Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism re...Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism remains poorly understood.In this study,ACR treatment was found to increase the levels of 8-hydroxy deoxyguanine(8-OHdG)and phosphorated histone H_(2)AX(γH_(2)AX),two DNA damage markers,thereby resulting in cell cycle arrest in the G2/M phase;whereas both A_(1) and D-A_(1) could prevent the phosphorylation of ataxia telangiectasia mutated(ATM)and checkpoint kinase 2(Chk2),and then regulate the expression of G2/M phase-related proteins,finally maintaining normal cell cycle progression.Moreover,A_(1) and D-A_(1) could increase the B cell lymphoma 2(Bcl-2)/Bcl2-associated X(Bax)ratio and decrease the expression of cleaved caspase-3 and cleaved caspase-9 proteins to alleviate ACR-induced cell apoptosis,which might be related to the inhibition of the mitogen-activated protein kinase(MAPK)pathway.More importantly,A_(1) showed no remarkable variation in inhibitory effect before and after digestion,indicating that it can endure gastrointestinal digestion and may be a promising phytochemical to alleviate ACR-induced intestinal cell damage.展开更多
Non-alcoholic fatty liver disease(NAFLD),a chronic liver disorder closely associated with metabolic dysfunction,has become a significant global health challenge.In recent years,procyanidin B1(PB1)has demonstrated pote...Non-alcoholic fatty liver disease(NAFLD),a chronic liver disorder closely associated with metabolic dysfunction,has become a significant global health challenge.In recent years,procyanidin B1(PB1)has demonstrated potential advantages in the prevention and personalized treatment of NAFLD through multi-target and multi-pathway intervention strategies,exerting comprehensive regulatory and synergistic effects.However,its precise therapeutic mechanisms remain unclear.This study employs network pharmacology to identify key targets and potential pathways involved in the treatment of NAFLD with PB1.Additionally,molecular docking analysis is conducted to validate the reliability of these targets.The findings provide a theoretical foundation for the development of PB1 as a potential therapeutic agent for NAFLD,offering insights for future experimental and clinical research.展开更多
Objective To study the co-effect of procyanidins extracted from the lotus seed pod （LSPC） and bilobalide （BIL） on ameliorating scopolamine-induced learning and memory impairment in young mice. Methods Fifty male K...Objective To study the co-effect of procyanidins extracted from the lotus seed pod （LSPC） and bilobalide （BIL） on ameliorating scopolamine-induced learning and memory impairment in young mice. Methods Fifty male Kunming mice with similar learning and memory capabilities were selected by Morris water maze test and were randomized into 5 groups （n=10 in each group）： control group, scopolamine group, L-（LSPC＋BIL） group （50 mg/kg LSPC＋10 mg/kg BIL）, M-（LSPC＋BIL） group （100 mg/kg LSPC＋20 mg/kg BIL）, H-（LSPC＋BIL） group （150 mg/kg LSPC＋30 mg/kg BIL）. Scopolamine model with impaired learning and memory was established by scopolamine treatment （1 mg/kg）, and after 10 min mice were tested. In L-, M-, and H- （LSPC＋BIL） groups, mice were treated with LSPC and BIL ig. for 30 days, while mice in the other 2 groups were treated with normal saline ig. instead. After the 30-day＇s treatment, the co-effect of LSPC and BIL on learning and memory was tested by Morris water maze and the step-down avoidance tests. Results The memory impairment caused by scopolamine in young mice could be ameliorated by co-treatment of LSPC and BIL, as indicated by significantly shorter escape latency and swimming distance in the Morris water maze test, when compared with those in the scopolamine group. In the step-down avoidance test, mice in all the 3 dose groups showed significantly smaller number of errors and longer latency than mice in the scopolamine group did. Conclusion Co-treatment of LSPE and BIL can ameliorate scopolamine-induced learning and memory impairment in young mice.展开更多
BACKGROUND Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity,but the mechanisms underlying these effects are unclear.AIM To investigate the effects of procyanidin B2(PB2)on non-alco...BACKGROUND Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity,but the mechanisms underlying these effects are unclear.AIM To investigate the effects of procyanidin B2(PB2)on non-alcoholic fatty liver disease and to explore the possible mechanism.METHODS Thirty male New Zealand white rabbits were randomized into three groups.All of them were fed either a high-fat-cholesterol diet(HCD)or chow diet.HCD-fed rabbits were treated with vehicle or PB2 daily for 12 wk.Body weight and food intake were evaluated once a week.Serum biomarkers,such as total cholesterols,triglycerides,and aspartate transaminase,were detected.All rabbits were sacrificed and histological parameters of liver were assessed by hematoxylin and eosin-stained sections.Moreover,several lipogenic genes and gut microbiota(by 16S rRNA sequencing)were investigated to explore the possible mechanism.RESULTS The HCD group had higher body weight,liver index,serum lipid profile,insulin resistance,serum glucose,and hepatic steatosis compared to the CHOW group.PB2 treatment prevented HCD-induced increases in body weight and hypertriglyceridemia in association with triglyceride accumulation in the liver.PB2 also ameliorated low-grade inflammation,which was reflected by serum lipopolysaccharides and improved insulin resistance.In rabbit liver,PB2 prevented the upregulation of steroid response element binding protein 1c and fatty acid synthase and the downregulation of carnitine palmitoyltransferase,compared to the HCD group.Moreover,HCD led to a decrease of Bacteroidetes in gut microbiota.PB2 significantly improved the proportions of Bacteroidetes at the phylum level and Akkermansia at the genus level.CONCLUSION Our results indicate the possible mechanism of PB2 to improve HCD-induced features of metabolic syndrome and provide a new dietary supplement.展开更多
