Effect of Mollusca shell extracts on inhibition of kimchi over-acidification.

Mollusca species shell such as oyster shell (OS) and snail shell (SS), are discarded after taking the meat, and the discarded shell causes the environmental problems. Therefore, recycling shell waste could potentially eliminate the environmental problems. This study aimed to evaluate the potential of OS and SS as natural calcium resources. The minerals, calcium, magnesium, potassium, phosphorus and sodium were analyzed in OS and SS extracts. Among them, the calcium content was the highest: 36.87 (%) and 33.42 (%) in the OS and SS extracts, respectively. Further, the content of ionized bioavailable form of calcium in OS and SS was higher than that of CaCO3 under simulated gastrointestinal digestion conditions. Additionally, OS and SS were added to kimchi, and their inhibitory effect on kimchi acidification was evaluated by assessing pH, titratable acidity and microbial analysis. As the results indicated that the addition of OS and SS had little effect on inhibiting the growth of lactic acid bacteria. However, it was confirmed that calcium neutralizes the organic acids produced during fermentation. Overall, the results of this study provide preliminary information on the re-use of OS and SS extracts as ionized natural calcium supplements and fermentation retardants.

Selenium reduction of ubiquinone via SQOR suppresses ferroptosis.

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here we demonstrate that, via its metabolic intermediate hydrogen selenide, selenium reduces ubiquinone in the mitochondria through catalysis by sulfide quinone oxidoreductase. Through this mechanism, selenium rapidly protects against lipid peroxidation and ferroptosis in a timescale that precedes selenoprotein production, doing so even when selenoprotein production has been eliminated. Our findings identify a regulatory mechanism against ferroptosis that implicates sulfide quinone oxidoreductase and expands our understanding of selenium in biology.

Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL/6 Mice.

This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2',7'-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.

Naringenin and Phytoestrogen 8-Prenylnaringenin Protect against Islet Dysfunction and Inhibit Apoptotic Signaling in Insulin-Deficient Diabetic Mice.

It has been shown that citrus flavanone naringenin and its prenyl derivative 8-prenylnaringenin (8-PN) possess various pharmacological activities in in vitro and in vivo models. Interestingly, it has been proposed that prenylation can enhance biological potentials, including the estrogen-like activities of flavonoids. The objective of this study was to investigate the anti-diabetic potential and molecular mechanism of 8-PN in streptozotocin (STZ)-induced insulin-deficient diabetic mice in comparison with naringenin reported to exhibit hypoglycemic effects. The oral administration of naringenin and 8-PN ameliorated impaired glucose homeostasis and islet dysfunction induced by STZ treatment. These protective effects were associated with the suppression of pancreatic ß-cell apoptosis and inflammatory responses in mice. Moreover, both naringenin and 8-PN normalized STZ-induced insulin-signaling defects in skeletal muscles and apoptotic protein expression in the liver. Importantly, 8-PN increased the protein expression levels of estrogen receptor-α (ERα) in the pancreas and liver and of fibroblast growth factor 21 in the liver, suggesting that 8-PN could act as an ERα agonist in the regulation of glucose homeostasis. This study provides novel insights into the mechanisms underlying preventive effects of naringenin and 8-PN on the impairment of glucose homeostasis in insulin-deficient diabetic mice.

Antioxidant activity and calcium bioaccessibility of Moringa oleifera leaf hydrolysate, as a potential calcium supplement in food.

Moringa oleifera leaf (ML) is rich in vitamins and minerals, specially abundant calcium, therefore it is widely used as a calcium supplement for food. This study aimed to investigate the antioxidant activity and calcium bioaccessibility of M. oleifera leaf hydrolysate (MLH) as a calcium supplement for kimchi. MLH was prepared under three different proteases, two different protease contents, and three different incubation times. Total phenol content (TPC), total flavonoid content (TFC), and antioxidant activities were investigated. Cellular activity and calcium bioaccessibility were also investigated. The highest calcium level of MLH was observed in 3% Protamex treatment for 4 h. TPC, TFC, and antioxidant activities of MLH in Protamex and Alcalase treatments were higher than those in Flavourzyme treatment (p < 0.05). Moreover, high cell viability and alkaline phosphatase activity were also observed in C2C12 cells. Kimchi containing MLH showed high calcium accessibility compared to kimchi alone. Taken together, the application of MLH could have potential as a calcium supplement for kimchi production.

