From an aqueous extract of“tian ma”(the steamed and dried rhizomes of Gastrodia elata),ten new compounds gastrodiben-zins A−D(1−4)and gastrotribenzins A−F(5−10),along with known analogues(11−20),having structure fea...From an aqueous extract of“tian ma”(the steamed and dried rhizomes of Gastrodia elata),ten new compounds gastrodiben-zins A−D(1−4)and gastrotribenzins A−F(5−10),along with known analogues(11−20),having structure features coupling between two and three p-hydroxybenzyl-derived units via carbon-and/or ether-bonds,were isolated and characterized by spectroscopic data analysis.Meanwhile,the new compounds 5a,6a,8a,22,and 23,as well as the known derivatives 13a,14a,15,17−21,24,25,and p-hydroxybenzyl aldehyde were isolated and identified from a refluxed aqueous solution of p-hydroxybenzyl alcohol.Methylation of 5a and 6a in methanol and ethylation of 6a,8a,13a,and 14a in ethanol produced 5 and 6 and 7,8,13,and 14,respectively.using ultra-performance liquid chromatography high-resolution electrospray ioniza-tion mass spectrometry(UPLC-HRESIMS)analysis of the refluxed solutions of p-hydroxybenzyl alcohol and the refluxed extracts of the fresh G.elata rhizome and“tian ma”extracts indicated consistent production and variation of the dimeric and trimeric derivatives of p-hydroxybenzyl alcohol upon extracting solvents and refluxing time.In various assays,the dimeric and trimeric derivatives showed more potent activities than p-hydroxybenzyl alcohol itself and gastrodin,which are the main known active constituents of“tian ma”.These results revealed for the first time that the more effective dimers and trimers can be produced through condensation of the co-occurring p-hydroxybenzyl alcohol during processing and decocting of the G.elata rhizomes,demonstrating insights into medicinal chemistry behind application protocols of traditional Chinese medicines.展开更多
Parkinson's disease(PD)is a neurodegeneration disease withα-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while patients are diagnosed with...Parkinson's disease(PD)is a neurodegeneration disease withα-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while patients are diagnosed with PD.Exploring the pathology at an early stage contributes to the development of the disease-modifying strategy.Although the“gut–brain”hypothesis is proposed to explain the underlying mechanism,where the earlier lesioned site in the brain of gastricα-synuclein and howα-synuclein further spreads are not fully understood.Here we report that caudal raphe nuclei(CRN)are the early lesion site of gastricα-synuclein propagating through the spinal cord,while locus coeruleus(LC)and substantia nigra pars compacta(SNpc)were further affected over a time frame of 7 months.Pathologicalα-synuclein propagation via CRN leads to neuron loss and disordered neuron activity,accompanied by abnormal motor and non-motor behavior.Potential neuron circuits are observed among CRN,LC,and SNpc,which contribute to the venerability of dopaminergic neurons in SNpc.These results show that CRN is the key region for the gastricα-synuclein spread to the midbrain.Our study provides valuable details for the“gut–brain”hypothesis and proposes a valuable PD model for future research on early PD intervention.展开更多
The EtOH extracts of the whole plants of Euphorbia helioscopia afforded 17 new jatrophane diterpenoid esters, helioscopianoids A–Q(1–17), along with eight known compounds(18–25). Their structures were elucidated by...The EtOH extracts of the whole plants of Euphorbia helioscopia afforded 17 new jatrophane diterpenoid esters, helioscopianoids A–Q(1–17), along with eight known compounds(18–25). Their structures were elucidated by extensive spectroscopic methods and Mo_2(OAc)_4-induced ECD analysis,and the structures of compounds 1, 2, and 7 were confirmed by X-ray crystallography. Compounds 1–17 were evaluated for inhibitory effects on P-glycoprotein(P-gp) in an adriamycin(ADM)-resistant human breast adenocarcinoma cell line(MCF-7/ADR) and neuroprotective effects against serum deprivationinduced and rotenone-induced PC12 cell damage. Compounds 8 and 16 increased the accumulation of ADM in MCF-7/ADR cells by approximately 3-fold at a concentration of 20 μmol/L. Compound 8 could attenuate rotenone-induced PC12 cell damage, and compounds 2, 8, and 12 showed neuroprotective activities against serum deprivation-induced PC12 cell damage.展开更多
基金support from the National Natural Sciences Foundation of China(NNSFCGrant Nos.81730093,81630094,and 81502942)+1 种基金CAMS Innovation Fund for Medical Science of China(2017-I2M-3-010 and 2016-I2M-1-004)the Drug Innovation Major Project(2018ZX09711001-001,China)is acknowledged is acknowledged.
