Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a we...Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.展开更多
Precise determination of cation diffusivity in garnet can provide critical information for quantitatively understanding the timescales and thermodynamics of various geological processes,but very few studies have been ...Precise determination of cation diffusivity in garnet can provide critical information for quantitatively understanding the timescales and thermodynamics of various geological processes,but very few studies have been performed for Fe-Mn interdiffusion.In this study,Fe-Mn interdiffusion rates in natural single crystals of Mn-bearing garnet with 750 ppm H2O are determined at 6 GPa and 1273-1573 K in a Kawai-type multi-anvil apparatus.Diffusion profiles were acquired by electron microprobe and fitted using Boltzmann-Matano equation.The experimental results show that the Fe-Mn interdiffusion coefficient(DFe-Mn)slightly decreases with increasing XFe.The experimentally determined DFe-Mn in Mn-bearing garnet can be fitted by the Arrhenius equation:DFe-Mn(m2/s)=D0XFenexp(-E*/RT),where E*=(1-XFe)E*Mn+XFeE*Fe,D0=8.06-6.04+9.87×10-9 m2/s,E*Mn=248±27 KJ/mol,E*Fe=226±59 KJ/mol,n=-1.36±0.51.The comparing the present results with previous experimental data suggest that water can greatly enhance the DFe-Mn in garnet.Our results indicate that the time required for homogenization of the compositional zoning of a garnet is much shorter than previously thought.展开更多
基金This work is supported by National Natural Science Foundation of China(82270500,81870324,82203304,82070464,U1401225,U21A20419)National Mega-Project for Innovative Drugs(2019ZX09735002)+1 种基金Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036,2017BT01Y093,China)National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,2017B090903004,China).
文摘Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.
基金supported by the National Natural Science Foundation of China (41973056,41773056)Key Research Program of Frontier Sciences of CAS (ZDBS-LY-DQC015)to B.Zhang+1 种基金the Fundamental Research Funds for the Central Universities (K20210168)Data presented as part of this study are available from Zenodo (https://doi.org/10.5281/zenodo.7080353).
文摘Precise determination of cation diffusivity in garnet can provide critical information for quantitatively understanding the timescales and thermodynamics of various geological processes,but very few studies have been performed for Fe-Mn interdiffusion.In this study,Fe-Mn interdiffusion rates in natural single crystals of Mn-bearing garnet with 750 ppm H2O are determined at 6 GPa and 1273-1573 K in a Kawai-type multi-anvil apparatus.Diffusion profiles were acquired by electron microprobe and fitted using Boltzmann-Matano equation.The experimental results show that the Fe-Mn interdiffusion coefficient(DFe-Mn)slightly decreases with increasing XFe.The experimentally determined DFe-Mn in Mn-bearing garnet can be fitted by the Arrhenius equation:DFe-Mn(m2/s)=D0XFenexp(-E*/RT),where E*=(1-XFe)E*Mn+XFeE*Fe,D0=8.06-6.04+9.87×10-9 m2/s,E*Mn=248±27 KJ/mol,E*Fe=226±59 KJ/mol,n=-1.36±0.51.The comparing the present results with previous experimental data suggest that water can greatly enhance the DFe-Mn in garnet.Our results indicate that the time required for homogenization of the compositional zoning of a garnet is much shorter than previously thought.