Selenium detoxification is required for cancer-cell survival.

The micronutrient selenium is incorporated via the selenocysteine biosynthesis pathway into the rare amino acid selenocysteine, which is required in selenoproteins such as glutathione peroxidases and thioredoxin reductases1,2. Here, we show that selenophosphate synthetase 2 (SEPHS2), an enzyme in the selenocysteine biosynthesis pathway, is essential for survival of cancer, but not normal, cells. SEPHS2 is required in cancer cells to detoxify selenide, an intermediate that is formed during selenocysteine biosynthesis. Breast and other cancer cells are selenophilic, owing to a secondary function of the cystine/glutamate antiporter SLC7A11 that promotes selenium uptake and selenocysteine biosynthesis, which, by allowing production of selenoproteins such as GPX4, protects cells against ferroptosis. However, this activity also becomes a liability for cancer cells because selenide is poisonous and must be processed by SEPHS2. Accordingly, we find that SEPHS2 protein levels are elevated in samples from people with breast cancer, and that loss of SEPHS2 impairs growth of orthotopic mammary-tumour xenografts in mice. Collectively, our results identify a vulnerability of cancer cells and define the role of selenium metabolism in cancer.

A 90-Day Repeated Oral Dose Toxicity Study of Alismatis Rhizoma Aqueous Extract in Rats.

Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.

Induction of Apoptosis and Inhibition of Epithelial Mesenchymal Transition by α-Mangostin in MG-63 Cell Lines.

Osteosarcoma is the most common bone primary malignant tumor and nearly 30% of patients still die from osteosarcoma due to metastasis or recurrence. Thus, it is necessary to develop effective new chemotherapeutic agents for osteosarcoma treatment. α-Mangostin is a xanthone derivative shown to have antioxidant and anticarcinogen properties. However, the molecular mechanisms underlying the antimetastatic effects of osteosarcoma remain unclear. In metastasis progression, epithelial mesenchymal transition (EMT) is a process that plays important roles in development, cell polarity, and increased invasion and migration. This study focused on the induction of apoptosis and inhibition of EMT process by α-mangostin in human osteosarcoma cell line MG63. α-Mangostin treatments on MG63 cells not only showed the several lines of evidence of apoptotic cell death but also inhibited cell migration, invasion, and EMT-inducing transcription factor. In conclusion, we demonstrate that the α-mangostin induces apoptosis via mitochondrial pathway and suppresses metastasis of osteosarcoma cells by inhibiting EMT.

The effects of low-pressure hyperbaric oxygen treatment before and after maximal exercise on lactate concentration, heart rate recovery, and antioxidant capacity.

The purpose of this study was to investigate the effects of low-pressure hyperbaric oxygen (HBO) treatment before and after maximal exercise on lactate concentration and heart rate and antioxidant capacity. Ten healthy male college students were recruited from amateur soccer players. Subjects were performed a maximal exercise 3 times at intervals of at least 7 days according to the treatment method (control, pretreatment, posttreatment). Lactate concentration, heart rate, and antioxidant capacity were measured before, post, and after recovery 30 min of maximal exercise. The lactate concentration and heart rate of recovery 30 min was significantly lower in the low-pressure HBO treated group after the maximal exercise compared with the control group and the low-pressure HBO treated group before maximal exercise, and it could affect the removal of the fatigue substance caused by the maximal exercise. These results suggest that the low-pressure HBO treatment which is a new possibility for recovery of peripheral fatigue.

Effect of Ganoderma applanatum mycelium extract on the inhibition of adipogenesis in 3T3-L1 adipocytes.