Objective Oxidative stress （OS） plays a crucial role in ischemic stroke. Grape seed procyanidin extract （GSPE） was reported to be a critical regulator of OS. We hypothesized that GSPE might also be protective in...Objective Oxidative stress （OS） plays a crucial role in ischemic stroke. Grape seed procyanidin extract （GSPE） was reported to be a critical regulator of OS. We hypothesized that GSPE might also be protective in ischemia-reperfusion brain injury. This study aimed to explore whether GSPE administration can protect mice from ischemia-reperfusion brain injury. Methods Transient middle cerebral artery occlusion （MCAO） was conducted followed by reperfusion for 24 hours to make ischemia-reperfusion brain injury in mice that received GSPE （MCAOG, n=60） or normal saline （MCAONS, n=60）. Sham-operated mice （GSPE group and normal saline group） were set as controls. The neurological severity score （NSS） was used to evaluate neural function impairment 1 hour, 24 hour, 3 days and 7 days after MCAO. Mice underwent brain T2WI imaging with a 3T animal MRI scanner 24 hours after reperfusion, and the stroke volume of brains were calculated according to abnormal signal intensity. Immunohistopathological analysis of brain tissues at 24 h after reperfusion was performed for neuronal nuclear antigen （NeuN）, CD34, Bcl-2, and Bax. Glutathione peroxidation （GSH-Px） activity and the level of malonaldehyde （MDA） of brain tissue were also examined. The above indexes were compared among the groups statistically.Results Significant functional improvement was observed 24 hours after MCAO in MCAOG group compared to MCAONS group （P〈0.05）. MCAOG group had smaller cerebral stroke volume （22.46 ± 11.45 mm3 vs. 47.84±9.06 mm3, P〈0.05） than MCAONS group 24 hours after MCAO. More mature NeuN-immunoreactive neurons and more CD34-positive cells in peri-infarct zones were observed in brain tissue of MCAOG mice 24 h after MCAO than that of MCAONS mice （both P〈0.05）. MCAONS mice had significantly higher number of Bax-positive cells in brain tissue than MCAOG （P〈0.05）. The mean MDA level was significantly lower （P〈0.05） and the GSH-Px activity was significantly higher （P〈0.05） in brains of MCAOG mice compared to those of MCAONS mice. Conclusion GSPE administration protects mice from ischemia-reperfusion brain injury through attenuating oxidative stress and apoptosis, promoting angiogenesis, and activating antioxidant enzyme GSH-Px. GSPE may represent a new therapeutical direction for the treatment of ischemia-reperfusion brain injury.展开更多
Objective： Procyanidins （PC） are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular ext...Objective： Procyanidins （PC） are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix （ECM） and preventing proteolysis by matrix metalloproteinases （MMPs）. Methods： Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma. Results： PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC （0.75-100 μg/mL） did not inhibit vascular and tumor cells proliferation. PC injections （30 mg PC/kg bodyweight） in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs. Conclusion： The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.展开更多
AIM： To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS： Normal rat hepatocytes as well as cells damaged by ethanol or ca...AIM： To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS： Normal rat hepatocytes as well as cells damaged by ethanol or carbon tetrachloride were incubated with different doses of grape procyanidins for 24 h. Cell proliferation, apoptosis and TNFα mRNA expression were subsequently determined using MTT assay, cell death ELISA and in situ hybridization. RESULTS： Proliferative levels of the control cells from ethanol and CCh injury groups significantly decreased while apoptosis and TNFα mRNA expression significantly increased compared to the normal control and grape procyanidins co-treatment groups （0.455 ± 0.051 vs 0.318 ±0.045, P 〈 0.05）. In comparison with the normal control, 50 and 100 mg/L grape procyanidins significantly stimulated cell growth, with a better effect observed with 100 mg/L grape procyanidins. CONCLUSION： Grape procyanidins inhibit the hepatocyte damage induced by ethanol and carbon tetrachloride, and stimulate normal hepatocyte proliferation.展开更多
Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 s...Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 subcutaneously injection,once daily treatment for 2 successive days.Results In comparison with HgCl 2 group,markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to （18.45±11.63） mmol/L and （15.93±9.36） mmol/L,（4.54±0.78） g/（g Cr） and （4.40±1.12） g/（g Cr）.N‐acetyl‐beta‐D‐glucosaminidase,lactate dehydrogenase,alkaline phosphatase in urine were depressed to （125.49±11.68） U/（g Cr）,（103.73±21.79） U/（g Cr）,（101.99±12.28） U/（g Cr）,and （113.19±23.74） U/（g Cr）,（71.14±21.80） U/（g Cr）,（73.64±21.51） U/（g Cr） in procyanidins and lycopene groups.Indicators of oxidative stress,for example,Glutathion was reduced to （45.58±9.89） μmol/（g pro） and （45.33±5.90） μmol/（g pro）,and antioxidant enzymes such as superoxide dismutase,glutathione‐peroxidase were enhanced to （43.07±10.97） U/（mg pro） and （39.94±6.04） U/（mg pro）,（83.85±18.48） U/（mg pro）,and （85.62±12.68） U/（mg pro）.Malondialdehyde was lowered to （0.95±0.12） （μmol/g pro） and （1.03±0.12） μmol/（g pro） in procyanidins and lycopene groups.ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively.Pathological changes were much better as well.Conclusion Procyanidins and Lycopene play some protective role against mercury kidney damage.展开更多
Objective This study aimed to explore the protective effect of procyanidin B2(PCB2)on acute liver injury induced by aflatoxin B1(AFB1)in rats.Methods Forty Sprague Dawley rats were randomly divided into control,AFB1,A...Objective This study aimed to explore the protective effect of procyanidin B2(PCB2)on acute liver injury induced by aflatoxin B1(AFB1)in rats.Methods Forty Sprague Dawley rats were randomly divided into control,AFB1,AFB1+PCB2,and PCB2 groups.The latter two groups were administrated PCB2 intragastrically(30 mg/kg body weight)for 7 d,whereas the control and AFB1 groups were given the same dose of double distilled water intragastrically.On the sixth day of treatment,the AFB1 and AFB1+PCB2 groups were intraperitoneally injected with AFB1(2 mg/kg).The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide(DMSO).On the eighth day,all rats were euthanized:serum and liver tissue were isolated for further examination.Hepatic histological features were assessed by hematoxylin and eosin-stained sections.Weight,organ coefficient(liver,spleen,and kidney),liver function(serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total bilirubin,and direct bilirubin),oxidative index(catalase,glutathione,superoxide dismutase,malondialdehyde,and 8-hydroxy-2′-deoxyguanosine),inflammation factor[hepatic interleukin-6(IL-6)m RNA expression and serum IL-6],and bcl-2/bax ratio were measured.Results AFB1 significantly caused hepatic histopathological damage,abnormal liver function,oxidative stress,inflammation,and bcl-2/bax ratio reduction compared with DMSO-treated controls.Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB1.Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB1.展开更多
A novel dimeric procyanidin glucoside,catechin 3-O-acetate-（4 α→8）-catechin 3-O-acetate-3＇-O- β-D-glucopyranoside（1）, along with five flavonoids and one lignan were isolated from the aerial parts of Polygonum ...A novel dimeric procyanidin glucoside,catechin 3-O-acetate-（4 α→8）-catechin 3-O-acetate-3＇-O- β-D-glucopyranoside（1）, along with five flavonoids and one lignan were isolated from the aerial parts of Polygonum aviculare.Their structures were elucidated by spectroscopic analyses including 1D,2D NMR,MS and CD methods.展开更多
