Eleven new secoiridoid aglycones involving unusual C9-skeleton:swerimilegenins A-F(1-6);bis-C9-skeleton:swerimilegenin G(7);and C_(10)-skeleton:swerimilegenins H−K(8−11),as well as six known ones,were isolated from th...Eleven new secoiridoid aglycones involving unusual C9-skeleton:swerimilegenins A-F(1-6);bis-C9-skeleton:swerimilegenin G(7);and C_(10)-skeleton:swerimilegenins H−K(8−11),as well as six known ones,were isolated from the low-polarity part of the traditional Chinese herb medicine Swertia mileensis.Their structures were determined by extensive spectroscopic data and X-ray diffraction.Biogenetically,swerimilegenin A(1)belonged to 10-nor-secoiridoid,and swerimilegenins B-F(2-6)were 1-nor-secoiridoids.Erythrocentaurin(12)and gentiogenal(15)showed moderate anti-HBV activity on HepG 2.2.15 cell line in vitro.展开更多
Fourteen avermectin B2 a aglycon derivatives were designed and synthesized after removing the oleandrose disaccharide of avermectin B2 a.Their structures were characterized by’H NMR,13 C NMR,HMRS.Preliminary bioassay...Fourteen avermectin B2 a aglycon derivatives were designed and synthesized after removing the oleandrose disaccharide of avermectin B2 a.Their structures were characterized by’H NMR,13 C NMR,HMRS.Preliminary bioassays indicated that these compounds exhibited good insecticidal activity against diamondback moth at 200 mg/L,with mortality no less than 90%.Compounds 10 b,12 a,12 c,17 demonstrated good acaricidal activity against the adult mites,larvae,and good inhibition rate of hatching to mite eggs of Tetranychus cinnabarinus.Compounds 5,10 b,10 c exhibited excellent fungicidal activity against fourteen fungal pathogens in vitro.3 D-QSAR analysis showed that the fungicidal activity of avermectin B2 a aglycon derivatives would be increased when a negatively charged and bulky group was introduced at 13-position,which will be instructive for the further modification of avermectin B2 aaglycon.展开更多
Six new 13-O-acylavermectin Bl aglycones(3-8) were synthesized from avermectin B1 aglycone and their bioactivities were evaluated against Spodoptera exigua, Spodoptera eridania, Tetranychus urticae and Aphis fabae.
Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for...Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.展开更多
Insignin A, a new C21-steroidal aglycone having the rare 15,16-seco pregnane skeleton was isolated from the acidic hydrolysis part of the 95% EtOH extract of Biondia insignis. It's structure was identified to be ...Insignin A, a new C21-steroidal aglycone having the rare 15,16-seco pregnane skeleton was isolated from the acidic hydrolysis part of the 95% EtOH extract of Biondia insignis. It's structure was identified to be 15R,16-epoxy-3?,14?,16?-trihydroxy-15,16-secopregn-5-ene-20-one based on the spectral data.展开更多
OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy.According to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investiga...OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy.According to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investigated the anti-inflammatory ingredients of licorice,but for the potency of flavonoid glycoside and their aglycones on inflammation are not evaluated.This study was designed to assess the contributions of licorice flavonoid glycosides and their aglycons to its anti-inflammatory and hypnotic effects.METHODS For the flavonoid aglycone's enrichment,the extract of licorice(EL)was fermented in submerged culture of the edible fungus Grifola frondosa HB0071 mycelia which can produce β-glucosidase and catalyze the flavonoid glycosides to aglycones.EL and fermented extract of licorice(FEL) were used in this study.The anti-inflammation test was carried out in arachidonic acid(AA)-induced ear edema model and the hypnotic test was performed by using electroencephalogram(EEG) analysis method in normal freely moving SD rats.The chemicals constituents were analyzed by HPLC.RESULTS During fermentation,the falvonoid glycosides of licorice were hydrolyzed by the time process.Along with fermentation time,the concentration of the major flavonoid glycosides,liquiritin and isoliquiritin were decreased obviously,and simultaneously their aglycons,liquiritigenin and isoliquiriti.genin were remarkably increased in FEL.Moreover,the content of another major constituent glycyrrhi.zic acid and glycyrrhetinic acid were not changed after the fermentation.In AA-induced mice ear ede.ma test,after topical application,FEL(effective dose range:5-20 μg·ear-1) showed more potent inhibito.ry activity than EL(effective dose range:25-100 μg·ear-1).On the other hand,oral administration of EL and FEL exhibited the same hypnotic potency and both enhanced the total sleep time including rapid eye movement(REM) sleep and non-REM sleep time.CONCLUSION These results suggested that the enrichment of flavonoid aglycons such as liquiritigenin and isoliquiritigenin enhanced the anti-inflam.matory potency of licorice extract,and this potentiation has nothing to do with glycyrrhizic acid or glycyr.rhetinic acid.In addition,enrichment of flavonoid aglycones did not alter the hypnotic effect of licorice.展开更多
