Potential antidepressant effects of a dietary supplement from the chlorella and lion's mane mushroom complex in aged SAMP8 mice.

Since the 1990s, the prevalence of mental illnesses, such as depression, has been increasing annually and has become a major burden on society. Due to the many side effects of antidepressant drugs, the development of a complementary therapy from natural materials is an urgent need. Therefore, this study used a complex extract of chlorella and lion's mane mushroom and evaluated its antidepressant effects. Six-month-old male senescence-accelerated mice prone-8 (SAMP8) were divided into positive control; negative control; and low, medium, and high-dose groups. All groups were treated with corticosterone (CORT) at 40 mg/Kg/day for 21- days to induce depression in the animals, and the effects of different test substances on animal behavior was observed. The positive control group was intraperitoneally injected with a tricyclic antidepressant (Fluoxetine, as tricyclic antidepressant), the control group was given ddH2O, and the test substance groups were administered test samples once daily for 21 days. The open field test (OFT) and forced swimming test (FST) were applied for behavior analyses of depression animal models. The OFT results showed that the mice in the positive control and the medium-, and high-dose groups demonstrated a significantly prolonged duration in the central area and a significantly increased travel distance. In the FST, the positive control and the medium, and high-dose groups displayed significantly reduced immobility times relative to the control group. The blood analysis results showed significant decreases in triglyceride and blood urea nitrogen levels relative to the positive control and the medium- and high-dose groups. Notably, in the positive control and the medium- and high-dose groups, brain-derived neurotrophic factor (BDNF) increase by more than in the control group. In summary, medium and high dose of extract of chlorella and lion's mane mushroom could improve depression behavior in animals and have the potential to be antidepressant health care products.

Coffeeberry Activates the CaMKII/CREB/BDNF Pathway, Normalizes Autophagy and Apoptosis Signaling in Nonalcoholic Fatty Liver Rodent Model.

Nonalcoholic fatty liver disease (NAFLD) shows extensive liver cell destruction with lipid accumulation, which is frequently accompanied by metabolic comorbidities and increases mortality. This study aimed to investigate the effects of coffeeberry (CB) on regulating the redox status, the CaMKII/CREB/BDNF pathway, autophagy, and apoptosis signaling by a NAFLD rodent model senescence-accelerated mice prone 8 (SAMP8). Three-month-old male SAMP8 mice were divided into a control group and three CB groups (50, 100, and 200 mg/kg BW), and fed for 12 weeks. The results show that CB reduced hepatic malondialdehyde and carbonyl protein levels. CB significantly enhanced Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) and reduced the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio. In addition, CB increased the silent information regulator T1 level, promoted Beclin 1 and microtubule-associated protein light chain 3 II expressions, and reduced phosphorylated mammalian target of rapamycin and its downstream p-p70s6k levels. CB also inhibited the expressions of apoptosis-related factors poly (ADP-ribose) polymerase-1 and the apoptosis-inducing factor. In conclusion, CB might protect the liver by reducing oxidative stress, activating the CaMKII/CREB/BDNF pathway, and improving autophagic and apoptotic expressions in a dose-dependent manner.

Docosahexaenoic acid inhibits the proliferation of Kras/TP53 double mutant pancreatic ductal adenocarcinoma cells through modulation of glutathione level and suppression of nucleotide synthesis.

The treatment of cancer cells obtained by blocking cellular metabolism has received a lot of attention recently. Previous studies have demonstrated that Kras mutation-mediated abnormal glucose metabolism would lead to an aberrant cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Previous literature has suggested that consumption of fish oil is associated with lower risk of pancreatic cancer. In this study, we investigated the anti-cancer effects of docosahexaenoic acid (DHA) in human PDAC cells in vitro and in vivo. Omega-3 polyunsaturated fatty acids (PUFAs) such as DHA and eicosapentaenoic acid (EPA) significantly inhibited the proliferation of human PDAC cells. The actions of DHA were evaluated through an induction of cell cycle arrest at G1 phase and noticed a decreased expression of cyclin A, cyclin E and cyclin B proteins in HPAF-II cells. Moreover, it was found that co-treatment of DHA and gemcitabine (GEM) effectively induced oxidative stress and cell death in HPAF-II cells. Interestingly, DHA leads to an increased oxidative glutathione /reduced glutathione (GSSG/GSH) ratio and induced cell apoptosis in HPAF-II cells. The findings in the study showed that supplementation of GSH or N-Acetyl Cysteine (NAC) could reverse DHA-mediated cell death in HPAF-II cells. Additionally, DHA significantly increased cellular level of cysteine, cellular NADP/NADPH ratio and the expression of cystathionase (CTH) and SLCA11/xCT antiporter proteins in HPAF-II cells. The action of DHA was, in part, associated with the inactivation of STAT3 cascade in HPAF-II cells. Treatment with xCT inhibitors, such as erastin or sulfasalazine (SSZ), inhibited the cell survival ability in DHA-treated HPAF-II cells. DHA also inhibited nucleotide synthesis in HPAF-II cells. It was demonstrated in a mouse-xenograft model that consumption of fish oil significantly inhibited the growth of pancreatic adenocarcinoma and decreased cellular nucleotide level in tumor tissues. Furthermore, fish oil consumption induced an increment of GSSG/GSH ratio, an upregulation of xCT and CTH proteins in tumor tissues. In conclusion, DHA significantly inhibited survival of PDAC cells both in vitro and in vivo through its recently identified novel mode of action, including an increment in the ratio of GSSG/GSH and NADP/NADPH respectively, and promoting reduction in the levels of nucleotide synthesis.

