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Objective In order to protect against Mycobacterium tuberculosis (MTB) infection, novel drugs and new targets should be screened from the vast source of plants. We investigated the potentiality of the herbal plant of Artemisia capillaris extract (AC) against Mycobacterium tuberculosis. Design In this study, we isolated ursolic acid and hydroquinone by bio-activity guided fractionation from the methanol extracts of AC, and tested the inhibitory effects against several strains of MTB. Anti-mycobacterial evaluation of these compounds was carried out using the MGIT™ 960 and resazurin assay. Mycobacterial morphological changes due to the treatment of these compounds were further evaluated by Transmission electron microscopy (TEM). Results Ursolic acid (UA) and hydroquinone (HQ) inhibited the growth of both susceptible and resistant strains of M. tuberculosis. The MIC (minimum inhibitory concentration) values of both UA and HQ were 12.5 μg/ml against the susceptible strains of M. tuberculosis. Also both UA and HQ showed 12.5–25 μg/ml of MIC values against MDR/XDR MTB strains. However, against clinical strains of MTB, UA was found sensitive against those strains that are sensitive against both INH and RFP but resistant against those strains that are resistant to INH. On the other hand HQ was sensitive against all clinical strains. TEM image-analysis of the strain H37Ra after treatment with UA revealed cell wall lysis, whereas HQ-treated cells showed deformed cytoplasmic morphology. Conclusion All these results indicate that AC extracts containing UA and HQ possess promising chemotherapeutic potency against MTB for future use. [ABSTRACT FROM AUTHOR]

We investigated the photoprotective activity of phloroglucinol on ultraviolet B ( UVB)-induced deleterious effects in hairless mice in vivo. To assess the photoprotective effect of phloroglucinol, phloroglucinol-treated HR-1 hairless male mice were exposed to UVB irradiation. The inhibitory activity of phloroglucinol on wrinkle formation was determined by analysis of skin replicas, epidermal thickness based on histological examination and collagen damage. Matrix metalloproteinase-1 ( MMP-1), matrix metalloproteinase-9 ( MMP-9) and tissue inhibitor of metalloproteinase ( TIMP) mRNA levels were measured by real-time PCR. UVB induced transcription of proinflammatory cytokines, including interleukin-1 beta ( IL-1 β, IL-6) and IL-8 ( IL-8). The protective effects of phloroglucinol on UVB-induced skin photoaging were examined by measuring protein levels of MMPs and mitogen-activated protein ( MAP) kinases. The results of these experiments suggest that phloroglucinol has a significant beneficial effect on the barrier function of the skin. In hairless mice, signs of photoaging and photodamage, including coarse wrinkle formation, epidermal thickness and elastic fiber degeneration, were reduced in severity by phloroglucinol application. The phloroglucinol-treated group showed remarkably decreased mRNA levels of MMP-1, MMP-9 and inflammatory cytokines in comparison with those of the UVB-induced group. Oral administration of phloroglucinol attenuated phosphorylation of MAP kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38. [ABSTRACT FROM AUTHOR]

The mechanism underlying the wogonin-mediated increase in the expression of suppressor of cytokine signaling 3 (SOCS3) is unclear. Promoter deletion assay results revealed that wogonin-induced SOCS3 expression is dependent on the AP-1 consensus sequences and two STAT responsive elements (TTACAAGAA and TTCCAGGAA) in the 5′-flanking region of the SOCS3 gene in SH-SY5Y cells. Wogonin-induced SOCS3 expression was blocked by inhibitors of PI3K, Akt, Raf, p38, JNK, MEK, and STAT3, respectively. However, JAK2 inhibitors did not inhibit wogonin-induced SOCS3 expression. These results indicate that SOCS3-inducing effect of wogonin is caused by the activation of PI3K-mediated MAPK signaling pathways (Akt, ERK1/2, p38, and JNK), and the subsequent activation of AP-1 consensus sequences and STAT responsive elements in SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

