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pterostilbene antagonizes homocysteine-induced oxidative stress,apoptosis and lipid deposition in vascular endothelial cells

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Food Science and Human Wellness 2023年第5期12卷 1683-1692页

作者： Qiao Jiang Li Wang Xu Si Yuanyuan Bian Weijia Zhang Huijun Cui Hailong Gui Ye Zhang Bin Li Dehong Tan College of Food Science Shenyang Agricultural UniversityShenyang 110866China State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China

Hyperhomocysteinemia(HHcy)causes oxidative stress, induces apoptosis, and leads to damage to the vascular endothelium is the starting point of atherosclerosis. pterostilbene(Pte)has been reported to have antioxidant and anti-apoptotic effects under various pathological conditions. The purpose of this study was to explore whether Pte can inhibit the oxidative stress and apoptosis of vascular endothelium induced by homocysteine(Hcy)and to explain the possible mechanism by which it occurs. The results showed that 20 μmol/L Pte significantly reduced the accumulation of reactive oxygen species, malondialdehyde, and lipids in cells induced by Hcy and promoted the activities of superoxide dismutase and catalase. The Hoechst 33342/PI staining assay showed that Pte antagonized Hcy-induced apoptosis. Pte inhibited Hcy-induced Akt dephosphorylation, increased p53, and decreased the Bcl-2/Bax ratio and caspase-9/caspase-3 activation in a dose-dependent manner. LY294002 pretreatment partially reversed the protective effect of Pte by blocking the PI3K/Akt pathway. Moreover, Pte reduced lipid deposition in human umbilical vein endothelial cells(HUVECs). This study proposes that Pte can inhibit Hcy-induced oxidative stress and apoptosis of HUVECs, and the PI3K/Akt/p53 signaling pathway of apoptosis was revealed. These results suggest that Pte exhibits significant potential for dealing with HHcy-induced vascular endothelial injury, such as atherosclerosis.

关键词： pterostilbene Hyperhomocysteinemia Methionine Polyphenols Atherosclerosis

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pterostilbene supresses inflammation-induced melanoma metastasis by impeding neutrophil elastase-mediated thrombospondin-1 degradation

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Chinese Herbal Medicines 2023年第1期15卷 94-101页

作者： Dan Su Shan Xu Kailin Ji Hailing Xu Yan Li Zhisheng Zhang Yuqing Shen Gaoyang Chen Department of Pharmacy Changzhou No.2 People’s HospitalAffiliated Hospital of Nanjing Medical UniversityChangzhou 213004China School of Pharmacy Changzhou UniversityChangzhou 213164China Department of Oncology The Second People’s Hospital of TaizhouTaizhou 225300China

Objective: Chronic inflammation plays a fatal role in tumor metastasis. pterostilbene(PTE) is a natural dimethylated analogue of resveratrol with anticancer and anti-inflammatory activities. This study aimed to investigate the inhibitory effect of PTE on inflammation-associated metastasis and explore the underlying mechanisms.Methods: Lipopolysaccharide(LPS)-induced lung inflammation and melanoma metastasis models were established in mice. After PTE treatment for four weeks, the organ index, histological changes, proinflammatory cytokines, and the expression and activity of neutrophil elastase(NE), a biomarker of neutrophil influx in the lungs, were analysed. Additionally, direct effects of PTE on NE-induced B16 cell migration were explored in wound healing and Transwell assays, and the expression of thrombospondin-1(TSP-1) and epithelial-mesenchymal transition(EMT) markers were also detected.Results: PTE obviously attenuated the LPS-induced metastasis of circulatory B16 cells to lungs by reducing the number of metastatic nodules on the lung surfaces and the lung weight/body weight ratio. PTE treatment also significantly reduced LPS-activated increase levels of tumor necrosis factor(TNF)-a and interleukin(IL)-6 in the lungs of tumor-bearing mice. In addition, increased expression and enzyme activity of NE and decreased expression of TSP-1 were observed, and these were blocked by PTE. In vitro, PTE at concentrations without cytotoxicity also markedly suppressed NE-triggered B16 cell migration, prevented NE-induced TSP-1 proteolysis and reversed the expression of vimentin, N-cadherin and Ecadherin.Conclusion: PTE could block inflammation-enhanced tumor metastasis, and the underlying mechanism might be associated with the inhibition of NE-mediated TSP-1 degradation.

