Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate t...Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate the influence of punicalagin on hypercholesterolemia in mice and its related mechanisms.After 6 weeks'intervention,punicalagin significantly reduced serum total cholesterol and low-density lipoprotein cholesterol(LDL-C)levels in mice fed a high-fat high-cholesterol(HFHC)diet.Meanwhile,punicalagin supplementation lowered hepatic cholesterol level,which corresponded to the down-regulation of cholesterol synthesis genes(Fdps,Cyp51)and up-regulated bile acid synthesis genes(Cyp7a1,Cyp27a1).In addition,bile acid reabsorption was retarded in punicalagin-fed mice through down-regulating ileal apical sodium-dependent BA transporter(ASBT).Furthermore,intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(Fgf15)pathway was inhibited while hepatic FXR-small heterodimeric partner(SHP)pathway was activated in punicalagin group.Microbiota analysis and targeted metabolomics showed that punicalagin decreased the abundance of bile-salt hydrolase(BSH)-producing bacteria(Clostridiaceae and Bifidobacteriaceae)and the ratio of primary BAs to secondary BAs.In conclusion,the cholesterol-lowering effect of punicalagin partly through down-regulating cholesterol synthesis and increasing cholesterol catabolism,which could be achieved by regulating gut microbiota,altering bile acid composition and modulating FXR signaling pathway.These findings indicate the potential application of punicalagin-related products as an alternative strategy for hypercholesterolemia prevention and mitigation.展开更多
The aim of this study was to investigate whether punicalagin(PU)could prevent obesity-related cardiac dysfunction by promoting DNA demethy lation,and to explore its possible mechanism.C57BL/6J mice were fed with stand...The aim of this study was to investigate whether punicalagin(PU)could prevent obesity-related cardiac dysfunction by promoting DNA demethy lation,and to explore its possible mechanism.C57BL/6J mice were fed with standard diet,high-fat diet(HFD),HFD supplemented with resveratrol,low-dose PU(LPU)and high-dose PU(HPU)for 8 weeks.Compared with HFD group,body weight was significantly lower in PU treatment groups,number of cardionwocytes and the protein level of myosin heavy chain 7B were significantly higher in PU treatment groups.Levels of 5-hydroxymethylcytosine and 5-formylcytosine were significantly lower in HFD group than in other groups.Compared with the HFD group,the protein level of ten-eleven translocation enzyme(TET)2 was significantly higher in PU treatment groups,p-AMP-activated protein kinase(AMPK)was significantly higher in LPU group.Levels of total antioxidant capacity and the protein levels of complexesⅡ/Ⅲ/Ⅴ,oxoglutarate dehydrogenase,succinate dehydrogenase B and fumarate hdrolase were significantly lower in HFD group than PU treatment group.The ratio of(succinic acid+fumaric acid)/a-ketoglutarate was significantly higher in HFD group than other groups.In conclusion,PU up-regulated TETs enzyme activities and TET2 protein stability through alleviating mitochondrial dysfunction and activating AMPK,so as to promote DNA demethylation,thus preventing obesity-related cardiac dysfunction.展开更多
Pomegranates is abundant in polyphenols and is well-known for its antioxidant activity. Punicalagin （PG） is a major poly- phenolic compound in the pomegranate peel. In certain conditions, PG can be hydrolyzed to pun...Pomegranates is abundant in polyphenols and is well-known for its antioxidant activity. Punicalagin （PG） is a major poly- phenolic compound in the pomegranate peel. In certain conditions, PG can be hydrolyzed to punicallin （PL） and ellagic acid （EA）, and PL can be further hydrolyzed to EA. PG, PL, and EA all play important roles in the antioxidant activity of pomegranate peels. This study was conducted to compare the in vitro antioxidant activity and in vivo anti-oxidative stress effects of PG, PL, and EA. For the in vitro test, 2,2-diphenyl-l-picrylhydrazyl radical （DPPH.） and superoxide anion （O2~） scavenging capacities, ferric-reducing