|
Inhibitory activity derived from Anastatica hierochuntica on D-Gal-induced cytotoxicity in primary cultured mouse hepatocytes at a concentration of 0 uM
|
Mus musculus
|
0.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Anastatins A and B, new skeletal flavonoids with hepatoprotective activities from the desert plant Anastatica hierochuntica.
Year : 2003
Volume : 13
Issue : 6
First Page : 1045
Last Page : 1049
Authors : Yoshikawa M, Xu F, Morikawa T, Ninomiya K, Matsuda H.
Abstract : New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show hepatoprotective effects on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.
|
Inhibitory activity derived from Anastatica hierochuntica on D-Gal-induced cytotoxicity in primary cultured mouse hepatocytes at a concentration of 10 uM
|
Mus musculus
|
7.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Anastatins A and B, new skeletal flavonoids with hepatoprotective activities from the desert plant Anastatica hierochuntica.
Year : 2003
Volume : 13
Issue : 6
First Page : 1045
Last Page : 1049
Authors : Yoshikawa M, Xu F, Morikawa T, Ninomiya K, Matsuda H.
Abstract : New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show hepatoprotective effects on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.
|
Inhibitory activity derived from Anastatica hierochuntica on D-Gal-induced cytotoxicity in primary cultured mouse hepatocytes at a concentration of 3 uM
|
Mus musculus
|
4.8
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Anastatins A and B, new skeletal flavonoids with hepatoprotective activities from the desert plant Anastatica hierochuntica.
Year : 2003
Volume : 13
Issue : 6
First Page : 1045
Last Page : 1049
Authors : Yoshikawa M, Xu F, Morikawa T, Ninomiya K, Matsuda H.
Abstract : New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show hepatoprotective effects on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.
|
Inhibitory activity derived from Anastatica hierochuntica on D-Gal-induced cytotoxicity in primary cultured mouse hepatocytes at a concentration of 30 uM
|
Mus musculus
|
45.2
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Anastatins A and B, new skeletal flavonoids with hepatoprotective activities from the desert plant Anastatica hierochuntica.
Year : 2003
Volume : 13
Issue : 6
First Page : 1045
Last Page : 1049
Authors : Yoshikawa M, Xu F, Morikawa T, Ninomiya K, Matsuda H.
Abstract : New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show hepatoprotective effects on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.
|
Hepatoprotective activity against D-galactosamine/TNFalpha-induced cell death in primary cultured mouse hepatocytes at 100 uM treated for 30 mins before TNFalpha challenge measured after 18 hrs by MTT assay relative to control
|
Mus musculus
|
129.0
%
|
|
Journal : J. Nat. Prod.
Title : Three new triterpenes from the seeds of Combretum quadrangulare and their hepatoprotective activity.
Year : 2001
Volume : 64
Issue : 3
First Page : 360
Last Page : 363
Authors : Adnyana IK, Tezuka Y, Banskota AH, Tran KQ, Kadota S.
Abstract : Three new triterpenes of the lupane type, 2alpha,6beta-dihydroxybetulinic acid (1) and 6beta-hydroxyhovenic acid (2), and an oleanane type, 6beta-hydroxyarjunic acid (3), together with several known compounds, have been isolated from the MeOH extract of the seeds of Combretum quadrangulare. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and their hepatoprotective activities were tested for D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes.
|
Hepatoprotective activity against D-galactosamine/TNFalpha-induced cell death in primary cultured mouse hepatocytes at 50 uM treated for 30 mins before TNFalpha challenge measured after 18 hrs by MTT assay relative to control
|
Mus musculus
|
68.2
%
|
|
Journal : J. Nat. Prod.
Title : Three new triterpenes from the seeds of Combretum quadrangulare and their hepatoprotective activity.
Year : 2001
Volume : 64
Issue : 3
First Page : 360
Last Page : 363
Authors : Adnyana IK, Tezuka Y, Banskota AH, Tran KQ, Kadota S.
