Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-infla...Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-inflammatory,microbiota regulating,and memory-improving potentials in previous in vitro and AlCl3-induced zebrafish studies.However,its effects of memory-improving and gutbrain axis regulating on Aβ-induced mammalian AD models have not been explored.In this study,intragastric administrated BTL-Ⅰ ameliorated cognitive deficits related to recognition and spatial memory impaired by Aβ_(1-42)intracerebroventricular injection in mice.BTL-Ⅰ maintained gut microbiota balance by increasing the abundance of Blautia,Muribaculaceae,Bacteroides,Akkermansia,etc.,and decreasing CAG-352,Clostridia UCG-014,different Lachnospiraceae groups,etc.,and Firmicutes/Bacteroidota ratio and elevated the levels of short-chain fatty acids.Additionally,it alleviated intestinal oxidative stress,inflammatory responses,and pathological damage.Furthermore,BTL-I reversed Aβ_(1-42)-induced activation of microglia and astrocytes in the hippocampus and inhibited the elevated oxidative stress and proinflammatory cytokines in both plasma and brain.The correlation analysis between the regulated taxa and biomarkers supports the role of gut microbiota in adjusting inflammation,oxidative stress,and memory.In conclusion,BTL-I may serve as a valuable drug lead for treating Alzheimer’s disease by systematically inhibiting microbiota imbalance,inflammation,and oxidative stress along the gut-brain axis.展开更多
In our ongoing search for new inhibitors of 5-lipoxygenase（5-LOX） from microbial resources,Aspergillus F06Z-509 was found to produce active components.Three active compounds named F06Z-509-A,B and C were obtained an...In our ongoing search for new inhibitors of 5-lipoxygenase（5-LOX） from microbial resources,Aspergillus F06Z-509 was found to produce active components.Three active compounds named F06Z-509-A,B and C were obtained and identified as butyrolactoneⅡ,ⅠandⅢby NMR and MS data analyses.They showed inhibitory activity against 5-LOX with IC50 of 21.43, 22.51 and 11.83μg/mL,respectively.Butyrolactones are shown to be inhibitors of 5-LOX for the first time.展开更多
Two new α,β-unsaturated butyrolactone derivatives, 4-(4″-hydroxybenzyl)-3-(3′-hydroxy-phenethyl)furan-2(5H)-one (1) and 3-(3′-hydroxyphenethyl)furan-2(5H)-one (2), together with one known phenolic compound (3), w...Two new α,β-unsaturated butyrolactone derivatives, 4-(4″-hydroxybenzyl)-3-(3′-hydroxy-phenethyl)furan-2(5H)-one (1) and 3-(3′-hydroxyphenethyl)furan-2(5H)-one (2), together with one known phenolic compound (3), were isolated from the tubers of Pleione bulbocodioides (Franch.) Rolfe. Their structures were elucidated by analysis of spectroscopic data.展开更多
A new butyrolactone derivative,namely butyrolactone Ⅷ （1）,and six known butyrolactones （2-7） were separated from the ethyl acetate （EtOAc） extract of the fermentation broth of a fungus,Aspergillus terreus MXH-2...A new butyrolactone derivative,namely butyrolactone Ⅷ （1）,and six known butyrolactones （2-7） were separated from the ethyl acetate （EtOAc） extract of the fermentation broth of a fungus,Aspergillus terreus MXH-23.The chemical structures of these metabolites were identified by analyzing their nuclear magnetic resonance （NMR） and mass spectrometry （MS）.Known butyrolactone derivatives contain an α,β-unsaturated γ-lactone ring with α-hydroxyl and y-benzyl,and butyrolactone Ⅷ （1） was the first butyrolactones contains α-benzyl and γ-hydroxyl on α,β-unsaturated lactone ring.All of the butyrolactone derivatives were tested for their anti-influenza （H 1N 1） effects.Derivatives 4 and 7 showed moderate antiviral activities while the newly-identified,derivative 1,did not.展开更多