关键词： inflammation melanoma metastasis neutrophil elastase pterostilbene thrombospondin-1

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Anti-inflammatory and anti-cancer potential of pterostilbene:A review

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Asian Pacific Journal of Tropical Biomedicine 2023年第12期13卷 497-506页

作者： Omchit Surien Siti Fathiah Masre Dayang Fredalina Basri Ahmad Rohi Ghazali Centre for Toxicology and Health Risk Studies(CORE) Faculty of Health SciencesUniversiti Kebangsaan Malaysia50300Kuala LumpurMalaysia Centre of Diagnostic Therapeutic&Investigative Studies(CODTIS)Faculty of Health SciencesUniversiti Kebangsaan Malaysia50300Kuala LumpurMalaysia

pterostilbene is a natural compound that can be found in various food plants such as blueberries,grapes,and peanuts.It has also been reported to be extracted from Pterocarpus indicus,a tree species native to India and Southeast Asia.pterostilbene exhibits various pharmacological activities such as antioxidants,anti-proliferation,anti-microbial,and anti-inflammatory activities with favorable pharmacokinetic properties,such as high oral bioavailability and longer half-life.The anti-inflammatory effect of pterostilbene has been reported to contribute to its therapeutic effects in many chronic inflammatory diseases.Besides,pterostilbene has anti-cancer activity on various types of cancers due to its ability to induce cell cycle arrest and apoptosis.Hence,in this review,we discuss the anti-inflammatory and anti-cancer activities of pterostilbene in preclinical studies.

关键词： pterostilbene Anti-cancer NF-κB Anti-inflammation Natural product Pterocarpus indicus

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Resveratrol and its derivative pterostilbene ameliorate intestine injury in intrauterine growth-retarded weanling piglets by modulating redox status and gut microbiota

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Journal of Animal Science and Biotechnology 2021年第4期12卷 1530-1542页

作者： Yanan Chen Hao Zhang Yueping Chen Peilu Jia Shuli Ji Yuying Zhang Tian Wang College of Animal Science and Technology Nanjing Agricultural UniversityNo.1 Weigang StreetNanjingJiangsu 210095People’s Republic of China

Background:Intestinal disorder is an important factor contributing to growth lag and high rates of morbidity and mortality of piglets with intrauterine growth retardation(IUGR).Resveratrol(RSV)and its derivative pterostilbene(PT)are natural stilbenes possessing various bioactivities,such as antioxidative and anti-inflammatory effects.This study compared the protective potential of RSV and PT on the intestinal redox status and gut microbiota in weanling piglets with IUGR.Methods:Eighteen male piglets of normal body weight(NBW)and 54 same-sex IUGR piglets were chosen according to their birth and weaning weights.The NBW piglets accepted a basal diet,while the IUGR piglets were allotted to one of three groups according to their body weight at weaning and received a basal diet,an RSV-supplemented diet(300 mg/kg),or a PT-supplemented diet(300 mg/kg),respectively.Results:Compared with IUGR piglets,both RSV and PT improved the IUGR-associated decrease in jejunal villus height and increases in plasma diamine oxidase activity and D-lactate level and jejunal apoptosis of piglets(P<0.05).Administering RSV and PT also enhanced jejunal superoxide dismutase activity and the mRNA and protein expression of superoxide dismutase 2 of IUGR piglets by promoting nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation(P<0.05).Comparatively,PT was more effective than RSV in elevating the villus height/crypt depth ratio and occludin mRNA and protein levels in the jejunum of IUGR piglets(P<0.05).PT was also superior to RSV in increasing Nrf2 nuclear translocation and inhibiting malondialdehyde accumulation in the jejunum of IUGR piglets(P<0.05).Additionally,RSV modulated the composition of cecal microbiota of IUGR piglets,as evidenced by increasing the prevalence of the phylum Bacteroidetes and the genera Prevotella,Faecalibacterium,and Parabacteroides and inhibiting the growth of the phylum Proteobacteria and its genera Escherichia and Actinobacillus(P<0.05).Moreover,RSV significantly increased the butyrate concentration i

