Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotect...Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.展开更多
Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of...Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control--media or media containing spermidine(5 μmol·L^(-1), SPD), alpha-difluoromethylornithine(2.5 mmol·L^(-1), DFMO), 4-Aminopyridine-(40 μ-mol·L^(-1), 4-AP), the polysaccharide extracts of RA or RAM(50, 100, or 200 mg·L^(-1)), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca^(2+)([Ca^(2+)]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca^(2+)]cyt and accelerated migration of IEC-6 cells, compared with the controls(P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca^(2+)]cyt, but also restored IEC-6 cell migration to control level(P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased(P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0:14.1:0.3:19.9:181.3:6.3 in RA and 1.0:4.3:0.1:5.7:2.8:2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.展开更多
Astragalus membranaceus(A.membranaceus)is a widely used traditional herb in China and Korea.A.membranaceus polysaccharides(AMP),which make up a major part of the root extract,have been shown to modulate immune modulat...Astragalus membranaceus(A.membranaceus)is a widely used traditional herb in China and Korea.A.membranaceus polysaccharides(AMP),which make up a major part of the root extract,have been shown to modulate immune modulations,especially activation of bone marrow-derived dendritic cells(BMDCs)and T cells.However,the immune stimulatory effect of AMP in the mouse in vivo and human peripheral blood DCs(PBDCs)has not been well investigated.In this study,we found that intravenous(i.v.)injection of AMP in C57 BL/6 mice induced remarkable elevations in co-stimulatory and MHC class I and II molecule levels in the splenic DCs and its subsets.The stimulatory effect of DCs by AMP was elevated 6 h after treatment,which rapidly decreased 18 h after injection.Furthermore,AMP promoted intracellular production of pro-inflammatory cytokines in spleen DC subsets,which contributed elevation of serum cytokine levels.Finally,the AMP promoted PBDC activation.Thus,these results demonstrate that AMP can be used as an immune stimulatory molecules in human and mouse.展开更多
A new water-soluble hetero-polysaccharlde, APSID3, was obtained from a hot-water extract of the roots of Astragalus membranaceus （Flsch.） Bunge by DEAE-Sepharose Fast Flow and Sephacryl S-300 chromatography. The mol...A new water-soluble hetero-polysaccharlde, APSID3, was obtained from a hot-water extract of the roots of Astragalus membranaceus （Flsch.） Bunge by DEAE-Sepharose Fast Flow and Sephacryl S-300 chromatography. The molecular weight of APSID3 was estimated to be 5.79 × 10^5 Da. Based on a sugar composlUon analysis, methylatlon analysis, partial hydrolysis and 13C nuclear magnetic resonance experimentation, It was concluded that the minimal repeat unit of APSID3 was composed of one terminal arablnose, one 1,5-1Inked arabinose, one 1,3-1Inked rhamnose, one 1,3,4-1Inked rhamnose, five 1,4-1Inked methyl galacturonates and six 1,4-1inked methyl glucuronates.展开更多
目的探讨黄芪总皂苷(total saponins of astragalus,TSA)对薄型子宫内膜的修复作用及相关机制。方法2022年1—4月,将36只雌性小鼠分为三组(n=12):假手术组(Sham组)、模型组(Model组)、治疗组(Model+TSA组)。宫腔灌注无水乙醇进行造模,...目的探讨黄芪总皂苷(total saponins of astragalus,TSA)对薄型子宫内膜的修复作用及相关机制。方法2022年1—4月,将36只雌性小鼠分为三组(n=12):假手术组(Sham组)、模型组(Model组)、治疗组(Model+TSA组)。宫腔灌注无水乙醇进行造模,治疗组小鼠腹腔注射TSA溶液(45 mg·kg^(-1)·d^(-1)),共3周。苏木精-伊红(HE)染色观察小鼠子宫内膜厚度及形态;扫描电子显微镜观察子宫内膜胞饮突;蛋白质印迹法检测各组小鼠子宫内膜容受性因子血管性血友病因子(vWF)、血管内皮生长因子(vEGF)、同源异型盒A10(HoxA10)、白血病抑制因子(LIF);观察小鼠妊娠胚胎数以评估生育力。结果与Sham组[(410.56±21.47)μm、(7.58±4.87)个、100.00±13.32、100.00±8.43、100.00±5.91、100.00±11.97、(10.98±1.24)个]相比,Model组小鼠子宫内膜厚度[(169.10±34.33)μm]、腺体数量[(1.00±0.86)个]、内膜容受性相关因子vWF(31.29±10.17)、vEGF(22.17±3.92)、HoxA10(30.26±6.37)、LIF(51.83±6.01),以及妊娠胚胎数[(2.42±1.37)个]明显降低(P<0.05);与Model组[(169.10±34.33)μm、1.00±0.86、31.29±10.17、22.17±3.92、30.26±6.37、51.83±6.01、(2.42±1.37)个]相比,Model+TSA组小鼠子宫内膜厚度[(337.89±32.18)μm)、腺体数量[(5.47±1.02)个]、vWF(69.18±5.88)、vEGF(49.40±11.37)、HoxA10(61.28±6.22)、LIF(90.29±12.77),以及妊娠胚胎数[(7.23±1.57)个]明显增加(P<0.05);Sham组小鼠子宫内膜可见成熟胞饮突表达;Model组小鼠子宫内膜未见明显成熟胞饮突,仅见少量小胞饮突表达;而Model+TSA组小鼠子宫内膜可见发育成熟的胞饮突。结论TSA可通过提高内膜容受性发挥对薄型子宫内膜的修复作用。展开更多
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.