A pair of Z and E isomers of cyclization of γ-ketoacid 7, which was prepared in six steps from 2,5-dimethoxyphenyl acetic acid 1, gave a pair of Z(20%) and E (4%) isomers of (2,5-dimethoxyphenyl)-methylene-butyrolact...A pair of Z and E isomers of cyclization of γ-ketoacid 7, which was prepared in six steps from 2,5-dimethoxyphenyl acetic acid 1, gave a pair of Z(20%) and E (4%) isomers of (2,5-dimethoxyphenyl)-methylene-butyrolactones展开更多
The somatic cell nuclear transfer （SCNT） technique has been applied successfully in a range of mammalian species giving rise to offspring, however, the efficiency of development to term has remained low. Oocyte meio...The somatic cell nuclear transfer （SCNT） technique has been applied successfully in a range of mammalian species giving rise to offspring, however, the efficiency of development to term has remained low. Oocyte meiotic arrest is an important option to make the SCNT more flexible and increase the number of cloned embryos produced. This paper showed that the use of butyrolactone I to arrest the meiotic division for 24 h prior to in vitro maturation （IVM） provided bovine oocytes capability of supporting development of blastocysts as efficiently as non arrested oocytes. In the SCNT group, cleavage rates were not affected by prematuration when adding butyrolactone I during IVM （57.9% vs. 62.4%; control vs. 10 μmol.L^-1 butyrolactone I）, developmental rates to biastocyst were unaffected （22.0% vs. 20.3%; control vs. 10 μmol.L^-1 butyrolactone I, p〉0.05） by the addition ofbutyrolactone I during IVM in cloned embryos. Moreover, the total cell numbers of blastocyst were not affected by butyrolactone I （total nucleus numbers, 132±16.5 vs. 128±19.4, p〉0.05）. In conclusion, the SCNT embryos from butyrolactone I- prematured bovine oocytes had the same developmental potential as the non treated one. The present study provided a method for laboratories of in vitro embryos production, mainly those working on the SCNT, where prematuration could be used to iiacrease the flexibility of the procedure.展开更多
A series of trans-4, 5-disubstituted -γ-butyrolactones are found to assume two different envelope conformations by means of nuclear magnetic resonance spectroscopy.
Objective To design and synthesize an amount of butyrolactone V derivatives,evaluate the anti-inflammatory effects of all the derivatives,look for potential drugs that inhibit inflammatory bowel disease(IBD),and deter...Objective To design and synthesize an amount of butyrolactone V derivatives,evaluate the anti-inflammatory effects of all the derivatives,look for potential drugs that inhibit inflammatory bowel disease(IBD),and determine the structure-activity relationship(SAR).Methods The butyrolactone V derivatives were synthesized with high yield by oxidation reaction,substitution reaction,and esterification reaction in sequence,and the production of nitric oxide was assessed in RAW264.7 cells treated with the lipopolysaccharide and the compounds.Then,the target compounds were studied for their activity in dextran sodium sulfate(DSS)-induced ulcerative colitis.Results A total of three series of compounds encompassing 60 derivatives of the natural product butyrolactone V were designed and synthesized.The results showed that compounds 5p and 7e could alleviate the symptoms of DSS-induced colitis in mice,including alleviating diarrhea,inhibiting the reduction of colon length,and reducing tissue damage.The preliminary mechanism exploration indicated that compounds 5p and 7e could improve the symptoms of IBD in mice mainly by reducing the expression of chemokines and exerting anti-inflammatory effects.Conclusion This study reports the synthesis and the derivatization of butyrolactone V and analysis on anti-inflammatory activity.The most effective compounds 5p and 7e have the potential to be further developed as drugs to treat IBD.展开更多
A novel 1,6-asymmetric induction has been observed in the iodolactonization of γ,δ-unsa- turated amides. The optically active γ-butyrolactone was synthesized by employing iodolactonization reaction as a key step.
