Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats.

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders.

Enhancement of 1,3-propanediol production from industrial by-product by Lactobacillus reuteri CH53.

BACKGROUND: 1,3-propanediol (1,3-PDO) is the most widely studied value-added product that can be produced by feeding glycerol to bacteria, including Lactobacillus sp. However, previous research reported that L. reuteri only produced small amounts and had low productivity of 1,3-PDO. It is urgent to develop procedures that improve the production and productivity of 1,3-PDO. RESULTS: We identified a novel L. reuteri CH53 isolate that efficiently converted glycerol into 1,3-PDO, and performed batch co-fermentation with glycerol and glucose to evaluate its production of 1,3-PDO and other products. We optimized the fermentation conditions and nitrogen sources to increase the productivity. Fed-batch fermentation using corn steep liquor (CSL) as a replacement for beef extract led to 1,3-PDO production (68.32 ± 0.84 g/L) and productivity (1.27 ± 0.02 g/L/h) at optimized conditions (unaerated and 100 rpm). When CSL was used as an alternative nitrogen source, the activity of the vitamin B12-dependent glycerol dehydratase (dhaB) and 1,3-propanediol oxidoreductase (dhaT) increased. Also, the productivity and yield of 1,3-PDO increased as well. These results showed the highest productivity in Lactobacillus species. In addition, hurdle to 1,3-PDO production in this strain were identified via analysis of the half-maximal inhibitory concentration for growth (IC50) of numerous substrates and metabolites. CONCLUSIONS: We used CSL as a low-cost nitrogen source to replace beef extract for 1,3-PDO production in L. reuteri CH53. These cells efficiently utilized crude glycerol and CSL to produce 1,3-PDO. This strain has great promise for the production of 1,3-PDO because it is generally recognized as safe (GRAS) and non-pathogenic. Also, this strain has high productivity and high conversion yield.

Electric Field-Responsive Gold Nanoantennas for the Induction of a Locoregional Tumor pH Change Using Electrolytic Ablation Therapy.

Electrolytic ablation (EA) is a burgeoning treatment for solid tumors, in which electrical energy catalyzes a chemical reaction to generate reactive species that can eradicate cancer cells. However, the application of this technique has been constrained owing to the limited spatial effectiveness and complexity of the electrode designs. Therefore, the incorporation of nanotechnology into EA is anticipated to be a significant improvement. Herein, we present a therapeutic approach based on difructose dianhydride IV-conjugated polyethylenimine-polyethylene glycol-modified gold nanorods as electric nanoantennas and nanoelectrocatalysts for EA. We demonstrate that square-wave direct current (DC) fields trigger a reaction between water molecules and chloride ions on the gold nanorod surface, generating electrolytic products including hydrogen, oxygen, and chlorine gases near the electrodes, changing the pH, and inducing cell death. These electric nanoantennas showed significant efficacy in treating colorectal cancer both in vitro and in vivo after DC treatment. These findings clearly indicate that gold nanoantennas enhance the effectiveness of EA by creating a localized electric field and catalyzing electrolytic reactions for the induction of locoregional pH changes within the tumor. By overcoming the limitations of traditional EA and offering an enhanced level of tumor specificity and control, this nanotechnology-integrated approach advances further innovations in cancer therapies.

Anti-inflammatory effects of Beopje curly dock (Rumex crispus L.) in LPS-induced RAW 264.7 cells and its active compounds.

