To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Base...To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Based on the combinatorial experiments,it was found that when API and PC were combined at the molar ratios of 4∶1 and 2∶1,they exhibited the antagonistic effects on histamine release(combination index CI>1);when they are combined at the molar ratios of 1∶1,1∶2 or 1∶4,they showed the synergistic effects on histamine release(CI<1).Among them,the combination of API and PC at a molar ratio of 1∶1 showed the better potent synergistic antihistamine release effect(CI=0.70).Histamine is a hallmark of the mast cell degranulation,consequently,the combination of API and PC at a molar ratio of 1∶1 yields the better efficiency in inhibiting the mast cell degranulation with the lowest IC_(50)value.Compared to the utilization of API or PC alone,the IC_(50)value was reduced by 11.150 and 6.503μmol/L,respectively.Compared to the positive control paeonol(PA),the treatment with the combination significantly reduced theβ-hex secretion,decreased the F-actin cytoskeleton rearrangement,and markedly suppressed the release of TNF-α,IL-4,and MCP-1.Further studies on the signaling pathways related to the mast cell degranulation indicated that the combination effectively inhibited the intracellular Ca^(2+)influx and significantly suppressed the phosphorylation of calmodulin-dependent protein kinase(CaMK)and phospholipase C/protein kinase C(PLC/PKC).In summary,the combination of API and PC at a molar ratio of 1∶1 exhibited the better synergistic antagonistic effect on the histamine release,inhibited the mast cell degranulation model activation by reducing Ca^(2+)influx and inhibiting the activation of Ca^(2+)/CaMK and PLC/PKC pathways,stabilized the cell membranes,regulated the inflammatory factor secretion,and exerted an effect in alleviating sensitive skin.展开更多
Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proan-thocyanidins （20, 40, 80 mg/kg） were intraperitoneally administered 1, 24, 48 and ...Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proan-thocyanidins （20, 40, 80 mg/kg） were intraperitoneally administered 1, 24, 48 and 72 hours before reperfusion. Results showed that ginkgo proanthocyanidins could effectively mitigate neurological disorders, shorten infarct volume, increase superoxide dismutase activity, and de-crease malondialdehyde and nitric oxide contents. Simultaneously, the study on grape seed proanthocyanidins （40 mg/kg） confirmed that different sources of proanthocyanidins have a similar effect. The neurological outcomes of ginkgo proanthocyanidins were similar to that of nimodipine in the treatmen＇t of cerebral ischemia/reperfusion injury. （Sur results suggestthat-ginkgo proanthocyanidins can effectively lessen cerebral ischemia/reperfusion injury and protect ischemic brain tissue and these effects are associated with antioxidant properties.展开更多
BACKGROUND： Current studies related to the effects of proanthocyanidins on Alzheimer＇s disease have focused primarily on the signal transduction pathway of cellular apoptosis. However, the influence of p53 gene expr...BACKGROUND： Current studies related to the effects of proanthocyanidins on Alzheimer＇s disease have focused primarily on the signal transduction pathway of cellular apoptosis. However, the influence of p53 gene expression on cell cycle regulation, with regard to the protective mechanisms of proanthocyanidins, has not been reported. OBJECTIVE： To observe the effect of proanthocyanidins on cell cycle distribution, cellular apoptosis and p53 gene expression in β-amyloid peptide （25-35） （Aβ25-35）-induced PC12 cells cultured in serum-free media, and to investigate the molecular neuroprotective mechanisms of proanthocyanidins with regard to cell cycle regulation. DESIGN, TIME AND SETTING： A parallel, controlled, at the Institute of Biochemistry and Molecular Biology cellular, and molecular study was performed Guangdong Medical College from July 2006 to July 2008. MATERIALS： Proanthocyanidins were provided by Nanjing Xuezi Medical and Chemical Research Center, China; Aβ25-35 was provided by Sigma, USA; PC12 cells were provided by the Institute of Basic Medical Science, Academy of Military Medical Sciences; and rabbit anti-p53 polyclonal antibody was provided by Santa Cruz Biotechnology, USA. METHODS： PC12 cells were cultured in serum-free media for 24 hours. Cells from the model group were treated with 25 μmol/L Aβ25-35 for 24 hours. Cells in the drug protection group were pre-treated with 30 mg/L proanthocyanidins for 1 hour and then treated with 25 μmol/LAβ2^-35 for 24 hours. The control group was not treated. MAIN OUTCOME MEASURES： Flow cytometry was used to detect cell cycle distribution and rate of apoptosis; reverse-transcriptase polymerase chain reaction was used to detect p53 mRNA expression; and Western blot was used to detect p53 protein expression. RESULTS： After treating with 25 μmol/LAβ25-35 for 24 hours, the rate of apoptosis and the percentage of cells in S phase were significantly increased （P 〈 0.01 ）, and p53 mRNA and protein expressions were decreased. Pretreatment with proanthocyanidins for 1 hour blocked the increase in apoptosis and the percentage of cells in S phase in Aβ25-35-induced PC12 cells （P 〈 0.01 ） and increased p53 mRNA and protein expressions. CONCLUSION： Proanthocyanidins blocked apoptosis and S-phase arrest in Aβ25-35-induced PC12 cells cultured in serum-free media. The protective mechanism could be related to increased p53 mRNA and protein expressions.展开更多
Occurrence of neurofibrillary tangles of the tau protein is a hallmark of tau-related neurodegenerative diseases, i.e. Alzheimer's disease(AD) and frontotemporal dementia. The pathological mechanism underlying AD ...Occurrence of neurofibrillary tangles of the tau protein is a hallmark of tau-related neurodegenerative diseases, i.e. Alzheimer's disease(AD) and frontotemporal dementia. The pathological mechanism underlying AD remains poorly understood, and effective treatments are still unavailable to mitigate the disease.Inhibiting of tau aggregation and disrupting the existing fibrils are key targets in drug discovery towards preventing or curing AD. In this study, grape seed proanthocyanidins(GSPs) was found to effectively inhibit the repeat domain of tau(tau-RD) aggregation and disaggregate tau-RD fibrils in a concentrationdependent manner by inhibiting β-sheet formation of tau-RD. In cells, GSPs relieved cytotoxicity induced by tau-RD aggregates. Molecular dynamics simulations indicated that strong hydrogen bonding,hydrophobic interaction and π-π stacking between GSPs and tau-RD protein were major reasons why GSPs had high inhibitory activity on tau-RD fibrillogenesis. These results provide preliminary data to develop GSPs into medicines, foodstuffs or nutritional supplements for AD patients, suggesting that GSPs could be a candidate molecule in the drug design for AD therapeutics.展开更多
