Changyanqing decoction produces anti-inflammatory effect by inhibiting the activation of nuclear factor-kappaB / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the changes in intestinal mucosal permeation in rats with methotrexate-induced small intestinal damage and investigate the protective effects of Changyanqing decoction.</p><p><b>METHODS</b>Rat enteritis model was established by methotrexate (MTX) and sodium chloride. The rats were randomly divided into normal control group, model group, N-acetylcysteine (NAC) group and Changyanqing decoction group, and Changyanqing decoction (100 mg/kg) or saline was administered daily in the corresponding groups by gastric irrigation for 6 days. The disease activity index (DAI), colonic mucosal damage index (CMDI) and histological score (HS) of the rats were observed and evaluated. The levels of mRNA expressions of TNF-alpha and IL-1beta were detected by semi-quantitative RT-PCR. The expression of IL-10 was detected by enzyme linked immunosorbent assay, and IkappaB expression was determined with Western blotting.</p><p><b>RESULTS</b>Compared with the normal control group, the model group showed significantly increased DAI, CMDI and HS. The DAI, CMDI, and HS in rats treated with Changyanqing decoction were significantly decreased in comparison with those in the model group (P<0.01). The expressions of TNF-alpha and IL-1beta were significantly higher in MTX-treated group than in the control group. The expression of TNF-alpha and IL-1beta mRNA in the Changyanqing group and NAC group were significantly lower, but IL-10 significantly higher than those of the MTX group. In MTX group, obvious NF-kappaB activation was observed, whose expression was significantly stronger in the cell nuclei, and the IkappaB in the cytoplasm was markedly degraded.</p><p><b>CONCLUSION</b>Changyanqing decoction offers protection on intestinal mucosa by inhibiting NF-kappaB activation to reduce TNF-alpha and IL-1beta mRNA expressions and increase IL-10 expression.</p>

Effects of Changyanqing decoction on the expressions of interleukin-10 and intercellular adhesion molecule-1 in rats with ulcerative colitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of Changyanqing decoction, a traditional Chinese medicinal preparation, on the expressions of interleukin-10 (IL-10) and intercellular adhesion molecule-1 (ICAM-1) in the colon mucosa of rats with ulcerative colitis.</p><p><b>METHODS</b>The rats with ulcerative colitis induced by trinitrobenzene sulphonic acid and ethanol enema were randomly divided into 3 groups, namely the model group, sulfasalazine (SASP) group, and Changyanqing decoction group. Daily treatment with intragastric administration and enema of normal saline, SASP (100 mg/kg), and Changyanqing decoction (39.75 mg/kg), respectively, were administered 24 h after the establishment of colitis till the end of the experiment. Another group of rats was used as the normal control group. The disease activity index (DAI) and colon mucosa damage index (CMDI) of the rats were calculated. The activity of myeloperoxidase (MPO) was measured by biochemical method, and the expressions of IL-10 and ICAM-1 protein were measured by ELISA and immunohistochemistry, respectively.</p><p><b>RESULTS</b>Compared with the normal group, the model group showed significantly increased DAI, CMDI, HS score and MPO activity in the colon tissues (P < 0.01), with also significantly increased expression of ICAM-1 (P < 0.01) and decreased expression of IL-10 in the rat colon mucosa (P < 0.01). Treatment with Changyanqing decoction resulted in a significant reduction in DAI, CMDI, HS score and MPO activity (P < 0.01), and decreased the expression of ICAM-1 (P < 0.01) and increased the expression of IL-10 (P < 0.01) in the colon mucosa. The expression of ICAM-1 in the colon mucosa was positively correlated to that of IL-10 (r = 0.927, P < 0.01) and the activity of MPO (r = 0.621, P < 0.01).</p><p><b>CONCLUSIONS</b>Changyanqing decoction has protective effect against rat ulcerative colitis, mediated probably by enhancement of IL-10 expression and reduction in ICAM-1 expression and neutrophil infiltration.</p>

Effect of angiotensin II on Rho-Rock pathway in rat hepatic stellate cell contraction / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanisms of angiotonin II (AngII)-induced Ca(2+)-independent pathways mediated by Rho kinase in hepatic stellate cells (HSCs).</p><p><b>METHODS</b>HSC-T6 cells were treated with 1 micromol/L of AngII, and the subsequent cell contraction was directly observed with silicone rubber membrane culture method. The cells with 10 micromol/L AngII treatment were examined for myosin light chain (MLC) phosphorylation level using Western blotting, and the effects of irbesartan (a specific inhibitor of AngII 1- receptor) and Y27632 (a Rho kinase inhibitor) on AngII-induced MLC phosphorylation were evaluated. RT-PCR was used to detect the expression of Rock2 in Ca(2+)- independent pathways mediated by Rho kinase.</p><p><b>RESULTS</b>AngII induced HSC contraction and time-dependent MLC phosphorylation changes, which peaked 15 min after the treatment followed by gradual reduction. Irbesartan or Y27632 treatment significantly lowered MLC phosphorylation level in AngII-induced cells (P<0.01). The mRNA expression of Rock2 increased significantly after AngII treatment (P<0.01), but decreased following subsequent irbesartan or Y27632 treatment.</p><p><b>CONCLUSION</b>AngII induces HSC contraction through Ca(2+)-independent pathways mediated by Rho kinase.</p>

Protective effect of curcumin against methotrexate-induced small intestinal damage in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the changes in intestinal mucosal permeability in rats with methotrexate (MTX)-induced small intestinal damage and investigate the protective effects of curcumin.</p><p><b>METHODS</b>The experiment was carried out using 4 groups of rats, namely the normal control group, enteritis model group, sulfasalazine (SASP) group and curcumin group. With the exception of the rats in the normal control group, all rats were subjected to intraperitoneal MTX injection to induce enteritis and received subsequent daily intragastric administration of SASP (100 mg/kg), curcumin (100 mg/kg), or normal saline for 5 days. The disease activity index (DAI), colonic mucosal damage index (CMDI) and histological score (HS) of the rats were evaluated. The levels of diamine oxidase (DAO) and D-lactate were assessed using spectrophotometric assay, and myeloperoxidase (MPO) activity and intracellular adhesion molecule-1 (ICAM-1) protein expression were measured by biochemical and immunohistochemical methods, respectively.</p><p><b>RESULTS</b>Compared with the normal control group, the rats in the model group showed significantly increased DAI, CMDI and HS and levels of DAO, D-lactate, ICAM-1 and MPO. Curcumin treatment resulted in significantly decreased DAI, CMDI, HS and lowered activities of D-lactate, ICAM-1 and MPO in comparison with the model group (P<0.01).</p><p><b>CONCLUSION</b>MTX induces increased mucosal permeability of the small intestines in rats, and curcumin may offer protective effects against MTX-induced rat enteritis by lowering the intestinal mucosal permeability.</p>