Coumarins belong to a diverse group of naturally occurring non-nutrient phytochemicals known as benzo-α- pyrones. In this study, esculetin, a 6,7-dihydroxy derivative of coumarin with pleiotropic biological activitie...Coumarins belong to a diverse group of naturally occurring non-nutrient phytochemicals known as benzo-α- pyrones. In this study, esculetin, a 6,7-dihydroxy derivative of coumarin with pleiotropic biological activities, was found to have no significant cytotoxic effect on normal murine macrophages, but it could increase the in vivo migration of the thioglycollate-elicited macrophages in a dose-dependent manner. Moreover, esculetin significantly increased the endocytic activity, and augmented the nitric oxide production and iNOS gene expression in LPS-treated macrophages. In addition, in vivo administration of esculetin into mice was shown to increase the mitogenesis of splenic lymphocytes towards Con A and LPS stimulations, and induced the LAK activity of splenic lymphocytes. Collectively, our results indicate that esculetin could exert immunomodulatory effects on murine macrophages and lymphocytes, both in vitro and in vivo, and this might be one of the possible mechanisms by which coumarins can exert their chemopreventive and anti-tumor activities in vivo. Cellular ＆ Molecular Immunology. 2005;2（3）： 181-188.展开更多
Esculetin,a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini,has a variety of pharmacological effects,especially in anti-inflammation.However,it is not clear whether escule...Esculetin,a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini,has a variety of pharmacological effects,especially in anti-inflammation.However,it is not clear whether esculetin has a therapeutic effect on sepsis.This study aimed to investigate the anti-inflammatory and protective effects of esculetin on early sepsis.The results showed that the lung injury was significantly relieved with the treatment of esculetin,accompanied with the restrained production of inflammatory factors including IL-1β,IL-6,TNF-α,CCL2 and iNOS during the early phase of E.coli-induced sepsis.Of note,activation of NF-κB and STAT1/STAT3 signals,the main upstream signals of many inflammatory factors,were attenuated by esculetin in both lung tissues from septic mice and LPS-stimulated macrophage.These findings suggested that the protection of esculetin against early sepsis should be related to its anti-inflammatory effect,which was at least partly due to its inhibition on NF-κB and STAT1/STAT3 signaling pathway in macrophage.Thus,esculetin could serve as a potential therapeutic agent by rebalancing innate immune response in macrophage for the treatment of early sepsis.展开更多
OBJECTIVE: To determine the effect of an esculetin formulation(at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s).METHODS: Sixty specific pathogen free-grade female Wi...OBJECTIVE: To determine the effect of an esculetin formulation(at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s).METHODS: Sixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups: blank control(n = 12), sham(n = 12), and model(n = 36). The model group were bilaterally ovariectomized. The sham group had the tissue surrounding the ovaries removed, while the ovaries were retained. After 3 months, the model group was randomly divided into three subgroups: OVX(n = 12), positive control(n = 12), and esculetin(n =12). The positive control group and the esculetin group were intragastrically administered diethylstilbestrol(0.046 mgkd^(-1)), respec·kg^(-1)tively,·d^(-1)) or esculetin(384 mgg^(-1) once per day for 6 consecu··-tive days; medication administration was then stopped for 1 d, before being administered for another 6 consecutive days. All rats were treated for 3months. Samples were collected at the end of the treatment period. An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density, and histomorphometric analysis was performed to measure bone mass, bone formation,and bone resorption. Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6(IL-6), osteoprotegerin(OPG), and receptor activator of nuclear factor-kappa B ligand(RANKL). Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells.RESULTS: Compared with the OVX group, the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume,and significantly smaller trabecular resorption surface. The percentage of trabecular formation surface, average osteoid width, trabecular bone mineralization rate, and cortical bone mineralization rate did not significantly differ between groups. Compared with the sham group, the esculetin group had significantly decreased serum levels of IL-6and RANKL, and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells; however, there was no significant difference between groups in OPG.CONCLUSION: Esculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells, and decreasing serum IL-6 concentration. This indicates that the therapeutic effect of esculetin on osteoporosis occurs via decreased bone resorption.展开更多
Molecularly imprinted polymers(MIPs)for solid-phase extraction and pre-concentration of esculetin have been successfully prepared by the bulk polymerization method using esculetin as a template molecule.Polymers of va...Molecularly imprinted polymers(MIPs)for solid-phase extraction and pre-concentration of esculetin have been successfully prepared by the bulk polymerization method using esculetin as a template molecule.Polymers of varying composition were prepared using different monomers(4-vinylpyridine,methacrylic acid,and acrylamide),ethylene glycol dimethacrylate as the cross-linker,2,2-azobis(2-methylpropinitrile)as the initiator,and different porogen solvents(ethanol,acetone/methanol,and acetonitrile).The best polymer was obtained when 4-vinylpyridine was used as the monomer and acetone/methanol(3:2)as the porogen solvent,whereas the template:-monomer:-cross-linker ratio was 1:4:20.The imprinting factor of the selected MIPs for esculetin was 3.77.The polymers were evaluated according to their selective recognition properties for esculetin and structurally-related compounds(esculin,scopoletin,coumarin,and 7-methoxycoumarin).Chemical and morphological characterizations of the polymers were investigated by FTIR and scanning electron microscope,which confirmed a high degree of polymerization.Surface area,pore volume,and pore size of the polymer were investigated by Brunauer-Emmett-Teller analysis.MIPs were also successfully used as solid-phase adsorbent materials for the extraction of esculetin from tobacco leaves.Esculetin contents in dried tobacco leaves were found to be(9.27±0.17)μg g-1.展开更多
文摘Coumarins belong to a diverse group of naturally occurring non-nutrient phytochemicals known as benzo-α- pyrones. In this study, esculetin, a 6,7-dihydroxy derivative of coumarin with pleiotropic biological activities, was found to have no significant cytotoxic effect on normal murine macrophages, but it could increase the in vivo migration of the thioglycollate-elicited macrophages in a dose-dependent manner. Moreover, esculetin significantly increased the endocytic activity, and augmented the nitric oxide production and iNOS gene expression in LPS-treated macrophages. In addition, in vivo administration of esculetin into mice was shown to increase the mitogenesis of splenic lymphocytes towards Con A and LPS stimulations, and induced the LAK activity of splenic lymphocytes. Collectively, our results indicate that esculetin could exert immunomodulatory effects on murine macrophages and lymphocytes, both in vitro and in vivo, and this might be one of the possible mechanisms by which coumarins can exert their chemopreventive and anti-tumor activities in vivo. Cellular ＆ Molecular Immunology. 2005;2（3）： 181-188.