A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperu...A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce hyperuricemia. Meanwhile, J99745(3, 10, and 30 mg/kg), allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 days. On the 7 th day,uric acid and creatinine in serum and urine, blood urea nitrogen(BUN), malondialdehyde(MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin(H&E) staining. Hepatic XOD, renal urate transporter 1(URAT1), glucose transporter type 9(GLUT9), organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid(FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our resultssuggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.展开更多
Compared with flavonoid glycosides,flavonoid aglycones are difficult to be separated since they have less hydroxyls.Collagen fiber(CF),a natural polymer,was once used as packing material for separation of kaempferol a...Compared with flavonoid glycosides,flavonoid aglycones are difficult to be separated since they have less hydroxyls.Collagen fiber(CF),a natural polymer,was once used as packing material for separation of kaempferol and querce-tin(the typical flavonoid aglycones)after crosslinking by glutaraldehyde mainly based on hydrogen bonding and hydrophobic interaction in column length-diameter ratio of 60∶1.Hydrophobic modification by grafting alkyl chains was then employed to enhance the hydrophobic interaction between CF and flavonoid aglycones,which can improve the separation efficiency and decrease column length-diameter ratio to 19∶1.In order to further improve the adsorption capacity and separation efficiency,the strategy of simultaneously grafting hydrophobic alkyl chains(-CH_(2)-CH_(2)-)and alkali groups(-NH_(2))was adopted in this work to enhance hydrophobic interaction,hydrogen bond-ing and electrostatic association to flavonoid aglycones at the same time through grafting polyethyleneimine(PEI).PEI modified CF(PEI-CF)maintained the fiber structure of CF,and had higher adsorption extent and rate to flavonoid aglycones through the enhanced synergetic effect of hydrophobic interaction,hydrogen bonding and electrostatic association.As a result,PEI-CF presented a satisfactory column separation efficiency for kaempferol and quercetin even the length-diameter ratio of column was decreased to 11∶1,which was much better than previously developed glutaradehyde-crosslinked collagen fiber and isobutyl-grafted collagen fiber,as well as commonly used polyamide and Sephadex LH-20.展开更多
An aqueous solution of the extracts from Rhododendron leaves from Sichuan Liangshan was extracted with solvents of increasing polarity, petroleum ether, ethyl ether, ethyl acetate and butanol. The main flavonoid aglyc...An aqueous solution of the extracts from Rhododendron leaves from Sichuan Liangshan was extracted with solvents of increasing polarity, petroleum ether, ethyl ether, ethyl acetate and butanol. The main flavonoid aglycons extracted into the ethyl ether phase are the subject of this study. The flavonoid aglycons—mycetin, quercetin, kaempferol and farrerol, were separated and identified by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometer/mass spectrometer (LC/MS/MS). A simple and rapid HPLC method was developed for quantitative determination of quercetin and kaempferol in Rhododendron leaves, ethanol extracts and Jinjuan oral liquid drug (Liquor Jinjuan). The analysis of quercetin is useful for quality control of medicinal materials and Liquor Jinjuan products.展开更多
基金This work was funded by the National Natural Science Foundation of China and Yunnan Province(U0832603)the National Science Foundation of China for Distinguished Young Scholars(81025023)+1 种基金the West Light Foundation of the Chinese Academy of Sciences,the International Foundation for Science(No.F/5202-1)the Youth Innovation Promotion Association,CAS.
