Pulsatillae radix extract alleviates DSS-induced colitis via modulating gut microbiota and inflammatory signaling pathway in mice.

Ethnopharmacological relevance: Ulcerative colitis (UC) is a chronic relapsing intestinal disease with complex pathogenesis. The increasing morbidity and mortality of UC become a global public health threat. Baitouweng decoction (BD), a formulated prescription of Traditional Chinese Medicine, has been applied to cure UC for many centuries. However, the therapeutic efficacy and working mechanisms of this medicine are not well studied. Aim of study: In this study we determined whether Pulsatillae radix, one of four ingredients in BD, had a therapeutic effect on colitis. And explore the underlying mechanism of Pulsatilla chinensis (Bunge) Regel radix in the improvement of DSS-induced colitis in mice model. Methods: The active compounds of Pulsatilla chinensis was identified by UPLC. The composition of the mice's cecum microbiota was determined by 16S rRNA sequencing. And gene expression profile of colon was detected by transcriptome. Results: The results showed that Pulsatillae radix significantly improved the clinical symptom, prevented the shorten of colon length, and decreased the diseased activity index (DAI) in an 3 % DSS-induced ulcerative colitis mouse model. We found that Pulsatillae radix reversed the dysbiosis of gut microbiota as evidenced by increase in the relative abundance of Bacteroidetes, Deferribacteres, and Proteobacteria phyla and decrease in Firmicutes, as well as by decrease in the genera levels of Bacteroides, Parabacteroides, Prevotella, Mucispirillum, Coprococcus, Oscillospira, and Escherichia. The results of transcriptome showed Pulsatillae radix administration led to 128 genes up-regulation, and 122 genes down-regulation, up-regulate NOD-like receptor signaling pathway, down-regulate Cytokine-cytokine receptor interaction, and TNF and IL-17 signaling pathways. Conclusion: in this study, we demonstrate Pulsatillae radix alleviates DSS-induced colitis probably via modulating gut microbiota and inflammatory signaling pathway in DSS-induced colitis mouse model.

Lactobacillus gasseri RW2014 Ameliorates Hyperlipidemia by Modulating Bile Acid Metabolism and Gut Microbiota Composition in Rats.

Hyperlipidemia is a leading risk of cardiovascular and cerebrovascular disease. Dietary supplementation with probiotics has been suggested as an alternative intervention to lower cholesterol. In the current study, we isolated a strain of Lactobacillus gasseri RW2014 (LGA) from the feces of a healthy infant fed with breast milk, and it displayed bile salt hydrolase (BSH) activity. Using this strain we determined its cholesterol-lowering and fatty liver-improving functions. SD rats were randomly divided into four groups. The control rats were fed a commercial chow diet and the other three groups were fed a high-fat diet (HFD) for a 7-week experiment period. After two weeks of feeding, the rats in PBS, simvastin, and LGA group were daily administered through oral gavage with 2 mL PBS, simvastin (1 mg/mL), and 2 × 109 CFU/mouse live LGA in PBS, respectively. After five weeks of such treatment, the rats were euthanized and tissue samples were collected. Blood lipid and inflammatory factors were measured by ELISA, gut microbiota was determined by 16S rRNA sequencing, and bile acids profiles were detected by metabolomics. We found that LGA group had lower levels of blood cholesterol and liver steatosis compared to the simvastin group. LGA also significantly reducedthe levels of inflammatory factors in the serum, including TNFα, IL-1ß, MCP-1, IL-6, and exotoxin (ET), and increased the levels of short-chain fatty acids in feces, including isobutyric acid, butyric acid, isovaleric acid, valeric acid, and hexanoic acid. In addition, LGA altered the compositions of gut microbiota as manifested by the increased ratio of Firmicutes/Bacteroides and the relative abundance of Blautia genus. Targeted metabolomics results showed that bile acids, especially free bile acids and secondary bile acids in feces, were increased in LGA rats compared with the control rats. Accordingly, the rats administrated with LGA also had a higher abundance of serum bile acids, including 23-norcholic acid, 7-ketolithocholic acid, ß-muricholic acid, cholic acid, and deoxycholic acid. Together, this study suggests that LGA may exert a cholesterol-lowering effect by modulating the metabolism of bile acids and the composition of gut microbiota.

Qingfeiyin Decoction Inhibits H1N1 Virus Infection via Modulation of Gut Microbiota and Inflammatory Pathways in a Murine Model.