Inflammation is a defense response of the body to stimuli. Curly dock (CD) is an herbal food with anti-inflammatory effects. Beopje is an herbal food processing method that reduces toxicity and enhances beneficial effects. This study investigated the effects of CD and Beopje curly dock (CD-B) extracts on lipopolysaccharide (LPS)-induced inflammatory damage in RAW 264.7 cells. Cell survival rate and nitrite concentration were determined using the MTT assay and Griess method, respectively. Enzyme-linked immunosorbent assay was used to detect the inflammatory cytokine levels. The mRNA and protein expression levels of inflammatory associated genes were detected by qPCR and Western blot, respectively. CD and CD-B extracts compositions were assessed by UPLC-Q-TOF MS analysis. Our results indicate that CD-B has a more significant inhibitory effect on the LPS-induced inflammatory response in RAW 264.7 cells than CD, suggesting that the Beopje process potentially enhances the anti-inflammatory effect of CD. PRACTICAL APPLICATIONS: Long-term inflammation can cause a variety of chronic diseases. Therefore, it is necessary to suppress the occurrence of body inflammation in time. This study preliminarily clarified the mechanism of herbal foods to alleviate inflammation by regulating the immune response, and further confirms that applying the Beopje process enhances the anti-inflammatory effect. This research can serve as a significant reference for future research, prevention and treatment of inflammation-related diseases, and the development of functional foods with anti-inflammatory activity. It also provides a theoretical basis for the further reasonable application of Beopje processing method.

Comparison of the antiobesity effects of the protopanaxadiol- and protopanaxatriol-type saponins of red ginseng.

A previous study demonstrated that ginseng crude saponins prevent obesity induced by a high-fat diet in rats. Ginseng crude saponins are known to contain a variety of bioactive saponins. The present study investigated and compared the antiobesity activity of protopanaxadiol (PD) and protopanaxatriol (PT) type saponins, major active compounds isolated from crude saponins. Male 4-week-old Sprague-Dawley rats were fed with normal diet (N) or high-fat diet (HF). After 5 weeks, the HF diet group was subdivided into the control HF diet, HF diet-PD and HF diet-PT group (50 mg/kg/day, 3 weeks, i.p.). Treatment with PD and PT in the HF diet group reduced the body weight, total food intake, fat contents, serum total cholesterol and leptin to levels equal to or below the N diet group. The hypothalamic expression of orexigenic neuropeptide Y was significantly decreased with PD or PT treatment, whereas that of anorexigenic cholecystokinin was increased, compared with the control HF diet group. In addition, PD type saponins had more potent antiobesity properties than PT saponins, indicating that PD-type saponins are the major components contributing to the antiobesity activities of ginseng crude saponins. The results suggest that the antiobesity activity of PD and PT type saponins may result from inhibiting energy gain, normalizing hypothalamic neuropeptides and serum biochemicals related to the control of obesity.

Production of lactosucrose from sucrose and lactose by a levansucrase from Zymomonas mobilis.

Lactosucrose (4(G)-beta-D-galactosylsucrose) is an oligosaccharide consisting of galactose, glucose, and fructose. In this study, we prepared lactosucrose from lactose and sucrose using a levansucrase derived from Zymomonas mobilis. Optimum conditions for lactosucrose formation were 23 degrees C, pH 7.0, 18.0% (w/v) lactose monohydrate, and 18% (w/v) sucrose as substrates, and 1 unit of enzyme/ml of reaction mixture. Under these conditions, the lactosucrose conversion efficiency was 28.5%. The product was purified and confirmed to be O-beta-D-galactopyranosyl-(1-->4)-O-beta-D-glucopyranosyl- (1-->2)-beta-D-fructofuranoside, or lactosucrose. A mixed-enzyme system containing a levansucrase and a glucose oxidase was applied in order to increase the efficiency of lactose and sucrose conversion to lactosucrose, which rose to 43.2% as s result.

Association between early nutritional risk and overall survival in patients with advanced pancreatic cancer: A single-center retrospective study.

