α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in var...α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.展开更多
Background:Necroptosis and pyroptosis are newly identified forms of programmed cell death,which play a vital role in development of many gastrointestinal disorders.Although plant polyphenols have been reported to prot...Background:Necroptosis and pyroptosis are newly identified forms of programmed cell death,which play a vital role in development of many gastrointestinal disorders.Although plant polyphenols have been reported to protect intestinal health,it is still unclear whether there is a beneficial role of plant polyphenols in modulating necroptosis and pyroptosis in intestinal porcine epithelial cell line(IPEC-1)infected with enterotoxigenic Escherichia coli(ETEC)K88.This research was conducted to explore whether plant polyphenols including protocatechuic acid(PCA)and quercetin(Que),attenuated inflammation and injury of IPEC-1 caused by ETEC K88 through regulating necroptosis and pyroptosis signaling pathways.Methods:IPEC-1 cells were treated with PCA(40μmol/L)or Que(10μmol/L)in the presence or absence of ETEC K88.Results:PCA and Que decreased ETEC K88 adhesion and endotoxin level(P<0.05)in cell supernatant.PCA and Que increased cell number(P<0.001)and decreased lactate dehydrogenases(LDH)activity(P<0.05)in cell supernatant after ETEC infection.PCA and Que improved transepithelial electrical resistance(TEER)(P<0.001)and reduced fluorescein isothiocyanate-labeled dextran(FD4)flux(P<0.001),and enhanced membrane protein abundance of occludin,claudin-1 and ZO-1(P<0.05),and rescued distribution of these tight junction proteins(P<0.05)after ETEC infection.PCA and Que also declined cell necrosis ratio(P<0.05).PCA and Que reduced mRNA abundance and concentration of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8(P<0.001),and down-regulated gene expression of toll-like receptors 4(TLR4)and its downstream signals(P<0.001)after ETEC infection.PCA and Que down-regulated protein abundance of total receptor interacting protein kinase 1(t-RIP1),phosphorylated-RIP1(p-RIP1),p-RIP1/t-RIP1,t-RIP3,p-RIP3,mixed lineage kinase domain-like protein(MLKL),p-MLKL,dynamin-related protein 1(DRP1),phosphoglycerate mutase 5(PGAM5)and high mobility group box 1(HMGB1)(P<0.05)after ETEC infection.Moreover,PCA and Que reduced protein abundance of nod-like receptor protein 3(NLRP3),nod-like receptors family CARD domain-containing protein 4(NLRC4),apoptosis-associated speck-like protein containing a CARD(ASC),gasdermin D(GSDMD)and caspase-1(P<0.05)after ETEC infection.Conclusions:In general,our data suggest that PCA and Que are capable of attenuating ETEC-caused intestinal inflammation and damage via inhibiting necroptosis and pyroptosis signaling pathways.展开更多
·AIM:To determine the effects of protocatechuic acid(PCA)on streptozocin-induced diabetic retinopathy(DR)in rats.·METHODS:Wistar rats were given a 50 mg/kg intraperitoneal injection of streptozocin to induce...·AIM:To determine the effects of protocatechuic acid(PCA)on streptozocin-induced diabetic retinopathy(DR)in rats.·METHODS:Wistar rats were given a 50 mg/kg intraperitoneal injection of streptozocin to induce diabetes.Animals were assigned randomly one of four groups(8 rats per group):control,diabetic,diabetic plus PCA(25 mg/kg·d),and diabetic plus PCA(50 mg/kg·d).After inducing diabetes,treatments were started one week later and continued for eight weeks.After the experiment,the rats were sacrificed,and their retinas were taken for biochemical and molecular analysis.·RESULTS:PCA administration diminished the blood glucose and glycated haemoglobin levels relative to the diabetic group.In diabetic rats,PCA lowered elevated levels of advanced glycosylated end products(AGEs)and receptor for AGEs(RAGE).In the retina of diabetic rats,PCA effectively decreased inflammatory cytokine,nuclear factor-κB,tumour necrosis factor-α,interleukin-1β,and vascular endothelial growth factor,and increased antioxidant markers glutathione,superoxide dismutase,and catalase.·CONCLUSION:The protective benefits of PCA against DR may be attributable to its suppression of the AGEs and RAGE and its antioxidant and anti-inflammatory properties.展开更多
