Safety evaluation of kaempferol glycosides-rich standardized roasted goji berry leaf extract.

Goji berry leaf (GL) has been used for medicinal foods for its pharmacological effects, including anti-oxidative and anti-obesity activities. Nevertheless, toxicological information on GL is limited for developing health functional ingredient. The aim of the research was to evaluate the single dose acute, 14-day repeated oral toxicity, and genotoxicity of standardized roasted GL extract (rGL) rich in kaempferol-3-O-sophoroside-7-O-glucoside. Tested rGL was found to be stable as kaempferol-3-O-sophoroside-7-O-glucoside, showing 0.7-2.1% of analytical standard variance. According to the single dose toxicity for 14 days, the lethal dose of rGL was determined to be ≥ 2000 mg/kg. Repeated doses of 0-1000 mg/kg of rGL per day for 14 days did not show any toxicity signs or gross pathological abnormalities. No genotoxic signs for the rGL treatment appeared via bacterial reverse mutation up to 5000 µg/plate. There was no significant increase in chromosomal aberration of rGL irrespective of metabolic activation by using CHO-K1 cells (p > 0.05). Regarding carcinogenic toxicity, chromosomal aberrations were not induced at 2000 mg of rGL/kg by using the in vivo bone marrow micronucleus test (p > 0.05). Results from the current study suggest that rGL could be used as a functional ingredient to provide various effects with safety assurance.

Effects of leucine-rich protein supplements in older adults with sarcopenia: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study examined whether leucine-rich protein supplements improve muscle strength, mass, and performance in sarcopenic older adults. METHODS: We searched PubMed-Medline, Embase, and Cochrane Library databases for randomized controlled trials comparing leucine-rich protein supplements with a control intervention in sarcopenic older adults. A pairwise meta-analysis using a fixed-effects model was performed. The primary outcome of interest was muscle strength regardless of the measures used. Effect sizes were computed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Six randomized controlled trials including a total of 699 participants were retrieved. Leucine-rich protein supplements improved participants' overall muscle strength, mass, and performance compared to the control group (SMD = 0.939; 95% CI, 0.440-1.438; P < 0.001). As the primary outcome, muscle strength improved significantly in the leucine group (SMD = 0.794; 95% CI, 0.104-1.485; P = 0.024). CONCLUSION: Leucine-rich protein supplements improve muscle strength in sarcopenic older adults. They may be suggested in nutritional treatment of sarcopenia.

Impact of flavonol extracts derived from green tea or targeted flavonols as secondary ingredients on intestinal glucose transport.

The purpose of the current study was to examine the effect of adding secondary ingredients such as green tea derived water-soluble polysaccharides (GTP) and flavonol aglycone rich fractions derived from cellulase treated green tea extract (FVN) into catechin rich green tea extracts (GTE) on wheat starch digestion and intestinal glucose transport using in vitro digestion with Caco-2 cells. Co-digestion of wheat starch with GTE (16.88 g L-1) or GTE + GTP + FVN (16.69 g L-1) appeared to promote starch hydrolysis compared to control (15.49 g L-1). In case of major flavonoids, addition of epigallocatechin gallate (EGCG), EGCG + myricetin (M) into wheat starch significantly increased the digestion of starch into glucose. Glucose transport rate decreased by 22.35% in wheat starch + GTE + GTP + FVN (1.39%), while the least amount of glucose (1.70%) was transported in EGCG mixed with M (1% of EGCG) as secondary ingredients among individual flavonoids formulation. It indicated that inhibitory effect on glucose transport was higher in addition of GTE, GTP, and FVN as excipients ingredients rather than targeted major flavonoids. Results from the current study suggest that whole green tea including flavonoid rich fractions could enhance hypoglycemic potential of GTE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05140-2.

Physicochemical properties and bioavailability of naturally formulated fat-soluble vitamins extracted from agricultural products for complementary use for natural vitamin supplements.

The purpose of the current study was to evaluate the physicochemical properties, digestive stability, storage stability, and intestinal absorption of formulated natural vitamins (FNV) by mixing fat-soluble vitamins extracted from agricultural products with their synthetic vitamin (SYNV) counterparts using a 6 to 4 ratio (w:w, dry weight). The FNV A, D, E, and K were evenly dispersed without crystal growth in the dispersion specifications for the functional tablet foods. The FNV A, D, E, and K had 89, 73, 65, and 36% of the digestive recovery, respectively, which was comparable to that of the SYNV. FNV D, E, and K were retained over 77%, but rapidly decreased to 15% after 6 months during accelerated storage at 25 30 and 35℃. The comparable radical scavenging capacity was found between the FNV and the SYNV. Results from the current study suggest that fat-soluble vitamins extracted from agricultural products could be reasonable complementary use for natural vitamin supplements.