Effect of Oligomeric Proanthocyanidin on the Antioxidant Status and Lung Function of Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND/AIM: Evidence exists that oxidative stress and oxidative damage play a pivotal role in chronic obstructive pulmonary disease (COPD). Oligomeric proanthocyanidins (OPCs) extracted from grape seeds have been shown to exhibit antioxidant capabilities greater than those of vitamin C and E. The objective of this study was to evaluate the effects of OPCs on antioxidant status and lung function in patients with COPD. PATIENTS AND METHODS: Patients were supplemented with 150 mg/day OPC (n=13) orally or with a placebo (n=14) for 8 weeks in a randomized double-blind clinical design. Changes in anthropometric values, lung function, oxidative state, and lipid profiles were assessed after OPC or placebo treatment for 8 weeks. RESULTS: The results showed that OPC supplementation significantly reduced the concentration of malondialdehyde, superoxide dismutase, and total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio. The concentration of HDL-C significantly increased in the OPC-treated group. The plasma triglyceride, TC and low-density lipoprotein cholesterol values and the activities of catalase and glutathione peroxidase also decreased, but did not significantly differ between the OPC- and placebo-treated groups. Lung function was not significantly different between the two groups after 8 weeks. CONCLUSION: OPC supplementation was effective in increasing the antioxidant capacity, in addition to improving the lipid profiles in patients with COPD.

Effects of Nutritional Intervention on the Survival of Patients with Cardiopulmonary Failure Undergoing Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND/AIM: This study aimed to examine the effects of nutritional intervention on the prognosis of patients with cardiopulmonary failure undergoing extracorporeal membrane oxygenation (ECMO) therapy in Taiwan. MATERIALS AND METHODS: An institutional review board-approved retrospective study was conducted on patients receiving ECMO therapy in the intensive care unit of the China Medical University Hospital, Taiwan, from January 2013 to December 2013. The study included 102 patients with cardiopulmonary failure receiving ECMO therapy. RESULTS: The data indicated that higher survival rates were closely related to lower age and APACHE II scores among the patients. In addition, compared to patients who deceased, those who survived had a higher total calorie intake. Most patients could tolerate bolus feeding and polymeric formulas. Furthermore, patients who underwent nutritional therapy with nutritional goals greater than 80% achieved a better outcome and lower mortality than other patients. CONCLUSION: Early nutritional intervention could benefit patients undergoing ECMO, and those who reached the delivery goal of 80% had significantly better outcomes than other patients. Enteral feeding can begin early and was well tolerated by patients receiving ECMO therapy. Following individual nutrition goals is critical for better outcomes, and this analysis might be useful in establishing individualized nutrition goals for oriental population when caring for critically ill patients.

Dithiothreitol enhanced arsenic-trioxide-induced cell apoptosis in cultured oral cancer cells via mitochondrial dysfunction and endoplasmic reticulum stress.

Arsenic is naturally occurring toxic metalloid and drinking As2 O3 containing water are recognized to be related to increased risk of neurotoxicity, liver injury, blackfoot disease, hypertension, and cancer. On the contrary, As2 O3 has been an ancient drug used in traditional Chinese medicine with substantial anticancer activities, especially in the treatment of acute promyelocytic leukemia as well as chronic wound healing. However, the cytotoxicity and detail mechanisms of As2 O3 action in solid cancer cells, such as oral cancer cells, are largely unknown. In this study, we have primarily cultured four pairs of tumor and nontumor cells from the oral cancer patients and treated the cells with As2 O3 alone or combined with dithiothreitol (DTT). The results showed that 0.5 µM As2 O3 plus 20 µM DTT caused a significant cell death of oral cancer cells but not the nontumor cells. Also As2 O3 plus DTT upregulated Bax and Bak, downregulated Bcl-2 and p53, caused a loss of mitochondria membrane potential in oral cancer cells. On the other way, As2 O3 also triggered endoplasmic reticulum stress and increased the levels of glucose-regulated protein 78, calpain 1 and 2. Our results suggest that DTT could synergistically enhance the effects of As2 O3 on killing oral cancer cells while nontoxic to the nontumor cells. The combination is promising for clinical practice in oral cancer therapy and worth further investigations. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 17-27, 2017.

