Background Piglets are highly susceptible to oxidative stress,which can reduce growth performance and cause intestinal damage.Piceatannol(PIC),a natural bioactive substance enriched in Chinese rhubarb(Rheum officinale...Background Piglets are highly susceptible to oxidative stress,which can reduce growth performance and cause intestinal damage.Piceatannol(PIC),a natural bioactive substance enriched in Chinese rhubarb(Rheum officinale)and certain dark purple fruits,shows excellent antioxidant properties in our previous cell-based high-throughput screening.However,its effect on piglet growth performance and antioxidant capacity as well as underling mechanism has not been thoroughly investigated.Methods One hundred weaned pigs(28 days of age,8.71±0.20 kg)were randomly assigned to 4 treatments with 5 replicates of 5 pigs per replicate.The experimental diets consisted of:1)basal diet,2)basal diet+100 mg/kg PIC,3)basal diet+200 mg/kg PIC,and 4)basal diet+300 mg/kg PIC.On d 15 and 35,one pig from each replicate was selected for sampling.The growth performance was monitored during a 35-day trial.In addition,H_(2)O_(2)-challenged IPEC-J2 cells served as an in vitro model to investigate the antioxidant mechanisms of PIC.IPEC-J2 cells were treated with 1,000μmol/L H_(2)O_(2)in the presence or absence of 10μmol/L PIC.Results Dietary PIC at 200 mg/kg significantly enhanced growth performance,as evidenced by increased average daily gain and feed conversion rate(P<0.05).PIC supplementation markedly improved systemic antioxidant capacity,with elevated serum total antioxidant capacity,catalase activity,and glutathione levels,along with reduced malondialdehyde content(P<0.05).Notably,PIC modulated the gut microbiota composition,increasing the amounts of beneficial genera(e.g.,Blautia and Faecalibacterium),and these microbial shifts significantly correlated with improved antioxidant indices.In vitro,PIC pretreatment effectively protected IPEC-J2 cells against H_(2)O_(2)-induced oxidative damage by reducing reactive oxygen species generation and lipid peroxidation(P<0.01).Mechanistically,PIC exerts its antioxidant effects through Nrf2 pathway activation,upregulating endogenous antioxidant enzymes(P<0.05)while simultaneously inhibiting apoptosis via the regulation of the Bcl-2/Bax ratio and caspase-3 cleavage(P<0.01).Conclusions PIC improved the growth performance and health status of weaned piglets through the regulation of Nrf2-mediated redox homeostasis and modulation of the related gut microbiota,offering a potential new natural antioxidants for mitigating weaning stress in piglets.展开更多
Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced ...Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.展开更多
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
In this study,three different target analytes from the fruit of myrtle(Rhodomyrtus tomentosa)were extracted via an enzymatic-homogenate synergistic extraction(EHSE)process,and 10 different aqueous solutions of natural...In this study,three different target analytes from the fruit of myrtle(Rhodomyrtus tomentosa)were extracted via an enzymatic-homogenate synergistic extraction(EHSE)process,and 10 different aqueous solutions of natural surfactants were selected as extraction solvents,thus enabling the simultaneous extraction of piceatannol,resveratrol,and myricetin from the fruit of myrtle(Rhodomyrtus tomentosa).Important factors affecting the yield of piceatannol,resveratrol,and myricetin,including enzyme type,enzyme concentration,pH,surfactant type and dosage,homogenization time,liquid-solid ratio,incubation and extraction time,incubation time and extraction temperature,were optimized via single-factor experiments.Three important parameters were optimized via the Box-Behnken design:the liquid-solid ratio,the incubation-extraction time,and the reaction temperature.The final optimum extraction process conditions were as follows:β-glucosidase concentration,3.0%,homogenate;time,3 min;pH,5;tea saponin concentration,0.8%;liquid-solid ratio,45 mL/g;incubation-extraction time,2.5 h;and temperature,67.5℃.With the optimized experimental parameters,the piceatannol,resveratrol,and myricetin yields were 742.12±37.11μg/g,18.58±0.94μg/g,and 24.83±1.25μg/g,respectively.Methodological validation and comparison experiments with traditional solvents demonstrated that EHSE is a successful,green,and safe method for extracting active plant components.This approach employs an ecologically benign water-based solution of tea saponin as the extraction solvent,and it combines enzymatic and homogenate procedures to increase extraction efficiency.This study provides a reasonable basis for the application and research of synergistic extraction technology and suggests that more diverse solvent choices should be considered.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