Objectives: Sosihotang (SSH) is an herbal medicine traditionally used against the common cold, and hepatic and gastric diseases, in Northeast Asia. In this study, we investigated whether SSH extract can protect against UVB‐induced skin damage and photoageing. Methods: HaCaT cells were treated with SSH extract and exposed UVB irradiation at 20 mJ/cm2. Hairless mice were orally administered SSH extract (100 mg/kg per mouse) as UVB irradiation was increased from 60 to 120 mJ/cm2 over the course of 12 weeks. Key findings: Treatment with SSH extract inhibited the upregulation of MMP‐1 and MMP‐9 expression in UVB‐irradiated HaCaT cells. In UVB‐irradiated hairless mice, treatment with SSH extract restored the levels of factors instrumental in skin hydration (TEWL, capacitance, HA and TGF‐β) and those regulating collagen content (procollagen, MMP‐1 and MMP‐9). This activity inhibited epidermal thickening and disorganization of collagen fibres. Administration of SSH extract also ameliorated the expression of UVB‐induced pro‐inflammatory cytokines (TNF‐α, IL‐1β and IL‐6) and phosphorylation of MAPK family members (MEK, JNK, ERK and p38) by upregulating the activity of antioxidant enzymes (SOD, CAT, Nrf‐2, HO‐1 and NQO‐1). Conclusions: These results indicate that SSH extract can be used therapeutically for the treatment of UVB‐induced skin damage and photoageing. [ABSTRACT FROM AUTHOR]

The continued spread of drug-resistant tuberculosis is one of the most pressing and complex challenges facing tuberculosis management worldwide. Therefore, developing a new class of drugs is necessary and urgently needed to cope with the increasing threat of drug-resistant tuberculosis. This study aims to discover a potential new class of tuberculosis drug candidates different from existing tuberculosis drugs. By screening a library of compounds, methyl (S)-1-((3-alkoxy-6,7-dimethoxyphenanthren-9-yl)methyl)-5-oxopyrrolidine-2-carboxylate (PP) derivatives with antitubercular activity were discovered. MIC ranges for PP1S, PP2S, and PP3S against clinically isolated drug-resistant Mycobacterium tuberculosis strains were 0.78 to 3.13, 0.19 to 1.56, and 0.78 to 6.25 μg/ml, respectively. PPs demonstrated antitubercular activities in macrophage and tuberculosis mouse models, showing no detectable toxicity in all assays tested. PPs specifically inhibited M. tuberculosis without significantly changing the intestinal microbiome in mice. Mutants selected in vitro suggest that the drug targets the PE-PGRS57, which has been found only in the genomes of the M. tuberculosis complex, highlighting the specificity and safety potency of this compound. As PPs show an excellent safety profile and highly selective toxicity specific to M. tuberculosis, PPs are considered a promising new candidate for the treatment of drug-resistant tuberculosis while maintaining microbiome homeostasis. This study identifies a new class of PP derivatives as Mycobacterium tuberculosis-targeting antimicrobials with microbiome-safe properties that do not disrupt normal flora, making them a promising candidate for the treatment of drug-resistant tuberculosis. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is a gram-positive bacterium that causes tooth decay. The exopolyssacharides, mostly glucans synthesized by the bacterium are responsible for establishing pathogenic bio-films associated with dental caries disease. The regulatory immune and inflammatory reactions implicated by the synthesized glucans are still not clearly understood. In this study, a water-soluble exopolyssacharide (WSP) was extracted from culture of Str. mutans. The structural properties of WSP, [α-(1 → 3, 1 → 6)-D-glucan] were confirmed using Fourier-transform infrared spectroscopy and 13C-nuclear magnetic resonance spectroscopy. Furthermore, the effects of WSP on the global gene expression of the macrophage-like RAW 264.7 cells were analyzed using mRNA-seq analysis. Using Gene Ontology analysis, we compiled a total of 24,421 genes that were upregulated or downregulated by more than 5.0-fold and 0.3-fold, respectively. Most of the transcripts were grouped under immune response and inflammation-related gene categories. Among the 802 immunity-related genes analyzed, chemokine ligand 7 (Ccl7), interleukin-1β (IL-1β), interleukin-1α (IL-1α) and interleukin-6 (IL-6) were upregulated after WSP exposure. In addition, among a total of 344 genes related to inflammation, Ccl7, IL-1α and IL-6 were upregulated. These results suggest that [α-(1 → 3, 1 → 6)-D-glucan] from Str. mutans produces activates macrophages and may contribute to the immune and inflammatory response to periodontal disease. [ABSTRACT FROM AUTHOR]

