Combinatorial Herbal Extracts Alleviate Alcohol-Induced Hepatic Disorders.

Plant-derived compounds can be useful for the management of liver disease. Traditionally, hepatic disorders have been treated with herbal extracts. Although many herbal extracts in Eastern medicine have been shown to possess hepatoprotective activities, single-origin herbal extracts primarily demonstrate either antioxidant or anti-inflammatory activities. The current study investigated the effects of combinatorial herbal extracts on alcohol-induced hepatic disorders in an ethanol-fed mouse model. Sixteen herbal combinations were evaluated as hepatoprotective formulations; the active constituents in these herbal extracts were daidzin, peonidin-3-glucoside, hesperidin, glycyrrhizin, and phosphatidylcholine. RNA sequencing analysis showed that exposure to ethanol altered hepatic gene expression profiles (compared to those of the non-alcohol-fed group), resulting in 79 differentially expressed genes. A majority of the differentially expressed genes in alcohol-induced hepatic disorders were associated with dysfunction of the normal cellular homeostasis in the liver; however, these genes were repressed by treatment with herbal extracts. Moreover, following treatment with herbal extracts, there were neither acute inflammatory responses in the liver tissue nor abnormalities in the cholesterol profile. These results suggest that combinatorial herbal extracts may alleviate alcohol-induced hepatic disorders by modulating the inflammatory response and lipid metabolism in the liver.

Pharmacokinetic study comparing pure desoxo-narchinol A and nardosinonediol with extracts from Nardostachys jatamansi.

Nardostachyos Radix et Rhizoma (NR) is a valuable medicinal herb widely used in Korea, India, and China for the treatment of many diseases. Desoxo-narchinol A (DA) and nardosinonediol (ND) are the two main bioactive compounds belonging to the sesquiterpene group. Desoxo-narchinol A possesses anti-inflammatory activity while ND exhibits anti-depressant and cardioprotective activities. A pharmacokinetic study is important to decide whether the isolated compounds or the NR extract have better pharmacological activity. Hence, we developed an analytical method for studying the pharmacokinetics of DA and ND after oral administration of the pure compounds and herbal extract. An optimized liquid chromatography-mass spectrometry method (LC-MS/MS) with solid-phase extraction (SPE) for sample preparation was developed. A ZORBAX Extend C18 column (2.1 × 50 mm, 3.5 µm) was used under gradient elution with acetonitrile and 0.1% formic acid in water as the mobile phase. Validation experiments assessing accuracy, precision, and stability were satisfactory; the lower limit of quantification was 5 ng/mL. For the pharmacokinetic study, three groups of rats were administrated pure DA, pure ND, or NR extract orally. Concentrations of DA and ND in their plasma were determined by the developed method. Pharmacokinetic parameters, including the time to achieve maximum plasma concentration (Tmax) and the area under the plasma concentration curve from time zero to infinity (AUC0-∞), were compared for the herbal extract and pure compounds. The Tmax of the pure compound and the NR extract for DA was 7.50 and 8.33 min, respectively, compared to 5.00 and 5.83 min for the pure compound and the NR extract for ND, respectively. The AUC0-∞ of the pure compound and the NR extract for DA was 156.34 and 133.90 µg min/mL, respectively, and that for the NR extract for ND was 6.42 and 4.15 µg min/mL, respectively. LC-MS/MS was used to determine DA and ND in rat plasma. The pharmacokinetic profile of each pure compound and those in the extract were characterized and compared.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment.

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from -0.39 at baseline to -0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer.

68Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [68Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7.

High grade anorectal stricture complicating Crohn's disease: endoscopic treatment using insulated-tip knife.

Endoscopic treatments have emerged as an alternative to surgery, in the treatment of benign colorectal stricture. Unlike endoscopic balloon dilatation, there is limited data on endoscopic electrocautery incision therapy for benign colorectal stricture, especially with regards to safety and long-term patency. We present a case of a 29-year-old female with Crohn's disease who had difficulty in defecation and passing thin stools. A pelvic magnetic resonance imaging scan, gastrograffin enema, and sigmoidoscopy showed a high-grade anorectal stricture. An endoscopic insulated-tip knife incision was successfully performed to resolve the problem. From our experience, we suggest that endoscopic insulated-tip knife treatment may be a feasible and effective modality for patients with short-segment, very rigid, fibrotic anorectal stricture.

Parthenolide enhances sensitivity of colorectal cancer cells to TRAIL by inducing death receptor 5 and promotes TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent. Recombinant human TRAIL has been evaluated in clinical trials, however, various malignant tumors are resistant to TRAIL. Parthenolide (PT) has recently been demonstrated as a highly effective anticancer agent and has been suggested to be used for combination therapy with other anticancer agents. In this study, we investigate the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. HT-29 (TRAIL-resistant) and HCT116 (TRAIL-sensitive) cells were treated with PT and/or TRAIL. The results demonstrated that combined treatment induced apoptosis which was determined using MTT, cell cycle analysis, Annexin V assay and Hoechst 33258 staining. Interestingly, we confirmed that HCT116 cells have much higher death receptor (DR) 5 than HT-29 cells and PT upregulates DR5 protein level and surface expression in both cell lines. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, p53 cytochrome C release, and caspase cascades. These results suggest that PT sensitizes TRAIL-induced apoptosis via upregulation of DR5 and mitochondria-dependent pathway. Combination treatment using PT and TRAIL may offer an effective strategy to overcome TRAIL resistance of certain CRC cells.

Fabrication of CuInTe2 and CuInTe(2-x)Se(x) ternary gradient quantum dots and their application to solar cells.

