Anti-inflammatory effects of the Aralia elata and Cirsium japonicum in Raw264.7 cells and in vivo colitis model in mice and dogs.

Ulcerative colitis (UC) is a severe inflammatory disease that has spread throughout the world. Cirsium japonicum (CJ) and Aralia elata (AE) are natural herbs with potent antioxidative antidiabetics and anti-inflammatory effects. In this investigation, we studied the defensive role of the combination of CJ and AE against LPS-induced inflammation in RAW 264.7 cells, dextran sulfate sodium (DSS)-induced colitis in mice, and acetic acid-induced colitis in dogs. MTT assay was performed to identify the toxic effect of CJ and AE extracts. NO, and MDA level was also measured by NO and MDA assay. To measure the pro-inflammatory protein expression, a western blot was performed. To induce colitis, 3% DSS was used for mice and 6% acetic acid was used for dogs. Histopathology and colonoscopy were executed to detect the effect of extracts. CJ and AE pretreatment reduced the level of NO, MDA, and the expression of pro-inflammatory proteins cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in RAW 264.7. Compared to the separate doses of CJ and AE, the combined dose of CJ and AE significantly reduced clinical symptoms induced by DSS in mice and acetic acid in dogs including weight loss, bloody stool, shortening of the colon, and the severity of colitis and degree of histological damage in the colon. Therefore, these results indicated that a combined dose of CJ and AE has a protective effect against LPS-induced RAW 264.7 cells, DSS-mediated colonic inflammation in mice, and acetic acid-induced colitis in dogs.

Corrigendum to "WS-5 Extract of Curcuma longa, Chaenomeles sinensis, and Zingiber officinale Contains Anti-AChE Compounds and Improves ß-Amyloid-Induced Memory Impairment in Mice".

[This corrects the article DOI: 10.1155/2019/5160293.].

Osmotic Demyelination Syndrome Associated with Hypernatremia Caused by Lactulose Enema in a Patient with Chronic Alcoholism.

A 44-year-old man with chronic alcoholism presented with seizure and loss of consciousness. He was diagnosed with alcoholic hepatic encephalopathy, and his neurologic symptoms recovered after lactulose enema treatment. His initial serum sodium level was 141mEq/L. However, his mental state became confused after treatment with lactulose enema for five days, and his serum sodium level increased to 178mEq/L. After five days of gradual correction of serum sodium level from 178mEq/L to 140mEq/L, the patient's mental state recovered, but motor weakness in both limbs remained. Therefore, magnetic resonance imaging of the brain was performed. T2-weighted brain images showed bilateral symmetrical hyperintensities in the central pons, basal ganglia, thalami, hippocampi and unci, which were consistent with central pontine and extrapontine myelinolysis. We report a rare case of osmotic demyelination syndrome that occurred as a result of a rapid increase from a normal sodium level to hypernatremia caused by lactulose enema administered to treat alcoholic hepatic encephalopathy.

Enhanced bioactivity of Zanthoxylum schinifolium fermented extract: Anti-inflammatory, anti-bacterial, and anti-melanogenic activity.

Fermented extracts have evolved to be a potential alternative to synthetic chemicals, owing to their anti-inflammatory and anti-bacterial properties. This study intends to assess the potential of fermented Zanthoxylum schinifolium extract for use in biomedical applications. Probiotic bacteria, Lactobacillus rhamnosus A6-5, were deployed as a seed culture for fermentation. The fermented extract showed greater tyrosinase inhibitory activity and reduced melanin production (58.3%) compared with the raw extract. Cytotoxicity assay inferred that 500 µg/mL is the ideal non-toxic concentration with maximum cell viability. In addition, DAPI staining did not show any damage to the chromatin structure of the cells. The anti-aging property of the fermented extract was confirmed by a decrease in IL-6 content. The fermented extract showed lower MIC (40 mg/mL) and MBC (60 mg/mL), indicating greater anti-bacterial activity than the raw extract. The results confirmed that the fermented Z. schinifolium extract has high biomedical properties compared with the raw extract and can be used as an ideal skin whitening agent.

