Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is curre...Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise.Recent studies have demonstrated that altered expressions of long non-coding RNAs(lncRNAs)in the brain affect neurodevelopment and manifest modulating functions during the depression.However,most lncRNAs have not yet been studied.Herein,we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors,as well as their corresponding response following antidepressant fluoxetine treatment.A chronic unpredictable mild stress(CUMS)mouse model was applied.A sixweek fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors.In addition,differential expression analysis of lncRNAs was performed following RNA-sequencing.A total of 282 lncRNAs(134 up-regulated and 148 down-regulated)were differentially expressed in CUMS-induced mice relative to non-stressed counterparts(P<0.05).Moreover,370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention.Gene Ontology(GO)analyses showed an association between significantly dysregulated lncRNAs and protein binding,oxygen binding,and transport activity,while the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways.Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus.The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.展开更多
Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medi...Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medicine(TCM),some were claimed to slow down aging.Qingyangshen(Cynanchum otophyllum schneid)is such a TCM.Here,we assayed the longevity effect of compound Otophylloside B(Ot B),a C-21 steroidal glycoside isolated from Qingyangshen,in Caenorhabditis elegans,which is a popular model for aging research.Our results showed that Ot B could modestly extend the lifespan of C.elegans,delay the age-related decline of body movement and improve the stress resistance.Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16.Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor(daf-2).In addition,Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis,for lifespan extension.展开更多
Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.S...Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.Since signaling pathways in aging of Caenorhabditis elegans(C.elegans),fruit flies and mice are evolutionarily conserved,compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human.Natural products have special resource advantage and with few side effect.Recently,many compounds or extracts from natural products slowing aging and extending lifespan have been reported.Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C.elegans or other species,and the prospect in developing antiaging medicine from natural products.展开更多
15 compounds,including two new ones crepidatuols A(1)and B(2)were isolated from the stems of Dendrobium crepidatum.The planar structures of these compounds were elucidated by spectroscopic methods(NMR,MS,UV,and IR)and...15 compounds,including two new ones crepidatuols A(1)and B(2)were isolated from the stems of Dendrobium crepidatum.The planar structures of these compounds were elucidated by spectroscopic methods(NMR,MS,UV,and IR)and comparison with those from literatures.10 compounds were send for enhancing activities on nerve growth factor(NGF)medicated neurite outgrowth in PC12 cells and the results indicated that crepidatuol A(1),confusarin and 3-(2-acetoxy-5-methoxy)-phenylpropanol showed enhancing activities at the concentration of 10.0μM.展开更多
Four new indole alkaloids,plasiaticines A-D(1-4),together with two known ones,were isolated from the seeds of Plantago asiatica.The structures of the new compounds were elucidated on the basis of comprehensive analysi...Four new indole alkaloids,plasiaticines A-D(1-4),together with two known ones,were isolated from the seeds of Plantago asiatica.The structures of the new compounds were elucidated on the basis of comprehensive analysis of spectroscopic data.All compounds were tested for their cytotoxic activity,and all compounds except 4 were tested for their acetylcholinesterase(AChE)inhibitory activities.展开更多
Three new lycopodine-type alkaloids,4a-hydroxyanhydrolycodoline(1),4a,6a-dihydroxyanhydrolycodoline(2),and 6-epi-8b-acetoxylycoclavine(3),and an artifact,lycoposerramine G nitrate(4),along with seventeen related known...Three new lycopodine-type alkaloids,4a-hydroxyanhydrolycodoline(1),4a,6a-dihydroxyanhydrolycodoline(2),and 6-epi-8b-acetoxylycoclavine(3),and an artifact,lycoposerramine G nitrate(4),along with seventeen related known compounds,were isolated from the club moss Lycopodium japonicum Thunb.ex Murray(Lycopodiaceae).Their structures were elucidated by extensive spectroscopic methods as well as X-ray analysis.Compounds 1–4 were evaluated for their acetylcholine esterase inhibitory activity.展开更多
Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum ...Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.展开更多
Three new Lycopodium alkaloids,obscurumines C-E(1-3),along with nine known compounds,were isolated from the club moss Lycopodium obscurum L.Structures of the new compounds were determined on the basis of their spectro...Three new Lycopodium alkaloids,obscurumines C-E(1-3),along with nine known compounds,were isolated from the club moss Lycopodium obscurum L.Structures of the new compounds were determined on the basis of their spectroscopic analysis and the relative configurations of 1 were established by X-ray crystallographic analysis.All the new isolates were tested for the acetylcholinesterase(AChE)inhibitory activity.展开更多