antioxidant power （FRAP）, and lipid peroxidation （LPO） inhibition capacities of PG, PL, and EA were tested. For the in vivo test, oxidatively stressed mice, which were induced by oxidized fish oil, were administrated PG, PL or EA （10 mg kg-1 d-1） for 21 days. The results showed that the in vitro antioxidant activity trends were EA〉PG〉PL〉Trolox in scavenging DPPH., PG〉PL〉EA=Trolox in scavenging O2~, EA〉PG=PL〉Trolox in FRAP, and Trolox〉PG〉EA〉PL in LPO inhibition. In the in vivo test, the EAt＇reatment increased the average daily weight gain and total antioxidant capacity （T-AOC） in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） in oxidatively stressed mice. It increased the superoxide dismutase （SOD） activity in the liver （P〈0.05） and intestine （P〈0.05）. It increased the glutathi- one peroxidase （GSH-Px） activity in the intestine （P〈0.05） and the intestinal villus height to crypt depth ratio （P〈0.05）. EA treatment decreased the malondialdehyde （MDA） content in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） and the mRNA expressions of the pro-inflammatory factors, TNF-a （P〈0.05）, IFN-y （P〈0.05） and IL-6 （P〈0.05）. PL increased the SOD （P〈0.05） and GSH-Px activities （P〈0.05） in the intestine and decreased the MDA content （P〈0.05） and the mRNA expressions of TNF-a （P〈0.05） and IL-6 （P〈0.05） in the intestine. PG increased the SOD activity （P〈0.05） and GSH-Px activity （P〈0.05） in the intestine and decreased the MDA content in the intestine （P〈0.05） and IL-6 mRNA expression in the intestine （P〈0.05）. In summary, EA, PL, and PG all had powerful in vitro antioxidant capacities, and they had different antioxidant advantages in acting against different types of radicals; EA was more effective than PL and PG in protecting against oxidative injury in vivo, especially for intestinal injury. These findings suggest that multiple polyphenol compounds in pomegranate peel may exert superior antioxidant activity than single purified polyphenols; when using pomegranate peels as health-promoting additive in animal feed, raising EA content by methods of hydrolysis or fermentation in advance could achieve better effects.展开更多
Plant polyphenols are reported to have bioactive properties, which may be used for protection against diseases. Therefore, the aim of this research was to investigate the antioxidant activities of a pomegranate tannin...Plant polyphenols are reported to have bioactive properties, which may be used for protection against diseases. Therefore, the aim of this research was to investigate the antioxidant activities of a pomegranate tannin polyphenol compound, punicalagin and pomegranate juice. The presence of punicalagin in pomegranate husk (US) and pomegranate juice (US & UK) was compared with a punicalagin standard using high performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS) which are highly sensitive and selective analytical methods for the separation and identification of phenolic compounds and anthocyanins. Antioxidant mechanisms involving DPPH radical scavenging activity, hydrogen peroxide scavenging, ferrous chelating and reducing ability were also studied on pomegranate juice and standard punicalagin. The present study shows a high degree of similarity of HPLC and LC-MS results between the punicalagin commercial standard (Sigma Aldrich) and US pomegranate husk extracted with methanol. In contrast, in the methanol juice extract obtained from US and UK, higher hydrogen peroxide scavenging activity was achieved by 0.1 mg/ml from both punicalagin and pomegranate juice when compared with butylated hydroxytoluene (BHT) or trolox (p ≤ 0.01). Punicalagin and pomegranate juice exhibited ferrous chelating ability significantly lower than Ethylenediaminetetraacetic acid. These findings confirmed that punicalagin was present in pomegranate husk compared to pomegranate juice, as measured using a punicalagin standard. The antioxidant mechanism experiments concluded that, the pomegranate juice has a significantly higher radical scavenging activity in comparison with punicalagin (p ≤ 0.01). However, punicalagin showed significant ferrous chelating activity and reducing power ability in a dose-dependent manner as compared with pomegranate juice.展开更多
Punlcalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin （purity L〉98%） on oxidative s...Punlcalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin （purity L〉98%） on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide （LPS） induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin （PU） against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU ＋ LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.展开更多
Objective：Bovine endometritis is one of the most common reproductive disorders in cattle.The aim of this study was to investigate the anti-inflammation potential of punicalagin in lipopolysaccharide（LPS）-induced bo...Objective：Bovine endometritis is one of the most common reproductive disorders in cattle.The aim of this study was to investigate the anti-inflammation potential of punicalagin in lipopolysaccharide（LPS）-induced bovine endometrial epithelial cells（bE ECs）and to uncover the underlying mechanisms.Methods：bE ECs were stimulated with different concentrations（1,10,30,50,and 100μg/ml）of LPS for 3,6,9,12,and 18 h.MTT assay was used to assess cell viability and to identify the conditions for inflammatory injury and effective concentrations of punicalagin.Quantitative real-time polymerase chain reaction（q RT-PCR）was used to assess gene expression of pro-inflammatory cytokines.Western blotting was used to assess levels of inflammation-related proteins.Results：Treatment of b EECs with 30μg/ml LPS for 12 h induced cell injury and reduced cell viability.Punicalagin（5,10,or 20μg/ml）pretreatment significantly decreased LPS-induced productions of interleukin（IL）-1β,IL-6,IL-8,and tumor necrosis factor-α（TNF-α）in bE ECs.Molecular research showed that punicalagin inhibited the activation of the upstream mediator nuclear factor-κB（NF-κB）by suppressing the production of inhibitorκBα（IκBα）and phosphorylation of p65.Results also indicated that punicalagin can suppress the phosphorylation of mitogen-activated protein kinases（MAPKs）including p38,c-Jun N-terminal kinase（JNK）,and extracellular signal-regulated kinase（ERK）.Conclusions：Punicalagin may attenuate LPS-induced inflammatory injury and provide a potential option for the treatment of dairy cows with Escherichia coli endometritis.展开更多
基金supported in part by the National Key Research and Development Program of China(2022YFD2100104)the Science and Technology Program of Shaanxi Province,China(2022JM-111)Graduate Innovation Fund of Dalian Polytechnic University。
文摘Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate the influence of punicalagin on hypercholesterolemia in mice and its related mechanisms.After 6 weeks'intervention,punicalagin significantly reduced serum total cholesterol and low-density lipoprotein cholesterol(LDL-C)levels in mice fed a high-fat high-cholesterol(HFHC)diet.Meanwhile,punicalagin supplementation lowered hepatic cholesterol level,which corresponded to the down-regulation of cholesterol synthesis genes(Fdps,Cyp51)and up-regulated bile acid synthesis genes(Cyp7a1,Cyp27a1).In addition,bile acid reabsorption was retarded in punicalagin-fed mice through down-regulating ileal apical sodium-dependent BA transporter(ASBT).Furthermore,intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(Fgf15)pathway was inhibited while hepatic FXR-small heterodimeric partner(SHP)pathway was activated in punicalagin group.Microbiota analysis and targeted metabolomics showed that punicalagin decreased the abundance of bile-salt hydrolase(BSH)-producing bacteria(Clostridiaceae and Bifidobacteriaceae)and the ratio of primary BAs to secondary BAs.In conclusion,the cholesterol-lowering effect of punicalagin partly through down-regulating cholesterol synthesis and increasing cholesterol catabolism,which could be achieved by regulating gut microbiota,altering bile acid composition and modulating FXR signaling pathway.These findings indicate the potential application of punicalagin-related products as an alternative strategy for hypercholesterolemia prevention and mitigation.