Due to the emergence of multidrug-resistant and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis , new antituberculosis drugs are urgently required to improve the efficacy of current tuberculosis (TB) treatment. To achieve this goal, ca. 1000 chemical compounds were screened for potential antimycobacterial activity, among which methyl 5-(2-diethylaminoethoxy)-7,12-dioxo-7,12 dihydrodinaphtho[1,2- b ;2′,3′- d ]furan-6-carboxylate (DNF-3) showed strong activity against all of the tested drug-susceptible and -resistant M. tuberculosis strains, with 50% minimum inhibitory concentrations (MIC 50 values) of 0.02–0.39 µg/mL both in culture broth and within murine RAW 264.7 macrophage cells. When DNF-3 was used in combination with rifampicin or streptomycin, it exhibited direct synergy against XDR-TB and an additive effect against M. tuberculosis H37Rv. DNF-3 displayed a long post-antibiotic effect (PAE) that was comparable with rifampicin but was superior to isoniazid, streptomycin and ethambutol. Importantly, DNF-3 showed no cytotoxicity to any cell line tested, with a selectivity index (SI) of >32. DNF-3 was also active against 27 nontuberculous mycobacteria (NTM) strains, Staphylococcus spp. and Streptococcus spp. Taken together, these results indicate that DNF-3 is a promising new candidate drug for treating TB. Further studies are warranted to establish the in vivo effect and therapeutic potential of DNF-3. [ABSTRACT FROM AUTHOR]

This study explores the antitubercular activity of α-viniferin, a bioactive phytochemical compound obtained from Carex humilis . α-Viniferin was active against both drug-susceptible and -resistant strains of Mycobacterium tuberculosis at MIC 50 s of 4.6 μM in culture broth medium and MIC 50 s of 2.3–4.6 μM inside macrophages and pneumocytes. In combination with streptomycin and ethambutol, α-viniferin exhibited an additive effect and partial synergy, respectively, against M. tuberculosis H37Rv. α-Viniferin also did not show cytotoxicity in any of the cell lines tested up to a concentration of 147 μM, which gives this compound a selectivity index of >32. Moreover, α-viniferin was active against 3 Staphylococcus species, including methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE). [ABSTRACT FROM AUTHOR]

Inflammation is a pathological process that is known to be involved in numerous diseases. Microbial infection or tissue injury activates inflammatory responses, resulting in the induction of proinflammatory proteins including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).Aster yomenais used in traditional Korean remedies to treat cough, asthma, and insect bites. Here, we investigated the effects ofA. yomenaextract (EAY) on the expression of COX-2 and iNOS induced by LPS. EAY inhibited NF-κB activation and IκBα degradation induced by LPS. EAY suppressed LPS-induced COX-2 and iNOS expression which are the target genes regulated through NF-κB activation in macrophages. EAY also suppressed LPS-induced nitrite production. These results suggest that EAY has the potential to be developed as a potent anti-inflammatory drug. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is a dangerous intracellular pathogen. In order to protect against mycobacterium infection, novel agents with anti-mycobacterial activity should be given emergency priority for evaluation. Ursolic acid (UA), a plant triterpenoid, shows promising bioactivities, including anti-mycobacterial potency. In this study, the action of UA against Mycobacterium tuberculosis H37Ra was evaluated, and the inhibitory concentration was found to range between 10 and 20 μg/ml in a resazurin assay and MGIT 960 instrument. The total mycolic acid in UA-treated H37Ra was detected and compared with INH-treated and non-treated bacterium by LC-MS/MS. Quantitative LC-MS/MS data confirmed that both UA and INH decreased mycolic acid biosynthesis in a dose-dependent manner. Thin-layer chromatogram (TLC) analysis showed that all mycolic acid subtypes were affected by UA treatment in the wild type but not in strains resistant to UA. Electron microscopy images also confirmed that UA treatment affected both H37Ra cell and intracellular content of H37Ra. Altogether, these data confirmed the promise of the inhibitory action of UA in mycolic acid, which might further delineate the mechanistic pathway of mycobacterial inhibition by UA. [ABSTRACT FROM AUTHOR]