WS-5 Extract of Curcuma longa, Chaenomeles sinensis, and Zingiber officinale Contains Anti-AChE Compounds and Improves ß-Amyloid-Induced Memory Impairment in Mice.

Alzheimer's disease (AD) is linked to an extensive neuron loss via accumulation of amyloid-beta (Aß) as senile plaques associated with reactive astrocytes and microglial activation in the brain. The objective of this study was to assess the therapeutic effect of WS-5 ethanol extract in vitro and in vivo against Aß-induced AD in mice and to identify the extract's active constituents. In the present study, WS-5 exerted a significant inhibitory effect on acetylcholinesterase (AChE). Analysis by transmission electron microscopy (TEM) revealed that WS-5 prevented Aß oligomerization via inhibition of Aß 1-42 aggregation. Evaluation of antioxidant activities using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) demonstrated that WS-5 possessed a high antioxidant activity, which was confirmed by measuring the total antioxidant status (TAS). Furthermore, the anti-inflammatory properties of WS-5 were examined using lipopolysaccharide-stimulated BV-2 microglial cells. WS-5 significantly inhibited the lipopolysaccharide-induced production of nitric oxide and two proinflammatory cytokines, TNF-α and IL-6. The memory impairment in mice with Aß-induced AD was studied using the Morris water maze and passive avoidance test. Immunohistochemistry was performed to monitor pathological changes in the hippocampus and cortex region of the mouse brain. The animal study showed that WS-5 (250 mg/kg) treatment improved learning and suppressed memory impairment as well as reduced Aß plaque accumulation in Aß-induced AD. HPLC analysis identified the extract's active compounds that exert anti-AChE activity. In summary, our findings suggest that WS-5 could be applied as a natural product therapy with a focus on neuroinflammation-related neurodegenerative disorders.

An Ethanolic Extract of Allium hookeri Root Alleviates Reflux Esophagitis and Modulates NF-κB Signaling.

Reflux esophagitis (RE) is a kind of gastroesophageal reflux disease, of which an esophageal inflammatory lesion is caused by the contents of the stomach and duodenum flowing back into the esophagus. Allium hookeri is a plant possessing both nutritional and medicinal properties. In our study, we investigated the inhibition effect of inflammation of A. hookeri root extract (AHE) on inflammatory RAW264.7 macrophage cells induced by lipopolysaccharide and rat models of RE. The results showed that AHE significantly reduced the production of nitric oxide (NO) and the protein expression levels of various mediators related to inflammation including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines such as interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α). Furthermore, AHE also inhibited the nuclear translocation of nuclear factor kappa B (NF-κB) by inhibiting the phosphorylation IκBα. In addition, AHE administration significantly ameliorated esophageal mucosal damage upon histological evaluation of RE in rats. AHE was also found to downregulate the expression levels of proteins such as COX-2, TNF-α, and IL-1ß in the rat esophagus. AHE markedly attenuated activation of NF-κB and phosphorylation of IκBα at the same time. These results indicated that AHE suppressed LPS-induced inflammatory responses in RAW264.7 cells and may help reduce the development of esophagitis through the modulation of inflammation by regulating NF-κB activation.

The Effect of Aronia Berry on Type 1 Diabetes In Vivo and In Vitro.