[Objectives]To compare content of proanthocyanidins and polysaccharides in wild Lycium ruthenicum.[Methods]The wild L.ruthenicum collected from different regions such as Qinghai,Inner Mongolia,Ningxia and Gansu Provin...[Objectives]To compare content of proanthocyanidins and polysaccharides in wild Lycium ruthenicum.[Methods]The wild L.ruthenicum collected from different regions such as Qinghai,Inner Mongolia,Ningxia and Gansu Province were taken as the research objects.The conventional indicators such as proanthocyanidins and polysaccharides of the experimental materials were determined,and the proanthocyanidins and polysaccharides of the experimental materials in different regions were compared and analyzed.The difference in content and correlation,and the cluster analysis method were used to divide clusters of the experimental materials.[Results]The absorbance of proanthocyanidins in the fruit of wild L.ruthenicum was No.4>No.1>No.5>No.6>No.3>No.2,among which the absorbance of anthocyanin(2.43)of wild L.ruthenicum variety No.4 was significantly higher than other experimental materials(P<0.05),and proanthocyanidin of No.2 had the lowest absorbance value of 1.35.There was no significant difference between No.3 and No.6(P>0.05),and there were significant differences among other experimental materials(P<0.05).The content of polysaccharides was:No.3>No.7>No.2>No.4>No.5>No.6>No.1;there was no significant difference between No.3 and No.7(P>0.05),but significantly higher than other materials(P<0.05).Besides,proanthocyanidins and polysaccharides showed significant variability,but there was no consistency in the correlation between them.[Conclusions]In terms of the absorbance of proanthocyanidins,the experimental materials No.1 and No.4 can be classified into a cluster;experimental materials No.2,No.3,No.5 and No.6 can be classified into another cluster.This can provide a theoretical basis for the introduction and breeding of fine varieties.展开更多
Cyclooxygenase-2(COX-2),an important enzyme,plays a pathological role in diseases,which can be inhibited by proanthocyanidins(PCs) effectively.In this paper,we investigated the inhibitive mechanism of COX-2 performed ...Cyclooxygenase-2(COX-2),an important enzyme,plays a pathological role in diseases,which can be inhibited by proanthocyanidins(PCs) effectively.In this paper,we investigated the inhibitive mechanism of COX-2 performed by PCs.Reverse transcription-polymerase chain reaction(RT-PCR) was performed to identify the mRNA expression level of COX-2 in A549 cell,which was induced by interleukin-1 beta(IL-1β).The pGL3 luciferase reporter vector containing the COX-2 gene promoter fragment(pGL3/COX-2p) was transfected into A549 cell induced by IL-1β,the interference on the COX-2 promoter activity from PCs was analyzed using a dualluciferase reporter assay,and the expressions of the nuclear factor κB composed of subunit p65(NF-κB/p65) and the inhibitor-κB(I-κB) were measured by the Western blotting and immunocytochemistry.The results exhibited that PCs not only inhibited the transcript of COX-2 mRNA and the COX-2 promoter activity,but also suppressed the nuclear translocation of NF-κB/p65 protein and the degradation of I-κB protein.展开更多
Besides（-）-epicatechin,epicatechin-（4β-8 ）-epicatechin（procyanidin B2）,epicatechin-（4β-6 ）-epicatechin （procyanidin B5）,epicatechin-（4β-8,2β-O-7）-epicatechin（proanthocyanidin A2） and epicatechin- （4...Besides（-）-epicatechin,epicatechin-（4β-8 ）-epicatechin（procyanidin B2）,epicatechin-（4β-6 ）-epicatechin （procyanidin B5）,epicatechin-（4β-8,2β-O-7）-epicatechin（proanthocyanidin A2） and epicatechin- （4β-8）-epicatechin-（4β-8）-epicatechin（procyanidin C1）,which were isolated before from Adansonia digitata, in this work an A-type proanthocyanidin trimer,i.e.epicatechin-（4β-8）-epicatechin-（4β-8,2β-0-7）- epicatechin,tetrameric procyanidin D1,i.e.epicatechin-（4β-8）-epicatechin-（4β-8）-epicatechin-（4β-8）- epicatechin and a polymeric compound were isolated from the pericarp（fruit wall） of the fruits for the first time from this plant.The antioxidant activity of different fractions and pure compounds was experimentally evaluated in the DPPH<sup>-</sup> assay.The ethyl acetate fraction,and most of the isolated compounds displayed a high activity(IC<sub>50</sub> 2.40-9.60μg/ml) compared with the reference antioxidant Trolox(IC<sub>50</sub> 12.18μg/ml) as a standard.展开更多
Objective: As a novel blood supply pattern, vasculogenic mimicry(VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However...Objective: As a novel blood supply pattern, vasculogenic mimicry(VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However, anti-angiogenic drugs have little effect on VM. The grape seed proanthocyanidins(GSPs), a kind of promising bioactive phytochemical, has shown anti-carcinogenesis and anti-angiogenic in several tumor models. However, GSPs regulation of VM and its possible mechanisms in a H22 hepatoma carcinoma model remain not clear. The aim of this study was to examine the effects of GSPs on proliferation and VM in a H22 hepatoma carcinoma model and to investigate the underlying mechanism. Methods: Seventy-five mice were divided into the control group and experimental groups treated with different concentration of GSPs. CD34-PAS dual staining was employed to identify the VM structure. The immunohistochemical staining for investigating the expression of VEGF, Eph A2 and MMP-2 protein was performed. Results: Treatment of the H22 model with Endostar(4 mg/kg), 50, 100, 200 mg/kg of the GSPs resulted in 6.87%, 17.81%, 27.43%, 53.52% inhibition in tumor growth, respectively. The mean weight of tumors were significantly lower in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups than in the control group(all P < 0.01). Similarly, compared with the control group, the number of VM channels were significantly reduced in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups(all P < 0.01). Immunohistochemistry showed significant decreases in the expression levels of VEGF, Eph A2 and MMP-2 protein in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups when compared with control group(all P < 0.001). Conclusion: This is the first report providing evidence that GSPs inhibit the VM structure by regulation of the VEGF/Eph A2/MMPs signaling pathway. Therefore, we concluded that GSPs has the potential of being a clinical anti-VM inhibitor.展开更多
Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was e...Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.展开更多
In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor explo...In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis.The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30%(V/V)in DESs.AB-8 macroporous resin and ethyl acetate were used for separation and refining,and the oligomer-rich proanthocyanidin components were eventually obtained.The ultraviolet(UV)and infrared(IR)spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin.To further clarify the chemical composition of proanthocyanidin,an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering(MDF)algorithm,combined with the full mass spectrometry(MS)/dd-MS2 scan mode that turns on the“if idle pick others”function.By using ultra-high performance liquid chromatography and high-resolution MS(UHPLC/HRMS),the analysis used both targeted and nontargeted methods to detect proanthocyanidins.Finally,50 oligomeric proanthocyanidin(OPC)compounds were identified,including 7 monomers,22 dimers,20 trimers,and 1 tetramer,most of which were procyanidins of proanthocyanidins(84%),and a small amount of prodelphinidin(14%)and other types of proanthocyanidins(2%),which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes.Meanwhile,the comparison with the grape seeds OPCs standard(United States Pharmacopeia)revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant,suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.展开更多