Cyclopropylamine is synthesized with γ butyrolactone and isopropanol by five steps of ring opening esterification, cyclization, hydrolysis, acylation and Hofmann degradation. Cyclization and hydrolysis are key steps ...Cyclopropylamine is synthesized with γ butyrolactone and isopropanol by five steps of ring opening esterification, cyclization, hydrolysis, acylation and Hofmann degradation. Cyclization and hydrolysis are key steps in the process, and Phase Transfer Catalysis (PTC) is used in the two steps respectively. In the cyclization reaction, because solid liquid PTC, sodium hydroxide is applied instead of expensive sodium alcoholate, the reaction can be carried out in mild conditions. The optimum re action conditions are as follows: 0.03∶1∶1.5 mole ratio of BTEAC to ester to sodium hydroxide, reacting at 50 ℃ for 2 h with yield of 92%. Hydrolysis of isopropyl cyclopropanecarboxylate is accelerated by liquid liquid PTC, and the order of catalytic activity is BTEAC>BTMAC>CTMAB>TBAB. The results show that the new synthesis method is superior to those from literature and feasible for production with simple routes, mild reaction conditions, cheap materials and total yield of 52.6%.展开更多
基金Supported by the Guangdong Provincial Natural Science Foundation(No.2022A1515010783)the Sustainable Development Program of Shenzhen Science and Technology Major Program(No.KCXFZ20240903093925033)+4 种基金the Guangdong Provincial Special Project in Science and Technology(No.2021A05240)the Special Project in Key Fields of Guangdong Provincial Higher Education Institutions(No.2021ZDZX2064)the Basic Research Project of Shenzhen Science and Technology Innovation Commission(No.JCYJ20220530162014032)the Zhanjiang Marine Youth Talent Innovation Project(No.2022E05010)the Program for Scientific Research Start-up Funds of Guangdong Ocean University(Nos.R18008,060302042201)。
文摘Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-inflammatory,microbiota regulating,and memory-improving potentials in previous in vitro and AlCl3-induced zebrafish studies.However,its effects of memory-improving and gutbrain axis regulating on Aβ-induced mammalian AD models have not been explored.In this study,intragastric administrated BTL-Ⅰ ameliorated cognitive deficits related to recognition and spatial memory impaired by Aβ_(1-42)intracerebroventricular injection in mice.BTL-Ⅰ maintained gut microbiota balance by increasing the abundance of Blautia,Muribaculaceae,Bacteroides,Akkermansia,etc.,and decreasing CAG-352,Clostridia UCG-014,different Lachnospiraceae groups,etc.,and Firmicutes/Bacteroidota ratio and elevated the levels of short-chain fatty acids.Additionally,it alleviated intestinal oxidative stress,inflammatory responses,and pathological damage.Furthermore,BTL-I reversed Aβ_(1-42)-induced activation of microglia and astrocytes in the hippocampus and inhibited the elevated oxidative stress and proinflammatory cytokines in both plasma and brain.The correlation analysis between the regulated taxa and biomarkers supports the role of gut microbiota in adjusting inflammation,oxidative stress,and memory.In conclusion,BTL-I may serve as a valuable drug lead for treating Alzheimer’s disease by systematically inhibiting microbiota imbalance,inflammation,and oxidative stress along the gut-brain axis.
基金National Basic Research Project of China(Grant No.2009CB526513)National New Drug Research and Development Proiect(Grant No.2008ZX09401-05)
文摘In our ongoing search for new inhibitors of 5-lipoxygenase（5-LOX） from microbial resources,Aspergillus F06Z-509 was found to produce active components.Three active compounds named F06Z-509-A,B and C were obtained and identified as butyrolactoneⅡ,ⅠandⅢby NMR and MS data analyses.They showed inhibitory activity against 5-LOX with IC50 of 21.43, 22.51 and 11.83μg/mL,respectively.Butyrolactones are shown to be inhibitors of 5-LOX for the first time.
文摘Two new α,β-unsaturated butyrolactone derivatives, 4-(4″-hydroxybenzyl)-3-(3′-hydroxy-phenethyl)furan-2(5H)-one (1) and 3-(3′-hydroxyphenethyl)furan-2(5H)-one (2), together with one known phenolic compound (3), were isolated from the tubers of Pleione bulbocodioides (Franch.) Rolfe. Their structures were elucidated by analysis of spectroscopic data.
基金supported by National Natural Science Foundation of China (Nos.41176120 and 30973627)the National High Technology Research and Development Program of China (No.2013AA092901)+3 种基金the Program for New Century Excellent Talents in University (No.NCET12-0499)Promotive Research Fund for Excellent Young and Middle-Aged Scientists of Shandong Province (BS 2010HZ027)the Public Projects of State Oceanic Administration (No. 2010418022-3)the Program for Changjiang Scholars and Innovative Research Team in University (No.IRT0944)
文摘A new butyrolactone derivative,namely butyrolactone Ⅷ （1）,and six known butyrolactones （2-7） were separated from the ethyl acetate （EtOAc） extract of the fermentation broth of a fungus,Aspergillus terreus MXH-23.The chemical structures of these metabolites were identified by analyzing their nuclear magnetic resonance （NMR） and mass spectrometry （MS）.Known butyrolactone derivatives contain an α,β-unsaturated γ-lactone ring with α-hydroxyl and y-benzyl,and butyrolactone Ⅷ （1） was the first butyrolactones contains α-benzyl and γ-hydroxyl on α,β-unsaturated lactone ring.All of the butyrolactone derivatives were tested for their anti-influenza （H 1N 1） effects.Derivatives 4 and 7 showed moderate antiviral activities while the newly-identified,derivative 1,did not.