Background: Weaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid(PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong(Eucommia ulmoides Ol...Background: Weaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid(PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong(Eucommia ulmoides Oliver), and is also considered as the main bioactive metabolite of polyphenol against oxidative stress and inflammation. This study aimed to investigate the effect of PCA on growth performance, intestinal barrier function, and gut microbiota in a weaned piglet model challenged with lipopolysaccharide(LPS).Methods: Thirty-six piglets(Pig Improvement Company line 337 × C48, 28 d of age, 8.87 kg ± 0.11 kg BW) were randomly allocated into 3 treatments and fed with a basal diet(CTL), a diet added 50 mg/kg of aureomycin(AUR), or a diet supplemented with 4000 mg/kg of PCA, respectively. The piglets were challenged with LPS(10 μg/kg BW) on d 14 and d 21 by intraperitoneal injection during the 21-d experiment. Animals(n = 6 from each group) were sacrificed after being anesthetized by sodium pentobarbital at 2 h after the last injection of LPS. The serum was collected for antioxidant indices and inflammatory cytokines analysis, the ileum was harvested for detecting mRNA and protein levels of tight junction proteins by PCR and immunohistochemical staining, and the cecum chyme was collected for intestinal flora analysis using 16 S rRNA gene sequencing.Results: Dietary supplementation of PCA or AUR significantly increased the expression of tight junction proteins including ZO-1 and claudin-1 in intestinal mucosa, and decreased the serum levels of thiobarbituric acid reactive substances(TBARS) and IL-6, as compared with CTL group. In addition, PCA also decreased the serum levels of IL-2 and TNF-α(P < 0.05). Analysis of gut microbiota indicated that PCA increased the Firmicutes/Bacteroidetes ratio(P < 0.05). Spearman's correlation analysis at the genus level revealed that PCA reduced the relative abundance of Prevotella 9, Prevotella 2, Holdemanella, and Ruminococcus torques group(P < 0.05), and increased the relative abundance of Roseburia and Desulfovibrio(P < 0.05), whereas AUR had no significant effect on these bacteria.Conclusions: These results demonstrated that both PCA and AUR had protective effect on oxidative stress, inflammation and intestinal barrier function in piglets challenged with LPS, and PCA potentially exerted the protective function by modulating intestinal flora in a way different from AUR.展开更多
[Objectives] This study was conducted to optimize the extraction process of protocatechuic acid from Emilia sonchifolia DC. [Methods] The optimal extraction conditions were determined by single factor,response surface...[Objectives] This study was conducted to optimize the extraction process of protocatechuic acid from Emilia sonchifolia DC. [Methods] The optimal extraction conditions were determined by single factor,response surface analysis and variance analysis,and the content of protocatechuic acid was determined by HPLC. [Results] The protocatechuic acid standard curve equation was: y = 1 435 x + 8 403,R^2= 0. 999 8,indicating a good linear relationship. The optimal extraction conditions were as follows: a temperature at 80 ℃,an extraction time of 1 h,a material-to-liquid ratio at 1:10 and an ultrasonic power of 600 W,and the content of protocatechuic acid extracted was 1. 93 mg/g. The method showed a RSD of 0. 41%,less than 2%,and the detection limit was 0. 0000047261 g/ml.The experimental sample X1 was the low-level 0. 1 mg/ml standard solution,which showed recovery of protocatechuic acid between 100.8% and 105.2%,with a RSD of 0. 013%;and the sample X2 was the high-level 1. 0 mg/ml standard solution,which exhibited recovery between 100. 6% and 102. 2%,with a RSD of 0.076%. Thus,the recovery was high,and the requirements of the performance index were met. [Conclusions] The detection method is stable and reliable and can produce satisfactory results.展开更多
Objective:To assess the nuclear factor-erythroid 2-related factor-2(Nrf2)modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich asci...Objective:To assess the nuclear factor-erythroid 2-related factor-2(Nrf2)modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice.Methods:Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power(FRAP)and 2,2-diphenyl-1-picrylhydrazyl(DPPH).Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction,and luciferase complementation reporter assays.In vivo efficacy was tested using the Ehrlich ascites carcinoma model.Results:FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid.Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2.Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1(HO-1),glutamate-cysteine ligase catalytic subunit(GCLC),and glutamate-cysteine ligase modifier subunit(GCLM)and the activity of NAD(P)H:quinone oxidoreductase 1(NQO1)when tested on HCT-116 cells using a cell-based assay system at 9 h.In addition,intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis.Conclusions:Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.展开更多