BACKGROUND & AIMS: We investigated the predictors of overall survival (OS) among Korean patients with advanced pancreatic cancer (PC) according to their baseline nutritional status. METHODS: We retrospectively reviewed the data of 412 inpatients with PC between January 2007 and February 2015 at the Department of Oncology of the Gangnam Severance Hospital, Korea. Data on demographic and clinical parameters were collected from electronic medical records, and OS was estimated using the Kaplan-Meier method. Stepwise Cox regression analysis was used to determine the factors associated with survival. Patients with a Nutritional Risk Screening (NRS) 2002 score <3 were classified as "no-risk; " those with a score of 3 were classified as "moderate-risk; " and those with a score of ≥4 were classified as "high-risk." RESULTS: Following nutritional screening at baseline, 194 patients (47.1%, mean age 61.8 ± 9.9 years) were classified as the "no risk" group; 81 patients (19.7%, mean age 65.4 ± 10.8 years), as the "moderate risk" group; and 137 patients (33.3%, mean age 67.8 ± 12.0 years), as the "high risk" group. Predictors of survival were NRS 2002 score (hazard ratio [HR] = 1.238; 95% confidence interval [CI] = 1.143-1.341), percentage of lymphocytes (HR = 0.973; 95% CI = 0.962-0.984), C-reactive protein level (HR = 1.003; 95% CI = 1.001-1.006), carcinoembryonic antigen level (HR = 1.000; 95% CI = 1.000-1.000), and carbohydrate antigen 19-9 level (HR = 1.000; 95% CI = 1.000-1.000). Kaplan-Meier survival analysis showed significant differences in the median OS among the NRS 2002 groups: "no risk" group: 12.3 ± 0.4 months (95% CI: 11.47-13.13 months); "moderate risk" group: 6.5 ± 0.9 months (95% CI: 4.78-8.17 months); and "high risk" group: 5.5 ± 0.6 months (95% CI: 4.31-6.69 months). CONCLUSIONS: A good baseline nutritional status was associated with OS among Korean patients with advanced PC. An improvement in the nutritional status of patients with advanced PC through baseline nutritional interventions is therefore necessary to prolong OS.

Rumex crispus and Cordyceps militaris Mixture Ameliorates Production of Pro-Inflammatory Cytokines Induced by Lipopolysaccharide in C57BL/6 Mice Splenocytes.

Rumex crispus (Rc) and Cordyceps militaris (Cm) mixture (Rc-Cm; AST2017-01) ameliorated production of proinflammatory cytokines, inflammation-related genes, and nitric oxide (NO) induced by lipopolysaccharide (LPS) in mouse splenocytes. Rc-Cm (6:4) and Taemyeongcheong (commercial healthy drink containing Rc-Cm) were co-administered along with LPS. Rc-Cm inhibited production of tumor necrosis factor α, interferon γ, interleukin (IL)-1ß, and IL-6 in LPS-induced splenocytes. However, levels of inflammatory cytokines were elevated in the absence of LPS treatment. Rc-Cm significantly suppressed mRNA expression of IL-1ß, IL-6, and the inflammation-related genes inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2), as well as NO production upon LPS co-treatment. Whereas Rc-Cm increased mRNA expression of IL-1ß, and IL-6, but did not up-regulate expression of iNOS and COX-2, or increase NO production without LPS co-treatment. Therefore, treatment of Rc-Cm to LPS-induced splenocytes ameliorated induction of pro-inflammatory cytokines, inflammation-related genes, and NO production. In the absence of LPS, Rc-Cm treatment up-regulated pro-inflammatory cytokines but did not alter expression of the inflammation-related genes iNOS and COX-2 or NO production. These results indicate that the natural phytochemicals chrysophanol and cordycepin in Rc-Cm promote anti-inflammatory activities and immune cell responses.

Influence of aeration during propagation of pitching yeast on fermentation and beer flavor.

The effect of yeast propagated at different aeration conditions on yeast physiology, fermentation ability, and beer quality was investigated using three strains of Saccharomyces cerevisiae. It was shown that yeast cells grown under continuous aeration conditions during propagation were almost two times higher as compared with discontinuous aeration conditions. The maximum of cell growth of all samples reached between 36 h and 48 h. The concentration of trehalose was increased under continuous aerated yeasts, whereas glycogen was decreased. It was also observed that the concentration of glycogen and trehalose in yeast cells had no direct effect on subsequent fermentation ability. The effect of yeast propagated under different aeration conditions on subsequent fermentation ability was different from yeast strains, in which the influence will be most pronounced at the first fermentation. Later, the yeasts might regain its original characteristics in the following fermentations. Generally, continuously propagated yeast had a positive effect on beer quality in subsequent fermentation. Hence, the concentration of aroma compounds obtained with yeast propagated under 6 1/h for 48 h aeration was lower than those grown under other aeration conditions in the bottom yeasts; in particular, the amounts of phenylethyl alcohol, ester, and fatty acids were decreased.

