Piceatannol, (E)-3, 3, 4, 5-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be contr...Piceatannol, (E)-3, 3, 4, 5-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be controlled more easily. The synthetic product was characterized by elemental analysis, IR, MS and 1H-NMR. Its analogs were synthesized by the similar method.展开更多
As a natural analog of resveratrol,piceatannol(Pic)exhibits good antioxidant and anti-inflammatory activities in different disease models.However,the role of Pic in type 1 diabetes mousemodel has not been reported yet...As a natural analog of resveratrol,piceatannol(Pic)exhibits good antioxidant and anti-inflammatory activities in different disease models.However,the role of Pic in type 1 diabetes mousemodel has not been reported yet.In this study,we investigated the in vivo effect of Pic in streptozotocin(STZ)-induced type 1 diabetic mice.Mice were injected with STZ to establish the type 1 diabetesmellitus(T1DM)model.After stable hyperglycemia was achieved,mice were then orally treated with Pic(40 mg/kg b.w.,i.g.)for 30 days.The results indicated that Pic supplementation efficiently alleviated the typical symptoms associated with T1DM,including body weight loss,polydipsia,hyperglycemia,and hypoinsulinemia.Pic treatment also improved the glucose tolerance of STZ-induced diabetic mice.In addition,Pic supplementation markedly decreased the expression of pro-inflammatory molecules TNF-αand IL-6,the expression of endoplasmic reticulum(ER)stress markers GRP78 and CHOP,and the level of oxidative stress in T1DM mice.Moreover,Pic administration also partly reversed the metabolic profiles of STZ-treated mice as detected by 1H Nuclear Magnetic Resonance(NMR)-based metabolomics.Our study suggested that the therapeutic potential of Pic in type 1 diabetes and the anti-diabetic effects of Pic may be associated with its activities to suppress oxidative stress,inflammation,and ER stress.展开更多
The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound...The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.展开更多