Objective:To investigate the potential activity of protocatechuic acid in female Wistar rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Thirty rats were divided into five groups of six each.Group 1...Objective:To investigate the potential activity of protocatechuic acid in female Wistar rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Thirty rats were divided into five groups of six each.Group 1 received 0.5%carboxy methyl cellulose orally and served as the normal control group;group 2 was treated orally with 1 mg/kg of letrozole daily for 21 days and served as the PCOS induced group;group 3 was orally administered with letrozole of 1 mg/kg for 21 days and further administered with standard drug of clomiphene citrate at a dose of 1 mg/kg body weight in 0.5%carboxy methyl cellulose per oral and served as the standard group;groups 4 and 5 were administered with letrozole of 1 mg/kg for 21 days and further treated with protocatechuic acid orally at low dose of 5 mg/kg body weight and high dose of 15 mg/kg body weight respectively for 15 days.At the end of the study period,rats were subjected for the estimation of invasive blood pressure and heart rate,biochemical estimations and antioxidant assay.In addition,ovarian histomorphology was examined.Results:The PCOS was confirmed in the letrozole induced rats with increased concentration of androgen,abnormal lipid levels,glucose,glycosylated haemoglobin and also depletion of antioxidants.After protocatechuic acid treatment,the increased levels of testosterone due to induction of PCOS were restored to normal levels.Additionally,there was a consistent decrease in luteinizing hormone and follicle stimulating hormone levels in the treatment groups,followed by decrease in the number of cysts after treatment with protocatechuic acid.Histopathological observations showed a remarkable recovery of the ovarian tissue and the presence of normalized structure of antral follicle.Protocatechuic acid treatment restored all the parameters to normalcy and abolished cysts formation in ovaries of female rats.Conclusions:Protocatechuic acid shows potential protective effects in letrozole-induced PCOS rats.The protective effect is comparable to that of clomiphene citrate and thus shows its potential in the treatment of PCOS.展开更多
A drug-drug molecular salt hydrate of berberine and protocatechuic acid has been prepared.Protocatechuic acid lost its carboxylic proton and turned to be protocatechuic anion to form a 1:1:1 organic salt hydrate with ...A drug-drug molecular salt hydrate of berberine and protocatechuic acid has been prepared.Protocatechuic acid lost its carboxylic proton and turned to be protocatechuic anion to form a 1:1:1 organic salt hydrate with berberine,[C_(20)H_(18)NO_4]+[C_7H_5O_4]^-?H_2O(1).Compound1 crystallizes in the triclinic system,space group P1 with a = 7.9849(5),b =10.5437(5),c = 14.3621(5)?,α = 77.983(4),β = 82.900(4),γ = 78.024(4)o,V = 1152.82(10) ?~3,Mr= 507.48,Dc= 1.462 g/cm^3,μ = 0.929 mm^(-1),F(000) = 532,Z = 2,the final R = 0.0488 and w R = 0.1322 for 3993 reflectionswith I > 2σ(I).The hydrate exhibited good solid state stability against humidity,which may result from strong hydrogen-bonding interactions between water molecules and carboxylate groups.The hydrate also exhibited acceptable solubility and dissolution rate.展开更多
Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction.Protocatechuic aldehyde(PCA)is a major phenolic acid in Chinese herb Danshen(Salvia miltiorrhiza root).This st...Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction.Protocatechuic aldehyde(PCA)is a major phenolic acid in Chinese herb Danshen(Salvia miltiorrhiza root).This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2(PKM2)function to protect cardiomyocytes.In rats subjected to isoprenaline,PCA attenuated heart injury and protected cardiomyocytes from apoptosis.Through DARTS and CETSA assays,we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation(OGD).In the nucleus,PCA increased the binding of PKM2 to β-Catenin via preserving PKM2 acetylation,and the complex,in cooperation with T-cell factor 4(TCF4),was required for transcriptional induction of genes encoding anti-apoptotic proteins,contributing to rescuing cardiomyocyte survival.In addition,PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2.Consistently,PCA increased the binding of PKM2 to β-Catenin,improved heart contractive function,normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation,but the protective effects were lost in Pkm2-deficient heart.Together,we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via β-Catenin/TCF4 signaling cascade,suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.展开更多
基金supported by the General Research Fund of Hong Kong (14105820)。
文摘α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.