Polydeoxyribonucleotide (PDRN) is an agonist of the A2A adenosine receptors. We evaluated the effects of PDRN on liver regeneration induced by partial hepatectomy (PH) in rats, focusing on cell proliferation. Proliferating cell nuclear antigen (PCNA) as an indicator of cell proliferation was targeted to determine whether PDRN treatment could promote proliferation of hepatic cells in regenerating liver. Male Sprague-Dawley rats were divided into three groups: normal group (n= 3) without PH (sham operated), control groups (n= 12) with saline injection after PH, and experimental groups (n= 12) with i.p. injection of 8 mg/kg of PDRN immediately after PH. Light microscopically, liver regeneration induced by PH involved proliferation of various hepatic cells including parenchymal cells and Kupffer cells. The disintegration (1 or 2 days after PH) and remodeling (4 days after PH) of hepatic plate and increase of sinusoids (6 days after PH) were sequentially observed. These regenerative processes occurred relatively earlier in the experimental groups. By western blotting, the expression of PCNA increased in the early stage, reached its peak at 1 and 2 days after PH, and decreased thereafter. By immunohistochemistry, the intensities of PCNA staining in the experimental groups were more obvious at various days after PH. By electron microscopy using immunogold labeling for PCNA, the gold particles were largely observed in heterochromatin and nucleolus in hepatic cells. The results of immunochemistry and western blotting for PCNA showed the similar pattern in most groups. These findings suggest that PDRN treatment to hepatectomized rat could accelerate liver regeneration through rapid cell proliferation. [ABSTRACT FROM PUBLISHER]

