Angelica gigas polysaccharide induces CR3-mediated macrophage activation and the cytotoxicity of natural killer cells against HCT-116 cells via NF-κB and MAPK signaling pathways.

Angelica gigas (A. gigas) is traditional medicinal herb that mainly exists in Korea and northeastern China. There have been relatively few studies conducted thus far on its polysaccharides and their bioactivities. We purified and described a novel water-soluble polysaccharide derived from A. gigas and investigated its immunoenhancing properties. The basic components of crude and purified polysaccharides (F1 and F2) were total sugar (41.07% - 70.55%), protein (1.12-10.33%), sulfate (2.9-5.5%), and uronic acids (0.5-31.05%) in total content. Our results demonstrated that the crude and fractions' molecular weights (Mw) varied from 42.2 to 285.2 × 103 g/mol. As the most effective polysaccharide, F2 significantly stimulated RAW264.7 cells to release nitric oxide (NO) and express several cytokines. Furthermore, F2 increased the expression of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-É£), natural killer cytotoxicity receptors (NKp44), and granzyme-B in NK-92 cells and enhanced the cytotoxicity against HCT-116 cells. In our experiments, we found that F2 stimulated RAW264.7 cells and NK-92 cells via MAPK and NF-κB pathways. The monosaccharide and methylation analysis of the high immunostimulant F2 polysaccharide findings revealed that the polysaccharide was primarily composed of 1 â†’ 4, 1 â†’ 6, 1 â†’ 3, 6, 1 â†’ 3 and 1 â†’ 3, 4, 6 galactopyranose residues, 1 â†’ 3 arabinofuranose residues, 1 â†’ 4 glucopyranose residues. These results demonstrated that the F2 polysaccharide of A. gigas which possesses potential immunostimulatory attributes, could be used to create a novel functional food.

The Influence of Tyrosol-Enriched Rhodiola sachalinensis Extracts Bioconverted by the Mycelium of Bovista plumbe on Scopolamine-Induced Cognitive, Behavioral, and Physiological Responses in Mice.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, which are accompanied by memory loss and cognitive disruption. Rhodiola sachalinensis (RSE) is a medicinal plant that has been used in northeastern Asia for various pharmacological activities. We attempted to carry out the bioconversion of RSE (Bio-RSE) using the mycelium of Bovista plumbe to obtain tyrosol-enriched Bio-RSE. The objective of this study was to investigate the effects of Bio-RSE on the activation of the cholinergic system and the inhibition of oxidative stress in mice with scopolamine (Sco)-induced memory impairment. Sco (1 mg/kg body weight, i.p.) impaired the mice's performance on the Y-maze test, passive avoidance test, and water maze test. However, the number of abnormal behaviors was reduced in the groups supplemented with Bio-RSE. Bio-RSE treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. Bio-RSE dramatically improved the cholinergic system by decreasing acetylcholinesterase activity and regulated oxidative stress by increasing antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)). The reduction in nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in the brain tissue due to scopolamine was restored by the administration of Bio-RSE. Bio-RSE also significantly decreased amyloid-beta 1-42 (Aß1-42) and amyloid precursor protein (APP) expression. Moreover, the increased malondialdehyde (MDA) level and low total antioxidant capacity in Sco-treated mouse brains were reversed by Bio-RSE, and an increase in Nrf2 and HO-1 was also observed. In conclusion, Bio-RSE protected against Sco-induced cognitive impairment by activating Nrf2/HO-1 signaling and may be developed as a potential beneficial material for AD.

Anti-Obesity Effect of Lactobacillus plantarum LB818 Is Associated with Regulation of Gut Microbiota in High-Fat Diet-Fed Obese Mice.

Worldwide, obesity has become a major risk factor associated with health risks such as diabetes, hypertension, hypercholesterolemia, cardiovascular disease, stroke, and certain forms of cancer. In this study, we estimated the anti-obesity effect of the bacterial strain Lactobacillus plantarum LB818 (designated as LB818) using male C57BL/6J mice, which were treated with high-fat diet (HFD) to induce obesity. Next, LB818 (109 colony-forming units [CFU]/mL) was orally administered for 8 weeks. The results showed that feeding HFD+LB818 (109 CFU/mL) ameliorated body weight gain and decreased total body fat by regulating fasting glucose levels in HFD-fed mice. LB818 treatment significantly lowered aspartate aminotransferase, alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), and elevated high-density lipoprotein levels in serum and decreased deposition of fat droplets in liver. LB818 treatment increased the respective abundances of essential bacteria, including Bacteroidetes, Akkermansia, Bifidobacterium, Lactobacillus, and increased the Bacteroidetes:Firmicutes ratio; however, it significantly decreased the levels of Firmicutes. Taken together, this study demonstrates that LB818 is effective in attenuating obesity and hepatic steatosis and regulated gut microbiota in HFD-fed obese mice.

Gamma Irradiated Rhodiola sachalinensis Extract Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Downregulating 5-Alpha Reductase and Restoring Testosterone in Rats.