Objective: To investigate the anti-tumor effect of procyanidin (WeiMaiNing, WMN) on a murine Lewis lung carcinoma cell line (3LL) and the influence on the cell cycle. Methods: The inhibitory rate of 3LL growth was det...Objective: To investigate the anti-tumor effect of procyanidin (WeiMaiNing, WMN) on a murine Lewis lung carcinoma cell line (3LL) and the influence on the cell cycle. Methods: The inhibitory rate of 3LL growth was detected in the model of murine Lewis lung carcinoma. The effect of the drug on 3LL cell cycle and the influence of the drug on the expression of cyclin D1 protein were investigated by flow cytometry, immunohistochemical staining. Results: The inhibitory rates of WMN in 3LL were 19.14%, 33.59% and 51.56% respectively at dosages 100 mg穔g-1穌-1, 150 mg穔g-1穌-1 and 250 mg穔g-1穌-1. The inhibitory effect was in a dose-dependent manner. We found WMN significantly increased (P<0.01) the number of 3LL cells in G0-G1 phase (35.97% vs. 27.2% at 150 mg穔g-1穌-1 WMN; 40.10% vs. 27.2% at 250 mg穔g-1穌-1 WMN) and decreased the expression of cyclin D1, PCNA protein. Conclusion: WeiMaiNing inhibits the growth of 3LL cells in vivo by decreasing the expression of PCNA and cyclin D1, blocking the cells in G0-G1 phase and preventing the cells transition from G1 to S phase while DNA is replicated.展开更多
BACKGROUND： Recently, grape seed procyanidin （GSP） has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis. OBJECTIVE： To study the ef...BACKGROUND： Recently, grape seed procyanidin （GSP） has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis. OBJECTIVE： To study the effects of GSP on nerve growth factor （NGF） expression and neurological function following cerebral ischemia/reperfusion injury in rats. DESIGN： Randomized controlled study based on SD rats. SETTING： Weifang Municipal People＇s Hospital. MATERIALS： Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company （batch number： 20060107）. Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS： The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP （40 mg/kg） group, or low-dose GSP （10 mg/kg） group （n = 12 per group）. Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection （2 mL/kg i.p.） once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP （20 or 5 mg/mL i.p., respectively, 2 mL/kg） with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES： NGF expression in the ischemic penumbra of the temporal cortex was detected by immunohistochemistry, and positive cells counted by light microscopy （×400）. The positive cell rate was calculated by [（positive cells/total cells）× 100%]. Neurological function was scored after 2-hour ischemia/48-hour reperfusion. Higher scores reflected more severe neurofunctional defect. RESULTS： The positive rate of NGF expression in all groups receiving ischemia/reperfusion was significantly higher than that in the sham operation group （q=3.87, P 〈 0.05）. The positive rate of NGF expression in the high-dose and low-dose GSP groups were significantly higher than that in the model group （q=4.12, P 〈 0.05）, and were greater in the high-dose compared to low-dose GSP groups （q=4.22, P 〈 0.05）. Neurological function scores in the high-dose and low-dose GSP groups were significantly lower than that in the ischemia/reperfusion model group （q=3.92, P 〈 0.05）. Neurological function score in the high-dose GSP group was significantly less than that in the low-dose GSP group （q=4.02, P 〈 0.05）. CONCLUSION： GSP may up-regulate brain-derived NGF expression in a dose-dependent manner following cerebral ischemia/reperfusion injury in order to improve neurological function and protect the brain.展开更多
Background:Irreversible cryodamage caused by oocyte vitrification limited its wild application in female fertility preservation.Antioxidants were always used to antagonist the oxidative stress caused by vitrification....Background:Irreversible cryodamage caused by oocyte vitrification limited its wild application in female fertility preservation.Antioxidants were always used to antagonist the oxidative stress caused by vitrification.However,the comprehensive mechanism underlying the protective role of antioxidants has not been studied.Procyanidin B2(PCB2)is a potent natural antioxidant and its functions in response to vitrification are still unknown.In this study,the effects of PCB2 on vitrified-thawed oocytes and subsequent embryo development were explored,and the mechanisms underlying the protective role of PCB2 were systematically elucidated.Results:Vitrification induced a marked decline in oocyte quality,while PCB2 could improve oocyte viability and further development after parthenogenetic activation.A subsequent study indicated that PCB2 effectively attenuated vitrification-induced oxidative stress,rescued mitochondrial dysfunction,and improved cell viability.Moreover,PCB2 also acts as a cortical tension regulator apart from strong antioxidant properties.Increased cortical tension caused by PCB2 would maintain normal spindle morphology and promote migration,ensure correct meiosis progression and finally reduce the aneuploidy rate in vitrified oocytes.Further study reveals that ATP biosynthesis plays a crucial role in cortical tension regulation,and PCB2 effectively increased the cortical tension through the electron transfer chain pathway.Additionally,PCB2 would elevate the cortical tension in embryo cells at morula and blastocyst stages and further improve blastocyst quality.What's more,targeted metabolomics shows that PCB2 has a beneficial effect on blastocyst formation by mediating saccharides and amino acids metabolism.Conclusions:Antioxidant PCB2 exhibits multi-protective roles in response to vitrification stimuli through mitochondria-mediated cortical tension regulation.展开更多
Inflammation plays an important role in the occurrence and development of many inflammatory diseases.The purpose of this study was to evaluate the anti-inflammatory effect and metabolic behavior of the dual targeting ...Inflammation plays an important role in the occurrence and development of many inflammatory diseases.The purpose of this study was to evaluate the anti-inflammatory effect and metabolic behavior of the dual targeting procyanidins(PC)nanoparticles on lipopolysaccharide(LPS)-stimulated inflammatory macrophages by metabolomics method.The double-targeting PC nanoparticles could specifi cally target both the CD44 receptor and mitochondria,while the single targeting PC-loaded nanoparticles that could target the CD44 receptor on the surface of macrophages.The double-targeting PC nanoparticles had better inhibitory effect than single-targeting PC nanoparticles on the leakage of lactate dehydrogenase and reactive oxygen species overexpression induced by LPS.Amino acid metabolism,energy metabolism and purine metabolism were disordered in LPS-treated group,and metabolic pathway analysis indicated that the double-targeting PC nanoparticles reversed some of LPS impacts.The changes of these potential biomarkers and their corresponding pathways are helpful to further understand the mechanism of PC nanoparticles in alleviating inflammation,and promote their application in nutrition intervention.展开更多