关键词： Gut microbiota Intestinal injury Intrauterine growth retardation Oxidative stress Piglets pterostilbene Resveratrol

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pterostilbene induces cell apoptosis and inhibits lipogenesis in SKOV3 ovarian cancer cells by activation of AMPK-induced inhibition of Akt/mTOR signaling cascade

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BIOCELL 2021年第1期45卷 89-101页

作者： ATTALLA EL-KOTT EMAN ELBEALY FAHMY ELSAID HAITHAM EL-MEKKAWY ABD-EL-KARIM ABD-LATEIF ABDULALI TAWEEL HEBA KHALIFA AHMAD KANDEEL KAREEM MORSY ESSAM IBRAHIM MASHAEL MOHAMMED BIN-MEFERIJ Biology Department College of ScienceKing Khalid UniversityAbha61413Saudi Arabia Zoology Department College of ScienceDamanhour UniversityDamanhour22511Egypt Biology Department College of Science for GirlsKing Khalid UniversityAbha61413Saudi Arabia Zoology Department College of ScienceMansoura UniversityMansoura35511Egypt Zoology Department College of ScienceFayoum UniversityFayoum63511Egypt Zoology Department Faculty of ScienceAl-Zawia UniversityAl-ZawiaLibya Biology Department Faculty of ScienceCairo UniversityCairo12611Egypt Research Center for Advanced Materials Science(RCAMS) King Khalid UniversityAbha61413Saudi Arabia Blood Products Quality Control and Research Department National Organization for Research and Control of BiologicalsCairo12611Egypt Biology Department College of SciencePrincess Nourah bint Abdulrahman UniversityRiyadhSaudi Arabia

This study investigates if the anti-tumor effect of pterostilbene in the SKOV3 ovarian cancer(OC)cell line involves inhibition of cell metabolism and tested in this effect involves modulating AMPK and Akt-induced regulation of mTORC1.Initially,SKOV3 cells were cultured in the humidified conditions in DMEM media for 24 h with or without increasing concentration of pterostilbene.Then,the cells were incubated with pterostilbene(IC_(50)=50μM)under similar conditions with or without pre-incubation with Dorsomorphin,an AMPK inhibitor.In a dose-dependent manner,pterostilbene inhibited SKOV3 cell survival and increased their lysate levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA).When SKOV3 cells were treated with 50μM pterostilbene,pterostilbene significantly suppressed cell migration and invasion,reduced lysate levels of lactic acid and the optical density of Oil Red O staining,and increased lysate glucose levels.It also increased levels of malondialdehyde(MDA),reactive oxygen species(ROS),and induced intrinsic cell apoptosis by upregulating protein levels of Bax and cleaved caspase-3 and reducing protein levels of Bcl-2.Besides,pterostilbene reduced mRNA levels of sterol regulatory element-binding protein 1(SREBP-1),fatty acid synthase(FAS),acetyl CoA carboxylase-1(ACC-1),and AMP-activated protein kinase(AMPK).Furthermore,pterostilbene increased the protein levels of p-AMPK,p-p53,p-raptor,p-TSC-2,but significantly decreased protein levels of p-Akt,p-TSC-2,p-mTOR,p-S6K1,and p-4E-BP.Treatment with Dorsomorphin(CC)abolished all the anti-tumorigenesis effects afforded by pterostilbene and prevented pterostilbene-induced phosphorylation of Akt,p53,and mTOR.In conclusion,the tumorsuppressive effect of pterostilbene in SKOV3 cells involves the induction of ROS and inhibition of dysregulation cell metabolism mainly due to AMPK-induced Akt-dependent or independent suppression of mTOR.