Ganoderma applanatum (GA) and related fungal species have been used for over 2000 years in China to prevent and treat various human diseases. However, there is no critical research evaluating the functionality of GA grown using submerged culture technology. This study aimed to evaluate the effects of submerged culture GA mycelium (GAM) and its active components (protocatechualdehyde [PCA]) on preadipocyte differentiation of 3T3-L1 cells. Mouse-derived preadipocyte 3T3-L1 cells were treated with differentiation inducers in the presence or absence of GAM extracts. We determined triglyceride accumulations, glycerol-3-phosphate dehydrogenase (GPDH) activities, and differentiation makers. PCA, the active component of GAM extract, was also used to treat 3T3-L1 cells. The MTT assay showed that the GAM extract (0.01-1 mg/mL) was not toxic to 3T3-L1 preadipocyte. Treatment of cells with GAM extracts and its active components significantly decreased the GPDH activity and lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Western blot analysis results showed that the protein expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) were inhibited by the GAM extract. In addition, adipogenic-specific genes such as perilipin, fatty acid synthase (FAS), fatty acid transport protein 1 (FATP1), and fatty acid-binding protein 4 (FABP4) decreased in a dose-dependent manner. Quantitative high-performance liquid chromatography analysis showed that the GAM extract contained 1.14 mg/g PCA. GAM extracts suppressed differentiation of 3T3-L1 preadipocytes, in part, through altered regulation of PPARγ, C/EBPα, and SREBP1. These results suggest that GAM extracts and PCA may suppress adipogenesis by inhibiting differentiation of preadipocytes.

Microarray-based gene expression profiling to elucidate effectiveness of fermented Codonopsis lanceolata in mice.

In this study, the effect of Codonopsis lanceolata fermented by lactic acid on controlling gene expression levels related to obesity was observed in an oligonucleotide chip microarray. Among 8170 genes, 393 genes were up regulated and 760 genes were down regulated in feeding the fermented C. lanceolata (FCL). Another 374 genes were up regulated and 527 genes down regulated without feeding the sample. The genes were not affected by the FCL sample. It was interesting that among those genes, Chytochrome P450, Dmbt1, LOC76487, and thyroid hormones, etc., were mostly up or down regulated. These genes are more related to lipid synthesis. We could conclude that the FCL possibly controlled the gene expression levels related to lipid synthesis, which resulted in reducing obesity. However, more detailed protein expression experiments should be carried out.

Therapeutic effect of Broussonetia papyrifera and Lonicera japonica in ovalbumin-induced murine asthma model.

Broussonetia papyrifera (L.) Vent. and Lonicera japonica Thunb. have been used in recent medicinal research for their antioxidative and anti-inflammatory properties. The present study investigated the therapeutic efficacy of B. papyrifera and L. japonica ethanolic extracts in a murine model of ovalbumin-induced asthma, in which intra-peritoneal (IP) injections and aerosol ovalbumin delivery were used to induce allergic asthma. Bronchioalveolar lavage fluid (BALF), serum samples, lungs and livers were collected from the experimental groups. In the groups treated with B. papyrifera and L. japonica extracts, CD3, CD4, serum IgE and IL-4 levels; activities of matrix metalloproteinase (MMP)-2 and MMP-9; and eotaxin levels in the BALF significantly decreased to near normal levels. Results of a histopathological analysis showed that the level of inflammation and mucous secretions reduced in the treated groups compared to the corresponding levels in the other groups. Moreover, results of a serum enzymatic analysis showed the non-toxic nature of the extracts in the B. papyrifera and L. japonica treated groups. Taken together, these results clearly indicate that the B. papyrifera and L. japonica extracts may be very effective against asthma and inflammation related diseases.

Effects of probiotic fermentation on the enhancement of biological and pharmacological activities of Codonopsis lanceolata extracted by high pressure treatment.

This study was designed to evaluate the enhancement of antioxidant, antimicrobial, enzymatic, cytotoxic, and cognitive activities of Codonopsis lanceolata extracted by high pressure treatment followed by probiotic fermentation. Dried C. lanceolata samples were subjected to 400 MPa for 20 min and then fermented with Bifidobacterium longum B6 (HPE-BLF) and Lactobacillus rhamnosus (HPE-LRF) at 37 °C for 7 days. Compared to conventional extraction (CE-NF, 6.69 mg GAE/g), the phenol amounts of HPE-BLF and HPE-LRF were significantly increased to more than 8 mg GAE/g, while the lowest flavonoid contents were observed for HPE-BLF (0.44 mg RE/mL) and HPE-LRF (0.45 mg RE/mL) (p<0.05). Cinnamic acid was the most abundant phenolic acid in the fermented C. lanceolata. The highest DPPH scavenging activities were observed for HPE-BLF and HPE-LRF, with minimum EC(50) values of 1.26 and 1.18 mg/mL, respectively. The HPE-BLF and HPE-LRF samples exhibited the most noticeable antimicrobial activities against Staphylococcus aureus, Listeria monocytogenes, Salmonella Typhimurium, and Shigella boydii (MICs<15 mg/mL). The fermented C. lanceolata samples effectively inhibited α-glucosidase and tyrosinase activities and potentially improved a scopolamine-induced memory deficit in mice. The application of a fermentation process can effectively improve the biological and pharmacological activities of high-pressure-extracted C. lanceolata by increasing the extraction efficacy and inducing probiotic conversion. The results suggest that the combined treatment of HPE and a fermentation process could be used as alternative extraction method over CE.