Effects of graded concentrations of supplemental selenium on selenium concentrations in tissues and prediction equations for estimating dietary selenium intake in pigs.

The experiment was conducted to determine the effects of graded dietary selenium (Se) on organ weight and Se concentrations in tissues and to develop equations for estimating dietary Se intake in pigs. Sixteen barrows (initial body weight = 30.0 ± 2.6) were allotted to four dietary treatments including graded Se supplementations with 0, 1, 5, and 50 mg/kg of diet. The experimental diets fed to the pigs for 30 d, and then the pigs were euthanized, and the organs, muscle, and urine samples were collected. The hair and blood samples of pigs were collected on d 15 and 30. Equations were developed for predicting daily Se intake using the Se concentration in plasma, hair, liver, kidneys, muscle, or urine. For graded dietary Se concentrations, linear and quadratic effects on the final body weight, weight and relative weight of liver and kidneys were not observed. The Se concentration in plasma, hair, liver, kidneys, muscle, and urine were linearly and quadratically increased as dietary Se concentration increased (P < 0.001). The dietary Se concentration was positively correlated with the Se concentrations in the plasma, organs, muscle, and urine (r > 0.81, P < 0.001). The equations for estimating dietary Se intake using the Se concentration in the plasma, hair, or organ as an independent variable were significant (P < 0.05). In conclusion, the dietary Se concentration was well reflected in the Se concentration in the plasma, hair, liver, kidneys, and urine. The Se concentration in the plasma, hair, liver, and kidneys can be used as an independent variable for estimating the Se intake.

Using Phytochemicals to Investigate the Activation of Nicotine Detoxification via Upregulation of CYP2A6 in Animal Models Exposed Tobacco Smoke Condensate by Intratracheal Instillation.

This study examined the efficacy of standardized Smilax china L. root extract (SSCR) containing chlorogenic acid on detoxifying nicotine from tobacco smoke condensate (TSC) in vitro and in vivo. Chlorogenic acid is an identified bioactive component in SSCR by ultraperformance liquid chromatography/photodiode array/electrospray ionization/mass spectroscopy (UPLC/PDA/ESI/MS). HepG2 liver cells and A549 lung cells were carried for measuring ROS and antioxidant enzymes. Sprague-Dawley rats were treated with nicotine by intratracheal instillation (ITI). Cell viabilities by pretreatments of 5, 12.5, and 25, 50 µg SSCR/mL ranged from 41 to 76% in HepG2 and 65 to 95% in A549. Pretreatments of SSCR inhibited TSC-mediated production of reactive oxygen species (ROS) by 8 and 10% in HepG2 and A549 cells, respectively. However, the expression of CAT, SOD1, and AOX1 was downregulated by SSCR in the both cells. The highest conversion of cotinine was observed at 50 µg/mL of SSCR after 120 min of incubation. SSCR upregulated CYP2A6 3-fold in A549 cells regardless of TSC cotreatment. When Sprague-Dawley rats were treated with nicotine by ITI or subjected to SSCR administration for 14 days, the levels of cotinine in urine increased in SSCR treatment only. The cellular level of antioxidant capacity at 10 or 100 mg/kg body weight/day of SSCR treatment was 1.89 and 1.86 times higher than those of nicotine-control. Results suggest that the intake of SSCR can detoxify nicotine by elevating nicotine conversion to cotinine and antioxidant capacity.

Enhanced Hydrogen Production by Co-cultures of Hydrogenase and Nitrogenase in Escherichia coli.

Rhodobacter sphaeroides is a bacterium that can produce hydrogen by interaction with hydrogenase and nitrogenase. We report a hydrogen production system using co-cultivation of hydrogenase in liquid medium and immobilized nitrogenase in Escherichia coli. The recombinant plasmid has been constructed to analyze the effect of hydrogen production on the expression of hupSL hydrogenase and nifHDK nitrogenase isolated from R. sphaeroides. All recombinant E. coli strains were cultured anaerobically, and cells for nitrogenase were immobilized in agar gel, whereas cells for hydrogenase were supplemented on the nitrogenase agar gel. The hupSL hydrogenase has been observed to enhance hydrogen production and hydrogenase activity under co-culture with nifHDK nitrogenase. The maximum hydrogen production has been obtained at an agar gel concentration and a cell concentration for co-culture of 2 % and 6.4 × 10(8) CFU. Thus, co-culture of hupSL hydrogenase and nifHDK nitrogenase provides a promising route for enhancing the hydrogen production and hydrogenase activity.