The effect of Rhodiola sachalinensis Boriss extract irradiated with 50 kGy gamma rays (HKC) on benign prostatic hyperplasia (BPH) was investigated. Seven-week-old male SD rats received a subcutaneous injection of 20 mg/kg of testosterone propionate (TP) to induce BPH. Then, the testosterone only group received testosterone, the testosterone + finasteride group received testosterone and finasteride (5 mg/kg), the testosterone + HKC group received testosterone and HKC extract (500 mg/kg). Prostate weight and the dihydrotestosterone (DHT) levels in serum or prostate tissue were determined. The mRNA expressions of 5-alpha reductase (AR) in prostate tissue were also measured. Compared to the control group, prostate weight was significantly improved in the TP group and decreased in the HKC and finasteride-treated groups. Furthermore, the mRNA expression of 5-AR in the prostate was significantly reduced in the HKC and finasteride-treated groups. Similarly, the expression levels of α-smooth muscle actin (α-SMA) and cytokeratin, which are associated with prostatic enlargement in the HKC and finasteride groups, were much lower than in the TP group. HKC treatment showed similar efficacy to finasteride treatment on rats with testosterone-induced BPH. HKC may be explored as a potential new drug for BPH treatment.

A Case-Control Study of Real-Life Experience with Ceftolozane-Tazobactam in Patients with Hematologic Malignancy and Pseudomonas aeruginosa Infection.

We present our experience in patients with hematologic malignancy and Pseudomonas aeruginosa infection treated with ceftolozane-tazobactam. We performed a single-center case-control study comparing patients with hematologic malignancy and P. aeruginosa infection treated with ceftolozane-tazobactam (study group) with similar patients not treated with ceftolozane-tazobactam (control group) to assess safety and efficacy. Nineteen cases and 38 controls were analyzed. Cases were younger (45.6 years versus 57.6 years; P = 0.012) and less frequently had bacteremia (52.6% versus 86.8%; P = 0.008). They also had worse Multinational Association for Supportive Care in Cancer (MASCC) scores (10.2 versus 16.1; P = 0.0001), more hospital-acquired infections (78.9% versus 47.4%; P = 0.013), and more extremely drug-resistant (XDR) P. aeruginosa infections (47.4% versus 21.1%; P = 0.015). Cases received a median of 14 days (7 to 18 days) of ceftolozane-tazobactam (monotherapy in 11 cases [57.9.6%]). Ceftolozane-tazobactam was mostly used as targeted therapy (16 cases; 84.2%) because of resistance (9 cases; 47.4%), failure (4 cases; 21.1%), and toxicity (3 cases; 15.8%). Ten cases had bacteremia (52.6%). The sources were pneumonia (26.3%), catheter-related bacteremia (21.1%), primary bacteremia (21.1%), and perianal/genital (15.7%), urinary (10.5%), and skin/soft tissue (5.3%) infection. No toxicity was attributed to ceftolozane-tazobactam. More than 60% had neutropenia, and 15.8% fulfilled the criteria for sepsis. There were no significant differences in clinical cure at day 14 (89.5% versus 71.1%; P = 0.183) or recurrence (15.8% versus 10.5%; P = 0.675). Thirty-day mortality was lower among cases (5.3% versus 28.9%; P = 0.045). Ceftolozane-tazobactam was well tolerated and at least as effective as other alternatives for P. aeruginosa infection in patients with hematologic malignancy, including neutropenic patients with sepsis caused by XDR strains.

Simultaneous determination of saikosaponin a, paeonol, and imperatorin, components of DA-9805, in rat plasma by LC-MS/MS and application to a pharmacokinetic study.

DA-9805 is a new botanical antiparkinson drug candidate formulated using an ethanolic extract of the root of Bupleurum falcatum, the root cortex of Paeonia suffruticosa, and the root of Angelica dahurica. In this study, a sensitive and rapid LC-MS/MS method was developed to simultaneously determine, saikosaponin a, paeonol, and imperatorin, three active/representative ingredients of DA-9805, in rat plasma. Plasma was extracted by mixture of ethyl acetate and methyl tertiary butyl ether. Chromatographic separation was carried out using a C18 column and a gradient elution of mobile phases consisting of 5mM formic acid in water and acetonitrile. Total chromatographic run time was 10.5min. Multiple reaction monitoring mode was used for mass spectrometry; the transitions were m/z 779.5→617.2 for saikosaponin a in negative-ion mode, m/z 167→149 for paeonol and m/z 271.1→203 for imperatorin in positive-ion mode. Calibration curves were constructed in the range of 0.5-1000ng/mL for saikosaponin a, 20-10000ng/mL for paeonol, and 0.2-1000ng/mL for imperatorin. All the validation data, including the selectivity, linearity, precision, accuracy, recovery, matrix effect, and stability satisfied the acceptance requirements. The method was successfully applied in a pharmacokinetic study of saikosaponin a, paeonol, and imperatorin following oral administration of DA-9805.

Anti-Inflammatory Effect of Ethanolic Extract of Sargassum serratifolium in Lipopolysaccharide-Stimulated BV2 Microglial Cells.

