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Although drugs have been reported to modulate the gut microbiota, the effects of anti-obesity drugs on the gut microbiota remain unclear. Lorcaserin (LS) and phentermine (PT) are commonly used anti-obesity drugs. However, to our best knowledge, no studies have simultaneously assessed the effects of LS and PT on obesity and gut microbiota. This study aimed to explore the relationship between the anti-obesity effects of LS and PT and re-modulation of host gut microbiota. To test hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with LS and PT via oral gavage for 8 weeks. After sacrifice, body weight, fat accumulation, and serum biomarkers were measured, and the gut microbial composition was analyzed using 16 s rRNA amplicon sequencing. LS and PT were observed to modulate the gut microbial composition and restore gut microbial dysbiosis, as indicated by an increased Firmicutes/Bacteroidetes ratio. Significantly modulated genera by LS and PT treatment were strongly correlated with obesity-related markers. Additionally, LS and PT increased the mRNA level of G protein-coupled receptor 120 (GPR120) in the colon tissue. ASV3566, which corresponds to Eubacterium coprostanoligenes, was correlated with GPR120 and obesity-related markers such as glutamic pyruvic transaminase (GPT) and serum triglyceride (TG). In conclusion, LS and PT can modulate the gut microbiota dysbiosis and the gut microbiota plays a role in mediating the anti-obesity effect of drugs. [ABSTRACT FROM AUTHOR]

Obesity is a chronicmetabolic disease caused by excessive body fat and has become a global public health problem. Evidence suggests that obesity and obesity-induced metabolic disorders are closely related to gut microbiota. Bupropion (BP), an antidepressant medicine, and Ephedra sinica Stapf [Ephedraceae; Ephedrae Herba], a herbal medicine, are sympathetic stimulants and have weight loss effects. However, to our best knowledge, no studies have simultaneously assessed the effects of drugs and herbal medicines on obesity and gut microbiota. This study aimed to determine the effects of BP and ES on weight loss and re-modulation of host gutmicrobiota. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with bupropion (BP; 30mg/kg/day) and Ephedra sinica Stapf extract (ES; 150mg/kg/day) via oral gavage for eight weeks. Further, we evaluated the effects of BP and ES on body weight and fat accumulation. In addition, we evaluated the effects of BP and ES on gutmicrobiota using 16S rRNA amplicon sequencing. Our results showed thatweight loss was confirmed in both BP and ES; however, it wasmore pronounced in ES. ES changed the overall composition of the gut microbiota by restoring the relative abundance of Oscillospiraceae, Lachnospiraceae, and the Firmicutes/Bacteroidetes ratio, an indicator of gut microbiota dysbiosis. Nine amplicon sequence variants (ASVs) of the gut microbiome were significantly recovered by BP and ES treatment, of which eight ASVs correlated with body weight and fat accumulation. Additionally, three ASVs were significantly recovered by ES treatment alone. In conclusion, the anti-obesity effects of BP and ES, especially fat accumulation, are related to the regulation of gut microbiota. Moreover, ES had a greater influence on the gut microbiota than BP. [ABSTRACT FROM AUTHOR]

Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D. [ABSTRACT FROM AUTHOR]

Silicon dioxide nanoparticles (SiONPs), which are metal oxide nanoparticles, have been used in a wide variety of applications. In this study, acute pulmonary responses were examined after the intranasal instillation of SiONPs in mice primed with or without lipopolysaccharide (LPS, intranasal, 5 µg/mouse). The exposure to SiONPs increased the inflammatory cell counts and proinflammatory cytokines in the bronchoalveolar lavage fluid. SiONPs induced airway inflammation with increases in the phosphorylation of mitogen-activated protein kinases (MAPKs). The ratios of the inflammatory responses induced by the SiONPs were increased in the acute pulmonary disease model primed by LPS. Taken together, SiONPs exhibited toxicity to the respiratory system, which was associated with MAPK phosphorylation. In addition, the exposure to SiONPs exacerbated any existing inflammatory pulmonary diseases. These data showed the additive, as well as synergistic, interaction effects of SiONPs and LPS. We conclude that the exposure to SiONPs causes potential toxicity in humans, especially those with respiratory diseases. [ABSTRACT FROM AUTHOR]