The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract （GSPE） relieves arsenic trioxide （As2O3）-induced renal inflammatory injury. Therefore, male Kunming mic...The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract （GSPE） relieves arsenic trioxide （As2O3）-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor （NF）-KB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-KB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.展开更多
Our previous study has revealed that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A,)can alleviate acrylamide(ACR)-induced intestine cell damage.However,the underlying mechanism remains unknown.In thi...Our previous study has revealed that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A,)can alleviate acrylamide(ACR)-induced intestine cell damage.However,the underlying mechanism remains unknown.In this study,we elucidated the molecular mechanism for and D-A_(1) to alleviate ACR-stimulated IPEC-J2 cell damage.ACR slightly activated nuclear factor erythroid 2-related factor 2(Nrf2)signaling and its target genes,but this activation could not reduce intestine cell damage.A_(1) and D-A_(1) could alleviate ACR-induced cell damage,but the effect was abrogated in cells transiently transfected with Nrf2 small interfering RNA(siRNA).Further investigation confirmed that A_(1) and D-A_(1) interacted with Ketch-like ECH-associated protein 1(Keapl),which boosted the stabilization of Nrf2,subsequently promoted the translocation of Nrf2 into the nucleus,and further increased the expression of antioxidant proteins,thereby inhibiting glutathione(GSH)consumption,maintaining redox balance and eventually alleviating ACR-induced cell damage.Importantly,there was no difference between A_(1) and D-A_(1) treated groups,indicating that A_(1) can tolerate gastrointestinal digestion and may be a potential compound to limit the toxicity of ACR.展开更多
This study was conducted to investigate the effects of cellulase dosage, enzymolysis time, pH and enzymolysis temperature on procyanidin extraction rate by single factor experiment, with tartary buckwheat shell as an ...This study was conducted to investigate the effects of cellulase dosage, enzymolysis time, pH and enzymolysis temperature on procyanidin extraction rate by single factor experiment, with tartary buckwheat shell as an experimental material.Main process parameters were optimized to obtain a regression model by response surface methodology. The results of variance analysis indicated that the regression model reflected the relationship between buckwheat shell procyanidin extraction rate with enzyme dosage, enzymolysis time, pH and enzymolysis temperature; and the optimal process parameters were enzyme dosage of 6.5 mg/g, enzymolysis time of 1.5 h, pH at 4.7 and enzymolysis temperature at 46 ℃. Three parallel experiments were conducted under these process parameters. In practice, the highest procyanidin extraction rate was 6.78 g/100 g. The relative error between the predicted value of regression model and the actual value was 1.3%. The regression equation fitted the real situation better.展开更多
[Objectives] To study the optimal conditions for extracting procyanidins fromLycium ruthenicum Murr. with sub-critical fluid R134 a( 1,1,1,2-tetrafluoroethane) in 1 L extraction kettle. [Methods]Taking the extraction ...[Objectives] To study the optimal conditions for extracting procyanidins fromLycium ruthenicum Murr. with sub-critical fluid R134 a( 1,1,1,2-tetrafluoroethane) in 1 L extraction kettle. [Methods]Taking the extraction rate of procyanidins as an indicator,the influence of pressure,temperature,and extraction time on extraction rate of procyanidins fromL. Ruthenicum Murr. was studied by single factor experimental methods and orthogonal array design. [Results]The order of factors affecting extraction rate of procyanidins was extraction temperature > extraction pressure > extraction time. The optimum extraction conditions were as follows: the extraction rate of procyanidins fromL. ruthenicum Murr. was the highest with extraction pressure of 1. 2 MPa,extraction temperature of 50℃ and extraction time of 90 min. The content of procyanidins in L. ruthenicum Murr. from different producing areas was determined by vanillin-HCl method under the optimal conditions. [Conclusions] The method has the advantages of easy operation,good selectivity,low extraction temperature and high extraction efficiency,which is suitable for extraction of procyanidins in L. ruthenicum Murr.展开更多
The number and quality of sperm are decreased due to bisphenol A(BPA) exposure, an endocrine-disrupting chemical on the male reproductive system, especially in advanced paternal age(APA). Procyanidin C-1(PCY-1), an an...The number and quality of sperm are decreased due to bisphenol A(BPA) exposure, an endocrine-disrupting chemical on the male reproductive system, especially in advanced paternal age(APA). Procyanidin C-1(PCY-1), an antioxidant from grape seed(Vitis vinifera L.), has demonstrated anti-viral, anti-melanogenic and immunostimulatory effects. Therefore, this study aims to determine the effects of PCY-1 intervention on sperm parameters, testis morphological changes, serum testosterone, oestradiol, and luteinizing hormone(LH) concentrations and the expression of apoptotic(Bax and Bcl-2) and mitochondria-related(Mfn1 and Opa1) genes in BPA-exposed aged mice. Results revealed that PCY-1 intervention improves aged male fertility in BPA-exposed conditions by decreasing abnormal sperms percentage and increasing spermatogenic cell diameter and epithelial height. PCY-1 also decreased oestradiol, and increased LH and testosterone levels. The gene expression of Bax was significantly down-regulated by PCY-1 intervention. In contrast, Bcl-2 was substantially up-regulated. Expression of Mfn1 and Opa1 genes were also significantly up-regulated in the PCY intervention group. Hence, it is demonstrated that PCY-1 was able to mitigate the adverse effects of BPA on reproductive parameters of aged mice. Collectively, we postulated that PCY-1 has a potential role in protecting the ageing male reproductive system against the damaging impacts of BPA.展开更多
基金supported by the project from National Natural Science Foundation of China(31671962)Excellent Youth Foundation of Education Department of Hunan Province(23B0229)Fundamental Research Funds for the Central Universities(2662019PY034).
