Objective: To explore the possibility of using traditional Chinese medicine (TCM) in treating β thalassemia, its clinical effect and molecular mechanism of the action.Methods: According to the TCM theory of“Shen pro...Objective: To explore the possibility of using traditional Chinese medicine (TCM) in treating β thalassemia, its clinical effect and molecular mechanism of the action.Methods: According to the TCM theory of“Shen producing marrow”, the composite recipe, Yisui Shenxueling Granule (YSSXL), consisting of Chinese drugs for nourishing Shen and supplementing marrow (NS&SM) was given orally to 7 8 patients with β thalassemia (49 of the severe type and 29 of moderate type ), 3 times a day, 10 g each time (for children, the dose would be reduced proper ly), with 3 months as one therapeutic course, and no blood transfusion used in t he course. The clinical therapeutic efficacy and hematologic parameters in patie nts were observed, and systemic gene analysis was conducted with PAGE, PCR, PCR SSCP, RT PCR and DNA sequences analysis and mRNA detection, in order to s tudy the molecular mechanism from the relationships between genetic mutation and clinical efficacy, gene expression and its regulation. Results: YSSXL showed obvious therapeutic effect in treating β thalassemia. Gene analysis revealed that it did not change the genetic mutatio n type, but could obviously increase hemoglobin, fetal hemoglobin (HbF), γ/(β+ γ) globin ratio, γ globin mRNA expression and GM CSF mRNA expression in patients, as well as the GM CSFmRMA in marrow of mice after 60 Co radia tion. Conclusion: YSSXL has a remarkable therapeutic effect on β tha lassemia, and its possible mechanism is its action in unlocking γ gene, in creasing the γ globin expression and enhancing HbF synthesis so as to compe nsate for the gene defect. This study has opened a new path for the treatment of β thalassemia with TCM.展开更多
BACKGROUND Liver fibrosis is a common health problem worldwide and there is still a lack of effective medicines.The Chinese herbal medicine,Gan Shen Fu Fang(GSFF)is composed of salvianolic acid B and diammonium glycyr...BACKGROUND Liver fibrosis is a common health problem worldwide and there is still a lack of effective medicines.The Chinese herbal medicine,Gan Shen Fu Fang(GSFF)is composed of salvianolic acid B and diammonium glycyrrhizinate.In this study,we observed the effects of GSFF on liver fibrosis in vivo and in vitro in an attempt to provide some hope for the treatment.AIM To observe the effects of GSFF on liver fibrosis in vivo and in vitro and investigate the mechanism from the perspective of the inflammatory response and extracellular signal-regulated kinase(ERK)phosphorylation.METHODS Common bile duct-ligated rats were used for in vivo experiments.Hepatic stellate cells-T6(HSC-T6)cells were used for in vitro experiments.Hematoxylin and eosin staining and Masson staining,biochemical assays,hydroxyproline(Hyp)assays,enzyme-linked immunoasorbent assay and western blotting were performed to evaluate the degree of liver fibrosis,liver function,the inflammatory response and ERK phosphorylation.The CCK8 assay,immunofluorescence and western blotting were applied to test the effect of GSFF on HSC-T6 cell activation and determine whether GSFF had an effect on ERK phosphorylation in HSC-T6 cells.RESULTS GSFF improved liver function and inhibited liver fibrosis in common bile ductligated rats after 3 wk of treatment,as demonstrated by histological changes,hydroxyproline assays and collagen I concentrations.GSFF alleviated inflammatory cell infiltration and reduced the synthesis of pro-inflammatory cytokines[tumor necrosis factor-α(TNF-α)and interlukin-1β]and NF-κB.In addition,GSFF decreased ERK phosphorylation.In vitro,GSFF inhibited the viability of HSC-T6 cells with and without transforming growth factorβ1(TGF-β1)stimulation and decreased the synthesis of collagen I.GSFF had the greatest effect at a concentration of 0.5μmol/L.GSFF inhibited the expression ofα-smooth muscle actin(α-SMA),a marker of HSC activation,in HSC-T6 cells.Consistent with the in vivo results,GSFF also inhibited the phosphorylation of ERK and downregulated the expression of NF-κB.CONCLUSION GSFF inhibited liver fibrosis progression in vivo and HSC-T6 cell activation in vitro.These effects may be related to an alleviated inflammatory response and downregulated ERK phosphorylation.展开更多
