Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α(HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evid...Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α(HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evidence has demonstrated that HIF-1α promotes tumor angiogenesis, metastasis, metabolism, and immune evasion. Natural products are an important source of antitumor drugs and numerous studies have highlighted the crucial role of these agents in modulating HIF-1α. The present review describes the role of HIF-1α in tumor progression, summarizes natural products used as HIF-1α inhibitors, and discusses the potential of developing natural products as HIF-1α inhibitors for the treatment of cancer.展开更多
Objective:To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins(TSPN)on cerebral ischemia-reperfusion injury and oxygenglucose deprivation...Objective:To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins(TSPN)on cerebral ischemia-reperfusion injury and oxygenglucose deprivation/reoxygenation(OGD/R)of cultured cortical neurons.Methods:The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay,flow cytometry and live/dead cell assays.The morphology of dendrites was detected by immunofluorescence.Middle cerebral artery occlusion(MCAO)was developed in rats as a model of cerebral ischemia-reperfusion.The neuroprotective effect of TSPN was evaluated by neurological scoring,tail suspension test,2,3,5-triphenyltetrazolium chloride(TTC)and Nissl stainings.Western blot analysis,immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin(mTOR)signaling pathway.Results:MTT showed that TSPN(50,25 and 12.5μg/m L)protected cortical neurons after OGD/R treatment(P<0.01 or P<0.05).Flow cytometry and live/dead cell assays indicated that 25μg/m L TSPN decreased neuronal apoptosis(P<0.05),and immunofluorescence showed that 25μg/m L TSPN restored the dendritic morphology of damaged neurons(P<0.05).Moreover,12.5μg/m L TSPN downregulated the expression of Beclin-1,Cleaved-caspase 3 and LC3 B-Ⅱ/LC3 B-Ⅰ,and upregulated the levels of phosphorylated(p)-Akt and p-mTOR(P<0.01 or P<0.05).In the MCAO model,50μg/m L TSPN improved defective neurological behavior and reduced infarct volume(P<0.05).Moreover,the expression of Beclin-1 and LC3 B in cerebral ischemic penumbra was downregulated after 50μg/m L TSPN treatment,whereas the p-mTOR level was upregulated(P<0.05 or P<0.01).Conclusions:TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss.TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage,which may be the mechanism that underlies the neuroprotective activity of TSPN.展开更多
In the present study, two new diterpenoid lactones, 3-deoxy-andrographoside(1) and 14-deoxy-15-methoxy-andrographolide(2), were isolated from the aerial parts of Andrographis paniculata. Their structures were elucidat...In the present study, two new diterpenoid lactones, 3-deoxy-andrographoside(1) and 14-deoxy-15-methoxy-andrographolide(2), were isolated from the aerial parts of Andrographis paniculata. Their structures were elucidated by combination of NMR, MS, and chemical methods. The configurations of 1 and 2 were established based on the analysis of ROESY data and single crystal X-ray diffraction experiment.展开更多
Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by exte...Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.展开更多
The fruits of Eucalyptus globulus Labill.are known to have a plenty of medicinal properties,such as anti-tumor,anti-inflammatory,and immunosuppressive activity.Our previous study found that the phloroglucinol-sesquite...The fruits of Eucalyptus globulus Labill.are known to have a plenty of medicinal properties,such as anti-tumor,anti-inflammatory,and immunosuppressive activity.Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of E.globulus were immunosuppressive active constituents,especially Eucalyptin C(EuC).Phosphoinositide 3-kinases-γ(PI3Kγ)plays a pivotal role in T cell mediated excessive immune responses.In this study,EuC was first discovered to be a novel selective PI3Kγinhibitor with an IC50 value of 0.9μmol·L^(−1) and selectivity over 40-fold towards the other PI3K isoforms.Molecular docking,molecular dynamics simulation,and cellular thermal shift assay showed that EuC bound to PI3Kγ.Furthermore,EuC suppressed the downstream of PI3Kγto induce the apoptosis and inhibit the activation of primary spleen cells derived from allergic contact dermatitis mice.This work highlights the role of the fruits of E.globulus as a source of bioactive plant with immunosuppressive activity.展开更多