Influenza virus-caused lung infection and its pandemic outbreaks are a persistent public health challenge. The H1N1 subtype is the most common type of influenza infection observed in humans. Maxingshigantang decoction, a classic formula of Chinese herbal medicine, has been used for the prevention and treatment of respiratory infection for many centuries. Qingfeiyin decoction, based on Maxingshigantang, has been used in the clinic for decades. To explore the underlying mechanisms, according to the traditional Chinese medicine theory "the lung and the large intestine are interior-exterior," which can be translated to the "gut-lung axis" in a contemporary term, the composition of gut microbiota was determined using 16S rRNA and the transcriptome of the colon was determined by RNA sequencing. The results showed that Qingfeiyin decoction decreased the viral load, alleviated the lung injury, increased the survival rate, partly restored the shortening of the colon caused by the H1N1 virus, and downregulated inflammatory pathways including MAPK, TNFα, and JAK-STAT signaling pathways. Qingfeiyin decoction increased the relative abundance of the genera of Coprococcus , Ruminococcus, Lactobacillus, and Prevotella and prevented the H1N1 virus-induced decrease in the abundance of the genera of Escherichia, Parabacteroides, Butyricimonas, and Anacrotruncus. These results will help better understand the mechanisms for Qingfeiyin decoction's protective effect against influenza virus infection.

Comparison of three kinds of self-expandable metallic stents induced granulation tissue hyperplasia in the rabbit trachea.

To compare stent-induced granulation tissue hyperplasia of bare (SEMS), polyurethane-covered (PU-SEMS) and electrospun nanofibre-covered (EN-SEMS) self-expandable metallic stents in the rabbit trachea. Twenty-seven rabbits were randomly assigned to 3 groups that received SEMS, PU-SEMS or EN-SEMS. Computed tomography and sacrifice were performed as scheduled. Haematoxylin-eosin and Masson's trichrome staining protocols were performed for pathological analysis. The data for tracheal ventilation area ratio, qualitative histological scoring, number of epithelial layers, and thicknesses of papillary projection and submucosa were documented and statistically analysed. All stents were successfully placed under the guidance of fluoroscopy without complications. Post-stenting 3 and 7 days, computed tomography revealed that the fully expandable EN-SEMS was similar to the SEMS and PU-SEMS. The mean stented tissue score in the SEMS group was higher than those of both the PU-SEMS and EN-SEMS groups at 3 days post-stenting. The pathological findings suggested that there was no papillary projection formation 3 days after stent placement. The thickness of papillary projection in the SEMS group was significantly higher than those of the PU-SEMS and EN-SEMS groups at 7 days post-stenting. After stenting 4 weeks, the tracheal ventilation area ratio of SEMS, PU-SEMS and EN-SEMS was 0.214 ± 0.021, 0.453 ± 0.028 and 0.619 ± 0.033, respectively. There were significant between-group differences. In conclusion, the stent-induced granulation tissue formation in EN-SEMS is less severe than that of PU-SEMS and SEMS. EN-SEMS has smaller radial force, and the tracheal ventilation ratio after stent placement better than that of PU-SEMS.

Arsenic trioxide-eluting electrospun nanofiber-covered self-expandable metallic stent reduces granulation tissue hyperplasia in rabbit trachea.

Stent-related granulation tissue hyperplasia is a major complication that limits the application of stents in airways. In this study, an arsenic trioxide-eluting electrospun nanofiber-covered self-expandable metallic stent (ATO-NFCS) was developed. Poly-L-lactide-caprolactone (PLCL) was selected as the drug-carrying polymer. Stents with two different ATO contents (0.4% ATO/PLCL and 1.2% ATO/PLCL) were fabricated. The in vitro release in simulated airway fluid suggested that the total ATO release time was 1 d. The growth of human embryonic pulmonary fibroblasts (CCC-HPF-1), normal human bronchial epithelial cells and airway smooth muscle cells was inhibited by ATO. When embedded in paravertebral muscle, the nanofiber membrane showed good short-term and long-term biological effects. In an animal study, placement of the ATO-NFCS in the trachea through a delivery system under fluoroscopy was feasible. The changes in liver and kidney function 1 and 7 d after ATO-NFCS placement were within the normal range. On pathological examination, the heart, liver, spleen, lungs and kidneys were normal. The effectiveness of the ATO-NFCS in reducing granulation tissue hyperplasia and collagen deposition was demonstrated in the rabbit airway (n = 18) at 4 weeks. The present study preliminarily investigated the efficacy of the ATO-NFCS in reducing granulation tissue formation in the trachea of rabbits. The results suggest that the ATO-NFCS is safe in vivo, easy to place, and effective for the suppression of granulation tissue formation.