Background:To date,there is no effective cure for the highly malignant brain tumor glioblastoma(GBM).GBM is the most common,aggressive central nervous system tumor(CNS).It commonly originates in glial cells such as mi...Background:To date,there is no effective cure for the highly malignant brain tumor glioblastoma(GBM).GBM is the most common,aggressive central nervous system tumor(CNS).It commonly originates in glial cells such as microglia,oligodendroglia,astrocytes,or subpopulations of cancer stem cells(CSCs).Glucose plays an important role in the,which energy metabolism of normal and cancer cells,but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation.The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM.Also,this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM.Method:In this study,we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors.Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index.Followed by the Morris water maze,an open field test,and rota rod was performed to evaluate the memory and motor coordination.To understand the glucose,and ketone level modification before and after treatment,the level of glucose and ketone was analyzed.Moreover,the zinc level is assessed using flame atomic absorption spectroscopy.Results:The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines.Also,it exerts a synergistic effect with the epigenetic modulator,oxyresveratrol,and zinc against GBM cell lines.Moreover,the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index.Conclusion:This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats.Also,it improved memory and motor coordination and reduced tumor growth.It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden.展开更多
Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position compari...Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position comparing with resveratrol(Res).Hence,ORes has stronger antioxidant activity than resveratrol.In present study,we employed a rat hepatic fibrosis model induced by carbon tetrachloride(CCl_(4))and administrated ORes via gavage feeding to study the protective effects and potential mechanisms of ORes against hepatic fibrosis.We demonstrated that rat liver oxidative damage induced by CCl_(4)was significantly alleviated after ORes feeding.Furthermore,the mRNA transcription levels ofα-smooth muscle actinn(˛-SMA),desmin,and two MMPs(MMP2 and MMP9)were reduced and the expression levels of transforming growth factorβ1(TGF-β1),p-small mother against decapen-taplegic protein(Smad)1/2 and p-extracellular signal-regulated kinases(ERK)1/2 in the liver tissue down-regulated dramatically.In a parallel study with Res,ORes showed more efficacious protective effect than Res against rat liver fibrosis,which is attributed to extended conjugation system due to the extra hydroxyl group at 2-position on ORes making it more electron-rich and susceptible to oxidation than Res.Therefore,dietary consumption of mulberry and other fruits containing ORes may be beneficial in the prevention of liver fibrosis.展开更多
OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carc...OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carcinoma(HCC)remain poorly understood.METHODS Two HCC cell lines,HepG2 and SMMC-7721 cells,were employed.Their proliferation was determined by CCK8 assay.The migration and invasion of cells were examined by wound healing and transwell assay.Metastasis of HCC was detected by in vivo experiment.Meanwhile,transcriptome analysis was applied to explore the mechanisms of OXY.The results of transcriptome analysis were validated by in vitro experiment.Further⁃more,western blot was used to measure the expression of LC3 and p62 protein.RESULTS OXY significantly inhibited the proliferation,migration and invasion of HCC cells in vitro.OXY suppressed the metastasis of HCC in Balb/c mice with attenuated side effects compared to Doxorubicin.Transcription profiling analysis revealed that OXY may affect autophagy related signaling pathway of HepG2 cells.Western blotting showed that OXY significantly inhibite autophagy by downregulating LC3 and upregulating p62 genes expression.CONCLUSION Our study demonstrated that OXY inhibits the metastasis of HCC by inhibiting autophagy,which suggested OXY to be a candidate for HCC metastasis.展开更多
Aim Oxyresveratrol （trans-2,3 ＇ ,4,5 ＇ -tetrahydroxystilbene, OXY） , a natural polyphenolic phyto- chemical presents in mulberry （Morus alba L. ） , has been reported to have various bioactivities. Though OXY has...Aim Oxyresveratrol （trans-2,3 ＇ ,4,5 ＇ -tetrahydroxystilbene, OXY） , a natural polyphenolic phyto- chemical presents in mulberry （Morus alba L. ） , has been reported to have various bioactivities. Though OXY has high structural similarity with resveratrol, which has been identified as a chemopreventive agent, little is known a- bout OXY＇s effect on cancer. The main objective of our study was to investigate the effect of OXY on metastasis in vivo. To establish an experimental metastasis model, male Kunming mice were challenged with H22 cells by tail vein injection, and were given different doses of OXY （20, 40,80 mg · kg^-1 body weight per day） for 14 days in- traperitoneally. Administration of OXY showed a clear anti-metastatic effect. Compared to control group （u - 10） , the numbers of pulmonary nodules and lung weight were significantly decreased in mice of 40 mg · kg^- 1 group （ n = 10, P 〈 0.05） , which results in 54.5% reduction in the number of metastases. Similar inhibitory effects were ob- served both at 20 and 80 mg · kg^-1 groups（n= 10, 34.2% and 35.7% , respectively）. OXY at the doses used caused an increase in spleen index （P 〈 0.05） but not thymus index. Further we observed animal body weights loss and food intake decrease （P 〈 0.05） , suggesting the toxicity of high dose used. Therefore, we suggest that oxyresveratrol may benefit human as a new preventive agent for cancer metastasis.展开更多