Epigallocatechin-3-gallate-induced free-radical production upon adipogenic differentiation in bovine bone-marrow mesenchymal stem cells.

Epigallocatechin-3-gallate (EGCG), a major component of catechin in green tea, has known effects on cancer, diabetes and obesity. We recently reported that the expression levels of various genes and proteins involved in adipogenesis decreases following EGCG treatment. We also assessed apoptosis in EGCG-exposed cells. Here, we explore the variability in free-radical production in bovine bone-marrow mesenchymal stem cells (BMSCs) treated with EGCG. Upon adipogenic differentiation, BMSCs were exposed to various EGCG concentrations (0, 0.1, 1, 5, or 10 µM) for 2, 4, or 6 days. We found that EGCG reduced cell viability and arrested the cell cycle at the gap 2/mitosis phase and that EGCG potentially enhanced the production of free radicals, including reactive oxygen species and reactive nitrogen species, in a concentration- and time-dependent manner. Immunostaining revealed that the expression of genes encoding CCAAT/enhancer-binding protein alpha and stearoyl-CoA desaturase were diminished by EGCG treatment. These findings suggest that EGCG alters free-radical production activity during adipogenic differentiation in BMSCs.

Acute pancreatitis secondary to ciprofloxacin therapy in patients with infectious colitis.

BACKGROUND/AIMS: Ciprofloxacin is considered to be a safe and effective treatment for acute infectious colitis. However, this drug may cause drug-induced pancreatitis, albeit rarely. METHODS: From March 2007 to February 2012, we studied 227 patients who were hospitalized for infectious colitis at St. Mary's Hospital. All of the patients received ciprofloxacin therapy for the treatment of infectious colitis. We observed a few cases of rare adverse events, including ciprofloxacin-induced acute pancreatitis diagnosed based on the Naranjo algorithm. RESULTS: During ciprofloxacin therapy, seven of 227 patients (3.1%) developed rare pancreatitis as defined by the Naranjo algorithm; pancreatic enzyme activity was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average interval until the development of pancreatitis was 5.5 days (range, 4 to 7 days). On abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in three of seven patients. Complicating acute pancreatitis was gradually but completely resolved after cessation of ciprofloxacin administration. The mean recovery time was 11.3 days (range, 8 to 15 days). CONCLUSIONS: We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Ciprofloxacin-induced pancreatitis presents a short latency, suggesting an idiosyncratic hypersensitivity reaction. Practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy.

Improvement of bacterial hydrogen production by ATP in mixed organic compounds extracted from Rhodobacter sphaeroides aerobically cultured under dark conditions.

The aim of this study was to increase the hydrogen production of recombinant Escherichia coli harboring HupSL hydrogenase by supplementing physiologically activating compounds extracted from Rhodobacter sphaeroides cultured under anaerobic dark condition after treating them with dimethyl sulfoxide, and the 0.5% extracts contained 4×10(-8)M ATP, which was 100-fold higher than that in the extracts from E. coli. In addition, it was found that the hydrogen production from recombinant E. coli harboring HupSL hydrogenase isolated from R. sphaeroides was doubled under anaerobic conditions when it was supplemented by the extracts from R. sphaeroides cultured aerobically in dark conditions, and this also showed consistent pattern with the increased level of HupSL hydrogenase expression. Therefore, we conclude that the mixed organic compounds extracted from R. sphaeroides have an ATP which enhances the hydrogen production by increasing the amount of HupSL hydrogenase.

Differences in the volatile compositions of ginseng species (Panax sp.).

The volatile compositions in dried white ginseng according to species (Panax ginseng, Panax notoginseng, and Panax quinquefolius) were analyzed and compared by applying multivariate statistical techniques to gas chromatography-mass spectrometry data sets. Main volatile compounds of ginseng species in the present study were sesquiterpenes, such as bicyclogermacrene, (E)-ß-farnesene, ß-panasinsene, calarene, α-humulene, ß-elemene, etc. In particular, α-selinene, α-terpinolene, ß-bisabolene, ß-phellandrene, ß-sesquiphellandrene, zingiberene, germacrene D, limonene, α-gurjunene, (E)-caryophyllene, δ-cadinene, (E)-ß-farnesene, α-humulene, bicyclogermacrene, longiborn-8-ene, ß-neoclovene, and (+)-spathulenol were mainly associated with the difference between P. ginseng and P. notoginseng versus P. quinquefolius species. On the other hand, the discrimination between P. ginseng and P. notoginseng could be constructed by hexanal, 2-pyrrolidinone, (E)-2-heptenal, (E)-2-octenal, heptanal, isospathulenol, (E,E)-2,4-decadienal, 3-octen-2-one, benzaldehyde, 2-pentylfuran, and (E)-2-nonenal.