A novel degradation method was investigated to synthesize highly biologically active flavan-3-ol derivatives in the presence of N-acetyl-L-cysteine(NAC)as a nucleophile under acidic conditions for polymerized proantho...A novel degradation method was investigated to synthesize highly biologically active flavan-3-ol derivatives in the presence of N-acetyl-L-cysteine(NAC)as a nucleophile under acidic conditions for polymerized proanthocyanidins degradation.The reaction conditions were optimized by the combination of single-factor test and central composite experimental design(CCD).Grape seed proanthocyanidins were reacted with NAC at a ratio of 1:3 with 0.3 M methanolic HC1,a temperature of 55°C,and a reaction time of 50 mins.Most of the degradation products were separated and prepared by one-step high-speed countercurrent chromatography(HSCCC)and preparative high-performance liquid chromatography(prep-HPLC).Three monomeric pro anthocyanidins and four new N-acetyl-L-cysteine derivatives were isolated from degradation products with total degradation yield of 55.44%and high purity over 95%.Furthermore,the neuroprotective abilities of these compounds to H2O2-treated PC-12 neuroblastoma cells were evaluated.NAC derivatives showed better antioxidant activity than their corresponding underivatized monomers and NAC,indicating that they had a better performance in protecting PC-12 cells from oxidative stress damage.展开更多
Grape pomace is one of the most abundant solid by-products generated during winemaking,rich in bioactive compounds,i.e.,proanthocyanidins.The major objective of this work was to characterize structurally oligomeric an...Grape pomace is one of the most abundant solid by-products generated during winemaking,rich in bioactive compounds,i.e.,proanthocyanidins.The major objective of this work was to characterize structurally oligomeric and polymeric proanthocyanidins of diff erent parts of grape pomace(seed,skin,and stem).Column chromatography techniques were used to isolate oligomeric and polymeric proanthocyanidins fractions from diff erent parts of grape pomace.The purifi ed grape seed proanthocyanidins were used to assess the effi ciency of the three most frequently-used acidic degradation methods,using benzyl mercaptan,phloroglucinol,and cysteamine as nucleophiles.The structural characterization of proanthocyanidins in the different parts of grape pomace was further performed by the phloroglucinolysis and ESI-MS analysis.The results showed signifi cant diff erences in the structural composition of proanthocyanidins among diff erent parts of pomace.A positive correlation was found between the mean degree of polymerization and percentage of galloylation,in both oligomeric and polymeric fractions.The results provided useful information for the preparation of diff erent proanthocyanidins products from grape pomace.展开更多
For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human...For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human health.Indeed,GSPs have demonstrated substantial health benefi ts for a variety of disorders such as cancer,atherosclerosis,and cardiovascular diseases,to just name a few.In particular,GSPs inhibit cell proliferation,migration and invasion,and induce apoptosis and cell cycle arrest in various human cancers,including head and neck carcinoma,gastrointestinal tumors,lung cancer,skin tumors,and reproductive tumors,which points them to be promising chemo-preventive and/or chemotherapeutic agents.In this setting,we summarized the eff ects of GSPs against various types of cancer with a focus on the detailed molecular mechanisms involving various signaling pathways of tumor cells,which may serve as a basis for development of improved chemo-preventive or therapeutic strategies for cancer.展开更多
Microneedles have shown considerable potential in treating ocular diseases,yet enhancing their architecture and functionality to improve therapeutic efficacy poses marked challenges.Here,inspired by the antioxidant st...Microneedles have shown considerable potential in treating ocular diseases,yet enhancing their architecture and functionality to improve therapeutic efficacy poses marked challenges.Here,inspired by the antioxidant strategy of blueberries and the wet adhesive mechanism of clingfish,we construct hierarchical and multifunctional microneedles.These microneedles possess both wet adhesive and antioxidant properties,making them highly effective for ocular wound healing.Constructed using polyacrylic acid-N-hydroxysuccinimide-based hydrogel with hexagonal structures,these generated microneedles ensure strong adhesion in wet environments.Furthermore,by incorporating proanthocyanidins(pAc)into the tips,the microneedle is imparted with excellent competence to scavenge reactive oxygen species(ROS).In the rat model of ocular alkali burns,the designed microneedle not only exhibited robust adhesion and desirable antioxidant properties in the moist ocular environment but also facilitated sustained drug release and effective treatment.These results suggest that our bioinspired microneedles with multifunctional properties offer substantial advancement over conventional approaches,positioning them as promising candidates for versatile wound healing applications.展开更多
Grape seed proanthocyanidin(GSP)is a type of plant polyphenol with a wide variety of biological activities,such as antioxidant properties.This study investigated the effects of GSP supplementation on growth performanc...Grape seed proanthocyanidin(GSP)is a type of plant polyphenol with a wide variety of biological activities,such as antioxidant properties.This study investigated the effects of GSP supplementation on growth performance and meat quality in growing-finishing pigs.A total of 180 pigs(with an initial average body weight of 30.37±0.66 kg)were randomly assigned to five treatments:a control diet or a control diet supplemented with GSP at 15,30,60,and 120 mg/kg.Each treatment group comprised six replicate pens(6 pigs per pen).Results showed that GSP supplementation linearly increased the average daily gain(P=0.048)and quadratically decreased the feed intake to gain ratio(P=0.049)with the lowest values at 30 and 60 mg/kg GSP.Serum concentrations of immunoglobulins(Ig)(IgA,IgG,IgM),total antioxidative capacity,catalase,and total superoxide dismutase were elevated with the peak levels at 30 mg/kg GSP(P<0.05).Serum glutathione peroxidase increased and malondialdehyde decreased quadratically(P<0.05),with peak and trough levels at 120 and 60 mg/kg GSP,respectively.The GSP also improved dressing percentage and muscle redness(a*45 min)with optimal levels at 30 and 60 mg/kg(P<0.05).Additionally,GSP supplementation quadratically reduced the muscle yellowness(b*24 h)and shear force(P<0.05),with the lowest values at 120 mg/kg.The expression level of myosin heavy chain I in muscle was quadratically increased with maximum expression at 30 and 60 mg/kg(P=0.015).Furthermore,the expression levels of fatty acid synthase,phosphoenolpyruvate carboxykinase(PEPCK),and glucokinase in the muscle were decreased quadratically(P<0.05)with the lowest values at 120 mg/kg.Additionally,GSP supplementation at 60 mg/kg upregulated the expression of hepatic hormonesensitive triglyceride lipase and PEPCK(P<0.05).These results suggest that GSP enhances carcass characteristics and meat quality in growing-finishing pigs,potentially through improved antioxidative capacity,modified muscle fiber type distribution,and altered glucose-lipid metabolism in muscle and liver.展开更多