Background:Sensitive skin affects a substantial portion of the global population and has significant implications for skin health and well-being.In addition to unpleasant sensory effects,individuals with sensitive ski...Background:Sensitive skin affects a substantial portion of the global population and has significant implications for skin health and well-being.In addition to unpleasant sensory effects,individuals with sensitive skin were likely to be more susceptible to hyperpigmentation.However,the association between sensitive skin and hyperpigmentation,as well as the underlying molecular mechanisms,remain unclear.Objective:This study aims to investigate the correlation and intrinsic mechanisms between sensitive skin and hyperpigmentation through network pharmacology combined with molecular docking.Materials and Methods:The targets associated with sensitive skin and hyperpigmentation were collected from the human gene database,GeneCards.Subsequently,the protein-protein interaction(PPI)network,Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Ontology(GO)enrichment analysis were performed to explore the biological connections between sensitive skin and hyperpigmentation.Additionally,the targets of 15 active compounds with reported lightening effects were collected from TCMSP,BATMAN and SymMap databases.Target analysis and molecular docking were performed to identify potential candidates for addressing hyperpigmentation on sensitive skin.The anti-melanogenesis effect of the identified candidate was verified in B16F10 cells.Results:A total of 16971 sensitive skin targets and 11382 hyperpigmentation targets were screened,and 9693 overlapping targets were identified,with a core set comprising 164 targets.The combination of PPI network,KEGG and GO analysis revealed the key role of tyrosinase and immune-mediated inflammation in pigmentation on sensitive skin.Among the 15 active compounds,oxyresveratrol was identified as having a high correlation with the core set targets and predicted strong inhibition of Tyrosine-protein Kinase Kit.The application of oxyresveratrol exhibited a dose-dependent suppression of melanin production in B16F10 cells.Conclusion:This study suggested the crucial roles of immune-mediated inflammation in sensitive skin and hyperpigmentation,as well as highlighted the potential of oxyresveratrol in addressing hyperpigmentation on sensitive skin.These comprehensive findings provide a deeper understanding of the connection mechanism between sensitive skin and hyperpigmentation,offering new insights for the development of targeted treatments and interventions.展开更多
Grape skin,one of the by-products of grape processing,is rich in oxyresveratrol and other bioactive compounds.Oxyresveratrol is a polyphenolic non-flavonoid with anti-inflammatory and anti-aging properties among other...Grape skin,one of the by-products of grape processing,is rich in oxyresveratrol and other bioactive compounds.Oxyresveratrol is a polyphenolic non-flavonoid with anti-inflammatory and anti-aging properties among other biological activities,but little research has been done on its antioxidant mechanism.This study aims to evaluate the regulation of oxyresveratrol on Keap1-Nrf2-ARE signaling pathway.Firstly,oxyresveratrol in grape skin was detected by HPLC-MS/MS,and then its interaction mechanism with Keap1 was investigated by molecular docking.The result of Western blot further confirmed that oxyresveratrol can bind with Nrf2 to induce its nuclear translocation.The Luciferase reporter gene analysis revealed the agonistic effects of oxyresveratrol on ARE.Oxyresveratrol increased not only the mRNA expression levels of ARE-mediated genes NQO1,HO-1,and GCLM,but also their protein expression levels,suggesting that oxyresveratrol inhibited H_(2)O_(2)-induced oxidative damage.Therefore,oxyresveratrol can be applied as a potential antioxidant by activating the Keap-Nrf2-ARE signaling pathway.展开更多
文摘Background:To date,there is no effective cure for the highly malignant brain tumor glioblastoma(GBM).GBM is the most common,aggressive central nervous system tumor(CNS).It commonly originates in glial cells such as microglia,oligodendroglia,astrocytes,or subpopulations of cancer stem cells(CSCs).Glucose plays an important role in the,which energy metabolism of normal and cancer cells,but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation.The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM.Also,this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM.Method:In this study,we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors.Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index.Followed by the Morris water maze,an open field test,and rota rod was performed to evaluate the memory and motor coordination.To understand the glucose,and ketone level modification before and after treatment,the level of glucose and ketone was analyzed.Moreover,the zinc level is assessed using flame atomic absorption spectroscopy.Results:The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines.Also,it exerts a synergistic effect with the epigenetic modulator,oxyresveratrol,and zinc against GBM cell lines.Moreover,the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index.Conclusion:This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats.Also,it improved memory and motor coordination and reduced tumor growth.It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden.