关键词： pterostilbene Ovarian cancer Lipogenesis Apoptosis AMPK

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Comparison of the protective effects of resveratrol and pterostilbene against intestinal damage and redox imbalance in weanling piglets

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Journal of Animal Science and Biotechnology 2020年第4期11卷 1204-1219页

作者： Hao Zhang Yanan Chen Yueping Chen Shuli Ji Peilu Jia Yue Li Tian Wang College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095JiangsuChina Postdoctoral Research Station of Clinical Veterinary Medicine College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095JiangsuChina Shanghai Key Laboratory of Veterinary Biotechnology Shanghai 200240China Postdoctoral Research Station of Food Science and Engineering College of Food Science and TechnologyNanjing Agricultural UniversityNanjing 210095JiangsuChina Institute of Animal Science Jiangsu Academy of Agricultural SciencesNanjing 210014China.

Background: Evidence indicates that early weaning predisposes piglets to intestinal oxidative stress and increases the risk of intestinal dysfunction;however, there are minimal satisfactory treatment strategies for these conditions.This study investigated the potential of resveratrol and its analog, pterostilbene, as antioxidant protectants for regulating intestinal morphology, barrier function, and redox status among weanling piglets.Methods: A total of 144 piglets were selected at 21 days of age and randomly allocated into one of four treatment groups, each of which included six replicates. Piglets in a sow-reared control group were suckling normally between ages 21 and 28 days, while those in weaned groups were fed a basal diet, supplemented with either 300 mg/kg of resveratrol or with 300 mg/kg of pterostilbene. Parameters associated with intestinal injury and redox status were analyzed at the end of the feeding trial.Results: Early weaning disrupted the intestinal function of young piglets, with evidence of increased diamine oxidase activity and D-lactate content in the plasma, shorter villi, an imbalance between cell proliferation and apoptosis, an impaired antioxidant defense system, and severe oxidative damage in the jejunum relative to suckling piglets. Feeding piglets with a resveratrol-supplemented diet partially increased villus height(P = 0.056) and tended to diminish apoptotic cell numbers(P = 0.084) in the jejunum compared with those fed a basal diet. Similarly, these beneficial effects were observed in the pterostilbene-fed piglets. pterostilbene improved the feed efficiency of weanling piglets between the ages of 21 and 28 days;it also resulted in diminished plasma diamine oxidase activity and D-lactate content relative to untreated weaned piglets(P pterostilbene restored jejunal antioxidant capacity, an effect that was nearly absent in the resveratrol-fed piglets. pterostilbene reduced the malondialdehyde and 8-hydroxy-2′-deoxyguanosine contents of jejunal mucosa possibly throu

关键词： Intestinal injury Oxidative damage Piglet pterostilbene Resveratrol Weaning stress

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Dietary pterostilbene Inhibited Colonic Inflammation in Dextran-Sodium-Sulfate-Treated Mice:A Perspective of Gut Microbiota

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Infectious Microbes & Diseases 2021年第1期3卷 22-29页

作者： Fang Li Qi Wang Yanhui Han Mingyue Song Xiaokun Cai Timothy Goulette Hang Xiao Department of Food Science University of MassachusettsAmherstAmherstMAUSA College of Food Science South China Agricultural UniversityGuangzhouGuangdongChina.