Background: Copper nanoparticles (Cu NPs) have great potential in electronics and biomedical fields because of their efficient thermodynamic and anti-microbial properties. However, their potential toxic effects and kinetic data following repeated exposure are still unclear. Methods: We evaluated the physicochemical properties of Cu NPs (25 nm) and copper microparticles (Cu MPs, 14-25 μm). Comparative in vivo toxicity of Cu NPs and Cu MPs was evaluated by conducting a 28-day repeated oral dose study at equivalent dose levels of 0, 100, 200, and 400 mg/kg/day (vehicle, 1 % hydroxypropyl methylcellulose). We determined Cu levels in the blood, tissues, urine, and feces by using inductively coupled plasma mass spectrometry. Results: The solubility of Cu NPs and Cu MPs was 84.5 and 17.2 %, respectively, in an acidic milieu; however, they scarcely dissolved in vehicle or intestinal milieus. The specific surface area of Cu NPs and Cu MPs was determined to be 14.7 and 0.16 m2/g, respectively. Cu NPs exhibited a dose-dependent increase of Cu content in the blood and tested organs, with particularly high levels of Cu in the liver, kidney, and spleen. Only for liver and kidney increased Cu levels were found in Cu MPs-treated rats. Cu NPs caused a dose-related increase in Cu levels in urine, whereas Cu MPs did not affect the urine Cu levels. Extremely high levels of Cu were detected in the feces of Cu MPs-treated rats, whereas much lower levels were detected in the feces of Cu NPs-treated rats. A comparative in vivo toxicity study showed that Cu NPs caused damages to red blood cells, thymus, spleen, liver, and kidney at ≥200 mg/kg/days, but Cu MPs did not cause any adverse effects even at the highest dose. Conclusions: Overall, the in vivo repeated dose toxicity study of Cu NPs and Cu MPs demonstrated that large surface area and high solubility in physiological milieus could directly influence the toxicological responses and biodistribution of Cu particles when administered orally. Under these experimental conditions, the no-observedadverse- effect levels of Cu NPs and Cu MPs were determined to be 100 and ≥400 mg/kg/day, respectively. [ABSTRACT FROM AUTHOR]

The type III secretion system (T3SS) in Pseudomonas aeruginosa has been linked to severe disease and poor clinical outcomes in animal and human studies. We aimed to investigate whether the ExoS and ExoT effector proteins of P. aeruginosa affect the expression of matrix metalloproteinase 12 (MMP-12) and MMP-13 via nuclear factor κB (NF-κB) signaling pathways. To understand the T3SS, we used ΔExoS, ΔExoT, and ExsA::Ω mutants, as well as P. aeruginosa strain K (PAK)-stimulated NCI-H292 cells. We investigated the effects of ΔExoS, ΔExoT, and ExsA::Ω on the development of pneumonia in mouse models. We examined the effects of ΔExoS, ΔExoT, and ExsA::Ω on MMP-12 and MMP-13 production in NCI-H292 cells. ΔExoS and ΔExoT markedly decreased the neutrophil count in bronchoalveolar lavage fluid, with a reduction in proinflammatory mediators, MMP-12, and MMP-13. ΔExoS and ΔExoT reduced NF-κB phosphorylation, together with MMP-12 and MMP-13 expression in PAK-infected mouse models and NCI-H292 cells. To conclude, P. aeruginosa infection induced the expression of MMPs, and P. aeruginosa T3SS appeared to be a key player in MMP-12 and MMP-13 expression, which is further controlled by NF-κB signaling. These findings might be useful in devising a novel therapeutic approach to chronic pulmonary infections that involves decreasing the ExoS and ExoT levels. [ABSTRACT FROM AUTHOR]