Atrophic acne scar treatment using triple combination therapy: dot peeling, subcision and fractional laser.

Atrophic scars are a common complication of acne. Many modalities are proposed but each does not yield satisfactory clinical outcomes. Thus, a new combination therapy is suggested that incorporates (i) dot peeling, the focal application and tattooing of higher trichloroacetic acid concentrations; (ii) subcision, the process by which there is separation of the acne scar from the underlying skin; and (iii) fractional laser irradiation. In this pilot study, the efficacy and safety of this method was investigated for the treatment of acne scars. Ten patients received this therapy for a year. Dot peeling and subcision were performed twice 2-3 months apart and fractional laser irradiation was performed every 3-4 weeks. Outcomes were assessed using scar severity scores and patients' subjective ratings. Acne scarring improved in all of the patients completing this study. Acne scar severity scores decreased by a mean of 55.3%. Eighty percent of the patients felt significant or marked improvement. There were no significant complications at the treatment sites. It would appear that triple combination therapy is a safe and very effective combination treatment modality for a variety of atrophic acne scars.

Systemic delivery and preclinical evaluation of Au nanoparticle containing beta-lapachone for radiosensitization.

Effective delivery of radiosensitizer to target tumor cells, causing preferentially increased tumor cytotoxicity, while simultaneously minimizing damage to healthy cells around the tumor, is an ideal strategy for the improvement of radiotherapeutic efficacy against human cancer. We aimed to enhance radiotherapeutic efficacy by using biocompatible gold nanoparticles (AuNP) as a vehicle for systemic delivery of ss-lapachone (lap). Lap is a novel anticancer agent displaying potent cytotoxicity against cancer cells expressing NAD(P)H:quinone oxidoreductase-1 enzyme (NQO1). Although lap is expected to be a very promising radiosensitizer, its poor solubility and non-specific distribution obstruct preclinical evaluation and clinical application. In this study, the property of AuNPs carrying lap (AuNPs/lap) for active-targeting tumor cells and improving in vivo radiotherapeutic efficacy was evaluated. Murine monoclonal anti-EGFR antibody was conjugated to the AuNPs/lap as a ligand for active targeting. The active tumor-targeting property of AuNPs/lap conjugating anti-EGFR antibody was validated in vitro experiments using cell lines expressing EGFR at different levels. In mice bearing xenograft human tumors, the intravenous injection of AuNPs/lap exhibited highly enhanced radiotherapeutic efficacy. AuNPs/lap offers a new modality for improvement of radiotherapeutic efficacy and feasibility of further clinical application for human cancer treatment.

Antimicrobial effects of silver nanoparticles.

The antimicrobial effects of silver (Ag) ion or salts are well known, but the effects of Ag nanoparticles on microorganisms and antimicrobial mechanism have not been revealed clearly. Stable Ag nanoparticles were prepared and their shape and size distribution characterized by particle characterizer and transmission electron microscopic study. The antimicrobial activity of Ag nanoparticles was investigated against yeast, Escherichia coli, and Staphylococcus aureus. In these tests, Muller Hinton agar plates were used and Ag nanoparticles of various concentrations were supplemented in liquid systems. As results, yeast and E. coli were inhibited at the low concentration of Ag nanoparticles, whereas the growth-inhibitory effects on S. aureus were mild. The free-radical generation effect of Ag nanoparticles on microbial growth inhibition was investigated by electron spin resonance spectroscopy. These results suggest that Ag nanoparticles can be used as effective growth inhibitors in various microorganisms, making them applicable to diverse medical devices and antimicrobial control systems.