文摘Eleven new secoiridoid aglycones involving unusual C9-skeleton:swerimilegenins A-F(1-6);bis-C9-skeleton:swerimilegenin G(7);and C_(10)-skeleton:swerimilegenins H−K(8−11),as well as six known ones,were isolated from the low-polarity part of the traditional Chinese herb medicine Swertia mileensis.Their structures were determined by extensive spectroscopic data and X-ray diffraction.Biogenetically,swerimilegenin A(1)belonged to 10-nor-secoiridoid,and swerimilegenins B-F(2-6)were 1-nor-secoiridoids.Erythrocentaurin(12)and gentiogenal(15)showed moderate anti-HBV activity on HepG 2.2.15 cell line in vitro.
基金supported by the National Key R&D Program of China (No.2018YFD0200100)
文摘Fourteen avermectin B2 a aglycon derivatives were designed and synthesized after removing the oleandrose disaccharide of avermectin B2 a.Their structures were characterized by’H NMR,13 C NMR,HMRS.Preliminary bioassays indicated that these compounds exhibited good insecticidal activity against diamondback moth at 200 mg/L,with mortality no less than 90%.Compounds 10 b,12 a,12 c,17 demonstrated good acaricidal activity against the adult mites,larvae,and good inhibition rate of hatching to mite eggs of Tetranychus cinnabarinus.Compounds 5,10 b,10 c exhibited excellent fungicidal activity against fourteen fungal pathogens in vitro.3 D-QSAR analysis showed that the fungicidal activity of avermectin B2 a aglycon derivatives would be increased when a negatively charged and bulky group was introduced at 13-position,which will be instructive for the further modification of avermectin B2 aaglycon.
文摘Six new 13-O-acylavermectin Bl aglycones(3-8) were synthesized from avermectin B1 aglycone and their bioactivities were evaluated against Spodoptera exigua, Spodoptera eridania, Tetranychus urticae and Aphis fabae.
基金supported by the Science and Technology Foundation of Basic Research Program of Guizhou Province([2023]General 371,[2020]1Y381)the Administration of Traditional Chinese Medicine of Guizhou Province(QZYY-2018-130)+3 种基金the project of Key Laboratory of Basic Pharmacology of Ministry of Education,Zunyi Medicial University(No.qianjiaoheKYzi[2022]395)the Cultivation Plan of the NSFC(National Natural Science Foundation of China)of the affiliated hospital of Guizhou Medical University(GYFYNSFC-2021-55,GYFYNSFC-2021-56)the Cultivation Plan of the NSFC(National Natural Science Foundation of China)of Guizhou Medical University(21NSFCP13)the Science and Technology Foundation of Health Commission of Guizhou Province(gzwkj 2022-221).
文摘Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.
文摘Insignin A, a new C21-steroidal aglycone having the rare 15,16-seco pregnane skeleton was isolated from the acidic hydrolysis part of the 95% EtOH extract of Biondia insignis. It's structure was identified to be 15R,16-epoxy-3?,14?,16?-trihydroxy-15,16-secopregn-5-ene-20-one based on the spectral data.