基金provided by National Key R&D Program of China(2022YFD1300403)National Natural Science Foundation of China(No.U22A20517,32272906,and 31802070)Wuhan Science and Technology Bureau(No.2022020801010391)。
文摘Background:Necroptosis and pyroptosis are newly identified forms of programmed cell death,which play a vital role in development of many gastrointestinal disorders.Although plant polyphenols have been reported to protect intestinal health,it is still unclear whether there is a beneficial role of plant polyphenols in modulating necroptosis and pyroptosis in intestinal porcine epithelial cell line(IPEC-1)infected with enterotoxigenic Escherichia coli(ETEC)K88.This research was conducted to explore whether plant polyphenols including protocatechuic acid(PCA)and quercetin(Que),attenuated inflammation and injury of IPEC-1 caused by ETEC K88 through regulating necroptosis and pyroptosis signaling pathways.Methods:IPEC-1 cells were treated with PCA(40μmol/L)or Que(10μmol/L)in the presence or absence of ETEC K88.Results:PCA and Que decreased ETEC K88 adhesion and endotoxin level(P<0.05)in cell supernatant.PCA and Que increased cell number(P<0.001)and decreased lactate dehydrogenases(LDH)activity(P<0.05)in cell supernatant after ETEC infection.PCA and Que improved transepithelial electrical resistance(TEER)(P<0.001)and reduced fluorescein isothiocyanate-labeled dextran(FD4)flux(P<0.001),and enhanced membrane protein abundance of occludin,claudin-1 and ZO-1(P<0.05),and rescued distribution of these tight junction proteins(P<0.05)after ETEC infection.PCA and Que also declined cell necrosis ratio(P<0.05).PCA and Que reduced mRNA abundance and concentration of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8(P<0.001),and down-regulated gene expression of toll-like receptors 4(TLR4)and its downstream signals(P<0.001)after ETEC infection.PCA and Que down-regulated protein abundance of total receptor interacting protein kinase 1(t-RIP1),phosphorylated-RIP1(p-RIP1),p-RIP1/t-RIP1,t-RIP3,p-RIP3,mixed lineage kinase domain-like protein(MLKL),p-MLKL,dynamin-related protein 1(DRP1),phosphoglycerate mutase 5(PGAM5)and high mobility group box 1(HMGB1)(P<0.05)after ETEC infection.Moreover,PCA and Que reduced protein abundance of nod-like receptor protein 3(NLRP3),nod-like receptors family CARD domain-containing protein 4(NLRC4),apoptosis-associated speck-like protein containing a CARD(ASC),gasdermin D(GSDMD)and caspase-1(P<0.05)after ETEC infection.Conclusions:In general,our data suggest that PCA and Que are capable of attenuating ETEC-caused intestinal inflammation and damage via inhibiting necroptosis and pyroptosis signaling pathways.
基金Supported by Model Construction of Regional Prevention and Treatment of Diabetic Retinopathy,Sichuan Science and Technology Support Program (No.2016FZ0091)。
文摘·AIM:To determine the effects of protocatechuic acid(PCA)on streptozocin-induced diabetic retinopathy(DR)in rats.·METHODS:Wistar rats were given a 50 mg/kg intraperitoneal injection of streptozocin to induce diabetes.Animals were assigned randomly one of four groups(8 rats per group):control,diabetic,diabetic plus PCA(25 mg/kg·d),and diabetic plus PCA(50 mg/kg·d).After inducing diabetes,treatments were started one week later and continued for eight weeks.After the experiment,the rats were sacrificed,and their retinas were taken for biochemical and molecular analysis.·RESULTS:PCA administration diminished the blood glucose and glycated haemoglobin levels relative to the diabetic group.In diabetic rats,PCA lowered elevated levels of advanced glycosylated end products(AGEs)and receptor for AGEs(RAGE).In the retina of diabetic rats,PCA effectively decreased inflammatory cytokine,nuclear factor-κB,tumour necrosis factor-α,interleukin-1β,and vascular endothelial growth factor,and increased antioxidant markers glutathione,superoxide dismutase,and catalase.·CONCLUSION:The protective benefits of PCA against DR may be attributable to its suppression of the AGEs and RAGE and its antioxidant and anti-inflammatory properties.