AIM:To investigate the chemical constituents of Vitex negundo.METHOD:Compounds were isolated by different chromatographic methods and their structures were elucidated on the basis of NMR spectroscopy.RESULTS:Four comp...AIM:To investigate the chemical constituents of Vitex negundo.METHOD:Compounds were isolated by different chromatographic methods and their structures were elucidated on the basis of NMR spectroscopy.RESULTS:Four compounds were isolated and identified as 2α,3α,24-trihydroxyurs-12,20(30)-dien-28-oic acid-28-O-β-D-glucopyranosyl ester(1),corosolic acid(2),vulgarsaponin A(3) and 2α,3α,24-trihydroxyurs-12-en-28-oic acid-28-O-β-Dglucopyranosyl ester(4),respectively.CONCLUSION:Compound 1 is a new triterpenoid glycoside.展开更多
Three new indole alkaloids, flueindolines A–C(1–3), along with nine known alkaloids(4–12), were isolated from the fruits of Flueggea virosa(Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indo...Three new indole alkaloids, flueindolines A–C(1–3), along with nine known alkaloids(4–12), were isolated from the fruits of Flueggea virosa(Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro(pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1–3 were herein also proposed.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 81973340,81630095,and 81573455)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No. 2017BT01Y036)+1 种基金the National Science and Technology Major Project (No.2018ZX09711001-008-008)the National High-level Personnel of Special Support Program (2019,ZHANG Dong-Mei)。
文摘Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α(HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evidence has demonstrated that HIF-1α promotes tumor angiogenesis, metastasis, metabolism, and immune evasion. Natural products are an important source of antitumor drugs and numerous studies have highlighted the crucial role of these agents in modulating HIF-1α. The present review describes the role of HIF-1α in tumor progression, summarizes natural products used as HIF-1α inhibitors, and discusses the potential of developing natural products as HIF-1α inhibitors for the treatment of cancer.
基金Supported by the National Key R&D Program of China(No.2017YFC1703800)the Key-Area Research and Development Program of Guangdong Province(Nos.2019B030335001 and 2020B1111110004)the Local Innovative and Research Teams Project of the Guangdong Pearl River Talents Program(No.2017BT01Y036)。
文摘Objective:To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins(TSPN)on cerebral ischemia-reperfusion injury and oxygenglucose deprivation/reoxygenation(OGD/R)of cultured cortical neurons.Methods:The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay,flow cytometry and live/dead cell assays.The morphology of dendrites was detected by immunofluorescence.Middle cerebral artery occlusion(MCAO)was developed in rats as a model of cerebral ischemia-reperfusion.The neuroprotective effect of TSPN was evaluated by neurological scoring,tail suspension test,2,3,5-triphenyltetrazolium chloride(TTC)and Nissl stainings.Western blot analysis,immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin(mTOR)signaling pathway.Results:MTT showed that TSPN(50,25 and 12.5μg/m L)protected cortical neurons after OGD/R treatment(P<0.01 or P<0.05).Flow cytometry and live/dead cell assays indicated that 25μg/m L TSPN decreased neuronal apoptosis(P<0.05),and immunofluorescence showed that 25μg/m L TSPN restored the dendritic morphology of damaged neurons(P<0.05).Moreover,12.5μg/m L TSPN downregulated the expression of Beclin-1,Cleaved-caspase 3 and LC3 B-Ⅱ/LC3 B-Ⅰ,and upregulated the levels of phosphorylated(p)-Akt and p-mTOR(P<0.01 or P<0.05).In the MCAO model,50μg/m L TSPN improved defective neurological behavior and reduced infarct volume(P<0.05).Moreover,the expression of Beclin-1 and LC3 B in cerebral ischemic penumbra was downregulated after 50μg/m L TSPN treatment,whereas the p-mTOR level was upregulated(P<0.05 or P<0.01).Conclusions:TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss.TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage,which may be the mechanism that underlies the neuroprotective activity of TSPN.