The Korean traditional seafood jeotgal is consumed directly or as an additive in other foods to improve flavor or fermentation efficiency. Saeujot, made from salted and fermented tiny shrimp (SFS; Acetes japonicus), is the best-selling jeotgal in Korea. In this study, we reveal the microbial diversity and dynamics in naturally fermented shrimp by denaturing gradient gel electrophoresis (DGGE). The population fingerprints of the predominant microbiota and its succession were generated by DGGE analysis of universal V3 16S rDNA polymerase chain reaction (PCR) amplicons. Overall, 17 strains were identified from sequencing of 30 DGGE bands. The DGGE profiles showed diverse bacterial populations in the sample, throughout the fermentation of SFS. Staphylococcus equorum, Halanaerobium saccharolyticum, Salimicrobium luteum, and Halomonas jeotgali were the dominant bacteria, and their levels steadily increased during the fermentation process. Certain other bacteria, such as Psychrobacter jeotgali and Halomonas alimentaria appeared during the early-fermentation process, while Alkalibacterium putridalgicola, Tetragenococcus muriaticus, and Salinicoccus jeotgali appeared during the late-fermentation process. The members of the order Bacillales were found to be predominant during the fermentation of SFS. Furthermore, S. equorum was identified as the dominant bacterial isolate by the traditional method of culturing under aerobic and facultative anaerobic conditions. We expect that this information will facilitate the design of autochthonous starter cultures for the production of SFS with desired characteristic sensory profiles and shorter ripening times. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the physiological effects of different selenium (Se) levels on the growth of white-rot fungus, Pleurotus eryngii, with special reference to the regulation of ligninolytic enzymes such as laccase and versatile peroxidase. The fungus was grown in medium supplemented with 1, 10, 100, 1,000 and 10,000 μM of sodium selenite. Mycelial growth was stronger at lower Se levels, but declined significantly at higher concentrations of 1,000 and 10,000 μM, highlighting its association in mediating toxic responses. Inhibition of fungal growth was accompanied with dense and entangled hyphae taking the shape of irregular short strips. Additionally, hyphal swellings and septation were noticed which lead to a reduction in the advancement of the mycelium. Along with the inhibition of fungal biomass, the reducing sugar and protein concentrations increased to about 30.2 and 3.5 mg/ml respectively in the growth medium. Additionally, the laccase gene expression showed a twofold upregulation at higher levels of Se, although the activity of the enzyme was compromised with an inverse relationship with increased gene transcripts. The versatile peroxidase transcript showed a complete downregulation at 10,000 μM after an upregulation at lower levels of Se. We also confirmed the direct relationship of different Se levels on laccase activity of Rhus vernicifera that showed similar behavior to the fungal laccase. The results of the present study suggest that Se supplementation regulates mRNA levels of laccase and versatile peroxidase depending on exposure and may play a role in the toxicity associated with Se. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV) is one of the major bio-active ingredients of huang qi which is the dried root of Astragalus membranaceus (a traditional Chinese medicinal plant). The pharmacological effects of AS-IV, including anti-oxidative, anti-cancer, and anti-diabetic effects have been actively studied, however, the effects of AS-IV on liver regeneration have not yet been fully described. Thus, the aim of this study was to explore the effects of AS-IV on regenerating liver after 70% partial hepatectomy (PHx) in rats. Differentially expressed mRNAs, proliferative marker and growth factors were analyzed. AS-IV (10 mg/kg) was administrated orally 2 h before surgery. We found 20 core genes showed effects of AS-IV, many of which were involved with functions related to DNA replication during cell division. AS-IV down-regulates MAPK signaling, PI3/Akt signaling, and cell cycle pathway. Hepatocyte growth factor (HGF) and cyclin D1 expression were also decreased by AS-IV administration. Transforming growth factor β1 (TGFβ1, growth regulation signal) was slightly increased. In short, AS-IV down-regulated proliferative signals and genes related to DNA replication. In conclusion, AS-IV showed anti-proliferative activity in regenerating liver tissue after 70% PHx. [ABSTRACT FROM AUTHOR]

The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome has been implicated in a variety of diseases, including atherosclerosis, neurodegenerative diseases, and infectious diseases. Thus, inhibitors of NLRP3 inflammasome have emerged as promising approaches to treat inflammation-related diseases. The aim of this study was to explore the effects of juglone (5-hydroxyl-1,4-naphthoquinone) on NLRP3 inflammasome activation. The inhibitory effects of juglone on nitric oxide (NO) production were assessed in lipopolysaccharide (LPS)-stimulated J774.1 cells by Griess assay, while its effects on reactive oxygen species (ROS) and NLRP3 ATPase activity were assessed. The expression levels of NLRP3, caspase-1, and pro-inflammatory cytokines (IL-1β, IL-18) and cytotoxicity of juglone in J774.1 cells were also determined. Juglone was non-toxic in J774.1 cells when used at 10 μM (p < 0.01). Juglone treatment inhibited the production of ROS and NO. The levels of NLRP3 and cleaved caspase-1, as well as the secretion of IL-1β and IL-18, were decreased by treatment with juglone in a concentration-dependent manner. Juglone also inhibited the ATPase activities of NLRP3 in LPS/ATP-stimulated J774.1 macrophages. Our results suggested that juglone could inhibit inflammatory cytokine production and NLRP3 inflammasome activation in macrophages, and should be considered as a therapeutic strategy for inflammation-related diseases. [ABSTRACT FROM AUTHOR]

A correction to the article " Effects of different selenium levels on growth and regulation of laccase and versatile peroxidase in white-rot fungus, Pleurotus eryngii" in the April 23, 2014 is presented.