文摘Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism remains poorly understood.In this study,ACR treatment was found to increase the levels of 8-hydroxy deoxyguanine(8-OHdG)and phosphorated histone H_(2)AX(γH_(2)AX),two DNA damage markers,thereby resulting in cell cycle arrest in the G2/M phase;whereas both A_(1) and D-A_(1) could prevent the phosphorylation of ataxia telangiectasia mutated(ATM)and checkpoint kinase 2(Chk2),and then regulate the expression of G2/M phase-related proteins,finally maintaining normal cell cycle progression.Moreover,A_(1) and D-A_(1) could increase the B cell lymphoma 2(Bcl-2)/Bcl2-associated X(Bax)ratio and decrease the expression of cleaved caspase-3 and cleaved caspase-9 proteins to alleviate ACR-induced cell apoptosis,which might be related to the inhibition of the mitogen-activated protein kinase(MAPK)pathway.More importantly,A_(1) showed no remarkable variation in inhibitory effect before and after digestion,indicating that it can endure gastrointestinal digestion and may be a promising phytochemical to alleviate ACR-induced intestinal cell damage.
基金funded by Livelihood Plan Project of Department of Science and Technology of Liaoning Province(2023-MSLH-090)Department of Education of Liaoning Province(LJ212410163061).
文摘Non-alcoholic fatty liver disease(NAFLD),a chronic liver disorder closely associated with metabolic dysfunction,has become a significant global health challenge.In recent years,procyanidin B1(PB1)has demonstrated potential advantages in the prevention and personalized treatment of NAFLD through multi-target and multi-pathway intervention strategies,exerting comprehensive regulatory and synergistic effects.However,its precise therapeutic mechanisms remain unclear.This study employs network pharmacology to identify key targets and potential pathways involved in the treatment of NAFLD with PB1.Additionally,molecular docking analysis is conducted to validate the reliability of these targets.The findings provide a theoretical foundation for the development of PB1 as a potential therapeutic agent for NAFLD,offering insights for future experimental and clinical research.
基金supported by the National Key Technology R&D Program of China (No.2006BAD27B08 and 2006BAD27B09-4)
文摘Objective To study the co-effect of procyanidins extracted from the lotus seed pod （LSPC） and bilobalide （BIL） on ameliorating scopolamine-induced learning and memory impairment in young mice. Methods Fifty male Kunming mice with similar learning and memory capabilities were selected by Morris water maze test and were randomized into 5 groups （n=10 in each group）： control group, scopolamine group, L-（LSPC＋BIL） group （50 mg/kg LSPC＋10 mg/kg BIL）, M-（LSPC＋BIL） group （100 mg/kg LSPC＋20 mg/kg BIL）, H-（LSPC＋BIL） group （150 mg/kg LSPC＋30 mg/kg BIL）. Scopolamine model with impaired learning and memory was established by scopolamine treatment （1 mg/kg）, and after 10 min mice were tested. In L-, M-, and H- （LSPC＋BIL） groups, mice were treated with LSPC and BIL ig. for 30 days, while mice in the other 2 groups were treated with normal saline ig. instead. After the 30-day＇s treatment, the co-effect of LSPC and BIL on learning and memory was tested by Morris water maze and the step-down avoidance tests. Results The memory impairment caused by scopolamine in young mice could be ameliorated by co-treatment of LSPC and BIL, as indicated by significantly shorter escape latency and swimming distance in the Morris water maze test, when compared with those in the scopolamine group. In the step-down avoidance test, mice in all the 3 dose groups showed significantly smaller number of errors and longer latency than mice in the scopolamine group did. Conclusion Co-treatment of LSPE and BIL can ameliorate scopolamine-induced learning and memory impairment in young mice.
基金Supported by Major Projects of Science and Technology in Jiangxi,No.20161ACG70012
文摘BACKGROUND Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity,but the mechanisms underlying these effects are unclear.AIM To investigate the effects of procyanidin B2(PB2)on non-alcoholic fatty liver disease and to explore the possible mechanism.METHODS Thirty male New Zealand white rabbits were randomized into three groups.All of them were fed either a high-fat-cholesterol diet(HCD)or chow diet.HCD-fed rabbits were treated with vehicle or PB2 daily for 12 wk.Body weight and food intake were evaluated once a week.Serum biomarkers,such as total cholesterols,triglycerides,and aspartate transaminase,were detected.All rabbits were sacrificed and histological parameters of liver were assessed by hematoxylin and eosin-stained sections.Moreover,several lipogenic genes and gut microbiota(by 16S rRNA sequencing)were investigated to explore the possible mechanism.RESULTS The HCD group had higher body weight,liver index,serum lipid profile,insulin resistance,serum glucose,and hepatic steatosis compared to the CHOW group.PB2 treatment prevented HCD-induced increases in body weight and hypertriglyceridemia in association with triglyceride accumulation in the liver.PB2 also ameliorated low-grade inflammation,which was reflected by serum lipopolysaccharides and improved insulin resistance.In rabbit liver,PB2 prevented the upregulation of steroid response element binding protein 1c and fatty acid synthase and the downregulation of carnitine palmitoyltransferase,compared to the HCD group.Moreover,HCD led to a decrease of Bacteroidetes in gut microbiota.PB2 significantly improved the proportions of Bacteroidetes at the phylum level and Akkermansia at the genus level.CONCLUSION Our results indicate the possible mechanism of PB2 to improve HCD-induced features of metabolic syndrome and provide a new dietary supplement.
