheat. After 12 wk, OVX rats exhibited increased weight gain, fat mass, skin temperature, hyperglycemia, and decreased bone mineral density (BMD) compared to sham rats. BWS prevented the increase of skin temperature and decrease of femur BMD, but did not improve energy glucose homeostasis as much as MJ-BWS. MJ-BWS prevented increases in body weight and fat mass. Energy expenditure was lowest in OVX-control, followed by BWS, MJ-BWS, and normal-control. Furthermore, MJ-BWS exhibited greater improvements in glucose and insulin tolerance than OVX-control and BWS. Phosphorylation of hepatic Akt and AMPK was potentiated, in ascending order of OVX-control, BWS, MJ-BWS, and normal-control, whereas PEPCK expression was decreased. CONCLUSIONS: MJ-BWS prevented and ameliorated the disturbances in energy and glucose metabolism in estrogen-deficient animals better than BWS. Therefore, besides flavonoids in BWS, other components such as phytoalexins produced in MJ-BWS during MeJA-treatment might play a crucial role in the improvement.