目的探讨白皮杉醇对脓毒症肺损伤小鼠代谢重编程的影响及可能机制。方法采用随机数字表法将32只雄性C57/B6小鼠随机分为4组,即对照组、模型组、低剂量治疗组和高剂量治疗组,每组各8只。对照组不做任何处理,其他3组使用脂多糖(lipopolysa...目的探讨白皮杉醇对脓毒症肺损伤小鼠代谢重编程的影响及可能机制。方法采用随机数字表法将32只雄性C57/B6小鼠随机分为4组,即对照组、模型组、低剂量治疗组和高剂量治疗组,每组各8只。对照组不做任何处理,其他3组使用脂多糖(lipopolysaccharide,LPS,10mg/kg)单次腹腔注射的方式构建脓毒症肺损伤小鼠模型,其中低剂量治疗组和高剂量治疗组小鼠于LPS注射前7天分别给予25mg/(kg·d)和100mg/(kg·d)的白皮杉醇灌胃,对照组和模型组给予等量0.9%氯化钠溶液灌胃。LPS腹腔注射12h后,留取小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和肺组织,通过形态学和分子生物学实验评估各组小鼠肺损伤状况。结果与对照组比较,模型组小鼠肺组织病理损伤较对照组更明显,主要表现为肺水肿和炎性细胞浸润,肺损伤评分更高(8.25±0.45分vs 1.31±0.23分),BALF中乳酸含量(0.65±0.12mmol/L vs 0.17±0.04mmol/L)和乳酸盐脱氢酶活性(8934.12±145.25U/L vs 4782.53±111.04U/L)增加,肺组织中IL-1β、IL-6和TNF-α的mRNA水平明显升高,肺组织中糖酵解标志蛋白(GLUT1、HK2、PDK2、PKM2)和组蛋白去乙酰化酶7(histone deacetylase 7,HDAC7)的蛋白表达明显上调,差异均有统计学意义(P<0.05);与模型组比较,低剂量治疗组和高剂量治疗组小鼠肺病理损伤明显减轻,肺损伤评分更低(5.69±0.92分、2.04±0.31分vs 8.25±0.45分),BALF中乳酸含量(0.42±0.03mmol/L、0.25±0.02mmol/L vs 0.65±0.12mmol/L)和乳酸盐脱氢酶活性(6822.24±172.02U/L、5872.02±93.07U/L vs 8934.12±145.25U/L)降低,肺组织中IL-1β、IL-6和TNF-α的mRNA水平明显降低,肺组织中GLUT1、HK2、PDK2、PKM2和HDAC7的蛋白表达均明显下降,差异均有统计学意义(P<0.05)。结论白皮杉醇可显著减轻脓毒症小鼠肺病理损伤和炎性反应,其机制可能与HDAC7介导的代谢重编程抑制有关。展开更多
研究白皮杉醇对阿尔茨海默病(Alzheimer s disease,AD)小鼠认知障碍的改善作用。取72只雄性昆明小鼠,随机分为6组,每组12只,即正常对照组、模型对照组、阳性对照组、白皮杉醇低、中、高剂量干预组。采用AlCl_(3)和D-半乳糖联合诱导的方...研究白皮杉醇对阿尔茨海默病(Alzheimer s disease,AD)小鼠认知障碍的改善作用。取72只雄性昆明小鼠,随机分为6组,每组12只,即正常对照组、模型对照组、阳性对照组、白皮杉醇低、中、高剂量干预组。采用AlCl_(3)和D-半乳糖联合诱导的方法连续干预70 d,建立阿尔茨海默病小鼠模型。在造模35 d开始用白皮杉醇连续干预,5周后通过Morris水迷宫实验评价小鼠的空间学习记忆能力,通过酶联免疫法(ELISA)检测小鼠海马体中Aβ_(1-42)及TNF-α蛋白表达水平、小鼠血清超氧化物歧化酶(SOD)活力、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量并结合相对脏器指数分析白皮杉醇对AD小鼠的保护效果。研究发现,与正常组比较,模型对照组小鼠逃避潜伏期显著性增加,记忆能力显著性降低,而白皮杉醇可有效提高模型小鼠认知行为和记忆能力(P<0.01);此外,与正常组比较,模型对照组小鼠脑组织中Aβ_(1-42)水平及炎症因子TNF-α表达水平明显升高,小胶质细胞活化明显增加,而白皮杉醇干预组小鼠Aβ_(1-42)、TNF-α及胶质细胞活化水平均显著降低(P<0.01)。进一步研究表明,白皮杉醇能有效提升小鼠血清SOD活力和GSH-Px水平,降低MDA含量,减轻氧化应激损伤。研究结果表明,白皮杉醇可以通过降低脑组织氧化应激及神经炎症反应,减少海马中β淀粉样蛋白的生成来改善阿尔茨海默病小鼠的认知功能障碍。展开更多
研究了一种白皮杉醇的简便合成方法,以3,4-二甲氧基苄醇为原料,经溴代、Arbuzov重排、Wittig-Horn-er反应和脱甲基4步反应得到白皮杉醇,并对目标产物的结构采用IR,1H NMR及13 C NMR进行了表征。讨论了白皮杉醇的抗氧化活性,包括还原力...研究了一种白皮杉醇的简便合成方法,以3,4-二甲氧基苄醇为原料,经溴代、Arbuzov重排、Wittig-Horn-er反应和脱甲基4步反应得到白皮杉醇,并对目标产物的结构采用IR,1H NMR及13 C NMR进行了表征。讨论了白皮杉醇的抗氧化活性,包括还原力、清除DPPH自由基和羟基自由基的能力,并与白藜芦醇、TBHQ、BHT和儿茶素作对比。结果表明:白皮杉醇具有较强的抗氧化性能,还原能力和清除羟基自由基的能力均高于白藜芦醇、TBHQ、BHT和儿茶素;其半抑制率IC50分别为DPPH自由基16.57μg/mL、羟基自由基270.00μg/mL。展开更多
文摘Piceatannol, (E)-3, 3, 4, 5-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be controlled more easily. The synthetic product was characterized by elemental analysis, IR, MS and 1H-NMR. Its analogs were synthesized by the similar method.