基金supported by National Natural Science Foundation of China(Nos.81473117 and 81502939)the Joint Fund of NSFC-Guangdong Province(No.U1401225)
文摘In the present study, two new diterpenoid lactones, 3-deoxy-andrographoside(1) and 14-deoxy-15-methoxy-andrographolide(2), were isolated from the aerial parts of Andrographis paniculata. Their structures were elucidated by combination of NMR, MS, and chemical methods. The configurations of 1 and 2 were established based on the analysis of ROESY data and single crystal X-ray diffraction experiment.
基金supported by the National Key R&D Program of China(No.2017YFC1703802)the National Natural Science Foundation of China(Nos.U1801287,81630095,and 81803398)+1 种基金the Science and Technology Planning Project of Guangdong Province(No.2018B020207008)the High-performance Super Computing Platform of Jinan University
文摘Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.
基金This work was supported by China Postdoctoral Science Foundation(Nos.2019M662006 and 2019TQ0357)the National Natural Science Foundation of China(Nos.81973206,81803392 and 81573309)+5 种基金the Major National Science and Technology Projects of the Chinese Thirteen Five-Year Plan(No.2017ZX09309024)the Funding of Double First-rate Discipline Innovation Team(Nos.CPU2018PZQ17,CPU2018PZQ18,and CPU2018GF05)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the Research and Innovation Project for College Graduates of Jiangsu Province 2017(No.KYCX170694)the National College Student Innovation Project for the R&D of Novel Drugs(No.201710316100)Jiangsu Province Graduate Student Training Innovation Project(No.KYLX16_1208).
文摘The fruits of Eucalyptus globulus Labill.are known to have a plenty of medicinal properties,such as anti-tumor,anti-inflammatory,and immunosuppressive activity.Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of E.globulus were immunosuppressive active constituents,especially Eucalyptin C(EuC).Phosphoinositide 3-kinases-γ(PI3Kγ)plays a pivotal role in T cell mediated excessive immune responses.In this study,EuC was first discovered to be a novel selective PI3Kγinhibitor with an IC50 value of 0.9μmol·L^(−1) and selectivity over 40-fold towards the other PI3K isoforms.Molecular docking,molecular dynamics simulation,and cellular thermal shift assay showed that EuC bound to PI3Kγ.Furthermore,EuC suppressed the downstream of PI3Kγto induce the apoptosis and inhibit the activation of primary spleen cells derived from allergic contact dermatitis mice.This work highlights the role of the fruits of E.globulus as a source of bioactive plant with immunosuppressive activity.
基金supported by the Program for Changjiang Scholars and Innovative Research Team in the University(No.IRT0965)the Team Project of Natural Science Foundation of Guangdong Province(No.8351063201000003)the Science and Technology Planning Project of Guangdong Province(No.2012A080204005)
文摘AIM:To investigate the chemical constituents of Vitex negundo.METHOD:Compounds were isolated by different chromatographic methods and their structures were elucidated on the basis of NMR spectroscopy.RESULTS:Four compounds were isolated and identified as 2α,3α,24-trihydroxyurs-12,20(30)-dien-28-oic acid-28-O-β-D-glucopyranosyl ester(1),corosolic acid(2),vulgarsaponin A(3) and 2α,3α,24-trihydroxyurs-12-en-28-oic acid-28-O-β-Dglucopyranosyl ester(4),respectively.CONCLUSION:Compound 1 is a new triterpenoid glycoside.
基金the National Key R & D Program of China (No. 2018YFC1706200)the National Natural Science Foundation of China (Nos. 81630095, 81622045, and 81803379)+2 种基金the Science & Technology Program of China (No.2019ZX09735002-003)the China Postdoctoral Science Foundation(Nos. 2019T120794, and 2018M633291)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No. 2017BT01Y036)。
文摘Three new indole alkaloids, flueindolines A–C(1–3), along with nine known alkaloids(4–12), were isolated from the fruits of Flueggea virosa(Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro(pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1–3 were herein also proposed.