Efficacy of salmeterol and magnesium isoglycyrrhizinate combination treatment in rats with chronic obstructive pulmonary disease.

The most classic treatment recommended in the current chronic obstructive pulmonary disease (COPD) guidelines is glucocorticoid and ß2 receptor agonist combination, such as salmeterol xinafoate and fluticasone propionate (Sal/Flu), causing many adverse reactions due to hormones. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating chronic inflammation, contributing to its structure is similar to steroidal anti-inflammatory drugs. In this study, we successfully established COPD rat model by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction, as characterized by lung function decline. We discovered that salmeterol xinafoate/MgIG combination could alleviated lung inflammation infiltration, airway wall thickness (AWT) and the secretion of bronchial mucin MUC5AC of COPD rats more than salmeterol xinafoate, MgIG, or salmeterol xinafoate and fluticasone propionate treatment did, as well as reduced inflammatory cells (white blood cells, neutrophils and lymphocytes) accumulation in bronchoalveolar lavage fluid and decreased TNF-α, IL-6 and IL-1ß production in the serum of COPD rats. Finally, we found that Moreover, the mechanism involved might be related to the suppression of JAK/STAT signaling pathway. Overall, our studies suggested that MgIG might be a potential alternative adjuvant drug for fluticasone propionate for the clinical treatment of patients with COPD.

Magnesium isoglycyrrhizinate inhibits airway inflammation in rats with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a kind of chronic lung diseases with the characteristics of airway remodeling and airflow obstruction. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating hepatitis. However, whether MgIG can treat other diseases and its action mechanism is still obscure. In this study, we evaluated the anti-inflammatory effect of MgIG in rats with COPD and investigated the underlying mechanisms. METHODS: Rat model of COPD was constructed by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction. Rats were randomly divided into 5 groups: control group, COPD model group, salmeterol fluticasone comparator group, low dose of MgIG group, and high dose of MgIG group. Except for normal control group, the other four groups received sensitization treatment by cigarette smoking and endotracheal-atomization of endotoxin lipopolysaccharide to construct COPD rats model. After model established successfully, the COPD rats in each group received corresponding dose of endotracheal-atomized normal saline, salmeterol fluticasone, and MgIG every day prior to exposure of cigarette smoke from days 30 to 45. Normal control group were treated with normal saline. Finally, All rats were euthanatized. Pulmonary function was measured. Cells in bronchoalveolar lavage fluid were classified, inflammatory factors IL-6 and TNF-α were determined, histopathological analysis was performed by HE staining, and expression of NLRP3 and cleaved caspase-1 in the lung tissue was also determined by Western blotting. RESULTS: It showed that MgIG treatment (0.40 or 0.80 mg/kg/day) could recover the weight and the clinical symptoms of rats with COPD, accompanied with lung inflammation infiltration reduction, airway wall attenuation, bronchial mucus secretion reduction. Additionally, MgIG administration reduced inflammatory cells (white blood cells, neutrophils, lymphocytes and monocytes) accumulation in bronchoalveolar lavage fluid and decreased IL-6 and TNF-α production in the serum of COPD rats. Furthermore, MgIG treatment also reduced the expression level of NLRP3 and cleaved caspase-1. CONCLUSION: It indicate that MgIG might be an alternative for COPD treatment, and its mechanism of action might be related to the suppression of NLRP3 inflammasome.

miRNA-150-5p associate with antihypertensive effect of epigallocatechin-3-gallate revealed by aorta miRNome analysis of spontaneously hypertensive rat.

AIMS: The antihypertensive mechanism (s) of the epigallocatechin-3-gallate (EGCG), a major effective component in green tea, might associate with microRNAs (miRNAs). Here, we aimed to investigate which microRNA in aorta of spontaneously hypertensive rats (SHRs) were modulated by administration of EGCG and its mechanism. MAIN METHODS: The pharmacokinetic behaviors of EGCG and epigallocatechin (EGC) in Sprague-Dawley rats were analyzed by HPLC and DRUG AND STATISTICS software. Blood pressure of SHRs was monitored by the tail-cuff method, the miRNomes of aorta from SHRs was analyzed with deep sequencing, and expression of hypertension-associated miRNAs with significant change and their host genes and target genes were validated by real-time PCR and Western blot. KEY FINDINGS: The plasma deposition of EGCG and EGC best fitted a mono-compartmental model with maximum plasma concentration post-dose (Cmax, 6.65 vs 4.45 µg/ml) and the corresponding time (Tmax, 15 vs 10 min). Systolic blood pressure (SBP) of SHRs decreased to the lowest point by 34.04 mmHg and recovered by 23.39 mmHg after 15 and 30 min of administration at dose of 300 mg/kg BW EGCG, respectively, and it decreased again at 60 min and recovered at time 2 h. Total 35 upregulated and 18 downregulated miRNAs were identified compared to the control group (p < .01) after EGCG administration. Expression of hypertension-associated miRNA-126a-3p and miRNA-150-5p were further validated. In turn, their host gene and target genes were up-regulated and down-regulated, respectively. SIGNIFICANCE: Our results indicated that miRNA-150-5p might be involved in the antihypertensive effect of EGCG through SP1/AT1R pathway.