基金supported by the National Natural Science Foundation of China(Nos.30772753,81173254,and 81673940)the Science and Technology Program of Guangzhou(No.20160701335)the First-class discipline construction major project of Guangzhou University of Chinese Medicine(Guangzhou University of Chinese Medicine Planning,2018-No.6)
文摘Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control--media or media containing spermidine(5 μmol·L^(-1), SPD), alpha-difluoromethylornithine(2.5 mmol·L^(-1), DFMO), 4-Aminopyridine-(40 μ-mol·L^(-1), 4-AP), the polysaccharide extracts of RA or RAM(50, 100, or 200 mg·L^(-1)), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca^(2+)([Ca^(2+)]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca^(2+)]cyt and accelerated migration of IEC-6 cells, compared with the controls(P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca^(2+)]cyt, but also restored IEC-6 cell migration to control level(P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased(P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0:14.1:0.3:19.9:181.3:6.3 in RA and 1.0:4.3:0.1:5.7:2.8:2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.
基金supported by the 2019 Yeungnam University Research Grant。
文摘Astragalus membranaceus(A.membranaceus)is a widely used traditional herb in China and Korea.A.membranaceus polysaccharides(AMP),which make up a major part of the root extract,have been shown to modulate immune modulations,especially activation of bone marrow-derived dendritic cells(BMDCs)and T cells.However,the immune stimulatory effect of AMP in the mouse in vivo and human peripheral blood DCs(PBDCs)has not been well investigated.In this study,we found that intravenous(i.v.)injection of AMP in C57 BL/6 mice induced remarkable elevations in co-stimulatory and MHC class I and II molecule levels in the splenic DCs and its subsets.The stimulatory effect of DCs by AMP was elevated 6 h after treatment,which rapidly decreased 18 h after injection.Furthermore,AMP promoted intracellular production of pro-inflammatory cytokines in spleen DC subsets,which contributed elevation of serum cytokine levels.Finally,the AMP promoted PBDC activation.Thus,these results demonstrate that AMP can be used as an immune stimulatory molecules in human and mouse.
文摘A new water-soluble hetero-polysaccharlde, APSID3, was obtained from a hot-water extract of the roots of Astragalus membranaceus （Flsch.） Bunge by DEAE-Sepharose Fast Flow and Sephacryl S-300 chromatography. The molecular weight of APSID3 was estimated to be 5.79 × 10^5 Da. Based on a sugar composlUon analysis, methylatlon analysis, partial hydrolysis and 13C nuclear magnetic resonance experimentation, It was concluded that the minimal repeat unit of APSID3 was composed of one terminal arablnose, one 1,5-1Inked arabinose, one 1,3-1Inked rhamnose, one 1,3,4-1Inked rhamnose, five 1,4-1Inked methyl galacturonates and six 1,4-1inked methyl glucuronates.
文摘目的探讨黄芪总皂苷(total saponins of astragalus,TSA)对薄型子宫内膜的修复作用及相关机制。方法2022年1—4月,将36只雌性小鼠分为三组(n=12):假手术组(Sham组)、模型组(Model组)、治疗组(Model+TSA组)。宫腔灌注无水乙醇进行造模,治疗组小鼠腹腔注射TSA溶液(45 mg·kg^(-1)·d^(-1)),共3周。苏木精-伊红(HE)染色观察小鼠子宫内膜厚度及形态;扫描电子显微镜观察子宫内膜胞饮突;蛋白质印迹法检测各组小鼠子宫内膜容受性因子血管性血友病因子(vWF)、血管内皮生长因子(vEGF)、同源异型盒A10(HoxA10)、白血病抑制因子(LIF);观察小鼠妊娠胚胎数以评估生育力。结果与Sham组[(410.56±21.47)μm、(7.58±4.87)个、100.00±13.32、100.00±8.43、100.00±5.91、100.00±11.97、(10.98±1.24)个]相比,Model组小鼠子宫内膜厚度[(169.10±34.33)μm]、腺体数量[(1.00±0.86)个]、内膜容受性相关因子vWF(31.29±10.17)、vEGF(22.17±3.92)、HoxA10(30.26±6.37)、LIF(51.83±6.01),以及妊娠胚胎数[(2.42±1.37)个]明显降低(P<0.05);与Model组[(169.10±34.33)μm、1.00±0.86、31.29±10.17、22.17±3.92、30.26±6.37、51.83±6.01、(2.42±1.37)个]相比,Model+TSA组小鼠子宫内膜厚度[(337.89±32.18)μm)、腺体数量[(5.47±1.02)个]、vWF(69.18±5.88)、vEGF(49.40±11.37)、HoxA10(61.28±6.22)、LIF(90.29±12.77),以及妊娠胚胎数[(7.23±1.57)个]明显增加(P<0.05);Sham组小鼠子宫内膜可见成熟胞饮突表达;Model组小鼠子宫内膜未见明显成熟胞饮突,仅见少量小胞饮突表达;而Model+TSA组小鼠子宫内膜可见发育成熟的胞饮突。结论TSA可通过提高内膜容受性发挥对薄型子宫内膜的修复作用。