Two rare lyconadin-type Lycopodium alkaloids,lyconadins G(1)and H(2),together with four known ones(3–6),were isolated from Lycopodium complanatum.The structures were determined on the basis of their spectroscopic ana...Two rare lyconadin-type Lycopodium alkaloids,lyconadins G(1)and H(2),together with four known ones(3–6),were isolated from Lycopodium complanatum.The structures were determined on the basis of their spectroscopic analyses,and the absolute configuration of 1 was established by an X-ray crystallographic analysis.It is the first time to establish the absolute configuration of lyconadin-type Lycopodium alkaloid by an X-ray diffraction experiment.In addition,these findings may provide more information for the biosynthesis of lyconadins.展开更多
Three new sesquilignans,1-3,a new sesquiterpenoid,4,and three known compounds were isolated from the stem barks of Illicium simonsii.The structures of new compounds(1-4)were elucidated by spectroscopic methods.A biosy...Three new sesquilignans,1-3,a new sesquiterpenoid,4,and three known compounds were isolated from the stem barks of Illicium simonsii.The structures of new compounds(1-4)were elucidated by spectroscopic methods.A biosynthetic pathway was proposed for simonsienols A-C(1-3).Anti-AChE activity and anti-BuChE activity were evaluated for all compounds except forα-cadinol ethyl ether(4).As a result,isodunnianol(7)exhibited anti-AChE activity with an IC50 value of 13.0μM.展开更多
The first total synthesis of(-)-huperzine W(1)has been achieved.Key element of the synthesis is a highly convergent assemblage for the two rings system of target molecule utilizing an efficient Suzuki-Miyaura coupling...The first total synthesis of(-)-huperzine W(1)has been achieved.Key element of the synthesis is a highly convergent assemblage for the two rings system of target molecule utilizing an efficient Suzuki-Miyaura coupling reaction between chiral iodide 2 and 2-allylpyrrolidinone 4.Evaluation of the AchE inhibition of synthetic huperzine W was also carried out.展开更多
基金This work was supported by the Scientific Research Projects of Universities in Inner Mongolia Autonomous Region(NJZY111)Natural Scientific Research Projects of Inner Mongolia Autonomous Region(2020MS03060)We thank Elsevier Ltd.,UK and FreeScience,China for their assistance in English editing of the manuscript.
文摘Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise.Recent studies have demonstrated that altered expressions of long non-coding RNAs(lncRNAs)in the brain affect neurodevelopment and manifest modulating functions during the depression.However,most lncRNAs have not yet been studied.Herein,we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors,as well as their corresponding response following antidepressant fluoxetine treatment.A chronic unpredictable mild stress(CUMS)mouse model was applied.A sixweek fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors.In addition,differential expression analysis of lncRNAs was performed following RNA-sequencing.A total of 282 lncRNAs(134 up-regulated and 148 down-regulated)were differentially expressed in CUMS-induced mice relative to non-stressed counterparts(P<0.05).Moreover,370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention.Gene Ontology(GO)analyses showed an association between significantly dysregulated lncRNAs and protein binding,oxygen binding,and transport activity,while the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways.Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus.The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.
基金the Yunnan provincial government(20080A007)the 100 Talents Program of the Chinese Academy of Sciences,the State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany(P2008-ZZ21 and T2009-KF05)。
文摘Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medicine(TCM),some were claimed to slow down aging.Qingyangshen(Cynanchum otophyllum schneid)is such a TCM.Here,we assayed the longevity effect of compound Otophylloside B(Ot B),a C-21 steroidal glycoside isolated from Qingyangshen,in Caenorhabditis elegans,which is a popular model for aging research.Our results showed that Ot B could modestly extend the lifespan of C.elegans,delay the age-related decline of body movement and improve the stress resistance.Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16.Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor(daf-2).In addition,Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis,for lifespan extension.
基金the Natural Science Foundation of China(81671405 and 81370453)Natural Science Foundation of Yunnan province(2013FA045 and 2015FB172)Open Funds of Guangdong Key Laboratory of Marine Materia Medica.
文摘Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.Since signaling pathways in aging of Caenorhabditis elegans(C.elegans),fruit flies and mice are evolutionarily conserved,compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human.Natural products have special resource advantage and with few side effect.Recently,many compounds or extracts from natural products slowing aging and extending lifespan have been reported.Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C.elegans or other species,and the prospect in developing antiaging medicine from natural products.
基金National Natural and Science Foundations of China(No.30800090)"Xi-Bu-Zhi-Guang"project(2009-2012)from Chinese Academy of Science and the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2010-ZZ012).