文摘From an aqueous extract of“tian ma”(the steamed and dried rhizomes of Gastrodia elata),ten new compounds gastrodiben-zins A−D(1−4)and gastrotribenzins A−F(5−10),along with known analogues(11−20),having structure features coupling between two and three p-hydroxybenzyl-derived units via carbon-and/or ether-bonds,were isolated and characterized by spectroscopic data analysis.Meanwhile,the new compounds 5a,6a,8a,22,and 23,as well as the known derivatives 13a,14a,15,17−21,24,25,and p-hydroxybenzyl aldehyde were isolated and identified from a refluxed aqueous solution of p-hydroxybenzyl alcohol.Methylation of 5a and 6a in methanol and ethylation of 6a,8a,13a,and 14a in ethanol produced 5 and 6 and 7,8,13,and 14,respectively.using ultra-performance liquid chromatography high-resolution electrospray ioniza-tion mass spectrometry(UPLC-HRESIMS)analysis of the refluxed solutions of p-hydroxybenzyl alcohol and the refluxed extracts of the fresh G.elata rhizome and“tian ma”extracts indicated consistent production and variation of the dimeric and trimeric derivatives of p-hydroxybenzyl alcohol upon extracting solvents and refluxing time.In various assays,the dimeric and trimeric derivatives showed more potent activities than p-hydroxybenzyl alcohol itself and gastrodin,which are the main known active constituents of“tian ma”.These results revealed for the first time that the more effective dimers and trimers can be produced through condensation of the co-occurring p-hydroxybenzyl alcohol during processing and decocting of the G.elata rhizomes,demonstrating insights into medicinal chemistry behind application protocols of traditional Chinese medicines.
基金This work was supported by the Natural Science Foundation of Beijing Municipality(No.7212156,China)CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1–026,China)National Natural Science Foundation of China,China(82373852).
文摘Parkinson's disease(PD)is a neurodegeneration disease withα-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while patients are diagnosed with PD.Exploring the pathology at an early stage contributes to the development of the disease-modifying strategy.Although the“gut–brain”hypothesis is proposed to explain the underlying mechanism,where the earlier lesioned site in the brain of gastricα-synuclein and howα-synuclein further spreads are not fully understood.Here we report that caudal raphe nuclei(CRN)are the early lesion site of gastricα-synuclein propagating through the spinal cord,while locus coeruleus(LC)and substantia nigra pars compacta(SNpc)were further affected over a time frame of 7 months.Pathologicalα-synuclein propagation via CRN leads to neuron loss and disordered neuron activity,accompanied by abnormal motor and non-motor behavior.Potential neuron circuits are observed among CRN,LC,and SNpc,which contribute to the venerability of dopaminergic neurons in SNpc.These results show that CRN is the key region for the gastricα-synuclein spread to the midbrain.Our study provides valuable details for the“gut–brain”hypothesis and proposes a valuable PD model for future research on early PD intervention.
基金supported by Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS,No.2016-I2M-1–010)
文摘The EtOH extracts of the whole plants of Euphorbia helioscopia afforded 17 new jatrophane diterpenoid esters, helioscopianoids A–Q(1–17), along with eight known compounds(18–25). Their structures were elucidated by extensive spectroscopic methods and Mo_2(OAc)_4-induced ECD analysis,and the structures of compounds 1, 2, and 7 were confirmed by X-ray crystallography. Compounds 1–17 were evaluated for inhibitory effects on P-glycoprotein(P-gp) in an adriamycin(ADM)-resistant human breast adenocarcinoma cell line(MCF-7/ADR) and neuroprotective effects against serum deprivationinduced and rotenone-induced PC12 cell damage. Compounds 8 and 16 increased the accumulation of ADM in MCF-7/ADR cells by approximately 3-fold at a concentration of 20 μmol/L. Compound 8 could attenuate rotenone-induced PC12 cell damage, and compounds 2, 8, and 12 showed neuroprotective activities against serum deprivation-induced PC12 cell damage.