基金Supported by Peking Union Medical College Youth Research Funds(3332016010)Peking Union Medical College Graduate Studen Innovation Fund(2015-1002-02-09)
文摘Objective Oxidative stress （OS） plays a crucial role in ischemic stroke. Grape seed procyanidin extract （GSPE） was reported to be a critical regulator of OS. We hypothesized that GSPE might also be protective in ischemia-reperfusion brain injury. This study aimed to explore whether GSPE administration can protect mice from ischemia-reperfusion brain injury. Methods Transient middle cerebral artery occlusion （MCAO） was conducted followed by reperfusion for 24 hours to make ischemia-reperfusion brain injury in mice that received GSPE （MCAOG, n=60） or normal saline （MCAONS, n=60）. Sham-operated mice （GSPE group and normal saline group） were set as controls. The neurological severity score （NSS） was used to evaluate neural function impairment 1 hour, 24 hour, 3 days and 7 days after MCAO. Mice underwent brain T2WI imaging with a 3T animal MRI scanner 24 hours after reperfusion, and the stroke volume of brains were calculated according to abnormal signal intensity. Immunohistopathological analysis of brain tissues at 24 h after reperfusion was performed for neuronal nuclear antigen （NeuN）, CD34, Bcl-2, and Bax. Glutathione peroxidation （GSH-Px） activity and the level of malonaldehyde （MDA） of brain tissue were also examined. The above indexes were compared among the groups statistically.Results Significant functional improvement was observed 24 hours after MCAO in MCAOG group compared to MCAONS group （P〈0.05）. MCAOG group had smaller cerebral stroke volume （22.46 ± 11.45 mm3 vs. 47.84±9.06 mm3, P〈0.05） than MCAONS group 24 hours after MCAO. More mature NeuN-immunoreactive neurons and more CD34-positive cells in peri-infarct zones were observed in brain tissue of MCAOG mice 24 h after MCAO than that of MCAONS mice （both P〈0.05）. MCAONS mice had significantly higher number of Bax-positive cells in brain tissue than MCAOG （P〈0.05）. The mean MDA level was significantly lower （P〈0.05） and the GSH-Px activity was significantly higher （P〈0.05） in brains of MCAOG mice compared to those of MCAONS mice. Conclusion GSPE administration protects mice from ischemia-reperfusion brain injury through attenuating oxidative stress and apoptosis, promoting angiogenesis, and activating antioxidant enzyme GSH-Px. GSPE may represent a new therapeutical direction for the treatment of ischemia-reperfusion brain injury.
基金supported by National "863" High-tech R & D Program of China(No. 2007AA03Z317)the National Natural Science Foundation of China(No.31070870)+1 种基金"973" Program of the Ministry of Science and Technology of China (No.2007CB714502, 2007CB936000)Shanghai Municipal Committee of Science and Techology (No. 08520740300, 1052nm06100 and 09JC1416500)
文摘Objective： Procyanidins （PC） are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix （ECM） and preventing proteolysis by matrix metalloproteinases （MMPs）. Methods： Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma. Results： PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC （0.75-100 μg/mL） did not inhibit vascular and tumor cells proliferation. PC injections （30 mg PC/kg bodyweight） in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs. Conclusion： The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.
文摘AIM： To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS： Normal rat hepatocytes as well as cells damaged by ethanol or carbon tetrachloride were incubated with different doses of grape procyanidins for 24 h. Cell proliferation, apoptosis and TNFα mRNA expression were subsequently determined using MTT assay, cell death ELISA and in situ hybridization. RESULTS： Proliferative levels of the control cells from ethanol and CCh injury groups significantly decreased while apoptosis and TNFα mRNA expression significantly increased compared to the normal control and grape procyanidins co-treatment groups （0.455 ± 0.051 vs 0.318 ±0.045, P 〈 0.05）. In comparison with the normal control, 50 and 100 mg/L grape procyanidins significantly stimulated cell growth, with a better effect observed with 100 mg/L grape procyanidins. CONCLUSION： Grape procyanidins inhibit the hepatocyte damage induced by ethanol and carbon tetrachloride, and stimulate normal hepatocyte proliferation.
文摘Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 subcutaneously injection,once daily treatment for 2 successive days.Results In comparison with HgCl 2 group,markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to （18.45±11.63） mmol/L and （15.93±9.36） mmol/L,（4.54±0.78） g/（g Cr） and （4.40±1.12） g/（g Cr）.N‐acetyl‐beta‐D‐glucosaminidase,lactate dehydrogenase,alkaline phosphatase in urine were depressed to （125.49±11.68） U/（g Cr）,（103.73±21.79） U/（g Cr）,（101.99±12.28） U/（g Cr）,and （113.19±23.74） U/（g Cr）,（71.14±21.80） U/（g Cr）,（73.64±21.51） U/（g Cr） in procyanidins and lycopene groups.Indicators of oxidative stress,for example,Glutathion was reduced to （45.58±9.89） μmol/（g pro） and （45.33±5.90） μmol/（g pro）,and antioxidant enzymes such as superoxide dismutase,glutathione‐peroxidase were enhanced to （43.07±10.97） U/（mg pro） and （39.94±6.04） U/（mg pro）,（83.85±18.48） U/（mg pro）,and （85.62±12.68） U/（mg pro）.Malondialdehyde was lowered to （0.95±0.12） （μmol/g pro） and （1.03±0.12） μmol/（g pro） in procyanidins and lycopene groups.ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively.Pathological changes were much better as well.Conclusion Procyanidins and Lycopene play some protective role against mercury kidney damage.
基金financially supported by National Natural Science Foundation of China[No.31360383]。
文摘Objective This study aimed to explore the protective effect of procyanidin B2(PCB2)on acute liver injury induced by aflatoxin B1(AFB1)in rats.Methods Forty Sprague Dawley rats were randomly divided into control,AFB1,AFB1+PCB2,and PCB2 groups.The latter two groups were administrated PCB2 intragastrically(30 mg/kg body weight)for 7 d,whereas the control and AFB1 groups were given the same dose of double distilled water intragastrically.On the sixth day of treatment,the AFB1 and AFB1+PCB2 groups were intraperitoneally injected with AFB1(2 mg/kg).The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide(DMSO).On the eighth day,all rats were euthanized:serum and liver tissue were isolated for further examination.Hepatic histological features were assessed by hematoxylin and eosin-stained sections.Weight,organ coefficient(liver,spleen,and kidney),liver function(serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total bilirubin,and direct bilirubin),oxidative index(catalase,glutathione,superoxide dismutase,malondialdehyde,and 8-hydroxy-2′-deoxyguanosine),inflammation factor[hepatic interleukin-6(IL-6)m RNA expression and serum IL-6],and bcl-2/bax ratio were measured.Results AFB1 significantly caused hepatic histopathological damage,abnormal liver function,oxidative stress,inflammation,and bcl-2/bax ratio reduction compared with DMSO-treated controls.Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB1.Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB1.
基金grants from the National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(No.2009ZX09301-001)the National Natural Sciences Foundation of China(No.30901851)
文摘A novel dimeric procyanidin glucoside,catechin 3-O-acetate-（4 α→8）-catechin 3-O-acetate-3＇-O- β-D-glucopyranoside（1）, along with five flavonoids and one lignan were isolated from the aerial parts of Polygonum aviculare.Their structures were elucidated by spectroscopic analyses including 1D,2D NMR,MS and CD methods.