基金partially supported by the funds from the National Natural Science Foundation of China (31772819, 31741115)Hunan Provincial Natural Science Foundation for Distinguished Young Scholars (2019JJ30012)Double-First-Class Construction Project of Hunan Province (kxk201801004)。
文摘Background: Weaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid(PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong(Eucommia ulmoides Oliver), and is also considered as the main bioactive metabolite of polyphenol against oxidative stress and inflammation. This study aimed to investigate the effect of PCA on growth performance, intestinal barrier function, and gut microbiota in a weaned piglet model challenged with lipopolysaccharide(LPS).Methods: Thirty-six piglets(Pig Improvement Company line 337 × C48, 28 d of age, 8.87 kg ± 0.11 kg BW) were randomly allocated into 3 treatments and fed with a basal diet(CTL), a diet added 50 mg/kg of aureomycin(AUR), or a diet supplemented with 4000 mg/kg of PCA, respectively. The piglets were challenged with LPS(10 μg/kg BW) on d 14 and d 21 by intraperitoneal injection during the 21-d experiment. Animals(n = 6 from each group) were sacrificed after being anesthetized by sodium pentobarbital at 2 h after the last injection of LPS. The serum was collected for antioxidant indices and inflammatory cytokines analysis, the ileum was harvested for detecting mRNA and protein levels of tight junction proteins by PCR and immunohistochemical staining, and the cecum chyme was collected for intestinal flora analysis using 16 S rRNA gene sequencing.Results: Dietary supplementation of PCA or AUR significantly increased the expression of tight junction proteins including ZO-1 and claudin-1 in intestinal mucosa, and decreased the serum levels of thiobarbituric acid reactive substances(TBARS) and IL-6, as compared with CTL group. In addition, PCA also decreased the serum levels of IL-2 and TNF-α(P < 0.05). Analysis of gut microbiota indicated that PCA increased the Firmicutes/Bacteroidetes ratio(P < 0.05). Spearman's correlation analysis at the genus level revealed that PCA reduced the relative abundance of Prevotella 9, Prevotella 2, Holdemanella, and Ruminococcus torques group(P < 0.05), and increased the relative abundance of Roseburia and Desulfovibrio(P < 0.05), whereas AUR had no significant effect on these bacteria.Conclusions: These results demonstrated that both PCA and AUR had protective effect on oxidative stress, inflammation and intestinal barrier function in piglets challenged with LPS, and PCA potentially exerted the protective function by modulating intestinal flora in a way different from AUR.
基金Supported by Basic and Applied Basic Research Plan of Hainan Province in2019 (2019RC245)Natural Science Foundation of Hainan Province in 2017(217157)。
文摘[Objectives] This study was conducted to optimize the extraction process of protocatechuic acid from Emilia sonchifolia DC. [Methods] The optimal extraction conditions were determined by single factor,response surface analysis and variance analysis,and the content of protocatechuic acid was determined by HPLC. [Results] The protocatechuic acid standard curve equation was: y = 1 435 x + 8 403,R^2= 0. 999 8,indicating a good linear relationship. The optimal extraction conditions were as follows: a temperature at 80 ℃,an extraction time of 1 h,a material-to-liquid ratio at 1:10 and an ultrasonic power of 600 W,and the content of protocatechuic acid extracted was 1. 93 mg/g. The method showed a RSD of 0. 41%,less than 2%,and the detection limit was 0. 0000047261 g/ml.The experimental sample X1 was the low-level 0. 1 mg/ml standard solution,which showed recovery of protocatechuic acid between 100.8% and 105.2%,with a RSD of 0. 013%;and the sample X2 was the high-level 1. 0 mg/ml standard solution,which exhibited recovery between 100. 6% and 102. 2%,with a RSD of 0.076%. Thus,the recovery was high,and the requirements of the performance index were met. [Conclusions] The detection method is stable and reliable and can produce satisfactory results.
文摘Objective:To assess the nuclear factor-erythroid 2-related factor-2(Nrf2)modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice.Methods:Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power(FRAP)and 2,2-diphenyl-1-picrylhydrazyl(DPPH).Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction,and luciferase complementation reporter assays.In vivo efficacy was tested using the Ehrlich ascites carcinoma model.Results:FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid.Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2.Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1(HO-1),glutamate-cysteine ligase catalytic subunit(GCLC),and glutamate-cysteine ligase modifier subunit(GCLM)and the activity of NAD(P)H:quinone oxidoreductase 1(NQO1)when tested on HCT-116 cells using a cell-based assay system at 9 h.In addition,intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis.Conclusions:Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.
