A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidat...A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.展开更多
目的研究姜黄素与高脂饮食小鼠胆囊胆固醇性结石关系及可能参与调控过程的因子。方法将C57BL6小鼠50只随机分为5组,其中一组予普通饲料,其余四组予高脂饮食饲料,同时灌喂不同剂量姜黄素[0、200、500、1 000 mg/(kg·d)],共4周。计...目的研究姜黄素与高脂饮食小鼠胆囊胆固醇性结石关系及可能参与调控过程的因子。方法将C57BL6小鼠50只随机分为5组,其中一组予普通饲料,其余四组予高脂饮食饲料,同时灌喂不同剂量姜黄素[0、200、500、1 000 mg/(kg·d)],共4周。计算小鼠胆囊结石成石率,收集小鼠血液、胆囊胆汁、胆囊、肝脏以及小肠。计算胆囊容积,称量肝脏质量,检测血液及胆汁胆固醇、甘油三酯等生化指标。用Realtime PCR及Western blotting方法分别检测小鼠小肠上皮NPC1L1及SREBP2 m RNA及蛋白表达。结果姜黄素能够降低小鼠胆囊结石的发生,大剂量姜黄素可降低胆囊结石发生率达60%,同时降低肝脏脂肪变性程度,降低小鼠血液胆固醇饱和度。同时,姜黄素可以抑制高脂饮食所致的NPC1L1 m RNA表达上调[(2.65±0.04)vs(2.06±0.07),(1.69±0.06),(1.33±0.05),P<0.01],且呈现剂量依赖关系,降低高脂饮食所致的NPC1L1蛋白高表达。姜黄素还可以抑制高脂饮食所致的SREBP2 m RNA表达上调[(1.34±0.08)vs(1.39±0.03),(1.19±0.01),(1.06±0.03),P<0.05],且呈现剂量依赖关系,降低高脂饮食所致的SREBP2蛋白表达上调。结论姜黄素能够降低高脂饮食小鼠胆囊结石的形成,NPC1L1和SREBP2可能参与了这个过程。展开更多
基金Supported by the China Agriculture Research System of MOF and MARA(CARS-21)the Financial Fund of the Ministry of Agriculture and Rural Affairs,China(No.NFZX2021)the National Natural Science Foundation of China(No.81973568)。
文摘A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.
文摘目的研究姜黄素与高脂饮食小鼠胆囊胆固醇性结石关系及可能参与调控过程的因子。方法将C57BL6小鼠50只随机分为5组,其中一组予普通饲料,其余四组予高脂饮食饲料,同时灌喂不同剂量姜黄素[0、200、500、1 000 mg/(kg·d)],共4周。计算小鼠胆囊结石成石率,收集小鼠血液、胆囊胆汁、胆囊、肝脏以及小肠。计算胆囊容积,称量肝脏质量,检测血液及胆汁胆固醇、甘油三酯等生化指标。用Realtime PCR及Western blotting方法分别检测小鼠小肠上皮NPC1L1及SREBP2 m RNA及蛋白表达。结果姜黄素能够降低小鼠胆囊结石的发生,大剂量姜黄素可降低胆囊结石发生率达60%,同时降低肝脏脂肪变性程度,降低小鼠血液胆固醇饱和度。同时,姜黄素可以抑制高脂饮食所致的NPC1L1 m RNA表达上调[(2.65±0.04)vs(2.06±0.07),(1.69±0.06),(1.33±0.05),P<0.01],且呈现剂量依赖关系,降低高脂饮食所致的NPC1L1蛋白高表达。姜黄素还可以抑制高脂饮食所致的SREBP2 m RNA表达上调[(1.34±0.08)vs(1.39±0.03),(1.19±0.01),(1.06±0.03),P<0.05],且呈现剂量依赖关系,降低高脂饮食所致的SREBP2蛋白表达上调。结论姜黄素能够降低高脂饮食小鼠胆囊结石的形成,NPC1L1和SREBP2可能参与了这个过程。