基金Grant from Hubei Province,China(GRANT number 2019ABA100)。
文摘Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position comparing with resveratrol(Res).Hence,ORes has stronger antioxidant activity than resveratrol.In present study,we employed a rat hepatic fibrosis model induced by carbon tetrachloride(CCl_(4))and administrated ORes via gavage feeding to study the protective effects and potential mechanisms of ORes against hepatic fibrosis.We demonstrated that rat liver oxidative damage induced by CCl_(4)was significantly alleviated after ORes feeding.Furthermore,the mRNA transcription levels ofα-smooth muscle actinn(˛-SMA),desmin,and two MMPs(MMP2 and MMP9)were reduced and the expression levels of transforming growth factorβ1(TGF-β1),p-small mother against decapen-taplegic protein(Smad)1/2 and p-extracellular signal-regulated kinases(ERK)1/2 in the liver tissue down-regulated dramatically.In a parallel study with Res,ORes showed more efficacious protective effect than Res against rat liver fibrosis,which is attributed to extended conjugation system due to the extra hydroxyl group at 2-position on ORes making it more electron-rich and susceptible to oxidation than Res.Therefore,dietary consumption of mulberry and other fruits containing ORes may be beneficial in the prevention of liver fibrosis.
文摘OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carcinoma(HCC)remain poorly understood.METHODS Two HCC cell lines,HepG2 and SMMC-7721 cells,were employed.Their proliferation was determined by CCK8 assay.The migration and invasion of cells were examined by wound healing and transwell assay.Metastasis of HCC was detected by in vivo experiment.Meanwhile,transcriptome analysis was applied to explore the mechanisms of OXY.The results of transcriptome analysis were validated by in vitro experiment.Further⁃more,western blot was used to measure the expression of LC3 and p62 protein.RESULTS OXY significantly inhibited the proliferation,migration and invasion of HCC cells in vitro.OXY suppressed the metastasis of HCC in Balb/c mice with attenuated side effects compared to Doxorubicin.Transcription profiling analysis revealed that OXY may affect autophagy related signaling pathway of HepG2 cells.Western blotting showed that OXY significantly inhibite autophagy by downregulating LC3 and upregulating p62 genes expression.CONCLUSION Our study demonstrated that OXY inhibits the metastasis of HCC by inhibiting autophagy,which suggested OXY to be a candidate for HCC metastasis.
文摘Aim Oxyresveratrol （trans-2,3 ＇ ,4,5 ＇ -tetrahydroxystilbene, OXY） , a natural polyphenolic phyto- chemical presents in mulberry （Morus alba L. ） , has been reported to have various bioactivities. Though OXY has high structural similarity with resveratrol, which has been identified as a chemopreventive agent, little is known a- bout OXY＇s effect on cancer. The main objective of our study was to investigate the effect of OXY on metastasis in vivo. To establish an experimental metastasis model, male Kunming mice were challenged with H22 cells by tail vein injection, and were given different doses of OXY （20, 40,80 mg · kg^-1 body weight per day） for 14 days in- traperitoneally. Administration of OXY showed a clear anti-metastatic effect. Compared to control group （u - 10） , the numbers of pulmonary nodules and lung weight were significantly decreased in mice of 40 mg · kg^- 1 group （ n = 10, P 〈 0.05） , which results in 54.5% reduction in the number of metastases. Similar inhibitory effects were ob- served both at 20 and 80 mg · kg^-1 groups（n= 10, 34.2% and 35.7% , respectively）. OXY at the doses used caused an increase in spleen index （P 〈 0.05） but not thymus index. Further we observed animal body weights loss and food intake decrease （P 〈 0.05） , suggesting the toxicity of high dose used. Therefore, we suggest that oxyresveratrol may benefit human as a new preventive agent for cancer metastasis.
