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
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。