基金University Grants Commission,Government of India(Post-Doctoral Fellowship for SC/ST,Award letter No#:PDFSS-2015-17-ST-TEL-10464).
文摘Objective:To investigate the potential activity of protocatechuic acid in female Wistar rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Thirty rats were divided into five groups of six each.Group 1 received 0.5%carboxy methyl cellulose orally and served as the normal control group;group 2 was treated orally with 1 mg/kg of letrozole daily for 21 days and served as the PCOS induced group;group 3 was orally administered with letrozole of 1 mg/kg for 21 days and further administered with standard drug of clomiphene citrate at a dose of 1 mg/kg body weight in 0.5%carboxy methyl cellulose per oral and served as the standard group;groups 4 and 5 were administered with letrozole of 1 mg/kg for 21 days and further treated with protocatechuic acid orally at low dose of 5 mg/kg body weight and high dose of 15 mg/kg body weight respectively for 15 days.At the end of the study period,rats were subjected for the estimation of invasive blood pressure and heart rate,biochemical estimations and antioxidant assay.In addition,ovarian histomorphology was examined.Results:The PCOS was confirmed in the letrozole induced rats with increased concentration of androgen,abnormal lipid levels,glucose,glycosylated haemoglobin and also depletion of antioxidants.After protocatechuic acid treatment,the increased levels of testosterone due to induction of PCOS were restored to normal levels.Additionally,there was a consistent decrease in luteinizing hormone and follicle stimulating hormone levels in the treatment groups,followed by decrease in the number of cysts after treatment with protocatechuic acid.Histopathological observations showed a remarkable recovery of the ovarian tissue and the presence of normalized structure of antral follicle.Protocatechuic acid treatment restored all the parameters to normalcy and abolished cysts formation in ovaries of female rats.Conclusions:Protocatechuic acid shows potential protective effects in letrozole-induced PCOS rats.The protective effect is comparable to that of clomiphene citrate and thus shows its potential in the treatment of PCOS.
基金supported bythe National Natural Science Foundation of China(21503105)the Natural Science Foundation of Fujian Province(2015J01599,2017J01584)Research Project for Fujian Provincial Universities(JK2015038)
文摘A drug-drug molecular salt hydrate of berberine and protocatechuic acid has been prepared.Protocatechuic acid lost its carboxylic proton and turned to be protocatechuic anion to form a 1:1:1 organic salt hydrate with berberine,[C_(20)H_(18)NO_4]+[C_7H_5O_4]^-?H_2O(1).Compound1 crystallizes in the triclinic system,space group P1 with a = 7.9849(5),b =10.5437(5),c = 14.3621(5)?,α = 77.983(4),β = 82.900(4),γ = 78.024(4)o,V = 1152.82(10) ?~3,Mr= 507.48,Dc= 1.462 g/cm^3,μ = 0.929 mm^(-1),F(000) = 532,Z = 2,the final R = 0.0488 and w R = 0.1322 for 3993 reflectionswith I > 2σ(I).The hydrate exhibited good solid state stability against humidity,which may result from strong hydrogen-bonding interactions between water molecules and carboxylate groups.The hydrate also exhibited acceptable solubility and dissolution rate.
基金supported by the National Key R&D Program of China(2019YFC1711000)the National Natural Science Foundation of China(81421005 and 81722048)“Double First-Class”University project(CPU2018GF04 and CPU2018GY09,China)。
文摘Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction.Protocatechuic aldehyde(PCA)is a major phenolic acid in Chinese herb Danshen(Salvia miltiorrhiza root).This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2(PKM2)function to protect cardiomyocytes.In rats subjected to isoprenaline,PCA attenuated heart injury and protected cardiomyocytes from apoptosis.Through DARTS and CETSA assays,we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation(OGD).In the nucleus,PCA increased the binding of PKM2 to β-Catenin via preserving PKM2 acetylation,and the complex,in cooperation with T-cell factor 4(TCF4),was required for transcriptional induction of genes encoding anti-apoptotic proteins,contributing to rescuing cardiomyocyte survival.In addition,PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2.Consistently,PCA increased the binding of PKM2 to β-Catenin,improved heart contractive function,normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation,but the protective effects were lost in Pkm2-deficient heart.Together,we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via β-Catenin/TCF4 signaling cascade,suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.