文摘Background:Sensitive skin affects a substantial portion of the global population and has significant implications for skin health and well-being.In addition to unpleasant sensory effects,individuals with sensitive skin were likely to be more susceptible to hyperpigmentation.However,the association between sensitive skin and hyperpigmentation,as well as the underlying molecular mechanisms,remain unclear.Objective:This study aims to investigate the correlation and intrinsic mechanisms between sensitive skin and hyperpigmentation through network pharmacology combined with molecular docking.Materials and Methods:The targets associated with sensitive skin and hyperpigmentation were collected from the human gene database,GeneCards.Subsequently,the protein-protein interaction(PPI)network,Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Ontology(GO)enrichment analysis were performed to explore the biological connections between sensitive skin and hyperpigmentation.Additionally,the targets of 15 active compounds with reported lightening effects were collected from TCMSP,BATMAN and SymMap databases.Target analysis and molecular docking were performed to identify potential candidates for addressing hyperpigmentation on sensitive skin.The anti-melanogenesis effect of the identified candidate was verified in B16F10 cells.Results:A total of 16971 sensitive skin targets and 11382 hyperpigmentation targets were screened,and 9693 overlapping targets were identified,with a core set comprising 164 targets.The combination of PPI network,KEGG and GO analysis revealed the key role of tyrosinase and immune-mediated inflammation in pigmentation on sensitive skin.Among the 15 active compounds,oxyresveratrol was identified as having a high correlation with the core set targets and predicted strong inhibition of Tyrosine-protein Kinase Kit.The application of oxyresveratrol exhibited a dose-dependent suppression of melanin production in B16F10 cells.Conclusion:This study suggested the crucial roles of immune-mediated inflammation in sensitive skin and hyperpigmentation,as well as highlighted the potential of oxyresveratrol in addressing hyperpigmentation on sensitive skin.These comprehensive findings provide a deeper understanding of the connection mechanism between sensitive skin and hyperpigmentation,offering new insights for the development of targeted treatments and interventions.
基金supported by the Agricultural Science and Technology Innovation Program of Jilin Province(KYJF2021JQ010,CXGC2021TD006 and CXGC2021RCY028)the Capital Construction Funds within the Provincial Budget in 2022(2022c043-12)+2 种基金the Science and Technology Development Project Foundation of Jilin Province(20210203182SF)the Administration of Traditional Chinese Medicine of Jilin Province(2021100)the National Key Research and Development Program(2021YFD1200103).
文摘Grape skin,one of the by-products of grape processing,is rich in oxyresveratrol and other bioactive compounds.Oxyresveratrol is a polyphenolic non-flavonoid with anti-inflammatory and anti-aging properties among other biological activities,but little research has been done on its antioxidant mechanism.This study aims to evaluate the regulation of oxyresveratrol on Keap1-Nrf2-ARE signaling pathway.Firstly,oxyresveratrol in grape skin was detected by HPLC-MS/MS,and then its interaction mechanism with Keap1 was investigated by molecular docking.The result of Western blot further confirmed that oxyresveratrol can bind with Nrf2 to induce its nuclear translocation.The Luciferase reporter gene analysis revealed the agonistic effects of oxyresveratrol on ARE.Oxyresveratrol increased not only the mRNA expression levels of ARE-mediated genes NQO1,HO-1,and GCLM,but also their protein expression levels,suggesting that oxyresveratrol inhibited H_(2)O_(2)-induced oxidative damage.Therefore,oxyresveratrol can be applied as a potential antioxidant by activating the Keap-Nrf2-ARE signaling pathway.