Sargassum serratifolium was found to contain high concentrations of meroterpenoids, having strong antioxidant, anti-inflammatory, and neuroprotective activities. This study aims to investigate the anti-inflammatory mechanisms of an ethanolic extract of S. serratifolium (ESS) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and to identify the anti-inflammatory components in ESS. The level of proinflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of inflammation-related proteins and mRNA was evaluated by Western blot and reverse transcription-polymerase chain reaction analysis, respectively. Anti-inflammatory activities of isolated components from ESS were analyzed in LPS-stimulated BV2 cells. ESS inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 and the expression of inducible NO synthase and cyclooxygenase-2. ESS also decreased the release of proinflammatory cytokines in a dose-dependent manner. LPS-induced nuclear factor-kappa B (κB) transcriptional activity and translocation into the nucleus were remarkably suppressed by ESS through the prevention of inhibitor κB-α degradation. The main anti-inflammatory components in ESS were identified as sargahydroquinoic acid, sargachromenol, and sargaquinoic acid based on the inhibition of NO production using LPS-stimulated BV2 cells. Furthermore, treatment with ESS significantly reduced levels of tumor necrosis factor-α and interleukin-1ß stimulated with LPS in mouse hippocampus. Our results indicate that ESS can be used as a functional food or therapeutic agent for the treatment of neuroinflammatory diseases.

2,4-dichlorophenoxyacetic acid-induced leaf senescence in mung bean (Vigna radiata L. Wilczek) and senescence inhibition by co-treatment with silver nanoparticles.

Leaf senescence induced by 2,4-dichlorophenoxyacetic acid (2,4-D) and senescence inhibition caused by supplementation with silver (Ag(+)) ions in the form of silver nitrate (AgNO(3)) or silver nanoparticles (AgNPs) were investigated in 8-day-old mung bean (Vigna radiata L. Wilczek) seedlings. Inhibition of root and shoot elongation were observed in mung bean seedlings treated with 500µM 2,4-D. Concomitantly, the activity of 1-aminocyclopropane-1-carboxylic acid synthase was significantly induced in leaf tissue. Leaf senescence induced by 2,4-D was closely associated with lipid peroxidation as well as increased levels of cytotoxic hydrogen peroxide (H(2)O(2)) and superoxide radicals (O(2)(·-)). Despite decreased catalase activity, the activities of peroxidase, superoxide dismutase, monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase were increased during 2,4-D-induced leaf senescence. Further, the levels of reduced ascorbate, oxidized ascorbate, and reduced glutathione were markedly decreased, whereas the level of oxidized glutathione increased. 2,4-D-induced leaf senescence in mung bean was accompanied by an increase in positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, nuclear DNA fragmentation, and the activity of a 15-kDa Ca(2+)-dependent DNase. Supplementation with 100µM AgNO(3) or AgNPs inhibited 2,4-D-induced leaf senescence. The present results suggest that increased oxidative stress (O(2)(·-) and H(2)O(2)) led to senescence in mung bean leaves. Furthermore, significantly induced antioxidative enzymes are not sufficient to protect mung bean cells from 2,4-D-induced harmful ROS.

Chemoprotective effects of a protein from the red algae Porphyra yezoensis on acetaminophen-induced liver injury in rats.

Seaweeds contribute to the maintenance of health through their nutritional and medicinal properties. The effects of PYP, a 14 kDa protein isolated from a hot-water extract of the marine alga Porphyra yezoensis, on AAP-induced liver injury in rats was evaluated. AAP induced acute liver injury and AAP-induced hepatotoxicity is the leading cause of liver failure. In this study, male Sprague-Dawley rats were assigned to one of three treatment groups: control, AAP, or AAP + PYP. Compared with the control group, liver tissue from the AAP group showed increased levels of caspase-3 activity and DNA fragmentation, decreased levels of GSH and increased serum GOT/GPT levels. In contrast, treatment with AAP + PYP produced levels of caspase-3 activity, DNA fragmentation, GSH and GOT/GPT that matched the values seen in the control group. It is concluded that PYP may prevent AAP-induced liver injury.

Regulatory effects of cytokine production in atopic allergic reaction by gammi-danguieumja.

Gammi-danguieumja (GD) is clinically used in South Korea for treating atopic dermatitis. However, its effects in experimental models remain unknown. We investigated a possible effect of GD on cytokines production using human T cell line (MOLT-4) or human mast cell line. As a result, GD (0.01 mg/mL)-containing medium in stimulated culture supernatants increased IL-2 and IFN-gamma, and decreased IL-4 secretion in MOLT-4. GD (0.01-1 mg/mL)-containing medium in stimulated culture supernatants dose-dependently and significantly decreased IL-8, IL-13, and tumor necrosis factor-alpha secretion on the phorbol 12-myristate 13-acetate and A23187-stimulated HMC-1. In addition, GD inhibited histamine release from activated mast cells. These results suggest that GD contributes to the regulation of atopic allergic reactions.