Proanthocyanidins （PAs） are the main products of the flavonoid biosynthetic pathway in seeds, but their biological function during seed germination is still unclear. We observed that seed germination is delayed with...Proanthocyanidins （PAs） are the main products of the flavonoid biosynthetic pathway in seeds, but their biological function during seed germination is still unclear. We observed that seed germination is delayed with the increase of exogenous PA concentration in Arabidopsis. A similar inhibitory effect occurred in peeled Brassica napus seeds, which was observed by measuring radicle elongation. Using abscisic acid （ABA）, a biosynthetic and metabolic inhibitor, and gene expression analysis by real-time polymerase chain reaction, we found that the inhibitory effect of PAs on seed germination is due to their promotion of ABA via de novo biogenesis, rather than by any inhibition of its degradation. Consistent with the relationship between PA content and ABA accumulation in seeds, PA-deficient mutants maintain a lower level of ABA compared with wild-types during germination. Our data suggest that PA distribution in the seed coat can act as a doorkeeper to seed germination. PA regulation of seed germination is mediated by the ABA signaling pathway.展开更多
Proanthocyanidins （PAs） as the end products of flavonoid biosynthetic pathway mainly accumulate in seed coat but their biological function is largely unknown. We studied the anti-oxidation ability in seed coat and g...Proanthocyanidins （PAs） as the end products of flavonoid biosynthetic pathway mainly accumulate in seed coat but their biological function is largely unknown. We studied the anti-oxidation ability in seed coat and germination changes under externally applied oxidative stresses in PAs-deficient mutants of Arabidopsis. Germination of PAs-deficient mutant seeds was faster than that of wild-type under low or no oxidative stress, suggesting a PAs-induced inhibition of germination. When the applied oxidative stress was high, germination of PAs-deficient mutants was lower than that of wild-type, suggesting a loss of PAs-related anti-oxidation ability in the mutants. Using ABA signaling mutants, our studies demonstrated that both ABA signaling pathway and PAs were important for the response to serve oxidative stress during seed germination. However, the discrepancy of the response between abi mutants and PAs mutants to oxidative stress suggests that ABA signaling pathway may not play a major role in PAs＂ action in alleviating oxidative stress. Under low or no oxidative stress, germination was mainly determined by the ABA content in seed and the PAs-deficient mutant seeds germinated faster due to their lower ABA content than wild-type. However, oxidative injury inhibited germination when PAs-deficient seeds germinated under high oxidative stress, Wild-type exhibited higher germination under the high ox- idative stress due to the PAs＇ anti-oxidation ability. Oxidative stress applied externally led to changes in endogenous PAs contents that coincided with the expression changes of PAs biogenesis genes. PAs modulated the activities of some key enzymes that controlled the levels of reactive oxygen species and the anti-oxidation capacity during the seed germination. This work suggests that PAs contribute to the adaptive mechanism that helps germination under environmental stresses by playing dual roles in both germination control and anti-oxidation reaction.展开更多
Proanthocyanidins naturally occur in various fruits,some vegetables and beverages.Increasing evidence has shown that dietary intake of proanthocyanidins is a promising alternative to tumor chemoprevention or chemother...Proanthocyanidins naturally occur in various fruits,some vegetables and beverages.Increasing evidence has shown that dietary intake of proanthocyanidins is a promising alternative to tumor chemoprevention or chemotherapy.Grape seeds are the most abundant source of proanthocyanidins,and grape seed proanthocyanidins(GSPs)show an anticancer effect on hepatocellular carcinoma(HCC),which accounts for approximately 85-90%of all primary liver malignancies.Although an increasing number of studies have investigated the effects of GSPs on HCC and the associated mechanisms,the precise mechanism of GSP therapy in HCC remains unclear.This study aimed to understand the cytotoxic effect of GSPs on HepG2 cells by investigating morphology and growth inhibition.Cell proliferation and apoptosis were estimated by an MTT assay and flow cytometry,and the protein expression of HepG2 cells was determined through Western blotting.The results indicated that GSPs could markedly inhibit HepG2 liver cancer cells and induce apoptosis,with the effects varying by dose and treatment time.Furthermore,GSPs inhibited the phosphorylation of extracellular regulated protein kinases(ERK),c-Jun NH2-terminal kinase(JNK),p38 mitogen-activated protein kinase(p38 MAPK),IκBα,pyruvate dehydrogenase kinase 1(PDK1),glycogen synthase kinase-3 beta(GSK3β)and protein kinase B(AKT),which accounted for the inactivation of mitogen-activated protein kinase/AKT(MAPK/AKT)pathways.These results indicate that GSPs are a potential source of natural chemopreventive agents for the treatment of HCC.展开更多
Agro-wastes contribute major social,economic,and environmental challenges for food production and circular economy systems.The current increasing demand for clean label food production and use of natural bioactive com...Agro-wastes contribute major social,economic,and environmental challenges for food production and circular economy systems.The current increasing demand for clean label food production and use of natural bioactive compounds could turn these challenges into opportunities providing avenues for proper utilization of agro-wastes to produce valuable products.This study aimed to investigate the potential use of kiwifruit(Actinidia chinensis)leaves as a source of proanthocyanidins(PAs)bioactive phenolic phytochemicals.Kiwifruit leaves PAs were extracted,purified,identified,and evaluated for their antioxidant and anti-proliferative activities.The structural composition of the purified PAs was characterized using HPLC-QTOF-MS/MS and MALDI-TOF-MS.The results showed that purified kiwifruit leaves PAs(PKLPs)comprised mainly procyanidins,propelargonidins,and prodelphindins ranging from dimers to hexamers with(epi)catechin as terminal units and(epi)afzelechin or(epi)gallocatechin as dominant extension units.This study reports the structure of novel PKLPs monomer fractions was unique compared to the PAs that extracted from the other plant sources.The PKLPs exhibited higher phenolic content than the skin and flesh of several kiwifruit cultivars.Moreover,the PKLPs exhibited higher in vitro antioxidant activity in chemical-based(DPPH,ABTS,and FRAP)assays and H2O2-induced injury cell model than ascorbic,Trolox,and catechin(p<0.01).A remarkable dose-dependent anti-proliferation activity(IC_(50)=186.04±2.61μg/mL)against HepG2 cells was observed.In conclusion,this study demonstrated that kiwifruit leaves waste could serve as a sustainable and low-cost source of PAs,a group of multi-functional bioactive compounds that plays a key role in the food and pharmaceutical industries.展开更多
