Objective: Quercetin-3-O-β-D-glucuronide(QG) can alleviate immunological bone marrow failure(BMF) by increasing platelet counts. However, the principal mechanism is less known. This study aimed at deciphering the pos...Objective: Quercetin-3-O-β-D-glucuronide(QG) can alleviate immunological bone marrow failure(BMF) by increasing platelet counts. However, the principal mechanism is less known. This study aimed at deciphering the possible underlying mechanism of QG that is indicated in thrombocytopenic purpura. Methods: In vitro and in vivo experiments were carried out for investigating the mechanism behind QG-facilitated inhibition of mitochondrial pathway-mediated excessive apoptosis of platelets through the phosphatidylinositol-3-kinase(PI3K)/AKT pathway. Results: Our results revealed that QG, the main effective ingredient of Herba Sarcandrae, increases the number of platelets and decreases the expression of Bax, Bad, Bid, and caspase-9 in immunological BMF, indicating the inhibition of mitochondrial pathway-mediated apoptosis. Moreover, we found that the protein and m RNA expressions, as well as the phosphorylated levels of PI3K and AKT, were increased significantly by QG, suggesting the activation of the PI3K/AKT pathway. Furthermore, the inhibition of the PI3K/AKT pathway by LY294002 antagonizes the effects of QG on platelet counts and mitochondrial pathway-mediated apoptosis. Conclusion: We demonstrate that QG inhibits the mitochondria pathway-mediated platelet apoptosis via the PI3K/AKT pathway in immunological BMF. This study thus sheds light on exploring the possible regulatory mechanism of traditional Chinese medicine in the treatment of thrombocytopenia induced by BMF.展开更多
Objective To search for the microorganisms which have the high selectivity of hydrolyzing glycyrrhizic acid(GL) into 18β-glycyrrhetinic acid-3-O-β-D-glucuronide(GAMG) without glycyrrhetinic acid(GA) byproduct.Method...Objective To search for the microorganisms which have the high selectivity of hydrolyzing glycyrrhizic acid(GL) into 18β-glycyrrhetinic acid-3-O-β-D-glucuronide(GAMG) without glycyrrhetinic acid(GA) byproduct.Methods GL was biotransformed by Aspergillus sp.,the products were separated by chromatography on reverse phase C18 column and semi-preparative HPLC,and their structures were elucidated on the basis of HR-ESI-MS,1D NMR(1H-NMR,13C-NMR,and NOESY) and 2D NMR(1H-1H COSY,HSQC,and HMBC) spectral analyses.Results Aspergillus sp.could partially hydrolyze GL into GAMG(3),along with two minor byproducts,3-O-β-D-glucuronopyranosyl-18β-liquiritic acid(1) and 3-O-β-D-glucuronopyranosyl-24-hydroxy-18β-glycyrrhetinic acid(2).Conclusion Aspergillus sp.has the high selectivity of hydrolyzing GL into GAMG without GA byproduct and the yield of GAMG is about 60%.The complete assignments of 1H-NMR and 13C-NMR data for compounds 1 and 2 are reported for the first time.展开更多
基金supported by the research project of health sciences of Shanghai Jing’an District (2019MS02)Shanghai Bao’shan science and technology commission (18-E-10)+1 种基金the research project of Shanghai municipal commission of health and family planning (201640144,20184Y0094)Shanghai science and technology commission (18401903800)。
文摘Objective: Quercetin-3-O-β-D-glucuronide(QG) can alleviate immunological bone marrow failure(BMF) by increasing platelet counts. However, the principal mechanism is less known. This study aimed at deciphering the possible underlying mechanism of QG that is indicated in thrombocytopenic purpura. Methods: In vitro and in vivo experiments were carried out for investigating the mechanism behind QG-facilitated inhibition of mitochondrial pathway-mediated excessive apoptosis of platelets through the phosphatidylinositol-3-kinase(PI3K)/AKT pathway. Results: Our results revealed that QG, the main effective ingredient of Herba Sarcandrae, increases the number of platelets and decreases the expression of Bax, Bad, Bid, and caspase-9 in immunological BMF, indicating the inhibition of mitochondrial pathway-mediated apoptosis. Moreover, we found that the protein and m RNA expressions, as well as the phosphorylated levels of PI3K and AKT, were increased significantly by QG, suggesting the activation of the PI3K/AKT pathway. Furthermore, the inhibition of the PI3K/AKT pathway by LY294002 antagonizes the effects of QG on platelet counts and mitochondrial pathway-mediated apoptosis. Conclusion: We demonstrate that QG inhibits the mitochondria pathway-mediated platelet apoptosis via the PI3K/AKT pathway in immunological BMF. This study thus sheds light on exploring the possible regulatory mechanism of traditional Chinese medicine in the treatment of thrombocytopenia induced by BMF.
基金National Science & Technology Pillar Program (2011BAI07B02-5)
文摘Objective To search for the microorganisms which have the high selectivity of hydrolyzing glycyrrhizic acid(GL) into 18β-glycyrrhetinic acid-3-O-β-D-glucuronide(GAMG) without glycyrrhetinic acid(GA) byproduct.Methods GL was biotransformed by Aspergillus sp.,the products were separated by chromatography on reverse phase C18 column and semi-preparative HPLC,and their structures were elucidated on the basis of HR-ESI-MS,1D NMR(1H-NMR,13C-NMR,and NOESY) and 2D NMR(1H-1H COSY,HSQC,and HMBC) spectral analyses.Results Aspergillus sp.could partially hydrolyze GL into GAMG(3),along with two minor byproducts,3-O-β-D-glucuronopyranosyl-18β-liquiritic acid(1) and 3-O-β-D-glucuronopyranosyl-24-hydroxy-18β-glycyrrhetinic acid(2).Conclusion Aspergillus sp.has the high selectivity of hydrolyzing GL into GAMG without GA byproduct and the yield of GAMG is about 60%.The complete assignments of 1H-NMR and 13C-NMR data for compounds 1 and 2 are reported for the first time.