Altered mRNA expression of hepatic lipogenic enzyme and PPARalpha in rats fed dietary levan from Zymomonas mobilis.

Levan or high molecular beta-2,6-linked fructose polymer is produced extracellularly from sucrose-based substrates by bacterial levansucrase. In the present study, to investigate the effect of levan feeding on serum leptin, hepatic lipogenic enzyme and peroxisome proliferation-activated receptor (PPAR) alpha expression in high-fat diet-induced obese rats, 4-week-old Sprague-Dawley male rats were fed high-fat diet (beef tallow, 40% of calories as fat), and, 6 weeks later, the rats were fed 0%, 1%, 5% or 10% levan-supplemented diets for 4 weeks. Serum leptin and insulin level were dose dependently reduced in levan-supplemented diet-fed rats. The mRNA expressions of hepatic fatty acid synthase and acetyl CoA carboxylase, which are the key enzymes in fatty acid synthesis, were down-regulated by dietary levan. However, dietary levan did not affect the gene expression of hepatic malic enzyme, phosphatidate phosphohydrolase and HMG CoA reductase. Also, the lipogenic enzyme gene expression in the white adipose tissue (WAT) was not affected by the diet treatments. However, hepatic PPARalpha mRNA expression was dose dependently up-regulated by dietary levan, whereas PPARgamma in the WAT was not changed. The results suggest that the in vivo hypolipidemic effect of dietary levan, including anti-obesity and lipid-lowering, may result from the inhibition of lipogenesis and stimulation of lipolysis, accompanied with regulation of hepatic lipogenic enzyme and PPARalpha gene expression.

Aglycone Isoflavones and Exopolysaccharides Produced by Lactobacillus acidophilus in Fermented Soybean Paste.

Bioconversion of aglycone-formed isoflavones from glycoside-formed isoflavones by commercial lactic acid bacteria in fermented soybean paste was evaluated. Enterococcus faecium KCTC 13410 showed the most resistant capacity and Lactobacillus acidophilus KCTC 3925 had a sensitive susceptibility at a high NaCl concentration (13.2%) in fermented soybean paste. Among the 5 strains tested, Lac. acidophilus KCTC 3925 showed the highest relative ratio of aglycone-formed isoflavones to total isoflavones in fermented soybean paste. Production of exopolysaccarides (EPS) by lactic acid bacteria was compared using de Man, Rogosa, and Sharpe medium containing 1% sucrose at 37°C for 48 h. Among the 5 lactic acid bacteria, Lac. acidophilus KCTC 3925 and Lactobacillus rhamnosus KCTC 3929 were investigated to produce EPS. Based on the results concerning growing susceptibility and conversion of aglycone-formed isoflavones/EPS production, it is anticipated that Lac. acidophilus KCTC 3925 may be used for preparation of Cheonggukjang, which contains relative low NaCl content.

Citri Reticulatae Viride Pericarpium extract induced apoptosis in SNU-C4, human colon cancer cells.

Citri Reticulatae Viride Pericarpium (CR) has been used traditionally in Korea to promote the Liver Qi activity and the function of digestive system. We investigated whether the immature peels of Citrus reticulata Blanco (Rutaceae) induced cell-death on SNU-C4, human colon cancer cells. Cytotoxicity of CR was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell death was identified as apoptosis using 4,6-diamidineo-2-phenylindole (DAPI) staining and terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of pro-apoptotic gene, Bax, was increased and the expression of anti-apoptotic gene, Bcl-2, was decreased by CR-treatment. The expression and activity of major apoptotic gene, caspase-3 was significantly increased by CR-treatment. Considering the above results, CR could induce the apoptosis on SNU-C4, human colon cancer cells via Bax-related caspase-3 activation. And it might provide the experimental data for the future clinical use of CR on colon cancer.

Nicotine administration decreases nitric oxide synthase expression in the hypothalamus of food-deprived rats.