Thuja orientalis (TO) may be used as a herbal remedy for the treatment of numerous inflammatory diseases. In the present study, the effects of TO were evaluated on airway inflammation in ovalbumin (OVA)-induced allergic asthma and RAW264.7 murine macrophage cells. The effects of TO on the production of proinflammatory mediators, were determined in RAW264.7 cells that had been stimulated with lipopolysaccharide (LPS). Furthermore, an in vivo experiment was performed on mice that were sensitized to OVA and then received an OVA airway challenge. TO was administered by daily oral gavage at a dose of 30 mg/kg, 21-23 days after the initial OVA sensitization. TO was shown to reduce nitric oxide production and reduce the relative mRNA expression levels of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, cyclooxygenase-2, matrix metalloproteinase (MMP)-9, and tumor necrosis factor-a in RAW264.7 cells stimulated with LPS. In addition, TO markedly decreased the inflammatory cell counts in bronchial alveolar lavage fluid, reduced the levels of IL-4, IL-5, IL-13, eotaxin and immunoglobulin E, and reduced airway hyperresponsivenes, in the OVA sensitized mice. Furthermore, TO attenuated airway inflammation and mucus hypersecretion, induced by the OVA challenge of the lung tissue. TO also reduced the expression of iNOS and MMP-9 in lung tissue. In conclusion, TO exerted anti-inflammatory effects in an OVA-induced allergic asthma model, and in LPS-stimulated RAW264.7 cells. These results suggest that TO may be a useful therapeutic agent for the treatment of inflammatory diseases, including allergic asthma. [ABSTRACT FROM AUTHOR]

Zingiber mioga (Thunb.) Roscoe (ZM) is a traditional medicine, used to treat inflammatory diseases. The present study aimed to evaluate the inhibitory effects of ZM on the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells and in a mouse model of ovalbumin (OVA)-induced allergic asthma. Mice received OVA sensitization on day 0 and 14, and were challenged with OVA between days 21 and 23. ZM was administered to the mice at a dose of 30 mg/kg, 1 h prior to OVA challenge. In LPS-stimulated RAW264.7 cells, ZM significantly decreased nitric oxide (NO) and tumor necrosis factor (TNF)-a production in a concentration-dependent manner, and mRNA expression of inducible NO synthase (iNOS), TNF-a and matrix metalloproteinase (MMP)-9 was reduced. In addition, treatment with ZM decreased the inflammatory cell count in bronchoalveolar lavage fluid from the mice, and reduced the expression of interleukin (IL)-4, IL-5, IL-13, eotaxin and immunoglobulin E. ZM also reduced airway hyperresponsiveness in OVA-challenged mice, and attenuated the infiltration of inflammatory cells and mucus production in the airways, with a decrease in the expression of iNOS and MMP-9 in lung tissue. In conclusion, the results of the present study indicate that ZM effectively inhibits inflammatory responses. Therefore, it may be that ZM has potential as a therapeutic agent for use in inflammatory diseases. [ABSTRACT FROM AUTHOR]

Picrasma quassioides (D.Don) Benn. (PQ) is used in traditional medicine for the treatment of inflammatory conditions, including gastritis. This study aimed to evaluate the inhibitory effects of PQ on the inflammatory responses in mice with allergic asthma induced by ovalbumin (OVA) and in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. To induce allergic asthma, the mice underwent OVA sensitization on days 0 and 14 and then were challenged with OVA from days 21-23. The mice were administered 15 and 30 mg/kg doses of PQ 1 h prior to the OVA challenge. The PQ treatment decreased the inflammatory cell count in the bronchoalveolar lavage fluid of the mice and reduced the levels of interleukin (IL)-4, IL-5, IL-13 and immunoglobulin (Ig)E when compared with those in the OVA group. The PQ treatment also reduced the airway hyperresponsiveness induced by the OVA challenge, attenuated the recruitment of inflammatory cells and the mucus production in the airways of the mice. In the LPS-stimulated RAW264.7 cells, the PQ treatment reduced the overexpression of inducible nitric oxide synthase (iNOS). The results indicated that PQ inhibits inflammatory responses in mice with OVA-sensitized/challenged allergic asthma and in LPS-stimulated RAW264.7 cells. These effects were considered to be associated with the suppression of iNOS expression. Therefore, PQ may have the potential to treat airway inflammatory diseases, including allergic asthma. [ABSTRACT FROM AUTHOR]