Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol cond...Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.展开更多
An integrated physiological and non-targeted metabolomics approach was used to construct a eugenol-based polymethoxyflavones nanoemulsion delivery system and examine its increased antibacterial activity on E.coli.Comp...An integrated physiological and non-targeted metabolomics approach was used to construct a eugenol-based polymethoxyflavones nanoemulsion delivery system and examine its increased antibacterial activity on E.coli.Compared with pure eugenol nanoemulsion(EG,MIC:640μg/mL),the polymethoxyflavones-eugenol nanoemulsion(EGP)exhibited significantly enhanced antimicrobial activity(MIC:320μg/mL).EGP treatment disrupted the integrity of E.coli cell membranes and walls,increased cell permeability.Non-targeted metabolomics analysis(compared with CK)revealed 685 upregulated and 642 downregulated differentially accumulating metabolites,lysine and glutamine are reduced in E.coli,and glutaric acid,aminoadipic acid,and D-lactic acid are increased.Pathway enrichment analysis showed that amino acid metabolism and energy metabolism were significantly disturbed by TCA cycle disruption.EGP exhibits superior antimicrobial efficacy against E.coli through a multi-targeted mechanism involving cell membrane disruption and metabolic pathway interference.This study provides valuable insights into the development of natural antimicrobial nanoemulsion as potential alternatives to synthetic preservatives for food safety applications.展开更多
Cancer is one of the two leading human fatal diseases.Drug development for cancer intervention has progressed well in past decades yet existing drugs face many limitations in applications and effectiveness and are oft...Cancer is one of the two leading human fatal diseases.Drug development for cancer intervention has progressed well in past decades yet existing drugs face many limitations in applications and effectiveness and are often associated with serious of side effects,which can further deteriorate the patients’quality of life.Recent development of natural product based and therapeutically sound anti-cancer agents have gained popularity in the field of functional foods,in which a few have demonstrated efficacy and minimal toxicity toward the prevention and treatment of carcinogenesis.With multiple active molecular components,citrus peels and derived extracts have demonstrated potent efficacious properties against various cancers due in large part to the rich content of flavonoids present in citrus peels.This review summarizes the results of currently available data regarding the in vivo anti-cancer activity of citrus peel flavonoids,and identifies opportunities for subsequent human clinical trials to assess preventive and therapeutic effects in the near future.展开更多
5-Demethylnobile tin(5-DMN),a hydroxylated polymethoxyflavone(OH-PMF)identified in aged citrus peels,has demonstrated health benefiting effects in previous studies.5-DMN undergoes biotransformation in vivo,yielding 5,...5-Demethylnobile tin(5-DMN),a hydroxylated polymethoxyflavone(OH-PMF)identified in aged citrus peels,has demonstrated health benefiting effects in previous studies.5-DMN undergoes biotransformation in vivo,yielding 5,3’-didemethylnobiletin(5,3’-DDMN),5,4’-didemethylnobiletin(5,4’-DDMN)and5,3’,4’-tridemethylnobiletin(5,3’,4’-TDMN).However,the anti-cancer effects of 5-DMN and its in vivo metabolites against HepG2 cells remain unclear.In this study,an efficient chemical synthetic method was developed to obtain 5-DMN and its 3 metabolites,and their molecular structures were confirmed by;H NMR and LC-MS.Cytotoxicity,cell cycle arrestment,apoptosis and caspase-3 expression were investigated to evaluate the anti-liver cancer effects of these OH-PMFs on HepG2 cells.The results showed that all 4 compounds inhibited the proliferation of HepG2 cells in a concentration-dependent manner.Their anti-proliferative activity was exerted through inducing G2/M phase arrestment,cell apoptosis and promoting expression of a key apoptotic protein called cleaved caspase-3.Our results indicated that 5,3’-DDMN and5,3’,4’-TDMN showed a stronger inhibitory activity on cell proliferation than 5-DMN,followed by 5,4’-DDMN.The expression of cleaved caspase-3 was the highest in cells treated with 5,4’-DDMN,implying that the apoptosis induced by other OH-PMFs might be mediated by other apoptotic execution proteins.Our research reveals the application potential and scientific evidence for the production and functionality of OH-PMFs.展开更多