文摘15 compounds,including two new ones crepidatuols A(1)and B(2)were isolated from the stems of Dendrobium crepidatum.The planar structures of these compounds were elucidated by spectroscopic methods(NMR,MS,UV,and IR)and comparison with those from literatures.10 compounds were send for enhancing activities on nerve growth factor(NGF)medicated neurite outgrowth in PC12 cells and the results indicated that crepidatuol A(1),confusarin and 3-(2-acetoxy-5-methoxy)-phenylpropanol showed enhancing activities at the concentration of 10.0μM.
基金supported financially by the grants from the Chinese Academy of Sciences(KSCX2-EW-Q-10 and KSCX1-YW-R-24)the NSFC(No.20802082 and 30830115)+1 种基金the Major State Basic Research Development Program of China(No.2009CB522303 and 2009CB940900)the project of recruited top talent of sciences and technology of Yunnan Province(2006PY01-47).
文摘Four new indole alkaloids,plasiaticines A-D(1-4),together with two known ones,were isolated from the seeds of Plantago asiatica.The structures of the new compounds were elucidated on the basis of comprehensive analysis of spectroscopic data.All compounds were tested for their cytotoxic activity,and all compounds except 4 were tested for their acetylcholinesterase(AChE)inhibitory activities.
基金the National Natural Science Foundation of China(Nos.90813004 and U0932602)the National Basic Research Program of China(973 Program No.2011CB915503).
文摘Three new lycopodine-type alkaloids,4a-hydroxyanhydrolycodoline(1),4a,6a-dihydroxyanhydrolycodoline(2),and 6-epi-8b-acetoxylycoclavine(3),and an artifact,lycoposerramine G nitrate(4),along with seventeen related known compounds,were isolated from the club moss Lycopodium japonicum Thunb.ex Murray(Lycopodiaceae).Their structures were elucidated by extensive spectroscopic methods as well as X-ray analysis.Compounds 1–4 were evaluated for their acetylcholine esterase inhibitory activity.
基金supported by the Natural Science Foundation of China(81671405,81370453)Natural Science Foundation of Yunnan province(2013FA045,2015FB172)Open Funds of Guangdong Key Laboratory of Marine Materia Mcdica(LMM2016-1).
文摘Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.
基金the National Basic Research Program of China(973 Program Nos.2011CB915503 and 2009CB522303)the National Natural Science Foundation of China(Nos.U0932602 and 90813004).
文摘Three new Lycopodium alkaloids,obscurumines C-E(1-3),along with nine known compounds,were isolated from the club moss Lycopodium obscurum L.Structures of the new compounds were determined on the basis of their spectroscopic analysis and the relative configurations of 1 were established by X-ray crystallographic analysis.All the new isolates were tested for the acetylcholinesterase(AChE)inhibitory activity.
基金This work was financially supported by the NSFC-Joint Foundation of Yunnan Province(No.U1502223)the National Natural Science Foundation of China(No.21402212)+1 种基金the Science and Technology Program of Yunnan Province(No.2015FB173)the CAS“Light of West China”Program and Youth Innovation Promotion Association CAS(X.-D.Wu).
文摘Two rare lyconadin-type Lycopodium alkaloids,lyconadins G(1)and H(2),together with four known ones(3–6),were isolated from Lycopodium complanatum.The structures were determined on the basis of their spectroscopic analyses,and the absolute configuration of 1 was established by an X-ray crystallographic analysis.It is the first time to establish the absolute configuration of lyconadin-type Lycopodium alkaloid by an X-ray diffraction experiment.In addition,these findings may provide more information for the biosynthesis of lyconadins.
基金supported by the National Natural Science Foundation(20872148).
文摘Three new sesquilignans,1-3,a new sesquiterpenoid,4,and three known compounds were isolated from the stem barks of Illicium simonsii.The structures of new compounds(1-4)were elucidated by spectroscopic methods.A biosynthetic pathway was proposed for simonsienols A-C(1-3).Anti-AChE activity and anti-BuChE activity were evaluated for all compounds except forα-cadinol ethyl ether(4).As a result,isodunnianol(7)exhibited anti-AChE activity with an IC50 value of 13.0μM.
基金the National Natural Science of China(No.20802084,21072200)Programs of“One Hundred Talented People”and“Western Light”Joint Scholar of Chinese Academy of Sciences for financial support.
文摘The first total synthesis of(-)-huperzine W(1)has been achieved.Key element of the synthesis is a highly convergent assemblage for the two rings system of target molecule utilizing an efficient Suzuki-Miyaura coupling reaction between chiral iodide 2 and 2-allylpyrrolidinone 4.Evaluation of the AchE inhibition of synthetic huperzine W was also carried out.