Bufalin inhibits gefitinib resistant NCI-H460 human lung cancer cell migration and invasion in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Bufalin, a component of Chan Su (frog), has been shown to have biological activities including anti-tumor effects. Gefitinib has been used as an anti-cancer drug in lung cancer patients; however, some patients eventually become gefitinib resistant. AIM OF THE STUDY: In this study, we investigated anti-metastasis effects of bufalin in gefitinib resistant NCI-H460 lung cancer cells. MATERIALS AND METHODS: The effects of the bufalin in gefitinib resistant NCI-H460 lung cancer cells were investigated on cell viability using flow cytometry. The adhesion capacity, wound healing assay, invasion and migration assay, and Western blot analysis were used to understand the molecular mechanisms in this study RESULTS: Under sub-lethal concentrations (from 2.5 up to 10nM), bufalin significantly inhibits cell adhension, migration and invasion nature of gefitinib resistant H460 cells. Western blotting assay revealed that bufalin depressed some of the key metastasis-related proteins, such as SOS-1, MMP-2 and Rho A underwent significant reduction. Phosphorylated Focal adhesion kinase (p-FAK), phosphorylated extracellular signal-regulated kinase (p-ERK1/2), Ras and E-cadherin were significantly reduced at 48h treatment. However, phosphorylated p38 (p-p38), phosphorylated c-Jun NH2-terminal kinase (p-JNK1/2) and NF-κBp65 were increased. CONCLUSIONS: Based on these observations, we suggest that bufalin can be used in anti-metastasis of gefitinib resistant NCI-H460 lung cancer cells in the future.

Inhibitory Effects of AVEMAR on Proliferation and Metastasis of Oral Cancer Cells.

Oral cancer is keeping its 4th rank on the death causing cancers among Taiwan males, and its metastatic and recurrent rates remain high and a life-threatening issue to the citizens. Fermented wheat germ extract (AVEMAR) is used in clinical cancer nutritional therapy in gastrointestinal cancers but not in oral cancer yet. In this study, the potential of AVEMAR to inhibit tumor proliferation and metastasis of oral cancer was first investigated. Antiproliferative activity of AVEMAR was determined in human oral squamous carcinoma SCC-4 cells by MTT methodology. Wound-healing migration, transwell invasion, and Western blotting assays were carried out to examine the in vitro antimetastatic effects and involved signaling molecules for AVEMAR in oral cancer cells. AVEMAR at 0.2-1.6 mg/ml significantly inhibited the cell viability with IC50 values of 1.19 and 0.98 mg/ml for 24-h and 48-h treatment. Furthermore, AVEMAR could induce cell apoptosis and inhibit the migration and invasion of metastatic SCC-4 cells at a similar dose range. Notably, AVEMAR suppressed the expression of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (u-PA), but not MMP-1 or MMP-9, in SCC-4 cells. These results strongly support the antiproliferation and in vitro antimetastatic capacity of AVEMAR which may extend its contributions from cancer nutrition supplements to preventive agent for oral cancer.

Tomato juice supplementation in young women reduces inflammatory adipokine levels independently of body fat reduction.

OBJECTIVES: Lycopene is a carotene and phytochemical known to protect against metabolic diseases. It is found in red fruits and vegetables, predominantly tomatoes. This study aimed to show the supplementation effect of tomato juice on indices associated with metabolic health and adipokine profiles in generally healthy people. METHODS: A total of 30 young females (20- to 30-years-old) with a body mass index (BMI) ≥ 20 were recruited, of whom 25 completed the entire study. The subjects continued with their normal diet and exercise schedule, but were given 280 mL of tomato juice (containing 32.5 mg of lycopene) daily for 2 mo. Metabolic indices, including anthropometric data and serum levels of glucose, lipids, adipokines, lycopene, and antioxidants, were compared pre- and postintervention. RESULTS: Tomato juice supplementation significantly reduced body weight, body fat, waist circumference, BMI, and serum levels of cholesterol, monocyte chemoattractant protein-1 (MCP-1), and thiobarbituric reactive substances, while significantly increasing serum levels of adiponectin, triglyceride, and lycopene. When subjects were stratified by body fat change, i.e., reduction or non-reduction (including increase or no change), the tomato juice-induced reduction in waist circumference, serum cholesterol, and MCP-1 levels and increase in adiponectin and lycopene levels were seen in both subgroups. The changes in waist circumference, cholesterol, MCP-1, and adiponectin levels remained significant after adjusting for each covariable individually, with the exception of lycopene. CONCLUSIONS: These results show that daily tomato juice supplementation reduces waist circumference, as well as serum cholesterol and inflammatory adipokine levels in young healthy women and that these effects are unrelated to body fat changes.

