AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was i...AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl(DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate(FTC) and thiobarbituric acid(TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1(CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinine oxidoreductase 1(NQO1), and γ-glutamylcysteine synthetase catalytic subunit(γ-GCSc) protein expression was measured by Western blot.RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation(P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE(160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes(P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression.CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.展开更多
目的通过网络药理学和分子对接技术分析白鲜皮“异病同治”皮炎、湿疹、银屑病的分子靶点及其相关作用机理。方法运用中药系统药理学数据库与分析平台(TCMSP)检索并筛选白鲜皮的主要活性成分,并运用STP数据库预测有效成分的作用靶点。借...目的通过网络药理学和分子对接技术分析白鲜皮“异病同治”皮炎、湿疹、银屑病的分子靶点及其相关作用机理。方法运用中药系统药理学数据库与分析平台(TCMSP)检索并筛选白鲜皮的主要活性成分,并运用STP数据库预测有效成分的作用靶点。借助TTD、OMIM、DrugBank、GeneCards、DisGeNET数据库获取治疗皮炎、湿疹、银屑病的有关靶点,借助Venny软件获取皮炎、湿疹、银屑病的相同靶点以及与白鲜皮有效成分作用靶点的交集靶点。利用Cytoscape绘制网络图,STRING数据库构建白鲜皮治疗皮炎、湿疹、银屑病的相同靶基因的蛋白互作网络图。运用Metascape数据库进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并运用R语言进行可视化处理。通过Discovery Studio 2019 Client、AutoDock Tools、PyMOL进行分子对接和可视化。结果经筛选白鲜皮有效成分15个,与皮炎、湿疹、银屑病相同靶点的交集靶点共64个。白鲜皮活性成分治疗皮炎、湿疹、银屑病的核心靶点依次为肿瘤坏死因子(TNF)、Toll样受体4(TLR4)、血管内皮生长因子A(VEGFA)、信号转导和转录激活因子3(STAT3)、信号转导和转录激活因子1(STAT1)等。核心通路为高级糖基化终末产物-受体(AGE-RAGE)、白细胞介素17(IL-17)、酪氨酸激酶-信号传导及转录活化因子(JAK-STAT)信号通路等。结论白鲜皮可能通过IL-17、JAK-STAT、AGE-RAGE等多个通路作用于TNF、TLR4、VEGFA等多个靶点,从而在皮炎、湿疹、银屑病中起到抗炎止痒的作用。展开更多
白鲜皮水提物能作用于2 ,4 ,6三硝基氯苯所致迟发型变态反应的效应相,有效地改善迟发型变态反应性肝损伤,在肝损伤12 h 分离的肝非实质细胞和肝细胞共培养体系中,白鲜皮水提物预处理肝非实质细胞明显地阻断了上清中谷丙转氨酶的释放,...白鲜皮水提物能作用于2 ,4 ,6三硝基氯苯所致迟发型变态反应的效应相,有效地改善迟发型变态反应性肝损伤,在肝损伤12 h 分离的肝非实质细胞和肝细胞共培养体系中,白鲜皮水提物预处理肝非实质细胞明显地阻断了上清中谷丙转氨酶的释放,作用呈量效关系和时效关系,而预处理肝细胞则无影响。同样,白鲜皮水提物对Con A 引起的脾淋巴细胞增殖无抑制活性,诱导相给药对肝损伤亦无保护作用。展开更多
基金Supported by National Science and Technology Major New Drugs Project of China,No.2012ZX09103201-012
文摘AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl(DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate(FTC) and thiobarbituric acid(TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1(CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinine oxidoreductase 1(NQO1), and γ-glutamylcysteine synthetase catalytic subunit(γ-GCSc) protein expression was measured by Western blot.RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation(P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE(160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes(P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression.CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.
文摘目的通过网络药理学和分子对接技术分析白鲜皮“异病同治”皮炎、湿疹、银屑病的分子靶点及其相关作用机理。方法运用中药系统药理学数据库与分析平台(TCMSP)检索并筛选白鲜皮的主要活性成分,并运用STP数据库预测有效成分的作用靶点。借助TTD、OMIM、DrugBank、GeneCards、DisGeNET数据库获取治疗皮炎、湿疹、银屑病的有关靶点,借助Venny软件获取皮炎、湿疹、银屑病的相同靶点以及与白鲜皮有效成分作用靶点的交集靶点。利用Cytoscape绘制网络图,STRING数据库构建白鲜皮治疗皮炎、湿疹、银屑病的相同靶基因的蛋白互作网络图。运用Metascape数据库进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并运用R语言进行可视化处理。通过Discovery Studio 2019 Client、AutoDock Tools、PyMOL进行分子对接和可视化。结果经筛选白鲜皮有效成分15个,与皮炎、湿疹、银屑病相同靶点的交集靶点共64个。白鲜皮活性成分治疗皮炎、湿疹、银屑病的核心靶点依次为肿瘤坏死因子(TNF)、Toll样受体4(TLR4)、血管内皮生长因子A(VEGFA)、信号转导和转录激活因子3(STAT3)、信号转导和转录激活因子1(STAT1)等。核心通路为高级糖基化终末产物-受体(AGE-RAGE)、白细胞介素17(IL-17)、酪氨酸激酶-信号传导及转录活化因子(JAK-STAT)信号通路等。结论白鲜皮可能通过IL-17、JAK-STAT、AGE-RAGE等多个通路作用于TNF、TLR4、VEGFA等多个靶点,从而在皮炎、湿疹、银屑病中起到抗炎止痒的作用。
文摘白鲜皮水提物能作用于2 ,4 ,6三硝基氯苯所致迟发型变态反应的效应相,有效地改善迟发型变态反应性肝损伤,在肝损伤12 h 分离的肝非实质细胞和肝细胞共培养体系中,白鲜皮水提物预处理肝非实质细胞明显地阻断了上清中谷丙转氨酶的释放,作用呈量效关系和时效关系,而预处理肝细胞则无影响。同样,白鲜皮水提物对Con A 引起的脾淋巴细胞增殖无抑制活性,诱导相给药对肝损伤亦无保护作用。