基金supported by the Key Project of Scientific Research Fund of Hunan Provincial Education Department(15A177)the Natural Science Foundation of Hunan Province(2019JJ40275).
文摘Esculetin,a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini,has a variety of pharmacological effects,especially in anti-inflammation.However,it is not clear whether esculetin has a therapeutic effect on sepsis.This study aimed to investigate the anti-inflammatory and protective effects of esculetin on early sepsis.The results showed that the lung injury was significantly relieved with the treatment of esculetin,accompanied with the restrained production of inflammatory factors including IL-1β,IL-6,TNF-α,CCL2 and iNOS during the early phase of E.coli-induced sepsis.Of note,activation of NF-κB and STAT1/STAT3 signals,the main upstream signals of many inflammatory factors,were attenuated by esculetin in both lung tissues from septic mice and LPS-stimulated macrophage.These findings suggested that the protection of esculetin against early sepsis should be related to its anti-inflammatory effect,which was at least partly due to its inhibition on NF-κB and STAT1/STAT3 signaling pathway in macrophage.Thus,esculetin could serve as a potential therapeutic agent by rebalancing innate immune response in macrophage for the treatment of early sepsis.
基金Supported by Independent Subject Selection Project of the China Academy of Chinese Medical Sciences:Research on the New Function of Cortex Fraxini in the Treatment of Osteoporosis(No.YZ-1411)
文摘OBJECTIVE: To determine the effect of an esculetin formulation(at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s).METHODS: Sixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups: blank control(n = 12), sham(n = 12), and model(n = 36). The model group were bilaterally ovariectomized. The sham group had the tissue surrounding the ovaries removed, while the ovaries were retained. After 3 months, the model group was randomly divided into three subgroups: OVX(n = 12), positive control(n = 12), and esculetin(n =12). The positive control group and the esculetin group were intragastrically administered diethylstilbestrol(0.046 mgkd^(-1)), respec·kg^(-1)tively,·d^(-1)) or esculetin(384 mgg^(-1) once per day for 6 consecu··-tive days; medication administration was then stopped for 1 d, before being administered for another 6 consecutive days. All rats were treated for 3months. Samples were collected at the end of the treatment period. An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density, and histomorphometric analysis was performed to measure bone mass, bone formation,and bone resorption. Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6(IL-6), osteoprotegerin(OPG), and receptor activator of nuclear factor-kappa B ligand(RANKL). Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells.RESULTS: Compared with the OVX group, the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume,and significantly smaller trabecular resorption surface. The percentage of trabecular formation surface, average osteoid width, trabecular bone mineralization rate, and cortical bone mineralization rate did not significantly differ between groups. Compared with the sham group, the esculetin group had significantly decreased serum levels of IL-6and RANKL, and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells; however, there was no significant difference between groups in OPG.CONCLUSION: Esculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells, and decreasing serum IL-6 concentration. This indicates that the therapeutic effect of esculetin on osteoporosis occurs via decreased bone resorption.
基金supported by the Yunnan Green Tobacco Production Research(2011YN01)the China Equipment and Education Resources System(CERS-1-75)
文摘Molecularly imprinted polymers(MIPs)for solid-phase extraction and pre-concentration of esculetin have been successfully prepared by the bulk polymerization method using esculetin as a template molecule.Polymers of varying composition were prepared using different monomers(4-vinylpyridine,methacrylic acid,and acrylamide),ethylene glycol dimethacrylate as the cross-linker,2,2-azobis(2-methylpropinitrile)as the initiator,and different porogen solvents(ethanol,acetone/methanol,and acetonitrile).The best polymer was obtained when 4-vinylpyridine was used as the monomer and acetone/methanol(3:2)as the porogen solvent,whereas the template:-monomer:-cross-linker ratio was 1:4:20.The imprinting factor of the selected MIPs for esculetin was 3.77.The polymers were evaluated according to their selective recognition properties for esculetin and structurally-related compounds(esculin,scopoletin,coumarin,and 7-methoxycoumarin).Chemical and morphological characterizations of the polymers were investigated by FTIR and scanning electron microscope,which confirmed a high degree of polymerization.Surface area,pore volume,and pore size of the polymer were investigated by Brunauer-Emmett-Teller analysis.MIPs were also successfully used as solid-phase adsorbent materials for the extraction of esculetin from tobacco leaves.Esculetin contents in dried tobacco leaves were found to be(9.27±0.17)μg g-1.