Cantharidin induces DNA damage and inhibits DNA repair-associated protein expressions in TSGH8301 human bladder cancer cell.

Cantharidin is an active component of mylabris, which has been used as a traditional Chinese medicine. Cantharidin has been shown to have antitumor activity against several types of human cancers in vitro and in animal models in vivo. We investigated whether cantharidin induces DNA damage and affects DNA damage repair-associated protein levels in TSGH8301 human bladder cancer cells. Using flow cytometry to measure viable cells, cantharidin was found to reduce the number of viable cells in a dose-dependent manner. Comet assay, 4',6-diamidino-2-phenylindole (DAPI) staining and DNA gel electrophoresis were used to measure DNA damage and condensation; the results indicated that cantharidin induced DNA damage (comet tail), DNA condensation (white DAPI staining) and DNA damage (DNA smear). Results from western blotting showed that cantharidin inhibited the expression of DNA-dependent serine/threonine protein kinase, poly-ADP ribose polymerase, phosphate-ataxia-telangiectasia and RAD3-related, O-6-methylguanine-DNA methyltransferase, breast cancer susceptibility protein 1, mediator of DNA damage checkpoint protein 1, phospho-histone H2A.X, but increased that of phosphorylated p53 following 6 and 24 h treatment. Confocal laser microscopy was used to examine the protein translocation; cantharidin suppressed the levels of p-H2A.X and MDC1 but increased the levels of p-p53 in TSGH8301 cells. In conclusion, we found that cantharidin-induced cell death may occur through the induction of DNA damage and suppression of DNA repair-associated protein expression in TSGH8301 cells.

Fermented wheat germ extract induced cell death and enhanced cytotoxicity of Cisplatin and 5-Fluorouracil on human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Due to the difficulties of early diagnosis, curative treatments are not available for most patients. Palliative treatments such as chemotherapy are often associated with low response rate, strong adverse effects and limited clinical benefits for patients. The alternative approaches such as fermented wheat germ extract (FWGE) with anti-tumor efficacy may provide improvements in the clinical outcome of current therapy for HCC. This study aimed to clarify antitumor efficacy of FWGE and the combination drug effect of FWGE with chemotherapeutic agents, cisplatin and 5-fluorouracil (5-Fu) in human HCC cells, HepG2, Hep3B, and HepJ5. The present study indicated that FWGE exhibited potential to suppress HepG2, Hep3B, and HepJ5 cells, with the half maximal inhibitory concentrations (IC50) of FWGE were 0.494, 0.371 and 1.524 mg/mL, respectively. FWGE also induced Poly (Adenosine diphosphate ribose) polymerase (PARP) associated cell death in Hep3B cells. Moreover, the FWGE treatment further enhanced the cytotoxicity of cisplatin in all tested HCC cells, and cytotoxicity of 5-Fu in a synergistic manner in HepJ5 cells. Collectively, the results identified the anti-tumor efficacy of FWGE in HCC cells and suggested that FWGE can be used as a supplement to effectively improve the tumor suppression efficiency of cisplatin and 5-Fu in HCC cells.

Crude extracts of Euchresta formosana radix inhibit invasion and migration of human hepatocellular carcinoma cells.

Crude extracts of Euchresta formosana radix (EFR) have previously been observed to induce the suppression of liver cancer Hep3B cell growth and induce apoptosis in response to overexpression of reactive oxygen species, GADD153, Bax and caspase-3, and to decrease the levels of mitochondrial membrane potential in vitro. In this study, the effect of EFR on cell migration and invasion by the human liver hepatocellular carcinoma (HCC) cell line Hep3B was examined. Hep3B cells treated in vitro with EFR migrated and invaded less than cells treated with phosphate-buffered saline (PBS) as a control. EFR inhibited migration and invasion by down-regulating the production of RhoA and ROCK1, FAK, and matrix metalloproteinase-1, -2, -9 and -10 relative to PBS only. These results show that EFR inhibits invasion and migration by liver cancer cells by down-regulating proteins associated with these processes, resulting in reduced metastasis. Thus, EFR should be considered as a possible therapeutic agent for inhibiting primary tumor growth and preventing metastasis.