文摘OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy.According to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investigated the anti-inflammatory ingredients of licorice,but for the potency of flavonoid glycoside and their aglycones on inflammation are not evaluated.This study was designed to assess the contributions of licorice flavonoid glycosides and their aglycons to its anti-inflammatory and hypnotic effects.METHODS For the flavonoid aglycone's enrichment,the extract of licorice(EL)was fermented in submerged culture of the edible fungus Grifola frondosa HB0071 mycelia which can produce β-glucosidase and catalyze the flavonoid glycosides to aglycones.EL and fermented extract of licorice(FEL) were used in this study.The anti-inflammation test was carried out in arachidonic acid(AA)-induced ear edema model and the hypnotic test was performed by using electroencephalogram(EEG) analysis method in normal freely moving SD rats.The chemicals constituents were analyzed by HPLC.RESULTS During fermentation,the falvonoid glycosides of licorice were hydrolyzed by the time process.Along with fermentation time,the concentration of the major flavonoid glycosides,liquiritin and isoliquiritin were decreased obviously,and simultaneously their aglycons,liquiritigenin and isoliquiriti.genin were remarkably increased in FEL.Moreover,the content of another major constituent glycyrrhi.zic acid and glycyrrhetinic acid were not changed after the fermentation.In AA-induced mice ear ede.ma test,after topical application,FEL(effective dose range:5-20 μg·ear-1) showed more potent inhibito.ry activity than EL(effective dose range:25-100 μg·ear-1).On the other hand,oral administration of EL and FEL exhibited the same hypnotic potency and both enhanced the total sleep time including rapid eye movement(REM) sleep and non-REM sleep time.CONCLUSION These results suggested that the enrichment of flavonoid aglycons such as liquiritigenin and isoliquiritigenin enhanced the anti-inflam.matory potency of licorice extract,and this potentiation has nothing to do with glycyrrhizic acid or glycyr.rhetinic acid.In addition,enrichment of flavonoid aglycones did not alter the hypnotic effect of licorice.
基金supported by National Natural Science Foundation of China(81573645,81202538 and 81673422)CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-3-007)National Science and Technology Major Projects for "Major New Drugs Innovation and Development"(2013ZX09508104and 2013ZX09402203)
文摘A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce hyperuricemia. Meanwhile, J99745(3, 10, and 30 mg/kg), allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 days. On the 7 th day,uric acid and creatinine in serum and urine, blood urea nitrogen(BUN), malondialdehyde(MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin(H&E) staining. Hepatic XOD, renal urate transporter 1(URAT1), glucose transporter type 9(GLUT9), organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid(FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our resultssuggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.
基金supported by National Natural Science Foundation of China(21978176).
文摘Compared with flavonoid glycosides,flavonoid aglycones are difficult to be separated since they have less hydroxyls.Collagen fiber(CF),a natural polymer,was once used as packing material for separation of kaempferol and querce-tin(the typical flavonoid aglycones)after crosslinking by glutaraldehyde mainly based on hydrogen bonding and hydrophobic interaction in column length-diameter ratio of 60∶1.Hydrophobic modification by grafting alkyl chains was then employed to enhance the hydrophobic interaction between CF and flavonoid aglycones,which can improve the separation efficiency and decrease column length-diameter ratio to 19∶1.In order to further improve the adsorption capacity and separation efficiency,the strategy of simultaneously grafting hydrophobic alkyl chains(-CH_(2)-CH_(2)-)and alkali groups(-NH_(2))was adopted in this work to enhance hydrophobic interaction,hydrogen bond-ing and electrostatic association to flavonoid aglycones at the same time through grafting polyethyleneimine(PEI).PEI modified CF(PEI-CF)maintained the fiber structure of CF,and had higher adsorption extent and rate to flavonoid aglycones through the enhanced synergetic effect of hydrophobic interaction,hydrogen bonding and electrostatic association.As a result,PEI-CF presented a satisfactory column separation efficiency for kaempferol and quercetin even the length-diameter ratio of column was decreased to 11∶1,which was much better than previously developed glutaradehyde-crosslinked collagen fiber and isobutyl-grafted collagen fiber,as well as commonly used polyamide and Sephadex LH-20.
文摘An aqueous solution of the extracts from Rhododendron leaves from Sichuan Liangshan was extracted with solvents of increasing polarity, petroleum ether, ethyl ether, ethyl acetate and butanol. The main flavonoid aglycons extracted into the ethyl ether phase are the subject of this study. The flavonoid aglycons—mycetin, quercetin, kaempferol and farrerol, were separated and identified by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometer/mass spectrometer (LC/MS/MS). A simple and rapid HPLC method was developed for quantitative determination of quercetin and kaempferol in Rhododendron leaves, ethanol extracts and Jinjuan oral liquid drug (Liquor Jinjuan). The analysis of quercetin is useful for quality control of medicinal materials and Liquor Jinjuan products.