基金supported by the Natural Science Foundation of Shandong Province (ZR2020QH294 and ZR2021QH342)。
文摘The aim of this study was to investigate whether punicalagin(PU)could prevent obesity-related cardiac dysfunction by promoting DNA demethy lation,and to explore its possible mechanism.C57BL/6J mice were fed with standard diet,high-fat diet(HFD),HFD supplemented with resveratrol,low-dose PU(LPU)and high-dose PU(HPU)for 8 weeks.Compared with HFD group,body weight was significantly lower in PU treatment groups,number of cardionwocytes and the protein level of myosin heavy chain 7B were significantly higher in PU treatment groups.Levels of 5-hydroxymethylcytosine and 5-formylcytosine were significantly lower in HFD group than in other groups.Compared with the HFD group,the protein level of ten-eleven translocation enzyme(TET)2 was significantly higher in PU treatment groups,p-AMP-activated protein kinase(AMPK)was significantly higher in LPU group.Levels of total antioxidant capacity and the protein levels of complexesⅡ/Ⅲ/Ⅴ,oxoglutarate dehydrogenase,succinate dehydrogenase B and fumarate hdrolase were significantly lower in HFD group than PU treatment group.The ratio of(succinic acid+fumaric acid)/a-ketoglutarate was significantly higher in HFD group than other groups.In conclusion,PU up-regulated TETs enzyme activities and TET2 protein stability through alleviating mitochondrial dysfunction and activating AMPK,so as to promote DNA demethylation,thus preventing obesity-related cardiac dysfunction.
基金supported by the Science and Technology Department of Zhejiang Province, China (2012C12906-4)the Modern Agro-industry Technology Research System of China (CARS-36)+1 种基金the National Key Technology R&D Program, China (2012BAD39B03-4)Agro-scientific Research in the Public Interest, China (201403047)
文摘Pomegranates is abundant in polyphenols and is well-known for its antioxidant activity. Punicalagin （PG） is a major poly- phenolic compound in the pomegranate peel. In certain conditions, PG can be hydrolyzed to punicallin （PL） and ellagic acid （EA）, and PL can be further hydrolyzed to EA. PG, PL, and EA all play important roles in the antioxidant activity of pomegranate peels. This study was conducted to compare the in vitro antioxidant activity and in vivo anti-oxidative stress effects of PG, PL, and EA. For the in vitro test, 2,2-diphenyl-l-picrylhydrazyl radical （DPPH.） and superoxide anion （O2~） scavenging capacities, ferric-reducing antioxidant power （FRAP）, and lipid peroxidation （LPO） inhibition capacities of PG, PL, and EA were tested. For the in vivo test, oxidatively stressed mice, which were induced by oxidized fish oil, were administrated PG, PL or EA （10 mg kg-1 d-1） for 21 days. The results showed that the in vitro antioxidant activity trends were EA〉PG〉PL〉Trolox in scavenging DPPH., PG〉PL〉EA=Trolox in scavenging O2~, EA〉PG=PL〉Trolox in FRAP, and Trolox〉PG〉EA〉PL in LPO inhibition. In the in vivo test, the EAt＇reatment increased the average daily weight gain and total antioxidant capacity （T-AOC） in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） in oxidatively stressed mice. It increased the superoxide dismutase （SOD） activity in the liver （P〈0.05） and intestine （P〈0.05）. It increased the glutathi- one peroxidase （GSH-Px） activity in the intestine （P〈0.05） and the intestinal villus height to crypt depth ratio （P〈0.05）. EA treatment decreased the malondialdehyde （MDA） content in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） and the mRNA expressions of the pro-inflammatory factors, TNF-a （P〈0.05）, IFN-y （P〈0.05） and IL-6 （P〈0.05）. PL increased the SOD （P〈0.05） and GSH-Px activities （P〈0.05） in the intestine and decreased the MDA content （P〈0.05） and the mRNA expressions of TNF-a （P〈0.05） and IL-6 （P〈0.05） in the intestine. PG increased the SOD activity （P〈0.05） and GSH-Px activity （P〈0.05） in the intestine and decreased the MDA content in the intestine （P〈0.05） and IL-6 mRNA expression in the intestine （P〈0.05）. In summary, EA, PL, and PG all had powerful in vitro antioxidant capacities, and they had different antioxidant advantages in acting against different types of radicals; EA was more effective than PL and PG in protecting against oxidative injury in vivo, especially for intestinal injury. These findings suggest that multiple polyphenol compounds in pomegranate peel may exert superior antioxidant activity than single purified polyphenols; when using pomegranate peels as health-promoting additive in animal feed, raising EA content by methods of hydrolysis or fermentation in advance could achieve better effects.