基金financially supported by the Innovation Capacity Building—Science and Technology Research Project of BAAFS(grant No.KJCX20251005)the Special Program on Science and Technology Innovation Capacity Building of BAAFS(grant No.KJCX 20240339)the National Key R&D Program of China(grant No.2022YFD130040311)。
文摘Background Piglets are highly susceptible to oxidative stress,which can reduce growth performance and cause intestinal damage.Piceatannol(PIC),a natural bioactive substance enriched in Chinese rhubarb(Rheum officinale)and certain dark purple fruits,shows excellent antioxidant properties in our previous cell-based high-throughput screening.However,its effect on piglet growth performance and antioxidant capacity as well as underling mechanism has not been thoroughly investigated.Methods One hundred weaned pigs(28 days of age,8.71±0.20 kg)were randomly assigned to 4 treatments with 5 replicates of 5 pigs per replicate.The experimental diets consisted of:1)basal diet,2)basal diet+100 mg/kg PIC,3)basal diet+200 mg/kg PIC,and 4)basal diet+300 mg/kg PIC.On d 15 and 35,one pig from each replicate was selected for sampling.The growth performance was monitored during a 35-day trial.In addition,H_(2)O_(2)-challenged IPEC-J2 cells served as an in vitro model to investigate the antioxidant mechanisms of PIC.IPEC-J2 cells were treated with 1,000μmol/L H_(2)O_(2)in the presence or absence of 10μmol/L PIC.Results Dietary PIC at 200 mg/kg significantly enhanced growth performance,as evidenced by increased average daily gain and feed conversion rate(P<0.05).PIC supplementation markedly improved systemic antioxidant capacity,with elevated serum total antioxidant capacity,catalase activity,and glutathione levels,along with reduced malondialdehyde content(P<0.05).Notably,PIC modulated the gut microbiota composition,increasing the amounts of beneficial genera(e.g.,Blautia and Faecalibacterium),and these microbial shifts significantly correlated with improved antioxidant indices.In vitro,PIC pretreatment effectively protected IPEC-J2 cells against H_(2)O_(2)-induced oxidative damage by reducing reactive oxygen species generation and lipid peroxidation(P<0.01).Mechanistically,PIC exerts its antioxidant effects through Nrf2 pathway activation,upregulating endogenous antioxidant enzymes(P<0.05)while simultaneously inhibiting apoptosis via the regulation of the Bcl-2/Bax ratio and caspase-3 cleavage(P<0.01).Conclusions PIC improved the growth performance and health status of weaned piglets through the regulation of Nrf2-mediated redox homeostasis and modulation of the related gut microbiota,offering a potential new natural antioxidants for mitigating weaning stress in piglets.
基金funded by the Deanship of Scientific Research at King Abdulaziz University,Jeddah,under Grant No.G:534-140-1443.
文摘Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.
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the National Natural Science Foundation of China(Grant no.NSFC 32271794)the Fund for High-Level Scientific and Technological Talents and Innovation Teams Selection Special Project of Yunnan Province(202105AD160024)for financial support.
文摘In this study,three different target analytes from the fruit of myrtle(Rhodomyrtus tomentosa)were extracted via an enzymatic-homogenate synergistic extraction(EHSE)process,and 10 different aqueous solutions of natural surfactants were selected as extraction solvents,thus enabling the simultaneous extraction of piceatannol,resveratrol,and myricetin from the fruit of myrtle(Rhodomyrtus tomentosa).Important factors affecting the yield of piceatannol,resveratrol,and myricetin,including enzyme type,enzyme concentration,pH,surfactant type and dosage,homogenization time,liquid-solid ratio,incubation and extraction time,incubation time and extraction temperature,were optimized via single-factor experiments.Three important parameters were optimized via the Box-Behnken design:the liquid-solid ratio,the incubation-extraction time,and the reaction temperature.The final optimum extraction process conditions were as follows:β-glucosidase concentration,3.0%,homogenate;time,3 min;pH,5;tea saponin concentration,0.8%;liquid-solid ratio,45 mL/g;incubation-extraction time,2.5 h;and temperature,67.5℃.With the optimized experimental parameters,the piceatannol,resveratrol,and myricetin yields were 742.12±37.11μg/g,18.58±0.94μg/g,and 24.83±1.25μg/g,respectively.Methodological validation and comparison experiments with traditional solvents demonstrated that EHSE is a successful,green,and safe method for extracting active plant components.This approach employs an ecologically benign water-based solution of tea saponin as the extraction solvent,and it combines enzymatic and homogenate procedures to increase extraction efficiency.This study provides a reasonable basis for the application and research of synergistic extraction technology and suggests that more diverse solvent choices should be considered.
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。