Wheat grains contain various bioactive substances,of which,condensed tannins(CT)are polymeric flavan-3-ols that accumulate in wheat seed coat influencing the end-use quality and nutritional value.However,the genetic a...Wheat grains contain various bioactive substances,of which,condensed tannins(CT)are polymeric flavan-3-ols that accumulate in wheat seed coat influencing the end-use quality and nutritional value.However,the genetic architecture underlying CT biosynthesis in wheat grain remains unclear.Here,we studied the deposition and genetic regulation of CT in wheat grains,and found that CT deposited specifically in the testa layer of red-grained wheat as catechin-and epicatechin-formed polymers.Genome-wide association study identified 22 genetic loci affecting CT content,one of which,TaTAN,a single dominant gene controlling CT presence,was mapped to chromosome 3A in a segregation population.Further pan-genome analysis,transcriptome profiling and ethyl methanesulfonate induced mutants sequencing revealed a R2R3-MYB transcription factor,TaMYB10-3A,as the causal gene.Three loss-of-function alleles in TaMYB10-3A caused by large fragment inversion-deletion and insertion were identified which abolish both CT deposition and red pigmentation,demonstrating the pleiotropic effect of TaMYB10-3A on CT presence and grain color.TaMYB10-3A directly trans-activates core flavonoid genes such as chalcone synthase and dihydroflavonol 4-reductase to initiate CT biosynthesis.Our investigation provides a comprehensive understanding of CT presence in wheat grains and lays a solid foundation for manipulating CT metabolites to improve wheat grain end-use quality and nutrition values in wheat.展开更多
文摘To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Based on the combinatorial experiments,it was found that when API and PC were combined at the molar ratios of 4∶1 and 2∶1,they exhibited the antagonistic effects on histamine release(combination index CI>1);when they are combined at the molar ratios of 1∶1,1∶2 or 1∶4,they showed the synergistic effects on histamine release(CI<1).Among them,the combination of API and PC at a molar ratio of 1∶1 showed the better potent synergistic antihistamine release effect(CI=0.70).Histamine is a hallmark of the mast cell degranulation,consequently,the combination of API and PC at a molar ratio of 1∶1 yields the better efficiency in inhibiting the mast cell degranulation with the lowest IC_(50)value.Compared to the utilization of API or PC alone,the IC_(50)value was reduced by 11.150 and 6.503μmol/L,respectively.Compared to the positive control paeonol(PA),the treatment with the combination significantly reduced theβ-hex secretion,decreased the F-actin cytoskeleton rearrangement,and markedly suppressed the release of TNF-α,IL-4,and MCP-1.Further studies on the signaling pathways related to the mast cell degranulation indicated that the combination effectively inhibited the intracellular Ca^(2+)influx and significantly suppressed the phosphorylation of calmodulin-dependent protein kinase(CaMK)and phospholipase C/protein kinase C(PLC/PKC).In summary,the combination of API and PC at a molar ratio of 1∶1 exhibited the better synergistic antagonistic effect on the histamine release,inhibited the mast cell degranulation model activation by reducing Ca^(2+)influx and inhibiting the activation of Ca^(2+)/CaMK and PLC/PKC pathways,stabilized the cell membranes,regulated the inflammatory factor secretion,and exerted an effect in alleviating sensitive skin.
文摘Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proan-thocyanidins （20, 40, 80 mg/kg） were intraperitoneally administered 1, 24, 48 and 72 hours before reperfusion. Results showed that ginkgo proanthocyanidins could effectively mitigate neurological disorders, shorten infarct volume, increase superoxide dismutase activity, and de-crease malondialdehyde and nitric oxide contents. Simultaneously, the study on grape seed proanthocyanidins （40 mg/kg） confirmed that different sources of proanthocyanidins have a similar effect. The neurological outcomes of ginkgo proanthocyanidins were similar to that of nimodipine in the treatmen＇t of cerebral ischemia/reperfusion injury. （Sur results suggestthat-ginkgo proanthocyanidins can effectively lessen cerebral ischemia/reperfusion injury and protect ischemic brain tissue and these effects are associated with antioxidant properties.
基金Key Discipline Key Projects in Guangdong Province (9808)
文摘BACKGROUND： Current studies related to the effects of proanthocyanidins on Alzheimer＇s disease have focused primarily on the signal transduction pathway of cellular apoptosis. However, the influence of p53 gene expression on cell cycle regulation, with regard to the protective mechanisms of proanthocyanidins, has not been reported. OBJECTIVE： To observe the effect of proanthocyanidins on cell cycle distribution, cellular apoptosis and p53 gene expression in β-amyloid peptide （25-35） （Aβ25-35）-induced PC12 cells cultured in serum-free media, and to investigate the molecular neuroprotective mechanisms of proanthocyanidins with regard to cell cycle regulation. DESIGN, TIME AND SETTING： A parallel, controlled, at the Institute of Biochemistry and Molecular Biology cellular, and molecular study was performed Guangdong Medical College from July 2006 to July 2008. MATERIALS： Proanthocyanidins were provided by Nanjing Xuezi Medical and Chemical Research Center, China; Aβ25-35 was provided by Sigma, USA; PC12 cells were provided by the Institute of Basic Medical Science, Academy of Military Medical Sciences; and rabbit anti-p53 polyclonal antibody was provided by Santa Cruz Biotechnology, USA. METHODS： PC12 cells were cultured in serum-free media for 24 hours. Cells from the model group were treated with 25 μmol/L Aβ25-35 for 24 hours. Cells in the drug protection group were pre-treated with 30 mg/L proanthocyanidins for 1 hour and then treated with 25 μmol/LAβ2^-35 for 24 hours. The control group was not treated. MAIN OUTCOME MEASURES： Flow cytometry was used to detect cell cycle distribution and rate of apoptosis; reverse-transcriptase polymerase chain reaction was used to detect p53 mRNA expression; and Western blot was used to detect p53 protein expression. RESULTS： After treating with 25 μmol/LAβ25-35 for 24 hours, the rate of apoptosis and the percentage of cells in S phase were significantly increased （P 〈 0.01 ）, and p53 mRNA and protein expressions were decreased. Pretreatment with proanthocyanidins for 1 hour blocked the increase in apoptosis and the percentage of cells in S phase in Aβ25-35-induced PC12 cells （P 〈 0.01 ） and increased p53 mRNA and protein expressions. CONCLUSION： Proanthocyanidins blocked apoptosis and S-phase arrest in Aβ25-35-induced PC12 cells cultured in serum-free media. The protective mechanism could be related to increased p53 mRNA and protein expressions.
基金supported by the National Natural Science Foundation of China (21878262)。
文摘Occurrence of neurofibrillary tangles of the tau protein is a hallmark of tau-related neurodegenerative diseases, i.e. Alzheimer's disease(AD) and frontotemporal dementia. The pathological mechanism underlying AD remains poorly understood, and effective treatments are still unavailable to mitigate the disease.Inhibiting of tau aggregation and disrupting the existing fibrils are key targets in drug discovery towards preventing or curing AD. In this study, grape seed proanthocyanidins(GSPs) was found to effectively inhibit the repeat domain of tau(tau-RD) aggregation and disaggregate tau-RD fibrils in a concentrationdependent manner by inhibiting β-sheet formation of tau-RD. In cells, GSPs relieved cytotoxicity induced by tau-RD aggregates. Molecular dynamics simulations indicated that strong hydrogen bonding,hydrophobic interaction and π-π stacking between GSPs and tau-RD protein were major reasons why GSPs had high inhibitory activity on tau-RD fibrillogenesis. These results provide preliminary data to develop GSPs into medicines, foodstuffs or nutritional supplements for AD patients, suggesting that GSPs could be a candidate molecule in the drug design for AD therapeutics.