基金This item was supported by National Funds of Natural Sciences (No. 3017119 9) and Natural Science Foundation of Guangxi Autonomous Region (No. 014402C)
文摘Objective: To explore the possibility of using traditional Chinese medicine (TCM) in treating β thalassemia, its clinical effect and molecular mechanism of the action.Methods: According to the TCM theory of“Shen producing marrow”, the composite recipe, Yisui Shenxueling Granule (YSSXL), consisting of Chinese drugs for nourishing Shen and supplementing marrow (NS&SM) was given orally to 7 8 patients with β thalassemia (49 of the severe type and 29 of moderate type ), 3 times a day, 10 g each time (for children, the dose would be reduced proper ly), with 3 months as one therapeutic course, and no blood transfusion used in t he course. The clinical therapeutic efficacy and hematologic parameters in patie nts were observed, and systemic gene analysis was conducted with PAGE, PCR, PCR SSCP, RT PCR and DNA sequences analysis and mRNA detection, in order to s tudy the molecular mechanism from the relationships between genetic mutation and clinical efficacy, gene expression and its regulation. Results: YSSXL showed obvious therapeutic effect in treating β thalassemia. Gene analysis revealed that it did not change the genetic mutatio n type, but could obviously increase hemoglobin, fetal hemoglobin (HbF), γ/(β+ γ) globin ratio, γ globin mRNA expression and GM CSF mRNA expression in patients, as well as the GM CSFmRMA in marrow of mice after 60 Co radia tion. Conclusion: YSSXL has a remarkable therapeutic effect on β tha lassemia, and its possible mechanism is its action in unlocking γ gene, in creasing the γ globin expression and enhancing HbF synthesis so as to compe nsate for the gene defect. This study has opened a new path for the treatment of β thalassemia with TCM.
基金Supported by the Innovation Team of the Beijing University of Chinese Medicine,No.2019-JYB-TD-006the National Natural Science Foundation of China,No.81873099Scientific Research Support Plan for the Construction of Doctoral Program of University of Tibetan Medicine.
文摘BACKGROUND Liver fibrosis is a common health problem worldwide and there is still a lack of effective medicines.The Chinese herbal medicine,Gan Shen Fu Fang(GSFF)is composed of salvianolic acid B and diammonium glycyrrhizinate.In this study,we observed the effects of GSFF on liver fibrosis in vivo and in vitro in an attempt to provide some hope for the treatment.AIM To observe the effects of GSFF on liver fibrosis in vivo and in vitro and investigate the mechanism from the perspective of the inflammatory response and extracellular signal-regulated kinase(ERK)phosphorylation.METHODS Common bile duct-ligated rats were used for in vivo experiments.Hepatic stellate cells-T6(HSC-T6)cells were used for in vitro experiments.Hematoxylin and eosin staining and Masson staining,biochemical assays,hydroxyproline(Hyp)assays,enzyme-linked immunoasorbent assay and western blotting were performed to evaluate the degree of liver fibrosis,liver function,the inflammatory response and ERK phosphorylation.The CCK8 assay,immunofluorescence and western blotting were applied to test the effect of GSFF on HSC-T6 cell activation and determine whether GSFF had an effect on ERK phosphorylation in HSC-T6 cells.RESULTS GSFF improved liver function and inhibited liver fibrosis in common bile ductligated rats after 3 wk of treatment,as demonstrated by histological changes,hydroxyproline assays and collagen I concentrations.GSFF alleviated inflammatory cell infiltration and reduced the synthesis of pro-inflammatory cytokines[tumor necrosis factor-α(TNF-α)and interlukin-1β]and NF-κB.In addition,GSFF decreased ERK phosphorylation.In vitro,GSFF inhibited the viability of HSC-T6 cells with and without transforming growth factorβ1(TGF-β1)stimulation and decreased the synthesis of collagen I.GSFF had the greatest effect at a concentration of 0.5μmol/L.GSFF inhibited the expression ofα-smooth muscle actin(α-SMA),a marker of HSC activation,in HSC-T6 cells.Consistent with the in vivo results,GSFF also inhibited the phosphorylation of ERK and downregulated the expression of NF-κB.CONCLUSION GSFF inhibited liver fibrosis progression in vivo and HSC-T6 cell activation in vitro.These effects may be related to an alleviated inflammatory response and downregulated ERK phosphorylation.