Effect of nicotine on nitric oxide synthase (NOS) expression in various hypothalamic regions was investigated in rats via nicotineamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Sprague-Dawley rats were divided into the fed group, the fed and nicotine-treated group, the food-deprived group, and the food-deprived and nicotine-treated group. The fed groups received abundant food and water, while food was withheld from the food-deprived groups for 48 h. The nicotine-treated groups were injected with nicotine. Following food deprivation, enhanced NAPDH-d expression was detected in the paraventricular nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area of the hypothalamus. Nicotine administration to the food-deprived rats resulted in decreased NADPH-d positivity. The present results indicate that nicotine administration is effective in limiting the enhancement in NOS expression following food restriction.

Levan fructotransferase from Arthrobacter oxydans J17-21 catalyzes the formation of the di-D-fructose dianhydride IV from levan.

A new levan fructotransferase (LFTase) isolated from Arthrobacter oxydans J17-21 was characterized for the production of difructose dianhydride IV (DFA IV). LFTase was purified to apparent homogeneity by Q-Sepharose ion exchange chromatography, Mono-Q HR 5/5 column chromatography, and gel permeation chromatography. The enzyme had an apparent molecular mass of 54000 Da. The optimum pH for the enzyme-catalyzed reaction was pH 6.5, and the optimum temperature was observed at 45 degrees C. The LFTase was activated by the presence of CaCl(2) and EDTA-2Na but inhibited strongly by MnCl(2) and CuSO(4) at 1 mM and completely by FeSO(4) and Ag(2)SO(4) at 1 mM. A bacterial levan from Zymomonas mobilis was incubated with an LFTase; final conversion yield from the levan to DFA IV was 35%. Neither inulin, levanbiose, sucrose, dextran, nor starch was hydrolyzed by LFTase. DFA IV was very stable at acidic pH and high temperature, thus indicating that DFA IV may be suitable for the food industry and related areas.

Coptidis rhizoma induces apoptosis in human colorectal cancer cells SNU-C4.

Coptidis rhizoma has been used as traditional herb medicine in gastrointestinal disorders in the Eastern Asia. We investigated whether the anticancer effects of the C. rhizoma induced apoptosis on human colorectal cancer cells SNU-C4. The cytotoxic effect of C. rhizoma was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To determine apoptotic cell death, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcription-polymerase chain reaction (RT-PCR) and caspase-3 enzyme assay were performed. In this study, C. rhizoma treatment (100 microg/ml) revealed typical morphological apoptotic features. Additionally, C. rhizoma treatment (100 microg/ml) increased levels of BAX and CASPASE-3, and decreased levels of BCL-2. Caspase-3 enzyme activity by treatment of C. rhizoma (100 microg/ml) also significantly increased compared to the control (p < 0.05). These data indicate that C. rhizoma caused cell death by apoptosis through caspase pathways on human colorectal cancer cells SNU-C4.

Antioxidative effects of Kimchi under different fermentation stage on radical-induced oxidative stress.

BACKGROUND/OBJECTIVES: Kimchi is a traditional Korean fermented vegetable containing several ingredients. We investigated the protective activity of methanol extract of kimchi under different fermentation stages against oxidative damage. MATERIALS/METHODS: Fresh kimchi (Fresh), optimally ripened kimchi (OptR), and over ripened kimchi (OvR) were fermented until the pH reached pH 5.6, pH 4.3, and pH 3.8, respectively. The radical scavenging activity and protective activity from oxidative stress of kimchi during fermentation were investigated under in vitro and cellular systems using LLC-PK1 cells. RESULTS: Kimchi exhibited strong radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl, nitric oxide, superoxide anion, and hydroxyl radical. In addition, the free radical generators led to loss of cell viability and elevated lipid peroxidation, while treatment with kimchi resulted in significantly increased cell viability and decreased lipid peroxidation. Furthermore, the protective effect against oxidative stress was related to regulation of cyclooxygenase-2, inducible nitric oxide synthase, nuclear factor-κB p65, and IκB expression. In particular, OvR showed the strongest protective effect from cellular oxidative stress among other kimchi. CONCLUSION: The current study indicated that kimchi, particularly OptR and OvR, played a protective role against free radical-induced oxidative stress. These findings suggest that kimchi is a promising functional food with an antioxidative effect and fermentation of kimchi led to elevation of antioxidative activity.