基金Supported by Science and Technology Program of Inner Mongolia(201602083)Special Fund for Scientific Research of Inner Mongolia Agricultural University"Special Program for Breeding(Selection)of Animal and Plant Varieties"(YZGC2017023)
文摘[Objectives]To compare content of proanthocyanidins and polysaccharides in wild Lycium ruthenicum.[Methods]The wild L.ruthenicum collected from different regions such as Qinghai,Inner Mongolia,Ningxia and Gansu Province were taken as the research objects.The conventional indicators such as proanthocyanidins and polysaccharides of the experimental materials were determined,and the proanthocyanidins and polysaccharides of the experimental materials in different regions were compared and analyzed.The difference in content and correlation,and the cluster analysis method were used to divide clusters of the experimental materials.[Results]The absorbance of proanthocyanidins in the fruit of wild L.ruthenicum was No.4>No.1>No.5>No.6>No.3>No.2,among which the absorbance of anthocyanin(2.43)of wild L.ruthenicum variety No.4 was significantly higher than other experimental materials(P<0.05),and proanthocyanidin of No.2 had the lowest absorbance value of 1.35.There was no significant difference between No.3 and No.6(P>0.05),and there were significant differences among other experimental materials(P<0.05).The content of polysaccharides was:No.3>No.7>No.2>No.4>No.5>No.6>No.1;there was no significant difference between No.3 and No.7(P>0.05),but significantly higher than other materials(P<0.05).Besides,proanthocyanidins and polysaccharides showed significant variability,but there was no consistency in the correlation between them.[Conclusions]In terms of the absorbance of proanthocyanidins,the experimental materials No.1 and No.4 can be classified into a cluster;experimental materials No.2,No.3,No.5 and No.6 can be classified into another cluster.This can provide a theoretical basis for the introduction and breeding of fine varieties.
基金the Special Supported by Guangdong Key Program (No.GX0307)the Guangdong Science and Technology Planning Project in the Field of Social Development (No.35025)
文摘Cyclooxygenase-2(COX-2),an important enzyme,plays a pathological role in diseases,which can be inhibited by proanthocyanidins(PCs) effectively.In this paper,we investigated the inhibitive mechanism of COX-2 performed by PCs.Reverse transcription-polymerase chain reaction(RT-PCR) was performed to identify the mRNA expression level of COX-2 in A549 cell,which was induced by interleukin-1 beta(IL-1β).The pGL3 luciferase reporter vector containing the COX-2 gene promoter fragment(pGL3/COX-2p) was transfected into A549 cell induced by IL-1β,the interference on the COX-2 promoter activity from PCs was analyzed using a dualluciferase reporter assay,and the expressions of the nuclear factor κB composed of subunit p65(NF-κB/p65) and the inhibitor-κB(I-κB) were measured by the Western blotting and immunocytochemistry.The results exhibited that PCs not only inhibited the transcript of COX-2 mRNA and the COX-2 promoter activity,but also suppressed the nuclear translocation of NF-κB/p65 protein and the degradation of I-κB protein.
文摘Besides（-）-epicatechin,epicatechin-（4β-8 ）-epicatechin（procyanidin B2）,epicatechin-（4β-6 ）-epicatechin （procyanidin B5）,epicatechin-（4β-8,2β-O-7）-epicatechin（proanthocyanidin A2） and epicatechin- （4β-8）-epicatechin-（4β-8）-epicatechin（procyanidin C1）,which were isolated before from Adansonia digitata, in this work an A-type proanthocyanidin trimer,i.e.epicatechin-（4β-8）-epicatechin-（4β-8,2β-0-7）- epicatechin,tetrameric procyanidin D1,i.e.epicatechin-（4β-8）-epicatechin-（4β-8）-epicatechin-（4β-8）- epicatechin and a polymeric compound were isolated from the pericarp（fruit wall） of the fruits for the first time from this plant.The antioxidant activity of different fractions and pure compounds was experimentally evaluated in the DPPH<sup>-</sup> assay.The ethyl acetate fraction,and most of the isolated compounds displayed a high activity(IC<sub>50</sub> 2.40-9.60μg/ml) compared with the reference antioxidant Trolox(IC<sub>50</sub> 12.18μg/ml) as a standard.
文摘Objective: As a novel blood supply pattern, vasculogenic mimicry(VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However, anti-angiogenic drugs have little effect on VM. The grape seed proanthocyanidins(GSPs), a kind of promising bioactive phytochemical, has shown anti-carcinogenesis and anti-angiogenic in several tumor models. However, GSPs regulation of VM and its possible mechanisms in a H22 hepatoma carcinoma model remain not clear. The aim of this study was to examine the effects of GSPs on proliferation and VM in a H22 hepatoma carcinoma model and to investigate the underlying mechanism. Methods: Seventy-five mice were divided into the control group and experimental groups treated with different concentration of GSPs. CD34-PAS dual staining was employed to identify the VM structure. The immunohistochemical staining for investigating the expression of VEGF, Eph A2 and MMP-2 protein was performed. Results: Treatment of the H22 model with Endostar(4 mg/kg), 50, 100, 200 mg/kg of the GSPs resulted in 6.87%, 17.81%, 27.43%, 53.52% inhibition in tumor growth, respectively. The mean weight of tumors were significantly lower in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups than in the control group(all P < 0.01). Similarly, compared with the control group, the number of VM channels were significantly reduced in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups(all P < 0.01). Immunohistochemistry showed significant decreases in the expression levels of VEGF, Eph A2 and MMP-2 protein in GSPs(100 mg/kg) and GSPs(200 mg/kg) groups when compared with control group(all P < 0.001). Conclusion: This is the first report providing evidence that GSPs inhibit the VM structure by regulation of the VEGF/Eph A2/MMPs signaling pathway. Therefore, we concluded that GSPs has the potential of being a clinical anti-VM inhibitor.
基金supported by Department of Oncology, the Affiliated Hospital of Qingdao University, China
文摘Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.
基金supported by the Science and Technology Program of Tianjin in China(Grant No.:23ZYJDSS00030)the Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,China(Grant Nos.:22HHZYSS00007 and 22HHZYJC00003).
文摘In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis.The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30%(V/V)in DESs.AB-8 macroporous resin and ethyl acetate were used for separation and refining,and the oligomer-rich proanthocyanidin components were eventually obtained.The ultraviolet(UV)and infrared(IR)spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin.To further clarify the chemical composition of proanthocyanidin,an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering(MDF)algorithm,combined with the full mass spectrometry(MS)/dd-MS2 scan mode that turns on the“if idle pick others”function.By using ultra-high performance liquid chromatography and high-resolution MS(UHPLC/HRMS),the analysis used both targeted and nontargeted methods to detect proanthocyanidins.Finally,50 oligomeric proanthocyanidin(OPC)compounds were identified,including 7 monomers,22 dimers,20 trimers,and 1 tetramer,most of which were procyanidins of proanthocyanidins(84%),and a small amount of prodelphinidin(14%)and other types of proanthocyanidins(2%),which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes.Meanwhile,the comparison with the grape seeds OPCs standard(United States Pharmacopeia)revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant,suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.
基金This work was supported by Guidance Plan of Natural Science Foundation of Liaoning in China(2019-ZD-0463).