Chenpi(Citri reticulatae Pericarpium,CRP),embodying the traditional concept of“homology of food and med-icine”,has been regarded as higher quality with prolonged aging.In this study,Xinhui-origin CRP was adopted and...Chenpi(Citri reticulatae Pericarpium,CRP),embodying the traditional concept of“homology of food and med-icine”,has been regarded as higher quality with prolonged aging.In this study,Xinhui-origin CRP was adopted and its main compounds were identified as hesperidin,isosinensetin,sinensetin,6-demethoxytangeretin,nobi-letin,3,5,6,7,8,3′,4′-heptamethoxyflavone,tangeretin,and 5-O-demethynobiletin.Over an aging period of 3-15 years,the contents of most flavonoids increased.Subsequently,the protective effect of CRP extracts against methylglyoxal(MGO)-induced toxicity was examined in RAW 264.7 macrophages.MGO is closely related to the progression of diabetic complications.Our results demonstrated that the 10-year CRP extract had the highest potential,with sinensetin being the responsible compound.Further experiments emphasized the role of transducin-like enhancer of split protein 2(TLE2)and Notch signaling pathway,which modulated the cellular responses of MGO exposure.Collectively,these findings highlight the beneficial effects of 10-year CRP and provide scientific evidence for its application in functional foods.展开更多
Nobiletin(NOB)is a kind of polymethoxyflavonoids(PMFs)exclusively present in citrus fruits.It exhibits diverse biological activities,with particular emphasis on its regulatory effect on lipid metabolism,which has garn...Nobiletin(NOB)is a kind of polymethoxyflavonoids(PMFs)exclusively present in citrus fruits.It exhibits diverse biological activities,with particular emphasis on its regulatory effect on lipid metabolism,which has garnered significant attention from researchers in recent years.The disorder of lipid metabolism serves as the underlying cause for a range of metabolic disorders.Both in vivo and in vitro studies have demonstrated that NOB and its metabolites possess the ability to regulate lipid metabolism in conditions associated with lipid metabolism disorders,including obesity,fatty liver,diabetes,and atherosclerosis.Furthermore,they can mitigate the progression of these diseases.The modulation of inflammatory state,reduction of oxidative stress,regulation of microbiota and lipid metabolism pathway are likely to be crucial mechanisms through which NOB exerts its effects on lipid metabolism.Additionally,NOB is a small molecule known to regulate circadian rhythm,which also serves as an important target for NOB in regulating lipid metabolism.This article presents a comprehensive review of the primary research findings on the impact of NOB and its metabolites on lipid metabolism disorders-related diseases,while also analyzing the mechanism of action underlying NOB's effects.These insights provide a solid theoretical foundation for further research and development into NOB,ultimately maximizing the beneficial impacts of citrus fruits.展开更多
基金Supported by the Science & Technology Planning Project of Hunan Province,China (No.2011FJ3214)
文摘Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.
基金supported by Technology innovation and application development project of Chongqing(NO.CSTB2022TIAD-KPX0056).
文摘An integrated physiological and non-targeted metabolomics approach was used to construct a eugenol-based polymethoxyflavones nanoemulsion delivery system and examine its increased antibacterial activity on E.coli.Compared with pure eugenol nanoemulsion(EG,MIC:640μg/mL),the polymethoxyflavones-eugenol nanoemulsion(EGP)exhibited significantly enhanced antimicrobial activity(MIC:320μg/mL).EGP treatment disrupted the integrity of E.coli cell membranes and walls,increased cell permeability.Non-targeted metabolomics analysis(compared with CK)revealed 685 upregulated and 642 downregulated differentially accumulating metabolites,lysine and glutamine are reduced in E.coli,and glutaric acid,aminoadipic acid,and D-lactic acid are increased.Pathway enrichment analysis showed that amino acid metabolism and energy metabolism were significantly disturbed by TCA cycle disruption.EGP exhibits superior antimicrobial efficacy against E.coli through a multi-targeted mechanism involving cell membrane disruption and metabolic pathway interference.This study provides valuable insights into the development of natural antimicrobial nanoemulsion as potential alternatives to synthetic preservatives for food safety applications.
文摘Cancer is one of the two leading human fatal diseases.Drug development for cancer intervention has progressed well in past decades yet existing drugs face many limitations in applications and effectiveness and are often associated with serious of side effects,which can further deteriorate the patients’quality of life.Recent development of natural product based and therapeutically sound anti-cancer agents have gained popularity in the field of functional foods,in which a few have demonstrated efficacy and minimal toxicity toward the prevention and treatment of carcinogenesis.With multiple active molecular components,citrus peels and derived extracts have demonstrated potent efficacious properties against various cancers due in large part to the rich content of flavonoids present in citrus peels.This review summarizes the results of currently available data regarding the in vivo anti-cancer activity of citrus peel flavonoids,and identifies opportunities for subsequent human clinical trials to assess preventive and therapeutic effects in the near future.
