Search

Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg(−1) · d(−1)) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg(−1) · d(−1)) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.

Objectives Anlotinib hydrochloride (AL3818) is a novel multitarget tyrosine kinase inhibitor which has the same targets as nintedanib, an effective drug has been approved for the treatment of idiopathic pulmonary fibrosis. Here, we examined whether anlotinib could also attenuate bleomycin-induced pulmonary fibrosis in mice and explored the antifibrosis mechanism. Methods We have evaluated the effect of anlotinib on bleomycin-induced pulmonary fibrosis in mice. Inflammatory cytokines in alveolar lavage fluid including IL-1β, IL-4, IL-6 and TNF-α were determined by ELISA. Biomarkers of oxidative stress were measured by corresponding kit. Histopathologic examination was analysed by H&E staining and immunohistochemistry. In vitro, we investigated whether anlotinib inhibited TGFβ/Smad3 and non-Smad pathways by luciferase assay or Western blotting. We also evaluated whether anlotinib inhibited TGF-β1-induced epithelial–mesenchymal transition (EMT) and promoted myofibroblast apoptosis in order to explore the possible molecular mechanism. Key findings The results indicated that anlotinib treatment remarkably attenuated inflammation, oxidative stress and pulmonary fibrosis in mouse lungs. Anlotinib could inhibit the TGF-β1 signalling pathway. Additionally, anlotinib not only profoundly inhibited TGF-β1-induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and promoted the apoptosis in fibroblasts. Conclusions In summary, the results suggest that anlotinib-mediated suppression of pulmonary fibrosis is related to the inhibition of TGF-β1 signalling pathway.

BACKGROUND AND PURPOSE Diosmetin exhibits a series of therapeutic efficacy but little is known of its effects on colitis. EXPERIMENTAL APPROACH In this study, two mouse models of DSS (the concentration of 3% and 5%)-induced colitis and Caco2 and IEC-6 cells were employed. The 16S amplicon sequencing was used to assess Gut microbiota changes by diosmetin. Various physical signs of mice (body weight, colon length and DAI score), proinflammatory cytokines and antioxidant enzymes were tested. KEY RESULTS The results showed that diosmetin can markedly decrease the disease activity index and microscopic colon tissue damage, increase the expression of tight junction protein (Occludin, Claudin-1 and Zo-1) and reduce the secretion of proinflammatory cytokines. And diosmetin also significantly inhibited colon oxidative damage through adjusting the levels of intracellular ROS, mitochondrial ROS, GSH-Px, SOD, MDA and GSH in vitro and in vivo. Furthermore, it was found that diosmetin can modulate the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were reported to be the crucial bacteria related to inflammatory bowel disease (IBD). Also, diosmetin significantly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, thereby inhibiting oxidative stress and inflammation. CONCLUSIONS AND IMPLICATIONS Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is regulated by diosmetin. It implies that diosmetin may be a novel candidate to alleviate DSS-induced colitis or a lead compound for future optimization and modification.

The focusing phenomenon is a difficult point during the electrokinetic remediation (EKR) of contaminated soil. It restricts the extraction and removal of heavy metals. There is still a lack of methods to discern focusing position rapidly and take proper measures. Therefore, a total of seven tests with or without intervening and regulating measures were conducted. Among the four tests without regulating and intervening measures, focusing position often appeared in low-voltage region after three days’ treatment. When using ammonium citrate as electrolyte, the highest removal efficiency of total chromium (Cr) (32.20%) was achieved. The intervening measure that adding citric acid near section 4 decreased the area of high-voltage and made it move towards cathode. Meanwhile, the removal efficiency of Cr(VI) (60.17%) was significantly improved. Using sodium dodecyl sulfate (SDS) as pretreatment agent and electrolyte made the position of high-voltage area move towards anode and removed 35.80% of total Cr and 53.47% of Cr(VI) eventually. Simultaneously, the energy consumption per gram of removed Cr was also the lowest. The focusing degree was reduced with intervening and regulating measures conducted but focusing position still existed in low voltage area, which further indicated that focusing position preferred to appear in low voltage area and we could discern focusing position through voltage distribution across the soil roughly.

Background: Pirfenidone(PFD) and nintedanib(NDN), the only two drugs for IPF, which should be accurately selected in treatment, has no relevant basic research for reference. Objective: Compare the effect of PFD and NDN in bleomycin(BLM)-induced pulmonary fibrosis model of different periods, so as to provide theoretical basis for clinical application. Methods: The BLM model of different periods were performed in Fig1. Results: 1) Anti-inflammatory and antioxidant capacity: The inhibition rate of NDN on inflammatory cell numbers was higher than that of PFD, while PFD has better inhibitory effect on IL-1β and IL-4 and NDN has higher inhibitory rate on IL-6 and IFN-γ. The activity of SOD in PFD group was higher than that of NDN group, while the content of MDA in lung tissues and the concentration of MPO in serum were significantly lower in NDN group than of PFD group. 2) Anti-fibrosis capacity: In prevention model, hydroxyproline content in PFD group was 140.29±3.59μg/right lung and NDN group was 162.87±2.91μg/right lung. In treatment models, HYP content was much less in NDN group than in PFD group. Pathological change was consistent with the HYP results. Conclusion: Both PFD and NDN have anti-inflammatory and antioxidative effects and selectively suppressed different biomarkers. PFD is more effective in the prophylactic model of fibrosis, while NDN has a better effect in early and late treatment models.

Background: Idiopathic pulmonary fibrosis is incurable and has no effective treatment. The marketed drugs are only pirfenidone and nintedanib. By evaluating the inhibition effects of pirfenidone and nintedanib on the proliferation, migration and activation of human lung fibroblasts (HFL1), the anti-fibrotic mechanism of two drugs was tested and compared to provide reference for accurate clinical medication. Methods: HFL1 cells were divided into control group, TGF-β1/ PDGF-stimulate-model group, and drug-add group. The effect of pirfenidone and nintedanib on the proliferation and migration of HFL1 were evaluated by MTT assay and scratch test, respectively. Anti-pulmonary fibrosis effects of pirfenidone and nintedanib were evaluated by detecting the inhibitory activity of each drug on the expression of fibroblasts activation markers. The inhibitory effects of pirfenidone and nintedanib on TGF-β/Smad3 signaling pathway were evaluated by Western Blotting. Results: The results of MTT assays showed that both pirfenidone and nintedanib could inhibit TGF-β-induced proliferation of fibroblasts. In addition, both pirfenidone and nintedanib inhibited the migration of HFL1; Both pirfenidone and nintedanib can inhibit the expression of fibroblast activation markers, and they can inhibit the activation of TGF-β/Smad3 protein signaling pathway by inhibiting the phosphorylation of Smad3. The inhibition rate of Smad3 phosphorylation by nintedanib was 51%, and the inhibition rate of pirfenidone on Smad3 phosphorylation was 13%. Conclusion: Both pirfenidone and nintedanib could inhibit the proliferation, migration and activation of myofibroblasts, And all of them can exert anti-pulmonary fibrosis through TGF-β signaling pathway.