基金the National Natural Science Foundation of China under Grant 21677076 and 31970897 to DWOutstanding Youth Foundation of Jiangsu Province(BK20190093)to DWQing Lan Project of Jiangsu Province to DW,the Fundamental Research Funds for the Central Universities No.30919011102 to DW,the Innovative and Entrepreneurial Talent Cultivation(Shuangchuang)Program of Jiangsu Province to DW.
文摘As a natural analog of resveratrol,piceatannol(Pic)exhibits good antioxidant and anti-inflammatory activities in different disease models.However,the role of Pic in type 1 diabetes mousemodel has not been reported yet.In this study,we investigated the in vivo effect of Pic in streptozotocin(STZ)-induced type 1 diabetic mice.Mice were injected with STZ to establish the type 1 diabetesmellitus(T1DM)model.After stable hyperglycemia was achieved,mice were then orally treated with Pic(40 mg/kg b.w.,i.g.)for 30 days.The results indicated that Pic supplementation efficiently alleviated the typical symptoms associated with T1DM,including body weight loss,polydipsia,hyperglycemia,and hypoinsulinemia.Pic treatment also improved the glucose tolerance of STZ-induced diabetic mice.In addition,Pic supplementation markedly decreased the expression of pro-inflammatory molecules TNF-αand IL-6,the expression of endoplasmic reticulum(ER)stress markers GRP78 and CHOP,and the level of oxidative stress in T1DM mice.Moreover,Pic administration also partly reversed the metabolic profiles of STZ-treated mice as detected by 1H Nuclear Magnetic Resonance(NMR)-based metabolomics.Our study suggested that the therapeutic potential of Pic in type 1 diabetes and the anti-diabetic effects of Pic may be associated with its activities to suppress oxidative stress,inflammation,and ER stress.
基金supported by the Natural Science Foundation of Beijing,China(7214215)the Beijing Municipal Administration of Hospitals Incubating Program(PZ2021025)+5 种基金the Science Foundation of Peking University Six Hospital(YJJ0008)the National Natural Science Foundation of China(82203579,81872502,81402308)the Science Foundation of Peking University Cancer Hospital(2020-23,2021-24,202126)the Clinical Medicine Plus X-Young Scholars Project(PKU2020LCXQ001)the“Double First Class”Disciplinary Development Foundation of Peking University(BMU2019LCKXJ011)The first author,Longtao Huangfu,would like to give special thanks to the Beijing Natural Science Foundation Committee for granting the first research grant。
文摘The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.
