The fruits of Amomum tsao-ko(Cao-Guo)were documented in Chinese Pharmacopoeia for the treatment of abdominal pain,vomiting,and plague.In our previous study,a series of diarylheptanes and flavonoids withα-glucosidase ...The fruits of Amomum tsao-ko(Cao-Guo)were documented in Chinese Pharmacopoeia for the treatment of abdominal pain,vomiting,and plague.In our previous study,a series of diarylheptanes and flavonoids withα-glucosidase and protein tyrosine phosphatase 1B(PTP1B)inhibitory activity have been reported from the middle-polarity part of A.tsao-ko,whereas the antidiabetic potency of the low-polarity constituents is still unclear.In this study,three new hydroxytetradecenals,(2E,4E,8Z,11Z)-6R-hydroxytetradeca-2,4,8,11-tetraenal(1),(2E,4E,8Z)-6R-hydroxytetradeca-2,4,8-trienal(2)and(2E,4E)-6R-hydroxytetradeca-2,4-dienal(3)were obtained from the volatile oils of A.tsao-ko.The structures of compounds 1–3 were determined using spectroscopic data involving 1D and 2D nuclear magnetic resonance(NMR),high-resolution mass spectra(HRMS),and specific rotation([α]D).Their hypoglycemic activity was evaluated against glycogen phosphorylase(GPa)and PTP1B.Compounds 1 and 2 displayed moderate activity against PTP1B with inhibition rates of 33.8%−50.3%at 100 and 200μM.Moreover,compound 1 exhibited an obvious inhibitory effect on GPa(IC50=31.7μM),whereas compound 2 was inactive.This study demonstrates hydroxytetradecenals as the characteristic components of A.tsao-ko with therapeutic potential in diabetes.展开更多
The plant hormones salicylic acid(SA)and jasmonic acid(JA)act in mutual negative-feedback regulation to balance plant growth-defense trade-off.Heterotrimeric Gα-Gβ-Gγproteins are hubs that regulate defense signalin...The plant hormones salicylic acid(SA)and jasmonic acid(JA)act in mutual negative-feedback regulation to balance plant growth-defense trade-off.Heterotrimeric Gα-Gβ-Gγproteins are hubs that regulate defense signaling.In Arabidopsis,the Gα(GPA1)and Gβ(AGB1)subunits are required for defense against biotrophic and necrotrophic pathogens;however,the upstream and downstream molecular mechanisms underlying G protein-mediated defense remain largely unclear.In this study,we found that G proteins are primarily negative regulators of JA signaling in response to pathogen attack.Both TCP14 and JAZs are transcriptional regulators in the JA pathways.We revealed that GPA1 interacts with TCP14 within nuclear foci,and AGB1 interacts with TCP14 and most of JAZ regulators,including JAZ3.Mechanistically,GPA1 slows the proteasomal degradation of the G protein-TCP14-JAZ3 complex,a process that is normally promoted by JA and the bacterial virulence effector HopBB1,thus boosting SA-based defense.In turn,GPA1 activity is regulated by JA-induced phosphorylation at a conserved residue located near the nucleotide-binding pocket and other residues within the N-terminalαhelix.The phosphomimic mutations do not affect GTP binding or hydrolysis but enhance GPA1 interaction with TCP14 and JAZ3,thereby preventing their degradation.This newly discovered phosphorylation-dependent mechanism of de-sequestering G protein partners to modulate transcriptional regulation may extend to both yeast and human cells.展开更多
基金the Yunnan Major Scientific and Technological Program(202202AE090035)Xingdian Yingcai Project(YNWR-QNBJ-2018-061)+2 种基金the Yunnan Fundamental Research Projects(202201AV070010,202301AS070069)Yunnan Province Science and Technology Department(202305AH340005)the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2022-KF12).
文摘The fruits of Amomum tsao-ko(Cao-Guo)were documented in Chinese Pharmacopoeia for the treatment of abdominal pain,vomiting,and plague.In our previous study,a series of diarylheptanes and flavonoids withα-glucosidase and protein tyrosine phosphatase 1B(PTP1B)inhibitory activity have been reported from the middle-polarity part of A.tsao-ko,whereas the antidiabetic potency of the low-polarity constituents is still unclear.In this study,three new hydroxytetradecenals,(2E,4E,8Z,11Z)-6R-hydroxytetradeca-2,4,8,11-tetraenal(1),(2E,4E,8Z)-6R-hydroxytetradeca-2,4,8-trienal(2)and(2E,4E)-6R-hydroxytetradeca-2,4-dienal(3)were obtained from the volatile oils of A.tsao-ko.The structures of compounds 1–3 were determined using spectroscopic data involving 1D and 2D nuclear magnetic resonance(NMR),high-resolution mass spectra(HRMS),and specific rotation([α]D).Their hypoglycemic activity was evaluated against glycogen phosphorylase(GPa)and PTP1B.Compounds 1 and 2 displayed moderate activity against PTP1B with inhibition rates of 33.8%−50.3%at 100 and 200μM.Moreover,compound 1 exhibited an obvious inhibitory effect on GPa(IC50=31.7μM),whereas compound 2 was inactive.This study demonstrates hydroxytetradecenals as the characteristic components of A.tsao-ko with therapeutic potential in diabetes.
基金supported by The Division of Chemical Sciences,Geosciences,and Biosciences,Office of Basic Energy Sciences of the US Department of Energy through grant DE-FG02-05er15671A.M.J.Funding was also provided by NIGMS(R01GM065989)and NSF(MCB-0718202 and IOS-2034929)awarded to A.M.J.,NIH grant(R35GM118105)awarded to H.G.D.,grant PID2021-1260060OB-I00 funded by MCIN/AEI/10.13039/501100011033by“ERDFAway of making Europe"to A.M.and L.J.
文摘The plant hormones salicylic acid(SA)and jasmonic acid(JA)act in mutual negative-feedback regulation to balance plant growth-defense trade-off.Heterotrimeric Gα-Gβ-Gγproteins are hubs that regulate defense signaling.In Arabidopsis,the Gα(GPA1)and Gβ(AGB1)subunits are required for defense against biotrophic and necrotrophic pathogens;however,the upstream and downstream molecular mechanisms underlying G protein-mediated defense remain largely unclear.In this study,we found that G proteins are primarily negative regulators of JA signaling in response to pathogen attack.Both TCP14 and JAZs are transcriptional regulators in the JA pathways.We revealed that GPA1 interacts with TCP14 within nuclear foci,and AGB1 interacts with TCP14 and most of JAZ regulators,including JAZ3.Mechanistically,GPA1 slows the proteasomal degradation of the G protein-TCP14-JAZ3 complex,a process that is normally promoted by JA and the bacterial virulence effector HopBB1,thus boosting SA-based defense.In turn,GPA1 activity is regulated by JA-induced phosphorylation at a conserved residue located near the nucleotide-binding pocket and other residues within the N-terminalαhelix.The phosphomimic mutations do not affect GTP binding or hydrolysis but enhance GPA1 interaction with TCP14 and JAZ3,thereby preventing their degradation.This newly discovered phosphorylation-dependent mechanism of de-sequestering G protein partners to modulate transcriptional regulation may extend to both yeast and human cells.