Effects of fermentation on the hemolytic activity and degradation of Camellia oleifera saponins by Lactobacillus crustorum and Bacillus subtilis.

The saponins, as components of tea seed meal, are undesirable hemolytic components and should be degraded for reducing their hemolytic activity in order to be used in animal feed. In this study, ß-glucuronidase was verified to be a potent hydrolase of tea seed saponins to reduce their hemolytic activity and a ß-glucuronidase-producing Lactobacillus crustorum strain was screened from raw bovine milk. Next, solid-state fermentation with the isolated L. crustorum and a Bacillus subtilis natto strain, which can produce cellulase and hence improve the fermentation performance of tea seed meal, was carried out for detoxification of tea seed meal. The 50% hemolytic dosage (HD50) value of tea seed saponins was increased from 6.69 to 27.43 µg mL-1. The results of LC-MS analysis showed that the percentage of saponin aglycones increased from 30.95 to 84.25% after the fermentation. According to the roles of sugar moieties in hemolytic activity, and the enzymatic hydrolysis characteristics of ß-glucuronidase, the degradation of tea seed saponins from glucosides to aglycones may contribute to the reduction of hemolytic activity. Therefore, tea seed meal may be used as animal feed after fermentation with the tested saponin-degrading microbial strains.

Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations.

The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

The effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability.

The mechanism by which copigments stabilize colour, by protecting anthocyanin chromophores from nucleophilic attack, seems well accepted. This study was to determine effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability. Molecular dynamics simulations were applied to explore molecular interactions. Phenolic acids intensified the colour by 19%∼27%. Colour fading during heating followed first-order reactions with half-lives of 3.66, 9.64, 3.50, and 3.39h, whereas anthocyanin degradation, determined by the pH differential method (or HPLC-PDA), followed second-order reactions with half-lives of 3.29 (3.40), 3.43 (3.39), 2.29 (0.39), and 2.72 (0.32)h alone or with gallic/ferulic/caffeic acids, respectively, suggesting that anthocyanin degradation was faster than the colour fading. The strongest protection of gallic acids might be attributed to the shortest distance (4.37Å) of its aromatic ring to the anthocyanin (AC) panel. Hyperchromic effects induced by phenolic acids were pronounced and they obscured the accelerated anthocyanin degradation due to self-association interruption.

Chemical composition, angiotensin-converting enzyme-inhibitory activity and antioxidant activities of few-flower wild rice (Zizania latifolia Turcz.).

BACKGROUND: The chemical compositions of the stem and leaf sheath of few-flower wild rice were analysed. In addition, their extracts were evaluated for diphenylpicrylhydrazyl (DPPH) free radical-scavenging activity, ferric-reducing antioxidant power and angiotensin-converting enzyme (ACE)-inhibitory activity, since these are important properties of sources of nutraceuticals or functional foods. RESULTS: The stems contained more ascorbic acid (0.06 g kg(-1) fresh weight), protein (28.18 g kg(-1) dry weight (DW)), reducing sugars (308.54 g kg(-1) DW), water-soluble pectin (20.63 g kg(-1) DW), Na(2) CO(3) -soluble pectin (44.14 g kg(-1) DW), K (8 g kg(-1) dry matter (DM), S (6 g kg(-1) DM) and P (5 g kg(-1) DM) but less starch, total dietary fibre, Si, Na and Ca than the leaf sheaths. The DPPH free radical-scavenging IC(50) values of the stem and leaf sheath extracts were 19.28 and 21.22 mg mL(-1) respectively. In addition, the ACE-inhibitory IC(50) value of the stem extracts was 38.54 mg mL(-1). CONCLUSION: Both the stem and leaf sheath extracts exhibited good antioxidant properties, while good ACE-inhibitory activity was detected only in the phosphate buffer solution extracts of the stem. Few-flower wild rice could be processed into formula feeds for fish, poultry, etc. or functional foods for persons with high blood pressure.