The compositions of volatiles and aroma-active compounds in dried omija fruits (Schisandra chinensis Baillon) according to the cultivation areas.

Differences in the compositions of volatiles from dried omija fruits (Schisandra chinensis Baillon) cultivated in different areas (Mungyeong, Jangsu, Jechon, and Hoengseong) in South Korea were determined by applying principal component analysis to gas chromatography-mass spectrometry data sets. Quantitative assessments revealed that terpene hydrocarbons, such as germacrene D, ß-selinene, α-ylangene, ß-elemene, α-selinene, and (E)-ß-farnesene, were the main volatiles in all omija fruit samples. On the other hand, (E)-ß-ocimene, calarene, (E)-ß-farnesene, ß-selinene, nonanal, 2-methylbutanoic acid, benzoic acid, 2,3-butanediol, and phenethyl alcohol were the major volatile components that contributed to the discrimination between omija fruit samples from the four cultivation areas. In addition, aroma-active compounds in four dried omija fruits were investigated and compared by gas chromatography-olfactometry using aroma extract dilution analysis. (E)-ß-Ocimene (floral and herbaceous), α-pinene (pine-like and woody), hexanal (cut grass-like), 5-methylfurfural (burnt sugar-like and sweet), and α-terpinene (minty, green, and fresh) were important aroma-active compounds in all omija samples. Interestingly, the flavor dilution factors of most aroma-active compounds were lower for omija sample cultivated in Hoengseong than for those cultivated in Mungyeong, Jangsu, and Jechon.

Enhancement of ornithine production in proline-supplemented Corynebacterium glutamicum by ornithine cyclodeaminase.

In this study, Corynebacterium glutamicum and its derived mutants were used to demonstrate the relationship between proline, glutamate and ornithine. The maximum ornithine production was shown in the culture medium (3295.0 mg/l) when the cells were cultured with 20 mM proline and was 15.5 times higher than in the presence of 1 mM proline. However, glutamate, which known as an intermediate in the process of converting proline to ornithine, did not have any positive effect on ornithine production. This suggests that the conversion of proline to ornithine through glutamate, is not possible in C. glutamicum. Comparative analysis between the wild-type strain, SJC8043 (argF-, argR-) and SJC8064 (argF-, argR- and ocd-), showed that C. glutamicum could regulate ornithine production by ornithine cyclodeaminase (Ocd) under proline-supplemented conditions. Therefore, proline directly caused an increase in the endogenous level of ornithine by Ocd, which would be a primary metabolite in the ornithine biosynthesis pathway.

Inhibition of c-Jun N-terminal kinase sensitizes tumor cells to flavonoid-induced apoptosis through down-regulation of JunD.

Reduction of susceptibility to apoptosis signals is a crucial step in carcinogenesis. Therefore, sensitization of tumor cells to apoptosis is a promising therapeutic strategy. c-Jun NH2-terminal kinase (JNK) has been implicated in stress-induced apoptosis. However, many studies also emphasize the role of JNK on cell survival, although its mechanisms are not completely understood. Previously, we found that inhibition of JNK activity promotes flavonoid-mediated apoptosis of human osteosarcoma cells. We thus determined whether inhibition of JNK sensitizes tumor cells to a bioflavonoid-induced apoptosis, and whether this effect of JNK is a general effect. As the results, quercetin and genistein as well as a flavonoid fraction induced apoptosis of tumor cells, which was further accelerated by specific JNK inhibitor, SP600125 or by small interfering RNA specific to JNK1/2. This effect was specific to types of cells because it was further apparent in tumorigenic cell lines. Inhibition of JNK by SP600125 also reduced flavonoid-stimulated nuclear induction of JunD which was known to have protective role in apoptosis, whereas JNK inhibition alone had little effect on apoptosis. The flavonoid-induced apoptosis of tumor cells was significantly enhanced by transfecting them with antisense JunD oligonucleotides. These results suggest that inhibition of JNK facilitates flavonoid-induced apoptosis through down-regulation of JunD, which is further sensitive to tumor cells. Therefore, combination with a specific JNK inhibitor further enhances the anti-cancer and chemopreventive potential of bio-flavonoids.