The EtOAc fraction of Alpinia katsumadai seeds showed significant inhibition on glycogen phosphorylase a(GPa)with inhibitory ratios of 97.9%and 64.6%at concentrations of 200 and 100μg/mL,respectively.Bioactivity-guid...The EtOAc fraction of Alpinia katsumadai seeds showed significant inhibition on glycogen phosphorylase a(GPa)with inhibitory ratios of 97.9%and 64.6%at concentrations of 200 and 100μg/mL,respectively.Bioactivity-guided isolation afforded 15 new diarylheptanoid-flavanone hybrids,katsumadainols B_(1)-B_(15)(1-15),together with eight known ones(16-23).Compounds 4-10 and 12-21 exhibited activity against GPa with IC_(50) values of 10.1-95.4μmol/L;compounds 4,5,16,and 17 displayed inhibitory effects onα-glucosidase with IC_(50) values of 7.1,12.4,7.2,and 8.3μmol/L,obviously higher than acarbose(IC_(50),209.1μmol/L);compounds 4-6,14,16-20,22,and 23 were PTP1B/TCPTP selective inhibitors with IC_(50) values of 40.7-95.8μmol/L;compounds 4,5,16,and 17 showed DPP4 inhibitory effects with inhibitory ratios of 50.0%-54.2%(200μmol/L).Diarylheptanoid-flavanone hybrids(4,5,16,and 17)with a p-hydroxybenzyl at C-6 position represent a promising class of multiple-target antidiabetic agents inhibiting GPa,α-glucosidase,PTP1B,and DPP4.展开更多
OBJECTIVE:To detect the effects of active compounds of Caodoukou(Semen Alpinia Katsumadai)(ACAK)on the proliferation,migration and invasion of pancreatic cancer,and explain the possible molecular mechanism of ACAK int...OBJECTIVE:To detect the effects of active compounds of Caodoukou(Semen Alpinia Katsumadai)(ACAK)on the proliferation,migration and invasion of pancreatic cancer,and explain the possible molecular mechanism of ACAK interacting with these processes.Methods:Cell counting kit-8 method,cell scratch repair experiment,Transwell migration and invasion experiment,immunohistochemistry,western blot assay and real-time polymerase chain reaction experiment were used to evaluate the effect of ACAK on the proliferation,migration and invasion of pancreatic cancer cells.The levels of active molecules involved in the phosphoinosmde-3-kinase(PI3K)/Akt/the mammalian target of rapamycin(m TOR)signal transduction were detected by Western blot assay.In addition,the function of ACAK in vivo was evaluated by xenotransplantation tumor model in nude mice.Results:The inhibitory effect of ACAK on the proliferation of pancreatic cancer cells showed certain time-dose dependence.The results of scratch repair test,Transwell test,Western blotting and real time polymerase chain reaction assay showed that ACAK could inhibit the migration and invasion of pancreatic cancer cells in vitro.In addition,the regulatory effect of ACAK on epithelialmesenchymal transition(EMT)is partly attributed to PI3K/Akt/mT OR signaling pathway.The experimental results in vivo showed that ACAK regulated the development of pancreatic cancer.Conclusions:ACAK can partly inhibit the activity of EMT and matrix metallopeptidases by down-regulating the downstream proteins of PI3K/Akt/mTOR signal pathway,thus inhibiting the ability of migration and invasion of pancreatic cancer.展开更多
基金This work was financially supported by the Yunnan Wanren Project(YNWR-QNBJ-2018-061)the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2020-KF05)+3 种基金the Postdoctoral Oriented Training Program of Yunnan Province(E131821261)the Special Research Assistant Project of Chinese Academy of Sciences(E12D9211Q1)the Yunnan Science Fund for Excellent Young Scholars(2019FI017)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province.
文摘The EtOAc fraction of Alpinia katsumadai seeds showed significant inhibition on glycogen phosphorylase a(GPa)with inhibitory ratios of 97.9%and 64.6%at concentrations of 200 and 100μg/mL,respectively.Bioactivity-guided isolation afforded 15 new diarylheptanoid-flavanone hybrids,katsumadainols B_(1)-B_(15)(1-15),together with eight known ones(16-23).Compounds 4-10 and 12-21 exhibited activity against GPa with IC_(50) values of 10.1-95.4μmol/L;compounds 4,5,16,and 17 displayed inhibitory effects onα-glucosidase with IC_(50) values of 7.1,12.4,7.2,and 8.3μmol/L,obviously higher than acarbose(IC_(50),209.1μmol/L);compounds 4-6,14,16-20,22,and 23 were PTP1B/TCPTP selective inhibitors with IC_(50) values of 40.7-95.8μmol/L;compounds 4,5,16,and 17 showed DPP4 inhibitory effects with inhibitory ratios of 50.0%-54.2%(200μmol/L).Diarylheptanoid-flavanone hybrids(4,5,16,and 17)with a p-hydroxybenzyl at C-6 position represent a promising class of multiple-target antidiabetic agents inhibiting GPa,α-glucosidase,PTP1B,and DPP4.
基金Sichuan Science and Technology program:Study on the Molecular Mechanism and Reversal Strategy of Drug Resistance in“T+A”Therapy for Liver Cancer,No.2022YSF0625)Joint Project from Luzhou city and Southwest Medical University:Study on Preparation and Anti-colon Cancer Activity of PEG-PLGA Nanoparticles from Active Fraction of Clove,No.20ykdhz0008)Grants from National Natural Science Foundation of China:Study on the Interaction between Granulin A and ENO1 and Its Molecular Mechanism of Inhibiting Tumor Growth and Metastasis(No.81773776)。
文摘OBJECTIVE:To detect the effects of active compounds of Caodoukou(Semen Alpinia Katsumadai)(ACAK)on the proliferation,migration and invasion of pancreatic cancer,and explain the possible molecular mechanism of ACAK interacting with these processes.Methods:Cell counting kit-8 method,cell scratch repair experiment,Transwell migration and invasion experiment,immunohistochemistry,western blot assay and real-time polymerase chain reaction experiment were used to evaluate the effect of ACAK on the proliferation,migration and invasion of pancreatic cancer cells.The levels of active molecules involved in the phosphoinosmde-3-kinase(PI3K)/Akt/the mammalian target of rapamycin(m TOR)signal transduction were detected by Western blot assay.In addition,the function of ACAK in vivo was evaluated by xenotransplantation tumor model in nude mice.Results:The inhibitory effect of ACAK on the proliferation of pancreatic cancer cells showed certain time-dose dependence.The results of scratch repair test,Transwell test,Western blotting and real time polymerase chain reaction assay showed that ACAK could inhibit the migration and invasion of pancreatic cancer cells in vitro.In addition,the regulatory effect of ACAK on epithelialmesenchymal transition(EMT)is partly attributed to PI3K/Akt/mT OR signaling pathway.The experimental results in vivo showed that ACAK regulated the development of pancreatic cancer.Conclusions:ACAK can partly inhibit the activity of EMT and matrix metallopeptidases by down-regulating the downstream proteins of PI3K/Akt/mTOR signal pathway,thus inhibiting the ability of migration and invasion of pancreatic cancer.
