Juhui Zhao

Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway

Chlorogenic acid (CGA) is a type of polyphenol with anti-inflammatory, antioxidant activities. Our previous studies showed CGA could efficiently inhibit carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. However, the specific underlying mechanism remains unclear. The aim of this study is to investigate the effects of CGA on liver inflammation and fibrosis induced by CCl(4) and whether they are related to inhibition of toll-like receptor 4 (TLR4) signaling pathway. Male Sprague-Dawley (SD) rats were administrated CCl(4) together with or without CGA for 8 weeks. Histopathological and biochemical analyses were carried out. The mRNA and protein expression levels of proinflammatory and profibrotic mediators were detected by RT-PCR and Western blot, respectively. The levels of serum proinflammatory cytokines were detected by ELISA. CGA significantly attenuated CCl(4)-induced liver damage and symptoms of liver fibrosis, accompanied by reduced serum transaminase levels, collagen I and α-smooth muscle actin (α-SMA) expression. As compared with the CCl(4)-treated group, the expression levels of TLR4, myeloid differentiation factor 88 (MyD88), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were reduced in the treatment group of CCl(4) and CGA, whereas bone morphogenetic protein and activin membrane-bound inhibitor (Bambi) expression was increased. CGA also suppressed CCl(4) induced nuclear factor-κB (NF-κB) activation. Moreover, the hepatic mRNA expression and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were significantly increased in CCl(4)-treated rats and attenuated by co-treatment with CGA. Our data indicate that CGA can efficiently inhibit CCl(4)-induced liver fibrosis in rats and the protective effect may be due to the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Chlorogenic acid against carbon tetrachloride-induced liver fibrosis in rats

This study examined the effects of chlorogenic acid (CGA) on liver fibrosis induced by carbon tetrachloride (CCl(4)) and explored the possible mechanisms of action. Liver fibrosis was induced in male Sprague-Dawley (SD) rats by the injection of 40% CCl(4) subcutaneously twice a week for eight weeks. At the same time, CGA (60 and 30mg/kg) was administered intragastrically once daily to a subset of rats. Upon pathological examination, the CGA-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis. The expression of collagen I and collagen III mRNA was increased markedly by the CCl(4) treatment but this increase was suppressed by CGA. As compared with the CGA-treated group, the expression of bcl-2, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-beta1) mRNA was increased in CCl(4) group, whereas Bax mRNA expression decreased. The expression of Bax and bcl-2 protein was confirmed by western blotting. Intragastric administration of CGA reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and glucose-regulated proteins 78 and 94 (GRP78 and GRP94) in rats injured by treatment with CCl(4). Our data indicate that CGA can efficiently inhibit CCl(4)-induced liver fibrosis in rats. Therefore, CGA could be an effective drug for preventing liver fibrosis.

Protective effect of a coffee preparation (Nescafe pure®) against carbon tetrachloride-induced liver fibrosis in rats

BACKGROUND & AIMS We examined the effects of a coffee preparation on liver fibrosis induced by carbon tetrachloride (CCl(4)) and explored the possible mechanisms. METHODS Rats were divided randomly into four groups: control, CCl(4), and two coffee preparation groups. Except for the control group, liver fibrosis was induced in male Sprague-Dawley (SD) rats by subcutaneous injection with 40% CCl(4) twice a week for 8 weeks. At the same time, a coffee preparation (300 mg/kg and 150 mg/kg) was administered to the two coffee preparation groups intragastrically once daily. RESULTS Upon pathological examination, a coffee preparation treatment significantly reduced liver damage and symptoms of liver fibrosis. The mRNA expression of collagen I, collagen III, bcl-2, vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) were markedly increased by CCl(4) treatment but suppressed by a coffee preparation treatment. Whereas compared with the CCl(4) group, the mRNA expression of Bax was increased in the coffee preparation group. The protein expression of Bax and bcl-2 were confirmed by western blot. Intragastric administration of a coffee preparation reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and the glucose-regulated proteins (GRP) 78 and 94 in rats increased by CCl(4). CONCLUSIONS Our data indicate that a coffee preparation can efficiently inhibit CCl(4)-induced liver fibrosis in rats. The coffee preparation may therefore be a potential functional food for preventing liver fibrosis.

A protease inhibitor against acute stress-induced visceral hypersensitivity and paracellular permeability in rats

In the present study, we investigated the effects of camostat mesilate (CM), a synthetic protease inhibitor, on visceral sensitivity and paracellular permeability induced by the acute restraint stress. We also explored the possible mechanisms underlying these effects. The acute restraint stress was induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk of Sprague-Dawley rats for 2h. Either CM (30, 100 and 300mg/kg) or saline was intragastrically administrated to the rats 30min before the acute restraint stress. Visceral perception was quantified as visceral motor response with an electromyography in a subset of rats. Paracellular permeability was determined in another subset of rats. We found that the visceral sensitivity and paracellular permeability were significantly reduced in the CM-treated rats. Moreover, the fecal protease activity was decreased in the CM-treated rats. The ZO-1 protein expression was markedly reduced by the stress treatment, but this decrease was suppressed by CM administration. Our data indicated that CM could efficiently inhibit visceral sensitivity and paracellular permeability induced by the acute restraint stress in rats. Therefore, CM might be an effective drug for the treatment of irritable bowel syndrome.

Endoscopic ultrasonography for preoperative staging of esophageal carcinoma

Abstract Objective: To evaluate the diagnostic value of endoscopic ultrasonography (EUS) in preoperative staging of esophageal carcinoma (EC). Material and methods: A total of 86 surgical patients with EC who were confirmed by endoscopy and biopsy underwent preoperative TN staging with EUS examination. The EUS findings were compared with surgical pathologic results. Results: The accuracy of EUS in T and N staging of EC was 82.6% and 84.9%, respectively. While determining whether EC invades the muscularis propria or outer membrane, EUS had the favorable sensitivity, specificity, positive predictive value and negative predictive value. The short-axis diameter of lymph nodes of 5mm had high sensitivity and negative predictive value to determine malignance with low specificity and positive predictive value. The short-axis diameter of 10mm presented the satisfactory sensitivity, specificity, positive predictive value and negative predictive value. Conclusion: EUS can accurately determine the TN staging of EC and provide a reliable basis for the treatment of EC.