文摘目的探讨白皮杉醇对脓毒症肺损伤小鼠代谢重编程的影响及可能机制。方法采用随机数字表法将32只雄性C57/B6小鼠随机分为4组,即对照组、模型组、低剂量治疗组和高剂量治疗组,每组各8只。对照组不做任何处理,其他3组使用脂多糖(lipopolysaccharide,LPS,10mg/kg)单次腹腔注射的方式构建脓毒症肺损伤小鼠模型,其中低剂量治疗组和高剂量治疗组小鼠于LPS注射前7天分别给予25mg/(kg·d)和100mg/(kg·d)的白皮杉醇灌胃,对照组和模型组给予等量0.9%氯化钠溶液灌胃。LPS腹腔注射12h后,留取小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和肺组织,通过形态学和分子生物学实验评估各组小鼠肺损伤状况。结果与对照组比较,模型组小鼠肺组织病理损伤较对照组更明显,主要表现为肺水肿和炎性细胞浸润,肺损伤评分更高(8.25±0.45分vs 1.31±0.23分),BALF中乳酸含量(0.65±0.12mmol/L vs 0.17±0.04mmol/L)和乳酸盐脱氢酶活性(8934.12±145.25U/L vs 4782.53±111.04U/L)增加,肺组织中IL-1β、IL-6和TNF-α的mRNA水平明显升高,肺组织中糖酵解标志蛋白(GLUT1、HK2、PDK2、PKM2)和组蛋白去乙酰化酶7(histone deacetylase 7,HDAC7)的蛋白表达明显上调,差异均有统计学意义(P<0.05);与模型组比较,低剂量治疗组和高剂量治疗组小鼠肺病理损伤明显减轻,肺损伤评分更低(5.69±0.92分、2.04±0.31分vs 8.25±0.45分),BALF中乳酸含量(0.42±0.03mmol/L、0.25±0.02mmol/L vs 0.65±0.12mmol/L)和乳酸盐脱氢酶活性(6822.24±172.02U/L、5872.02±93.07U/L vs 8934.12±145.25U/L)降低,肺组织中IL-1β、IL-6和TNF-α的mRNA水平明显降低,肺组织中GLUT1、HK2、PDK2、PKM2和HDAC7的蛋白表达均明显下降,差异均有统计学意义(P<0.05)。结论白皮杉醇可显著减轻脓毒症小鼠肺病理损伤和炎性反应,其机制可能与HDAC7介导的代谢重编程抑制有关。
文摘研究白皮杉醇对阿尔茨海默病(Alzheimer s disease,AD)小鼠认知障碍的改善作用。取72只雄性昆明小鼠,随机分为6组,每组12只,即正常对照组、模型对照组、阳性对照组、白皮杉醇低、中、高剂量干预组。采用AlCl_(3)和D-半乳糖联合诱导的方法连续干预70 d,建立阿尔茨海默病小鼠模型。在造模35 d开始用白皮杉醇连续干预,5周后通过Morris水迷宫实验评价小鼠的空间学习记忆能力,通过酶联免疫法(ELISA)检测小鼠海马体中Aβ_(1-42)及TNF-α蛋白表达水平、小鼠血清超氧化物歧化酶(SOD)活力、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量并结合相对脏器指数分析白皮杉醇对AD小鼠的保护效果。研究发现,与正常组比较,模型对照组小鼠逃避潜伏期显著性增加,记忆能力显著性降低,而白皮杉醇可有效提高模型小鼠认知行为和记忆能力(P<0.01);此外,与正常组比较,模型对照组小鼠脑组织中Aβ_(1-42)水平及炎症因子TNF-α表达水平明显升高,小胶质细胞活化明显增加,而白皮杉醇干预组小鼠Aβ_(1-42)、TNF-α及胶质细胞活化水平均显著降低(P<0.01)。进一步研究表明,白皮杉醇能有效提升小鼠血清SOD活力和GSH-Px水平,降低MDA含量,减轻氧化应激损伤。研究结果表明,白皮杉醇可以通过降低脑组织氧化应激及神经炎症反应,减少海马中β淀粉样蛋白的生成来改善阿尔茨海默病小鼠的认知功能障碍。
文摘研究了一种白皮杉醇的简便合成方法,以3,4-二甲氧基苄醇为原料,经溴代、Arbuzov重排、Wittig-Horn-er反应和脱甲基4步反应得到白皮杉醇,并对目标产物的结构采用IR,1H NMR及13 C NMR进行了表征。讨论了白皮杉醇的抗氧化活性,包括还原力、清除DPPH自由基和羟基自由基的能力,并与白藜芦醇、TBHQ、BHT和儿茶素作对比。结果表明:白皮杉醇具有较强的抗氧化性能,还原能力和清除羟基自由基的能力均高于白藜芦醇、TBHQ、BHT和儿茶素;其半抑制率IC50分别为DPPH自由基16.57μg/mL、羟基自由基270.00μg/mL。