The number of diabetic patients worldwide is increasing, and complications such as stroke and cardiovascular disease are becoming a serious cause of death. Diabetes mellitus is classified into two types according to the etiopathogenic mechanism and insulin dependence. Type 1 diabetes (T1D), an insulin-dependent diabetes mellitus, is caused by damage and destruction of pancreatic ß cells that produce insulin. It is a disease that is characterized by hyperglycemia and hypoinsulinemia. Aronia berry has been used as a medicinal food in Europe. Aronia contains a variety of ingredients such as polyphenols, anthocyanins, flavonoids, and tannins. Especially, anthocyanin content in aronia berry is known to be much higher than in other plants and berries. It is known for exerting antioxidant, anti-inflammation, and anti-aging effects. Therefore, this study was conducted to investigate the effects of aronia berry extract intake in multiple low-dose streptozotocin (STZ)-induced T1D and to confirm the functional properties of aronia berry. ICR mice (6-week male) were divided into four groups: control (normal control group), STZ (100 mg/kg of STZ-induced T1D group), AR 10 (STZ with oral administration of aronia 10 mg/kg), and AR 100 (STZ with oral administration of aronia 100 mg/kg). Afterward, STZ was injected in a single dose to induce T1D, and the extract was orally administered daily. Dietary intake and body weight were measured twice a week. We confirmed that aronia berry has the effect of decreasing the increase of blood glucose level and also has the protection effect of pancreas ß cell (RINm5F cell). This study confirms the anti-diabetic activity of aronia berry, and it can be expected to increase the utilization according to the results.

The Anti-Stress Effect of Mentha arvensis in Immobilized Rats.

Stress can lead to inflammation, accelerated aging, and some chronic diseases condition. Mentha arvensis (MA) is a traditional medicine having antioxidant and anti-inflammatory activities. The present study investigated the anti-stress role of MA and fermented MA (FMA) extract in immobilized rats. We studied the lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells and rats were immobilized for 2 h per day for 14 days using a restraining cage. MA (100 mg/kg) and FMA (100 mg/kg) were orally administered to rats 1 h prior to immobilization. Using high-performance liquid chromatography (HPLC) analysis, we determined the rosmarinic acid content of MA and FMA. The generation of malondialdehyde (MDA) and nitric oxide (NO) in RAW 246.7 cells were suppressed by both MA and FMA. In rats, MA and FMA notably improved the body weight, daily food intake, and duodenum histology. MDA and NO level were gradually decreased by MA and FMA treatment. MA and FMA significantly controlled the stress-related hormones by decreasing corticosterone and ß-endorphin and increasing serotonin level. Moreover, protein expression levels of mitogen activated protein kinases (MAPK) and cyclooxygenase-2 (COX-2) were markedly downregulated by MA and FMA. Taken together, MA and FMA could ameliorate immobilized-stress by reducing oxidative stress, regulating stress-related hormones, and MAPK/COX-2 signaling pathways in rats. Particularly, FMA has shown greater anti-stress activities than MA.

Unraveling Metabolic Variation for Blueberry and Chokeberry Cultivars Harvested from Different Geo-Climatic Regions in Korea.

Temporal geo-climatic variations are presumably vital determinants of phenotypic traits and quality characteristics of berries manifested through reconfigured metabolomes. We performed an untargeted mass spectrometry (MS)-based metabolomic analysis of blueberry (Vaccinium spp.) and chokeberry (Aronia melanocarpa) sample extracts harvested from different geo-climatic regions in Korea. The multivariate statistical analysis indicated distinct metabolite compositions of berry groups based on different species and regions. The amino acids levels were relatively more abundant in chokeberry than in blueberry, while the sugar contents were comparatively higher in blueberry. However, the metabolite compositions were also dependent on geo-climatic conditions, especially latitude. Notwithstanding the cultivar types, amino acids, and sucrose were relatively more abundant in berries harvested from 35°N and 36°N geo-climatic regions, respectively, characterized by distinct duration of sunshine and rainfall patterns. The present study showed the ability of a metabolomics approach for recapitulating the significance of geo-climatic parameters for quality characterization of commercial berry types.

