Alcoholic liver disease(ALD) has become one of the leading causes of death in the world. Berbamine(BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medi...Alcoholic liver disease(ALD) has become one of the leading causes of death in the world. Berbamine(BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125-40 μmol·L^-1 had no effect on macrophages and hepatocytes proliferation. BM at 5-20 μmol·L^-1 significantly inhibited lipopolysaccharide(LPS) or acetate-induced IL-1β and IL-6 m RNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg^-1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanolfed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride(TG) and total cholesterol(TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines m RNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation of NF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD.展开更多
This study aimed to investigate the mechanisms of Yu-Ping-Feng-San(YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis(AD). AD mouse model was established with fluorescein isothiocyana...This study aimed to investigate the mechanisms of Yu-Ping-Feng-San(YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis(AD). AD mouse model was established with fluorescein isothiocyanate(FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells(DCs)and group 2 innate lymphoid cells(ILC2 s) were detected by flow cytometry. Human immortalized keratinocyte(Ha Ca T) cells were stimulated with Poly(I:C)/TNF-α in vitro to assess thymic stromal lymphopoietin(TSLP), interleukin(IL)-33 and nuclear factor-κB(NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay(ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2 s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.展开更多
基金National Natural Science Foundation of China(NSFC)(No.81701573)Key Technologies of Prevention and Control for Major and Infectious Diseases Project of Suzhou(No.GWZX201604)Youth Medical Talent Project of Jiangsu(No.QNRC2016214)。
文摘Alcoholic liver disease(ALD) has become one of the leading causes of death in the world. Berbamine(BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125-40 μmol·L^-1 had no effect on macrophages and hepatocytes proliferation. BM at 5-20 μmol·L^-1 significantly inhibited lipopolysaccharide(LPS) or acetate-induced IL-1β and IL-6 m RNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg^-1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanolfed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride(TG) and total cholesterol(TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines m RNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation of NF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD.
基金supported by the National Natural Science Foundation of China(Nos.81473395,81473390,and 81703733)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20141466)Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of China(No.JKLPSE201603)
文摘This study aimed to investigate the mechanisms of Yu-Ping-Feng-San(YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis(AD). AD mouse model was established with fluorescein isothiocyanate(FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells(DCs)and group 2 innate lymphoid cells(ILC2 s) were detected by flow cytometry. Human immortalized keratinocyte(Ha Ca T) cells were stimulated with Poly(I:C)/TNF-α in vitro to assess thymic stromal lymphopoietin(TSLP), interleukin(IL)-33 and nuclear factor-κB(NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay(ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2 s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.