Kimchi protects against azoxymethane/dextran sulfate sodium-induced colorectal carcinogenesis in mice.

The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans.

Fisetin antagonizes cell fusion, cytoskeletal organization and bone resorption in RANKL-differentiated murine macrophages.

Osteoclastogenesis is comprised of several stage s including progenitor survival, differentiation to mononuclear preosteoclasts, cell fusion to multinuclear mature osteoclasts, and activation to osteoclasts with bone resorbing activity. Botanical antioxidants are now being increasingly investigated for their health-promoting effects on bone. This study investigated that fisetin, a flavonol found naturally in many fruits and vegetables, suppressed osteoclastogenesis by disturbing receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated signaling pathway and demoting osteoclastogenic protein induction. Nontoxic fisetin at ≤10 µM inhibited the induction of RANK, tumor necrosis factor receptor associated factor 6 (TRAF6) and the activation of NF-κB in RANKL-stimulated RAW 264.7 macrophages. In RANKL-differentiated osteoclasts cell fusion protein of E-cadherin was induced, which was dampened by fisetin. The formation of tartrate-resistance acid phosphatase-positive multinucleated osteoclasts was suppressed by adding fisetin to RANKL-exposed macrophages. It was also found that fisetin reduced actin ring formation and gelsolin induction of osteclasts enhanced by RANKL through disturbing c-Src-proline-rich tyrosine kinase 2 signaling. Fisetin deterred preosteoclasts from the cell-cell fusion and the organization of the cytoskeleton to seal the resorbing area and to secret protons for bone resorption. Consistently, the 5 day-treatment of fisetin diminished RANKL-induced cellular expression of carbonic anhydrase II and integrin ß3 concurrently with a reduction of osteoclast bone-resorbing activity. Therefore, fisetin was a natural therapeutic agent retarding osteoclast fusion and cytoskeletal organization such as actin rings and ruffled boarder, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone.

Neuroprotective effects of consuming bovine colostrum after focal brain ischemia/reperfusion injury in rat model.

To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-1beta, IL-6, and TNF-alpha) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-1beta, IL-6, and TNF-alpha levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model.

Treatment with Astragali radix and Angelicae radix enhances erythropoietin gene expression in the cyclophosphamide-induced anemic rat.

Anemia is a common cause of morbidity and disease and reduces the quality of life. This study examined the effect of a combination treatment (AAC) using Astragali radix (AMW) and Angelicae radix (AGW) in cyclophosphamide (CYP)-induced anemic rats on erythropoietin (EPO) expression and hematological parameters. Male 4-week-old Sprague-Dawley rats were divided into five groups with or without CYP-induced anemia and individual or the combined herbal treatments according to the experimental protocol. After treatment, reverse transcription-polymerase chain reaction was used to evaluate the effects of AAC on erythropoietin expression, and blood and serological parameters were measured. The EPO mRNA levels were lower in the CYP-treated group, compared to the normal group, and higher in the AAC-treated group. In the CYP-treated group, the serum iron concentration, total iron-binding capacity, and vitamin B(12) level were lower, but these were normal or almost normal in the AAC-treated group. The CYP-treated group gained less weight than the normal group, but weight gain was partially normalized in the AAC group. The feed efficiency ratio was lowest in the CYP group, but the differences were not significant. The numbers of red blood cells, white blood cells, and platelets, the hematocrit, and the hemoglobin level were measured. The results revealed a reduced number of blood cells in the CYP-treated group, whereas the AAC-, AMW-, and AGW-treated groups showed significantly enhanced blood cell numbers compared to the CYP-treated control group and the AAC-treated group. AAC enhanced EPO mRNA expression in the CYP-induced anemic rat and improved the hematological parameters and vitamin B(12) status.