Aronia Berry Extract Ameliorates the Severity of Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis (UC), is a group of inflammatory conditions of the colon and small intestine. UC is a chronic inflammatory disorder of the colon and rectum that includes intervals of acute exacerbation. Although recent studies have suggested that proinflammatory cytokines might have initiated the inflammatory responses in UC, its etiology remains unclear. Aronia berries are rich in dietary polyphenols such as phenolic acids, anthocyanins, flavonoids, and proanthocyanidins with various health benefits, including antioxidant, anti-inflammatory, and antiaging activities. The objective of this study was to determine whether Aronia berry can be an effective intervention for the treatment of UC. BALB/c mice were administered 5% dextran sulfate sodium (DSS) to induce UC. They were then given Aronia berry extracts at concentrations of 10 or 100 mg/kg. During the induction of UC, the expression levels of nuclear factor-kappa B were increased in colonic epithelial cells and immune cells, leading to increased proinflammatory cytokine levels. Aronia berry extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. Furthermore, oral administration of Aronia berry extract inhibited prostaglandin E2 production in DSS-induced colitis and decreased the levels of nitric oxide, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated macrophages. These results suggest that Aronia berry extract could efficiently ameliorate clinical signs and inflammatory mediators of UC. Therefore, Aronia berry might be a promising natural treatment for UC.

Aronia melanocarpa (Black Chokeberry) Reduces Ethanol-Induced Gastric Damage via Regulation of HSP-70, NF-κB, and MCP-1 Signaling.

Aronia melanocarpa (Michx.) Ell. belongs to the Rosaceae family. The purpose of this study is to explore the gastroprotective effect of the Aronia melanocarpa hydro-alcoholic extract (AMHAE) against ethanol-induced gastric ulcer in a rat model. Different concentrations (50, 100, and 200 mg/kg) of AMHAE, or 30 mg/kg of omeprazole, significantly inhibited the gastric injury formation. The ethanol-induced ulcer group showed significant increases of malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, nuclear factor-kappaB p65 (NF-κB p65), and monocyte chemoattractant protein (MCP)-1, and decreased activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-px), and interleukin (IL)-4. However, AMHAE (200 mg/kg) pretreatment significantly reversed the altered pathophysiological levels of these biomolecules to near normal stages. The gastroprotective activity of AMHAE was abolished by pretreatment with l-NAME, naloxone, capsazepine, and indomethacin, demonstrating the participation of nitric oxide (NO), opioids, TRPV (vanilloid receptor-related transient receptor potential), and prostaglandins in AMHAE-assisted gastroprotection against ethanol-induced gastric injuries. This gastroprotective effect of AMHAE might be due to the downregulation of TNF-α-based NF-κB, MCP-1 signaling and strong antioxidant properties.

Biomolecule-loaded chitosan nanoparticles induce apoptosis and molecular changes in cancer cell line (SiHa).

The present study reports on the synthesis of chitosan nanoparticles (CNPs) using methanol extracts of Gymnema sylvestre (GS) leaves and Cinnamomum zeylanicum (CZ) bark. Biomolecule-loaded nanoparticles induced apoptosis in a human cervical cancer (SiHa) cell line, and experiments were carried out to elucidate the underlying molecular mechanisms. FT-IR and XRD showed possible functional groups of the biomolecules and the crystalline nature of CNPs, respectively. Transmission electron microscopy images revealed that synthesized GSCNPs and CZCNPs had a smooth spherical shape with average sizes of about 58-80 and 60-120nm, respectively. Dynamic light scattering studies indicated that both GSCNPs and CZCNs were structurally stable with homogenous and heterogeneous natures, respectively. Furthermore, synthesized GSCNPs and CZCNPs exhibited dose-dependent cytotoxicity against the SiHa cancer cell line, with inhibitory concentration (IC50) values of 102.17µg/ml, 87.75µg/ml, 132.74µg/ml and 90.35µg/ml for GS leaf extract, GSCNPs, CZBE and CZCNPs, respectively.

Synergistic Effect between Cryptotanshinone and Antibiotics against Clinic Methicillin and Vancomycin-Resistant Staphylococcus aureus.