文摘A novel degradation method was investigated to synthesize highly biologically active flavan-3-ol derivatives in the presence of N-acetyl-L-cysteine(NAC)as a nucleophile under acidic conditions for polymerized proanthocyanidins degradation.The reaction conditions were optimized by the combination of single-factor test and central composite experimental design(CCD).Grape seed proanthocyanidins were reacted with NAC at a ratio of 1:3 with 0.3 M methanolic HC1,a temperature of 55°C,and a reaction time of 50 mins.Most of the degradation products were separated and prepared by one-step high-speed countercurrent chromatography(HSCCC)and preparative high-performance liquid chromatography(prep-HPLC).Three monomeric pro anthocyanidins and four new N-acetyl-L-cysteine derivatives were isolated from degradation products with total degradation yield of 55.44%and high purity over 95%.Furthermore,the neuroprotective abilities of these compounds to H2O2-treated PC-12 neuroblastoma cells were evaluated.NAC derivatives showed better antioxidant activity than their corresponding underivatized monomers and NAC,indicating that they had a better performance in protecting PC-12 cells from oxidative stress damage.
文摘Grape pomace is one of the most abundant solid by-products generated during winemaking,rich in bioactive compounds,i.e.,proanthocyanidins.The major objective of this work was to characterize structurally oligomeric and polymeric proanthocyanidins of diff erent parts of grape pomace(seed,skin,and stem).Column chromatography techniques were used to isolate oligomeric and polymeric proanthocyanidins fractions from diff erent parts of grape pomace.The purifi ed grape seed proanthocyanidins were used to assess the effi ciency of the three most frequently-used acidic degradation methods,using benzyl mercaptan,phloroglucinol,and cysteamine as nucleophiles.The structural characterization of proanthocyanidins in the different parts of grape pomace was further performed by the phloroglucinolysis and ESI-MS analysis.The results showed signifi cant diff erences in the structural composition of proanthocyanidins among diff erent parts of pomace.A positive correlation was found between the mean degree of polymerization and percentage of galloylation,in both oligomeric and polymeric fractions.The results provided useful information for the preparation of diff erent proanthocyanidins products from grape pomace.
文摘For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human health.Indeed,GSPs have demonstrated substantial health benefi ts for a variety of disorders such as cancer,atherosclerosis,and cardiovascular diseases,to just name a few.In particular,GSPs inhibit cell proliferation,migration and invasion,and induce apoptosis and cell cycle arrest in various human cancers,including head and neck carcinoma,gastrointestinal tumors,lung cancer,skin tumors,and reproductive tumors,which points them to be promising chemo-preventive and/or chemotherapeutic agents.In this setting,we summarized the eff ects of GSPs against various types of cancer with a focus on the detailed molecular mechanisms involving various signaling pathways of tumor cells,which may serve as a basis for development of improved chemo-preventive or therapeutic strategies for cancer.
基金supported by the National Key Re search and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(82101184)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2024A1515010457)the Shenzhen Medical Research Fund(A2303017)the Shenzhen Science and Technology Program(JCYJ20210324133214038 and JCYJ20210324102809024).
文摘Microneedles have shown considerable potential in treating ocular diseases,yet enhancing their architecture and functionality to improve therapeutic efficacy poses marked challenges.Here,inspired by the antioxidant strategy of blueberries and the wet adhesive mechanism of clingfish,we construct hierarchical and multifunctional microneedles.These microneedles possess both wet adhesive and antioxidant properties,making them highly effective for ocular wound healing.Constructed using polyacrylic acid-N-hydroxysuccinimide-based hydrogel with hexagonal structures,these generated microneedles ensure strong adhesion in wet environments.Furthermore,by incorporating proanthocyanidins(pAc)into the tips,the microneedle is imparted with excellent competence to scavenge reactive oxygen species(ROS).In the rat model of ocular alkali burns,the designed microneedle not only exhibited robust adhesion and desirable antioxidant properties in the moist ocular environment but also facilitated sustained drug release and effective treatment.These results suggest that our bioinspired microneedles with multifunctional properties offer substantial advancement over conventional approaches,positioning them as promising candidates for versatile wound healing applications.
基金supported by the National Key R&D Program of China(2023YFD1301200)the Porcine Innovation Team of Sichuan Province(SCCXTD-2024-8).
文摘Grape seed proanthocyanidin(GSP)is a type of plant polyphenol with a wide variety of biological activities,such as antioxidant properties.This study investigated the effects of GSP supplementation on growth performance and meat quality in growing-finishing pigs.A total of 180 pigs(with an initial average body weight of 30.37±0.66 kg)were randomly assigned to five treatments:a control diet or a control diet supplemented with GSP at 15,30,60,and 120 mg/kg.Each treatment group comprised six replicate pens(6 pigs per pen).Results showed that GSP supplementation linearly increased the average daily gain(P=0.048)and quadratically decreased the feed intake to gain ratio(P=0.049)with the lowest values at 30 and 60 mg/kg GSP.Serum concentrations of immunoglobulins(Ig)(IgA,IgG,IgM),total antioxidative capacity,catalase,and total superoxide dismutase were elevated with the peak levels at 30 mg/kg GSP(P<0.05).Serum glutathione peroxidase increased and malondialdehyde decreased quadratically(P<0.05),with peak and trough levels at 120 and 60 mg/kg GSP,respectively.The GSP also improved dressing percentage and muscle redness(a*45 min)with optimal levels at 30 and 60 mg/kg(P<0.05).Additionally,GSP supplementation quadratically reduced the muscle yellowness(b*24 h)and shear force(P<0.05),with the lowest values at 120 mg/kg.The expression level of myosin heavy chain I in muscle was quadratically increased with maximum expression at 30 and 60 mg/kg(P=0.015).Furthermore,the expression levels of fatty acid synthase,phosphoenolpyruvate carboxykinase(PEPCK),and glucokinase in the muscle were decreased quadratically(P<0.05)with the lowest values at 120 mg/kg.Additionally,GSP supplementation at 60 mg/kg upregulated the expression of hepatic hormonesensitive triglyceride lipase and PEPCK(P<0.05).These results suggest that GSP enhances carcass characteristics and meat quality in growing-finishing pigs,potentially through improved antioxidative capacity,modified muscle fiber type distribution,and altered glucose-lipid metabolism in muscle and liver.
基金the Hong Kong Research Grants Council (CUHK 262809)the Hong Kong Baptist University Strategic Development Fund (SDF 090910P03)the National Basic Research Program of China (973 project,2012CB114300)
文摘Proanthocyanidins （PAs） are the main products of the flavonoid biosynthetic pathway in seeds, but their biological function during seed germination is still unclear. We observed that seed germination is delayed with the increase of exogenous PA concentration in Arabidopsis. A similar inhibitory effect occurred in peeled Brassica napus seeds, which was observed by measuring radicle elongation. Using abscisic acid （ABA）, a biosynthetic and metabolic inhibitor, and gene expression analysis by real-time polymerase chain reaction, we found that the inhibitory effect of PAs on seed germination is due to their promotion of ABA via de novo biogenesis, rather than by any inhibition of its degradation. Consistent with the relationship between PA content and ABA accumulation in seeds, PA-deficient mutants maintain a lower level of ABA compared with wild-types during germination. Our data suggest that PA distribution in the seed coat can act as a doorkeeper to seed germination. PA regulation of seed germination is mediated by the ABA signaling pathway.