文摘5-Demethylnobile tin(5-DMN),a hydroxylated polymethoxyflavone(OH-PMF)identified in aged citrus peels,has demonstrated health benefiting effects in previous studies.5-DMN undergoes biotransformation in vivo,yielding 5,3’-didemethylnobiletin(5,3’-DDMN),5,4’-didemethylnobiletin(5,4’-DDMN)and5,3’,4’-tridemethylnobiletin(5,3’,4’-TDMN).However,the anti-cancer effects of 5-DMN and its in vivo metabolites against HepG2 cells remain unclear.In this study,an efficient chemical synthetic method was developed to obtain 5-DMN and its 3 metabolites,and their molecular structures were confirmed by;H NMR and LC-MS.Cytotoxicity,cell cycle arrestment,apoptosis and caspase-3 expression were investigated to evaluate the anti-liver cancer effects of these OH-PMFs on HepG2 cells.The results showed that all 4 compounds inhibited the proliferation of HepG2 cells in a concentration-dependent manner.Their anti-proliferative activity was exerted through inducing G2/M phase arrestment,cell apoptosis and promoting expression of a key apoptotic protein called cleaved caspase-3.Our results indicated that 5,3’-DDMN and5,3’,4’-TDMN showed a stronger inhibitory activity on cell proliferation than 5-DMN,followed by 5,4’-DDMN.The expression of cleaved caspase-3 was the highest in cells treated with 5,4’-DDMN,implying that the apoptosis induced by other OH-PMFs might be mediated by other apoptotic execution proteins.Our research reveals the application potential and scientific evidence for the production and functionality of OH-PMFs.
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2022A1515012098 and No.2024A1515010489).
文摘Chenpi(Citri reticulatae Pericarpium,CRP),embodying the traditional concept of“homology of food and med-icine”,has been regarded as higher quality with prolonged aging.In this study,Xinhui-origin CRP was adopted and its main compounds were identified as hesperidin,isosinensetin,sinensetin,6-demethoxytangeretin,nobi-letin,3,5,6,7,8,3′,4′-heptamethoxyflavone,tangeretin,and 5-O-demethynobiletin.Over an aging period of 3-15 years,the contents of most flavonoids increased.Subsequently,the protective effect of CRP extracts against methylglyoxal(MGO)-induced toxicity was examined in RAW 264.7 macrophages.MGO is closely related to the progression of diabetic complications.Our results demonstrated that the 10-year CRP extract had the highest potential,with sinensetin being the responsible compound.Further experiments emphasized the role of transducin-like enhancer of split protein 2(TLE2)and Notch signaling pathway,which modulated the cellular responses of MGO exposure.Collectively,these findings highlight the beneficial effects of 10-year CRP and provide scientific evidence for its application in functional foods.
基金supported by the Guangdong Key R&D Program(Grant number:2022B0202030001).
文摘Nobiletin(NOB)is a kind of polymethoxyflavonoids(PMFs)exclusively present in citrus fruits.It exhibits diverse biological activities,with particular emphasis on its regulatory effect on lipid metabolism,which has garnered significant attention from researchers in recent years.The disorder of lipid metabolism serves as the underlying cause for a range of metabolic disorders.Both in vivo and in vitro studies have demonstrated that NOB and its metabolites possess the ability to regulate lipid metabolism in conditions associated with lipid metabolism disorders,including obesity,fatty liver,diabetes,and atherosclerosis.Furthermore,they can mitigate the progression of these diseases.The modulation of inflammatory state,reduction of oxidative stress,regulation of microbiota and lipid metabolism pathway are likely to be crucial mechanisms through which NOB exerts its effects on lipid metabolism.Additionally,NOB is a small molecule known to regulate circadian rhythm,which also serves as an important target for NOB in regulating lipid metabolism.This article presents a comprehensive review of the primary research findings on the impact of NOB and its metabolites on lipid metabolism disorders-related diseases,while also analyzing the mechanism of action underlying NOB's effects.These insights provide a solid theoretical foundation for further research and development into NOB,ultimately maximizing the beneficial impacts of citrus fruits.