文摘Plant polyphenols are reported to have bioactive properties, which may be used for protection against diseases. Therefore, the aim of this research was to investigate the antioxidant activities of a pomegranate tannin polyphenol compound, punicalagin and pomegranate juice. The presence of punicalagin in pomegranate husk (US) and pomegranate juice (US & UK) was compared with a punicalagin standard using high performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS) which are highly sensitive and selective analytical methods for the separation and identification of phenolic compounds and anthocyanins. Antioxidant mechanisms involving DPPH radical scavenging activity, hydrogen peroxide scavenging, ferrous chelating and reducing ability were also studied on pomegranate juice and standard punicalagin. The present study shows a high degree of similarity of HPLC and LC-MS results between the punicalagin commercial standard (Sigma Aldrich) and US pomegranate husk extracted with methanol. In contrast, in the methanol juice extract obtained from US and UK, higher hydrogen peroxide scavenging activity was achieved by 0.1 mg/ml from both punicalagin and pomegranate juice when compared with butylated hydroxytoluene (BHT) or trolox (p ≤ 0.01). Punicalagin and pomegranate juice exhibited ferrous chelating ability significantly lower than Ethylenediaminetetraacetic acid. These findings confirmed that punicalagin was present in pomegranate husk compared to pomegranate juice, as measured using a punicalagin standard. The antioxidant mechanism experiments concluded that, the pomegranate juice has a significantly higher radical scavenging activity in comparison with punicalagin (p ≤ 0.01). However, punicalagin showed significant ferrous chelating activity and reducing power ability in a dose-dependent manner as compared with pomegranate juice.
基金This work was supported by National Natural Science Foundation of China Grants 81125005 and 81430027 （to F.S.）, the National Basic Research Program of China （2014CB943100）.
文摘Punlcalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin （purity L〉98%） on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide （LPS） induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin （PU） against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU ＋ LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.
基金supported by the National Key Technology R&D Program of China(No.2013BAD10B04)the Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions(No.CIT&TCD20130324),China
文摘Objective：Bovine endometritis is one of the most common reproductive disorders in cattle.The aim of this study was to investigate the anti-inflammation potential of punicalagin in lipopolysaccharide（LPS）-induced bovine endometrial epithelial cells（bE ECs）and to uncover the underlying mechanisms.Methods：bE ECs were stimulated with different concentrations（1,10,30,50,and 100μg/ml）of LPS for 3,6,9,12,and 18 h.MTT assay was used to assess cell viability and to identify the conditions for inflammatory injury and effective concentrations of punicalagin.Quantitative real-time polymerase chain reaction（q RT-PCR）was used to assess gene expression of pro-inflammatory cytokines.Western blotting was used to assess levels of inflammation-related proteins.Results：Treatment of b EECs with 30μg/ml LPS for 12 h induced cell injury and reduced cell viability.Punicalagin（5,10,or 20μg/ml）pretreatment significantly decreased LPS-induced productions of interleukin（IL）-1β,IL-6,IL-8,and tumor necrosis factor-α（TNF-α）in bE ECs.Molecular research showed that punicalagin inhibited the activation of the upstream mediator nuclear factor-κB（NF-κB）by suppressing the production of inhibitorκBα（IκBα）and phosphorylation of p65.Results also indicated that punicalagin can suppress the phosphorylation of mitogen-activated protein kinases（MAPKs）including p38,c-Jun N-terminal kinase（JNK）,and extracellular signal-regulated kinase（ERK）.Conclusions：Punicalagin may attenuate LPS-induced inflammatory injury and provide a potential option for the treatment of dairy cows with Escherichia coli endometritis.