基金The authors would like to acknowledge Dr.K.R.Mahadik,Principal,Poona College of Pharmacy,Bharati Vidyapeeth Deemed University,Pune,India for providing necessary facilities to carry out the study.Research support was provided by Indus Biotech Private Limited but played no role in collection,analysis and interpretation of data.
文摘Objective: To investigate the anti-tumor effect of procyanidin (WeiMaiNing, WMN) on a murine Lewis lung carcinoma cell line (3LL) and the influence on the cell cycle. Methods: The inhibitory rate of 3LL growth was detected in the model of murine Lewis lung carcinoma. The effect of the drug on 3LL cell cycle and the influence of the drug on the expression of cyclin D1 protein were investigated by flow cytometry, immunohistochemical staining. Results: The inhibitory rates of WMN in 3LL were 19.14%, 33.59% and 51.56% respectively at dosages 100 mg穔g-1穌-1, 150 mg穔g-1穌-1 and 250 mg穔g-1穌-1. The inhibitory effect was in a dose-dependent manner. We found WMN significantly increased (P<0.01) the number of 3LL cells in G0-G1 phase (35.97% vs. 27.2% at 150 mg穔g-1穌-1 WMN; 40.10% vs. 27.2% at 250 mg穔g-1穌-1 WMN) and decreased the expression of cyclin D1, PCNA protein. Conclusion: WeiMaiNing inhibits the growth of 3LL cells in vivo by decreasing the expression of PCNA and cyclin D1, blocking the cells in G0-G1 phase and preventing the cells transition from G1 to S phase while DNA is replicated.
文摘BACKGROUND： Recently, grape seed procyanidin （GSP） has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis. OBJECTIVE： To study the effects of GSP on nerve growth factor （NGF） expression and neurological function following cerebral ischemia/reperfusion injury in rats. DESIGN： Randomized controlled study based on SD rats. SETTING： Weifang Municipal People＇s Hospital. MATERIALS： Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company （batch number： 20060107）. Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS： The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP （40 mg/kg） group, or low-dose GSP （10 mg/kg） group （n = 12 per group）. Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection （2 mL/kg i.p.） once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP （20 or 5 mg/mL i.p., respectively, 2 mL/kg） with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES： NGF expression in the ischemic penumbra of the temporal cortex was detected by immunohistochemistry, and positive cells counted by light microscopy （×400）. The positive cell rate was calculated by [（positive cells/total cells）× 100%]. Neurological function was scored after 2-hour ischemia/48-hour reperfusion. Higher scores reflected more severe neurofunctional defect. RESULTS： The positive rate of NGF expression in all groups receiving ischemia/reperfusion was significantly higher than that in the sham operation group （q=3.87, P 〈 0.05）. The positive rate of NGF expression in the high-dose and low-dose GSP groups were significantly higher than that in the model group （q=4.12, P 〈 0.05）, and were greater in the high-dose compared to low-dose GSP groups （q=4.22, P 〈 0.05）. Neurological function scores in the high-dose and low-dose GSP groups were significantly lower than that in the ischemia/reperfusion model group （q=3.92, P 〈 0.05）. Neurological function score in the high-dose GSP group was significantly less than that in the low-dose GSP group （q=4.02, P 〈 0.05）. CONCLUSION： GSP may up-regulate brain-derived NGF expression in a dose-dependent manner following cerebral ischemia/reperfusion injury in order to improve neurological function and protect the brain.
基金National Key Research and Development Program Topics,Grant/Award Number:2021YFD1200402Chinese Universities Scientific Fund,Grant/Award Number:2021TC061+6 种基金Natural Science Foundation of Hebei province,Grant/Award Number:H2020206254Special Program for Training and Guiding Outstanding Young and Middle-aged Talents,Grant/Award Number:SKLSGIHP2021A01National Natural Science Foundation of China,Grant/Award Number:81901562&31372307Key research and development projects in Hebei province,Grant/Award Number:18226604DProgram of Young and Middle-aged Scientific and technological Innovation Leaders of the Xinjiang Production and Construction Corps,Grant/Award Number:2018CB025Xinghuo program of the First Hospital of Hebei Medical University,Grant/Award Number:XH202005The Central Guidance on Local Science and Technology Development Fund of Hebei Province,Grant/Award Number:226Z7713G。
文摘Background:Irreversible cryodamage caused by oocyte vitrification limited its wild application in female fertility preservation.Antioxidants were always used to antagonist the oxidative stress caused by vitrification.However,the comprehensive mechanism underlying the protective role of antioxidants has not been studied.Procyanidin B2(PCB2)is a potent natural antioxidant and its functions in response to vitrification are still unknown.In this study,the effects of PCB2 on vitrified-thawed oocytes and subsequent embryo development were explored,and the mechanisms underlying the protective role of PCB2 were systematically elucidated.Results:Vitrification induced a marked decline in oocyte quality,while PCB2 could improve oocyte viability and further development after parthenogenetic activation.A subsequent study indicated that PCB2 effectively attenuated vitrification-induced oxidative stress,rescued mitochondrial dysfunction,and improved cell viability.Moreover,PCB2 also acts as a cortical tension regulator apart from strong antioxidant properties.Increased cortical tension caused by PCB2 would maintain normal spindle morphology and promote migration,ensure correct meiosis progression and finally reduce the aneuploidy rate in vitrified oocytes.Further study reveals that ATP biosynthesis plays a crucial role in cortical tension regulation,and PCB2 effectively increased the cortical tension through the electron transfer chain pathway.Additionally,PCB2 would elevate the cortical tension in embryo cells at morula and blastocyst stages and further improve blastocyst quality.What's more,targeted metabolomics shows that PCB2 has a beneficial effect on blastocyst formation by mediating saccharides and amino acids metabolism.Conclusions:Antioxidant PCB2 exhibits multi-protective roles in response to vitrification stimuli through mitochondria-mediated cortical tension regulation.
基金supported by the National Science Fund for Distinguished Young Scholars of China(31925031).