Cryptotanshinone (CT), a major tanshinone of medicinal plant Salvia miltiorrhiza Bunge, demonstrated strong antibacterial activity against clinic isolated methicillin and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) in this experiment. The CT was determined against clinic isolated MRSA 1-16 with MIC and MBC values ranging from 4 to 32 and 8 to 128 µ g/mL; for MSSA 1-2 from 16 to 32 µ g/mL and 64 to 128 µ g/mL; for VRSA 1-2 from 2 to 4 µ g/mL and 4 to 16 µ g/mL, respectively. The range of MIC50 and MIC90 of CT was 0.5-8 µ g/mL and 4-64 µ g/mL, respectively. The combination effects of CT with antibiotics were synergistic (FIC index <0.5) against most of tested clinic isolated MRSA, MSSA, and VRSA except additive, MRSA 4 and 16 in oxacillin, MRSA 6, 12, and 15 in ampicillin, and MRSA 6, 11, and 15 in vancomycin (FIC index < 0.75-1.0). Furthermore, a time-kill study showed that the growth of the tested bacteria was completely attenuated after 2-6 h of treatment with the 1/2 MIC of CT, regardless of whether it was administered alone or with ampicillin, oxacillin, or vancomycin. The results suggest that CT could be employed as a natural antibacterial agent against multidrug-resistant pathogens infection.

Comparative analysis of chemical compositions and antimicrobial activities of essential oils from Abies holophylla and Abies koreana activities of essential oils from Abies holophylla and Abies koreana.

The chemical compositions and antibacterial and antifungal activities of essential oils extracted from Abies holophylla and A. koreana were investigated. GC-MS analysis revealed that 38 compounds comprised 95.88% of the A. holophylla essential oil, with the main components being bicyclo[2.2.1]heptan-2-ol (28.05%), delta3-carene (13.85%), alpha-pinene (11.68%), camphene (10.41%), dl-limonene (7.61%), beta-myrcene (7.11%), trans-caryophyllene (5.36%), and alpha- bisabolol (3.67%). In the essential oil from A. koreana, 36 compounds comprised 98.67% of the oil, and the main compounds were bornyl ester (41.79%), camphene (15.31%), alpha-pinene (11.19%), dl-limonene (8.58%), fenchyl acetate (5.55%), and alpha-terpinene (2.29%). Both essential oils showed great potential of antibacterial activity against several bacteria tested, in the range of 2.2-8.8 mug per disc by the agar disc diffusion method, and minimal inhibitory concentration (MIC) values of 5.5-21.8 mg/ml by the microdilution method. Both oils showed very effective antifungal activities toward all pathogenic strains tested, including Candida glabrata, with MIC values in the range of 0.5-2.2 mg/ml. As a whole, A.koreanaoil showed better antibacterial and antifungal properties than A.holophylla oil.

Comparison of chemical compositions and antimicrobial activities of essential oils from three conifer trees; Pinus densiflora, Cryptomeria japonica, and Chamaecyparis obtusa.

The chemical compositions, and antibacterial and antifungal effects of essential oils extracted from three coniferous species, Pinus densiflora, Cryptomeria japonica, and Chamaecyparis obtusa, were investigated. Gas chromatography mass analysis of the essential oils revealed that the major components and the percentage of each essential oil were 16.66% beta-phellandrene and 14.85% alpha-pinene in P. densiflora; 31.45% kaur-16-ene and 11.06% sabinene in C. japonica; and 18.75% bicyclo [2, 2, 1] heptan-2-ol and 17.41% 2-carene in Ch. obtusa. The antimicrobial assay by agar disc diffusion method showed that 2.2 microg of Ch. obtusa oil inhibited most effectively the growth of Escherichia coli ATCC 33312 and Klebsiella oxytoca ATCC 10031, whereas the C. japonica oil gave weak antimicrobial activity. The minimal inhibitory concentration (MIC) values for bacterial strains were in the range of 5.45-21.8 mg/ml depending on essential oils, but most Gram-negative bacteria were resistant even at 21.8 mg oil/ml. P. densiflora oil showed the most effective antifungal activity and the MIC values for Cryptococcus neoformans B42419 and Candida glabrata YFCC 062CCM 11658 were as low as 0.545 and 2.18 mg/ml, respectively. Cryp. neoformans B42419 was the most sensitive to all essential oils in the range of 0.545-2.18 mg/ml. Our data clearly showed that the essential oils from the three conifers had effective antimicrobial activity, especially against fungi.