Dietary interventions based on the use of bioactive nutraceuticals might offer an effective adjuvant therapeutic and preventive method for inflammatory bowel disease by reshaping colitis-associated bacterial dysbiosis.The current study aimed to determine the antiinflammatory effect of pterostilbene(PTE,a methylated derivative of resveratrol)and its potential modulatory roles in gut microbiota in a dextran sodium sulfate(DSS)-induced colitis mouse model.Our results supported our hypothesis that dietary PTE exerted protective effects against colonic inflammation;evidenced by the reduced colonic tissue damage,decreased disease activity index,and lowered production of pro-inflammatory cytokines such as interferon gamma,interleukin(IL)-2,IL-4,and IL-6 in the colon of DSS-treated mice.Moreover,a-diversity analysis indicated that dietary PTE significantly improved gut microbial evenness and diversity.Noteworthy,PTE modified gut microbiota composition toward a healthier profile by boosting the richness of Bifidobacterium and decreasing the distribution of pathogenic Bilophila and Rc4-4.Pearson correlation analysis also revealed strong associations between the shifting of gut microbiota and expression of inflammatory cytokines in the colon.Overall,our study demonstrated that dietary PTE alleviated the severity of colitis in DSS-treated mice and gut microbiota may play an indispensable role in this process mechanistically.

关键词： pterostilbene anti-inflammation gut microbiota

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pterostilbene accelerates wound healing by modulating diabetes-induced estrogen receptorβsuppression in hematopoietic stem cells

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Burns & Trauma 2021年第1期9卷 629-641页

作者： Weiguo Xie Xueqing Zhou Weigang Hu Zhigang Chu Qiongfang Ruan Haimou Zhang Min Li Hongyu Zhang Xiaodong Huang Paul Yao Institute of Burns Tongren Hospital of Wuhan University(Wuhan Third Hospital)Wuhan 430060China State Key Lab of Biocatalysis and Enzyme Engineering School of Life SciencesHubei UniversityWuhan430062China Department of Hematology Peking University Shenzhen HospitalShenzhen518036China

Background:Delayed wound healing is one of the major complications of diabetes mellitus and is characterized by prolonged inflammation,delayed re-epithelialization and consistent oxidative stress,although the detailed mechanism remains unknown.In this study,we aimed to investigate the potential role and effect of pterostilbene(PTE)and hematopoietic stem cells(HSCs)on diabetic wound healing.Methods:Diabetic rats were used to measure the epigenetic changes in both HSCs and peripheral blood mononuclear cells(PBMCs).A cutaneous burn injury was induced in the rats and PTE-treated diabetic HSCs were transplanted for evaluation of wound healing.In addition,several biomedical parameters,including gene expression,oxidative stress,mitochondrial function and inflammation in macrophages,were also measured.Results:Our data showed that PTE had a much stronger effect than resveratrol on accelerating diabetic wound healing,likely because PTE can ameliorate diabetes-induced epigenetic changes to estrogen receptorβpromoter in HSCs,while resveratrol cannot.Further investigation showed that bone marrow transplantation of PTE-treated diabetic HSCs restores diabetes-induced suppression of estrogen receptorβand its target genes,including nuclear respiratory factor-1 and superoxide dismutase 2,and protects against diabetes-induced oxidative stress,mitochondrial dysfunction and elevated pro-inflammatory cytokines in both PBMCs and macrophages,subsequently accelerating cutaneous wound healing.Conclusions:HSC may play an important role in wound healing through transferring epigenetic modifications to subsequent PBMCs and macrophages by differentiation,while PTE accelerates diabetic wound healing by modulating diabetes-induced epigenetic changes in HSCs.Thus,PTE may be a novel therapeutic strategy for diabetic wound healing.

关键词： Hematopoietic stem cells Inflammation Oxidative stress pterostilbene Wound healing

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pterostilbene attenuates high glucose-induced oxidative injury in hippocampal neuronal cells by activating nuclear factor erythroid 2-related factor 2

Pterostilbene attenuates high glucose-induced oxidative inju...