We report the first synthesis of colloidal CuInTe2, CuInTe2-xSex gradient alloyed quantum dots (QDs) through a simple hot injection method. We confirmed the composition of synthesized QDs to cationic rich phase of CuIn1.5Te2.5 and Cu0.23In0.36Te0.19Se0.22 with XPS and ICP analysis, and we have also found that the gradient alloyed Cu0.23In0.36Te0.19Se0.22 QDs exhibit greatly improved stability over the CuIn1.5Te2.5 QDs. The solution-processed solar cell based on the gradient alloyed Cu0.23In0.36Te0.19Se0.22 QDs exhibited 17.4 mA/cm(2) of short circuit current density (Jsc), 0.40 V of open circuit voltage (Voc), 44.1% of fill factor (FF), and 3.1% of overall power conversion efficiency at 100 mW/cm(2) AM 1.5G illumination.

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study.

BACKGROUND: Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. METHODS: A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. RESULTS: Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. CONCLUSION: The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01634256

Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis.

Parthenolide (PT), a principal active component in medicinal plants, has been used conventionally to treat migraine and inflammation. This component has recently been reported to induce apoptosis in cancer cells, through mitochondrial dysfunction. In the present study, we investigated PT-mediated cell death signaling pathway by focusing on the involvement of Bcl-2 family members in human colorectal cancer cells. We also investigated the inhibitory effect of PT on tumor growth in xenografts. Using the human colorectal cancer cell lines HT-29, SW620 and LS174T, we demonstrated that treatment of these cancer cells with PT induces apoptosis using MTT, Annexin V assay and Hoechst 33258 staining. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, cytochrome c release and caspase activation. Moreover, intraperitoneal injection of PT showed significant inhibition of tumor growth, angiogenesis in the xenograft model. These results demonstrate that PT exhibits anti-cancer activity in human colorectal cancer in vitro and in vivo. These findings may also provide a novel approach for the treatment of colorectal cancer.

Bifidus fermentation increases hypolipidemic and hypoglycemic effects of red ginseng.

Antihyperlipidemic and antihyperglycemic effects of Red Ginseng (RG, steamed and dried root of Panax ginseng C. A. Meyer, family Araliaceae), major component of which is ginsenoside Rg3, and Bifidodoterium-fermented RG (FRG), major component of which is ginsenoside Rh2, were investigated. Orally administered RG and FRG potently reduced the serum triglyceride levels in corn-oil-induced hypertriglycemidemic mice as well as total cholesterol and triglyceride levels in Triton WR-1339-induced hyperlipidemic mice. Of the saponin and polysaccharide fractions of RG and FRG, the polysaccharide fraction inhibited postprandial blood glucose elevation of maltose- or starch-loaded mice and reduced the blood triglyceride levels in corn-oil-induced hypertriglycemidemic mice. The saponin fraction and its ginsenosides Rg3 and Rh2 reduced blood triglyceride and total cholesterol levels in Triton WR1339-induced hyperlipidemic mice. The inhibitory effect of FRG and its main constituents against hyperlipidemia and hyperglycemia in mice were more potent than those of RG. These findings suggest that hypolipidemic and hypoglycemic effects of RG can be enforced by Bifidus fermentation and FRG may improve hyperlipidemia and hyperglycemia.

Synthesis of novel phytosphingosine derivatives and their preliminary biological evaluation for enhancing radiation therapy.

Eight d-ribo-phytosphingosine derivatives were synthesized from d-ribo-phytosphingosine and diverse acyl chlorides with N,N-diisopropylethylamine in tetrahydrofuran for 1h at room temperature. Effect of these compounds on IR-induced cell death was evaluated on blood cancer cells (Jurkat). Among these, 3d showed the highest enhancement of radiosensitizing effect.

Design and evaluation of the tandem target for a simultaneous production of [11C]CH4 and [18F]-fluoride.

The tandem target for a simultaneous production of [11C]CH4 and [(18)F]-fluoride has been designed and evaluated. A separate recovery system has been applied for a simultaneous collection of [11C]CH4 and [(18)F]-fluoride after a bombardment. The [11C]CH4 target was placed in front, and the [18F]-fluoride target was posted successively. An aluminum grid was employed between the two target cavities to improve the burst pressure of the titanium foil during an irradiation. It was demonstrated that a useful amount of [11C]CH4 and [18F]-fluoride can be produced simultaneously by this newly designed system.

Effect of ginseng polysaccharide on the stability of lactic acid bacteria during freeze-drying process and storage.

Lactic acid bacteria (LAB) quickly attenuate or are killed during the freeze-drying process and storage. The effect of some natural polysaccharides, which are known as potent antitumor and immunomodulating substances, on the viability of the LAB, Lactobacillus acidophilus and Bifidobacterium breve, on freeze-drying and storage were investigated. Among the polysaccharides tested, red ginseng polysaccharide (RGP) and chitosan significantly inhibited the cell death of the LAB during freeze-drying, and fucoidan and RGP most potently protected the cell death of the LAB during storage. The stabilities of the LAB on the addition of RGP and fucoidan were comparable to that of skimmed milk. However, white ginseng polysaccharide (WGP) did not promote storage stability. When 5% skimmed milk/5% RGP treated LAB were freeze-dried and stored, their viabilities were found to be significantly higher those treated with 5% or 10% RGP. The stabilizing effect of 5% RGP/5% skimmed milk during LAB freeze-drying and storage stability was comparable to that of treatment with 10% skimmed milk. Based on these findings, we believe that RGP beneficially improves the stability of LAB during the freeze-dry process and storage.