文摘Inflammation plays an important role in the occurrence and development of many inflammatory diseases.The purpose of this study was to evaluate the anti-inflammatory effect and metabolic behavior of the dual targeting procyanidins(PC)nanoparticles on lipopolysaccharide(LPS)-stimulated inflammatory macrophages by metabolomics method.The double-targeting PC nanoparticles could specifi cally target both the CD44 receptor and mitochondria,while the single targeting PC-loaded nanoparticles that could target the CD44 receptor on the surface of macrophages.The double-targeting PC nanoparticles had better inhibitory effect than single-targeting PC nanoparticles on the leakage of lactate dehydrogenase and reactive oxygen species overexpression induced by LPS.Amino acid metabolism,energy metabolism and purine metabolism were disordered in LPS-treated group,and metabolic pathway analysis indicated that the double-targeting PC nanoparticles reversed some of LPS impacts.The changes of these potential biomarkers and their corresponding pathways are helpful to further understand the mechanism of PC nanoparticles in alleviating inflammation,and promote their application in nutrition intervention.
基金supported by the National Natural Science Foundation of China(No.81560517)the Key Areas of Science and Technology Research Project of Xinjiang Production and Construction Corps(No.2014BA039,No.2015AG014)the International Cooperative Project of Shihezi University(No.GJHZ201602)
文摘The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract （GSPE） relieves arsenic trioxide （As2O3）-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor （NF）-KB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-KB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.
基金supported by the project from National Natural Science Foundation of China (31671962)Fundamental Research Funds for the Central Universities (2662019PY034)。
文摘Our previous study has revealed that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A,)can alleviate acrylamide(ACR)-induced intestine cell damage.However,the underlying mechanism remains unknown.In this study,we elucidated the molecular mechanism for and D-A_(1) to alleviate ACR-stimulated IPEC-J2 cell damage.ACR slightly activated nuclear factor erythroid 2-related factor 2(Nrf2)signaling and its target genes,but this activation could not reduce intestine cell damage.A_(1) and D-A_(1) could alleviate ACR-induced cell damage,but the effect was abrogated in cells transiently transfected with Nrf2 small interfering RNA(siRNA).Further investigation confirmed that A_(1) and D-A_(1) interacted with Ketch-like ECH-associated protein 1(Keapl),which boosted the stabilization of Nrf2,subsequently promoted the translocation of Nrf2 into the nucleus,and further increased the expression of antioxidant proteins,thereby inhibiting glutathione(GSH)consumption,maintaining redox balance and eventually alleviating ACR-induced cell damage.Importantly,there was no difference between A_(1) and D-A_(1) treated groups,indicating that A_(1) can tolerate gastrointestinal digestion and may be a potential compound to limit the toxicity of ACR.
基金Supported by Shanxi Soft Science Research Program(2014041020-2)
文摘This study was conducted to investigate the effects of cellulase dosage, enzymolysis time, pH and enzymolysis temperature on procyanidin extraction rate by single factor experiment, with tartary buckwheat shell as an experimental material.Main process parameters were optimized to obtain a regression model by response surface methodology. The results of variance analysis indicated that the regression model reflected the relationship between buckwheat shell procyanidin extraction rate with enzyme dosage, enzymolysis time, pH and enzymolysis temperature; and the optimal process parameters were enzyme dosage of 6.5 mg/g, enzymolysis time of 1.5 h, pH at 4.7 and enzymolysis temperature at 46 ℃. Three parallel experiments were conducted under these process parameters. In practice, the highest procyanidin extraction rate was 6.78 g/100 g. The relative error between the predicted value of regression model and the actual value was 1.3%. The regression equation fitted the real situation better.
基金Supported by 2016 Instrument Functional Development Project of Lanzhou Regional Center of Resources and Environmental Science Instrument,CAS(2018gl11)
文摘[Objectives] To study the optimal conditions for extracting procyanidins fromLycium ruthenicum Murr. with sub-critical fluid R134 a( 1,1,1,2-tetrafluoroethane) in 1 L extraction kettle. [Methods]Taking the extraction rate of procyanidins as an indicator,the influence of pressure,temperature,and extraction time on extraction rate of procyanidins fromL. Ruthenicum Murr. was studied by single factor experimental methods and orthogonal array design. [Results]The order of factors affecting extraction rate of procyanidins was extraction temperature > extraction pressure > extraction time. The optimum extraction conditions were as follows: the extraction rate of procyanidins fromL. ruthenicum Murr. was the highest with extraction pressure of 1. 2 MPa,extraction temperature of 50℃ and extraction time of 90 min. The content of procyanidins in L. ruthenicum Murr. from different producing areas was determined by vanillin-HCl method under the optimal conditions. [Conclusions] The method has the advantages of easy operation,good selectivity,low extraction temperature and high extraction efficiency,which is suitable for extraction of procyanidins in L. ruthenicum Murr.
基金supported financially by Universiti Teknologi MARA grants (600-IRMI/DANA KCM 5/3/LESTARI – 224/2017), (600-IRMI/My RA 5/3/GIP-030/2017)Ministry of Higher Education (MOHE) grant (600-IRMI/RAGS 5/3 - 72/2015)。
文摘The number and quality of sperm are decreased due to bisphenol A(BPA) exposure, an endocrine-disrupting chemical on the male reproductive system, especially in advanced paternal age(APA). Procyanidin C-1(PCY-1), an antioxidant from grape seed(Vitis vinifera L.), has demonstrated anti-viral, anti-melanogenic and immunostimulatory effects. Therefore, this study aims to determine the effects of PCY-1 intervention on sperm parameters, testis morphological changes, serum testosterone, oestradiol, and luteinizing hormone(LH) concentrations and the expression of apoptotic(Bax and Bcl-2) and mitochondria-related(Mfn1 and Opa1) genes in BPA-exposed aged mice. Results revealed that PCY-1 intervention improves aged male fertility in BPA-exposed conditions by decreasing abnormal sperms percentage and increasing spermatogenic cell diameter and epithelial height. PCY-1 also decreased oestradiol, and increased LH and testosterone levels. The gene expression of Bax was significantly down-regulated by PCY-1 intervention. In contrast, Bcl-2 was substantially up-regulated. Expression of Mfn1 and Opa1 genes were also significantly up-regulated in the PCY intervention group. Hence, it is demonstrated that PCY-1 was able to mitigate the adverse effects of BPA on reproductive parameters of aged mice. Collectively, we postulated that PCY-1 has a potential role in protecting the ageing male reproductive system against the damaging impacts of BPA.