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第十三届中国医师协会神经外科医师年会

作者： Yang Yang Chongxi Fan Bodong Wang Zhiqiang Ma Dongjin Wang Bing Gong Shouyin Di Shuai Jiang Yue Li Tian Li Zhi Yang Erping Luo Department of Biomedical Engineering The Fourth Military Medical University Department of Thoracic and Cardiovascular Surgery Affiliated Drum Tower Hospital of Nanjing University Medical School Department of Thoracic Surgery Tangdu HospitalThe Fourth Military Medical University Graduate Management Team The Fourth Military Medical University Department of Aerospace Medicine The Fourth Military Medical University

In the present study,neuroblastoma（SH-SY5 Y）cells were used to investigate the mechanisms mediating the potential protective effects of pterostilbene（PTE）against mitochondrial metabolic impairment and oxidative stress induced by hyperglycemia for mimicking the diabetic encephalopathy.High glucose medium（100 mM）decreased cellular viability after 24 h incubation which was evidenced by:（i）reduced mitochondrial complex I and III activities;（ii）reduced mitochondrial cytochrome C;（iii）increased reactive oxygen species（ROS）generation;（iv）decreased mitochondrial membrane potential（ΔΨm）;and（v）increased lactate dehydrogenase（LDH）levels.PTE（2.5,5,and 10 μM for 24 h）was nontoxic and induced the nuclear transition of Nrf2.Pretreatment of PTE（2.5,5,and 10 μM for 2 h）displayed a dose-dependently neuroprotective effect,as indicated by significantly prevented high glucose-induced loss of cellular viability,generation of ROS,reduced mitochondrial complex I and III activities,reduced mitochondrial cytochrome C,decreased ΔΨm,and increased LDH levels.Moreover,the levels of nuclear factor erythroid 2-related factor 2（Nrf2）,heme oxygenase-1（HO-1）and glutathione S-transferase（GST）were elevated after PTE treatment.In addition,the elevation of nuclear Nrf2 by PTE treatment（10 μM for 2 h）was abolished by Nrf2 siRNA.Importantly,Nrf2 siRNA induced the opposite changes in mitochondrial complex I and III activities,mitochondrial cytochrome C,reactive species generation,ΔΨm,and LDH.Overall,the present findings were the first to show that pterostilbene attenuated high glucose-induced central nervous system injury in vitro through the activation of Nrf2 signaling,displaying protective effects against mitochondrial dysfunction-derived oxidative stress.

关键词： High glucose Oxidative stress pterostilbene Nuclear factor erythroid 2-related factor 2 signaling Neuroprotection

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pterostilbene inhibits FcεRI signaling in mast cells during anaphylaxis

Pterostilbene inhibits FcεRI signaling in mast cells during...

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第十四届全国免疫学学术大会

作者： Chongyang Wang Liangchang Li Chang Xu guanghai Yan Yanbian University

In this study,the role and mechanism of pterostilbene(Pts) in mast cell degranulation in vitro and in vivo were investigated.The results showed that Pts inhibited mast cell-mediated local passive allergic reactions in mice.In addition,treatment with Pts reduced both histamine release and calcium influx in rat peritoneal mast cells and RBL-2 H3 cells and reduced Ig E-mediated mast cell activation.Furthermore,the mechanism underlying Pts inhibition of mast cell signaling was probed via studying the effects of Pts on liver kinase B1(LKB1),including the use of the LKB1 activator metformin and siRNA knockdown of LKB1.The data showed that Pts reduced the release of inflammatory mediators such as tumor necrosis factor-a,interleukin-6,leukotriene C4,and prostaglandin D2 in mast cells by activating the LKB1/adenosine monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway.Furthermore,Pts inhibited phosphorylation of FcεRI and FcεRI-mediated degranulation in RBL-2 H3 cells.These effects were attenuated after LKB1 knockdown.Taken together,Pts could inhibit FcεRI signaling through activation of the LKB1/AMPK signaling pathway in Ig E-mediated mast cell activation.Thus,Pts might be an effective therapeutic agent for mast cell mediated allergic diseases.

关键词： pterostilbene mast cell degranulation LKB1 AMPK FcεRI signaling

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