Chemical composition and antimicrobial activity of essential oil from cones of Pinus koraiensis.

The essential oil from the cones of Pinus koraiensis was prepared after removing the seeds, and its chemical composition analyzed using gas chromatography-mass spectrometry (GC-MS). Hydrodistillation of the P. koraiensis cones yielded 1.07% (v/w) of essential oil, which was almost three times the amount of essential oil extracted from the needles of the same plant. Moreover, the antimicrobial activities of the oil against the growth of Gram-positive bacteria, Gram-negative bacteria, and fungi were evaluated using the agar disc diffusion method and broth microdilution method. Eighty-seven components, comprising about 96.8% of the total oil, were identified. The most abundant oil components were limonene (27.90%), alpha-pinene (23.89%), beta-pinene (12.02%), 3-carene (4.95%), beta-myrcene (4.53%), isolongifolene (3.35%), (-)-bornyl acetate (2.02%), caryophyllene (1.71%), and camphene (1.54%). The essential oil was confirmed to have significant antimicrobial activities, especially against pathogenic fungal strains such as Candida glabrata YFCC 062 and Cryptococcus neoformans B 42419. Therefore, the present results indicate that the essential oil from the cones of Pinus koraiensis can be used in various ways as a nontoxic and environmentally friendly disinfectant.

Antiinflammatory effect of Daesiho, a Korean traditional prescription for cerebral infarct patients.

Daesiho, a prescription composed of eight herbal mixtures, has been widely used in the treatment of cerebral infarct in Oriental medicine. However, the mechanisms by which the formula affects the production of pro-inflammatory cytokines in cerebral infarct patients remains unknown. The levels of secretory protein pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, were significantly increased in both lipopolysaccharide (LPS) and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from cerebral infarct patients and LPS-stimulated THP-1 differentiated macrophage-like cells (THP-1/M). However, pretreatment with Daesiho significantly inhibited the secretion of pro-inflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6, in stimulated PBMCs and THP-1/M cells. In addition, Daesiho significantly suppressed mRNA expression of pro-inflammatory cytokines. Therefore, these data indicate that Daesiho may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression of the production of pro-inflammatory cytokines via inhibition of mRNA expression.

Anti-inflammatory effect of oyaksungisan in peripheral blood mononuclear cells from cerebral infarction patients.

Oyaksungisan, the herbal prescription composed of eleven herbs, has been widely used in treatment of cerebral infarct in Oriental Medicine. However, the mechanisms by which the herbal formula affects on the production of pro- and anti-inflammatory cytokines in cerebral infarction patients remain unknown yet. The secretory levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and IL-10 were significantly increased in both LPS and PHA-stimulated peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients. However, pretreatment with oyaksungisan significantly inhibited the secretion of pro- and anti-inflammatory in PBMCs. Also, oyaksungisan induced a significant increase of transforming growth factor (TGF)-beta1 in PBMCs. Thus, these data indicate that oyaksungisan may be beneficial in the cessation of inflammatory processes of cerebral infarct through suppression of TNF-alpha, IL-1beta, IL-6, and IL-10 and induction of TGF-beta1.

Molecular cloning and expression analysis of two hepcidin genes from olive flounder Paralichthys olivaceus.

Hepcidin is a cysteine-rich cationic antimicrobial peptide central to iron metabolism. We report a comparative analysis of the sequences, gene organization and expression of two hepcidin genes from olive flounder Paralichthys olivaceus. Both consist of two introns and three exons that encode a prepropeptide (81 amino acids for hepcidin I and 89 amino acids for hepcidin II). A TATA box and several consensus-binding motifs for transcription factors were found upstream of the transcriptional starting site. Hepcidin II was predominantly expressed in the liver and highly inducible under the effect of lipopolysaccharide (LPS), while a large amount of hepcidin I transcripts was detected in various tissues but did not appear to have a significant effect during LPS-stimulation.