文摘Proanthocyanidins （PAs） as the end products of flavonoid biosynthetic pathway mainly accumulate in seed coat but their biological function is largely unknown. We studied the anti-oxidation ability in seed coat and germination changes under externally applied oxidative stresses in PAs-deficient mutants of Arabidopsis. Germination of PAs-deficient mutant seeds was faster than that of wild-type under low or no oxidative stress, suggesting a PAs-induced inhibition of germination. When the applied oxidative stress was high, germination of PAs-deficient mutants was lower than that of wild-type, suggesting a loss of PAs-related anti-oxidation ability in the mutants. Using ABA signaling mutants, our studies demonstrated that both ABA signaling pathway and PAs were important for the response to serve oxidative stress during seed germination. However, the discrepancy of the response between abi mutants and PAs mutants to oxidative stress suggests that ABA signaling pathway may not play a major role in PAs＂ action in alleviating oxidative stress. Under low or no oxidative stress, germination was mainly determined by the ABA content in seed and the PAs-deficient mutant seeds germinated faster due to their lower ABA content than wild-type. However, oxidative injury inhibited germination when PAs-deficient seeds germinated under high oxidative stress, Wild-type exhibited higher germination under the high ox- idative stress due to the PAs＇ anti-oxidation ability. Oxidative stress applied externally led to changes in endogenous PAs contents that coincided with the expression changes of PAs biogenesis genes. PAs modulated the activities of some key enzymes that controlled the levels of reactive oxygen species and the anti-oxidation capacity during the seed germination. This work suggests that PAs contribute to the adaptive mechanism that helps germination under environmental stresses by playing dual roles in both germination control and anti-oxidation reaction.
基金provided by the Research Cooperation Fund Project of Agricultural University of China and Xinjiang Agricultural University in 2016(grant number:2017TC010).
文摘Proanthocyanidins naturally occur in various fruits,some vegetables and beverages.Increasing evidence has shown that dietary intake of proanthocyanidins is a promising alternative to tumor chemoprevention or chemotherapy.Grape seeds are the most abundant source of proanthocyanidins,and grape seed proanthocyanidins(GSPs)show an anticancer effect on hepatocellular carcinoma(HCC),which accounts for approximately 85-90%of all primary liver malignancies.Although an increasing number of studies have investigated the effects of GSPs on HCC and the associated mechanisms,the precise mechanism of GSP therapy in HCC remains unclear.This study aimed to understand the cytotoxic effect of GSPs on HepG2 cells by investigating morphology and growth inhibition.Cell proliferation and apoptosis were estimated by an MTT assay and flow cytometry,and the protein expression of HepG2 cells was determined through Western blotting.The results indicated that GSPs could markedly inhibit HepG2 liver cancer cells and induce apoptosis,with the effects varying by dose and treatment time.Furthermore,GSPs inhibited the phosphorylation of extracellular regulated protein kinases(ERK),c-Jun NH2-terminal kinase(JNK),p38 mitogen-activated protein kinase(p38 MAPK),IκBα,pyruvate dehydrogenase kinase 1(PDK1),glycogen synthase kinase-3 beta(GSK3β)and protein kinase B(AKT),which accounted for the inactivation of mitogen-activated protein kinase/AKT(MAPK/AKT)pathways.These results indicate that GSPs are a potential source of natural chemopreventive agents for the treatment of HCC.
基金This study was supported by the National Key Research and Development Program of China(grant no:2017YFD0400704).
文摘Agro-wastes contribute major social,economic,and environmental challenges for food production and circular economy systems.The current increasing demand for clean label food production and use of natural bioactive compounds could turn these challenges into opportunities providing avenues for proper utilization of agro-wastes to produce valuable products.This study aimed to investigate the potential use of kiwifruit(Actinidia chinensis)leaves as a source of proanthocyanidins(PAs)bioactive phenolic phytochemicals.Kiwifruit leaves PAs were extracted,purified,identified,and evaluated for their antioxidant and anti-proliferative activities.The structural composition of the purified PAs was characterized using HPLC-QTOF-MS/MS and MALDI-TOF-MS.The results showed that purified kiwifruit leaves PAs(PKLPs)comprised mainly procyanidins,propelargonidins,and prodelphindins ranging from dimers to hexamers with(epi)catechin as terminal units and(epi)afzelechin or(epi)gallocatechin as dominant extension units.This study reports the structure of novel PKLPs monomer fractions was unique compared to the PAs that extracted from the other plant sources.The PKLPs exhibited higher phenolic content than the skin and flesh of several kiwifruit cultivars.Moreover,the PKLPs exhibited higher in vitro antioxidant activity in chemical-based(DPPH,ABTS,and FRAP)assays and H2O2-induced injury cell model than ascorbic,Trolox,and catechin(p<0.01).A remarkable dose-dependent anti-proliferation activity(IC_(50)=186.04±2.61μg/mL)against HepG2 cells was observed.In conclusion,this study demonstrated that kiwifruit leaves waste could serve as a sustainable and low-cost source of PAs,a group of multi-functional bioactive compounds that plays a key role in the food and pharmaceutical industries.
基金supported by the Key R&D Program of Shandong Province (2024LZGC007, 2024CXPT072, 2022LZGC001)Shandong Provincial Natural Science Foundation (ZR2024YQ069)+1 种基金the National Natural Science Foundation of China (32201863,32272181)the Taishan Scholars Program
文摘Wheat grains contain various bioactive substances,of which,condensed tannins(CT)are polymeric flavan-3-ols that accumulate in wheat seed coat influencing the end-use quality and nutritional value.However,the genetic architecture underlying CT biosynthesis in wheat grain remains unclear.Here,we studied the deposition and genetic regulation of CT in wheat grains,and found that CT deposited specifically in the testa layer of red-grained wheat as catechin-and epicatechin-formed polymers.Genome-wide association study identified 22 genetic loci affecting CT content,one of which,TaTAN,a single dominant gene controlling CT presence,was mapped to chromosome 3A in a segregation population.Further pan-genome analysis,transcriptome profiling and ethyl methanesulfonate induced mutants sequencing revealed a R2R3-MYB transcription factor,TaMYB10-3A,as the causal gene.Three loss-of-function alleles in TaMYB10-3A caused by large fragment inversion-deletion and insertion were identified which abolish both CT deposition and red pigmentation,demonstrating the pleiotropic effect of TaMYB10-3A on CT presence and grain color.TaMYB10-3A directly trans-activates core flavonoid genes such as chalcone synthase and dihydroflavonol 4-reductase to initiate CT biosynthesis.Our investigation provides a comprehensive understanding of CT presence in wheat grains and lays a solid foundation for manipulating CT metabolites to improve wheat grain end-use quality and nutrition values in wheat.