文摘A pair of Z and E isomers of cyclization of γ-ketoacid 7, which was prepared in six steps from 2,5-dimethoxyphenyl acetic acid 1, gave a pair of Z(20%) and E (4%) isomers of (2,5-dimethoxyphenyl)-methylene-butyrolactones
基金Supported by the Scientific Research Fund of Heilongjiang Provincial Education Department (11531028)Heilongjiang Postdoctoral Fund (LBH-Z11245)
文摘The somatic cell nuclear transfer （SCNT） technique has been applied successfully in a range of mammalian species giving rise to offspring, however, the efficiency of development to term has remained low. Oocyte meiotic arrest is an important option to make the SCNT more flexible and increase the number of cloned embryos produced. This paper showed that the use of butyrolactone I to arrest the meiotic division for 24 h prior to in vitro maturation （IVM） provided bovine oocytes capability of supporting development of blastocysts as efficiently as non arrested oocytes. In the SCNT group, cleavage rates were not affected by prematuration when adding butyrolactone I during IVM （57.9% vs. 62.4%; control vs. 10 μmol.L^-1 butyrolactone I）, developmental rates to biastocyst were unaffected （22.0% vs. 20.3%; control vs. 10 μmol.L^-1 butyrolactone I, p〉0.05） by the addition ofbutyrolactone I during IVM in cloned embryos. Moreover, the total cell numbers of blastocyst were not affected by butyrolactone I （total nucleus numbers, 132±16.5 vs. 128±19.4, p〉0.05）. In conclusion, the SCNT embryos from butyrolactone I- prematured bovine oocytes had the same developmental potential as the non treated one. The present study provided a method for laboratories of in vitro embryos production, mainly those working on the SCNT, where prematuration could be used to iiacrease the flexibility of the procedure.
文摘A series of trans-4, 5-disubstituted -γ-butyrolactones are found to assume two different envelope conformations by means of nuclear magnetic resonance spectroscopy.
基金funded by the National Natural Science Foundation of China(Nos.81725021,81903461,and 82173705)the Natural Science Foundation of Hubei Province,China(No.ZRMS2023000340).
文摘Objective To design and synthesize an amount of butyrolactone V derivatives,evaluate the anti-inflammatory effects of all the derivatives,look for potential drugs that inhibit inflammatory bowel disease(IBD),and determine the structure-activity relationship(SAR).Methods The butyrolactone V derivatives were synthesized with high yield by oxidation reaction,substitution reaction,and esterification reaction in sequence,and the production of nitric oxide was assessed in RAW264.7 cells treated with the lipopolysaccharide and the compounds.Then,the target compounds were studied for their activity in dextran sodium sulfate(DSS)-induced ulcerative colitis.Results A total of three series of compounds encompassing 60 derivatives of the natural product butyrolactone V were designed and synthesized.The results showed that compounds 5p and 7e could alleviate the symptoms of DSS-induced colitis in mice,including alleviating diarrhea,inhibiting the reduction of colon length,and reducing tissue damage.The preliminary mechanism exploration indicated that compounds 5p and 7e could improve the symptoms of IBD in mice mainly by reducing the expression of chemokines and exerting anti-inflammatory effects.Conclusion This study reports the synthesis and the derivatization of butyrolactone V and analysis on anti-inflammatory activity.The most effective compounds 5p and 7e have the potential to be further developed as drugs to treat IBD.
文摘A novel 1,6-asymmetric induction has been observed in the iodolactonization of γ,δ-unsa- turated amides. The optically active γ-butyrolactone was synthesized by employing iodolactonization reaction as a key step.
基金The Science and Research Foundation of Education Commission of Hunan Province
文摘Cyclopropylamine is synthesized with γ butyrolactone and isopropanol by five steps of ring opening esterification, cyclization, hydrolysis, acylation and Hofmann degradation. Cyclization and hydrolysis are key steps in the process, and Phase Transfer Catalysis (PTC) is used in the two steps respectively. In the cyclization reaction, because solid liquid PTC, sodium hydroxide is applied instead of expensive sodium alcoholate, the reaction can be carried out in mild conditions. The optimum re action conditions are as follows: 0.03∶1∶1.5 mole ratio of BTEAC to ester to sodium hydroxide, reacting at 50 ℃ for 2 h with yield of 92%. Hydrolysis of isopropyl cyclopropanecarboxylate is accelerated by liquid liquid PTC, and the order of catalytic activity is BTEAC>BTMAC>CTMAB>TBAB. The results show that the new synthesis method is superior to those from literature and feasible for production with simple routes, mild reaction conditions, cheap materials and total yield of 52.6%.