Abstract : Three new triterpenes of the lupane type, 2alpha,6beta-dihydroxybetulinic acid (1) and 6beta-hydroxyhovenic acid (2), and an oleanane type, 6beta-hydroxyarjunic acid (3), together with several known compounds, have been isolated from the MeOH extract of the seeds of Combretum quadrangulare. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and their hepatoprotective activities were tested for D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes.
|
Hepatoprotective activity against D-galactosamine/TNFalpha-induced cell death in primary cultured mouse hepatocytes at 25 uM treated for 30 mins before TNFalpha challenge measured after 18 hrs by MTT assay relative to control
|
Mus musculus
|
44.9
%
|
|
Journal : J. Nat. Prod.
Title : Three new triterpenes from the seeds of Combretum quadrangulare and their hepatoprotective activity.
Year : 2001
Volume : 64
Issue : 3
First Page : 360
Last Page : 363
Authors : Adnyana IK, Tezuka Y, Banskota AH, Tran KQ, Kadota S.
Abstract : Three new triterpenes of the lupane type, 2alpha,6beta-dihydroxybetulinic acid (1) and 6beta-hydroxyhovenic acid (2), and an oleanane type, 6beta-hydroxyarjunic acid (3), together with several known compounds, have been isolated from the MeOH extract of the seeds of Combretum quadrangulare. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and their hepatoprotective activities were tested for D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes.
|
Hepatoprotective activity in mouse hepatocytes assessed inhibition of D-galactosamine/TNFalpha-induced cell death at 12.5 uM administered before 30 mins of TNFalpha challenge measured after 18 hrs
|
Mus musculus
|
43.4
%
|
|
Journal : J. Nat. Prod.
Title : Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity.
Year : 2001
Volume : 64
Issue : 4
First Page : 456
Last Page : 461
Authors : Tran QL, Adnyana IK, Tezuka Y, Nagaoka T, Tran QK, Kadota S.
Abstract : The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re (12--16), were also identified in the extract. Among the compounds isolated, majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.
|
Hepatoprotective activity in mouse hepatocytes assessed inhibition of D-galactosamine/TNFalpha-induced cell death at 25 uM administered before 30 mins of TNFalpha challenge measured after 18 hrs
|
Mus musculus
|
99.7
%
|
|
Journal : J. Nat. Prod.
Title : Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity.
Year : 2001
Volume : 64
Issue : 4
First Page : 456
Last Page : 461
Authors : Tran QL, Adnyana IK, Tezuka Y, Nagaoka T, Tran QK, Kadota S.
Abstract : The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re (12--16), were also identified in the extract. Among the compounds isolated, majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.
|
Hepatoprotective activity in mouse hepatocytes assessed inhibition of D-galactosamine/TNFalpha-induced cell death at 50 uM administered before 30 mins of TNFalpha challenge measured after 18 hrs
|
Mus musculus
|
149.7
%
|
|
Journal : J. Nat. Prod.
Title : Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity.
Year : 2001
Volume : 64
Issue : 4
First Page : 456
Last Page : 461
Authors : Tran QL, Adnyana IK, Tezuka Y, Nagaoka T, Tran QK, Kadota S.
Abstract : The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re (12--16), were also identified in the extract. Among the compounds isolated, majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.
|
Hepatoprotective activity against mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cell death at 25 uM after 18 hrs by MTT assay
|
Mus musculus
|
38.1
%
|
|
Journal : J. Nat. Prod.
Title : Quadranosides I-V, new triterpene glucosides from the seeds of Combretum quadrangulare.
Year : 2000
Volume : 63
Issue : 4
First Page : 496
Last Page : 500
Authors : Adnyana IK, Tezuka Y, Banskota AH, Xiong Q, Tran KQ, Kadota S.
Abstract : Five new triterpene glucosides, quadranosides I-V (1-5), have been isolated from a MeOH extract of the seeds of Combretum quadrangulare, together with 13 known compounds. The structures of compounds 1-5 were elucidated on the basis of spectroscopic analysis. Among the new triterpene glucosides, three compounds (1, 2, 5) showed significant hepatoprotective effects against D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes.
|
Hepatoprotective activity against mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cell death at 50 uM after 18 hrs by MTT assay
|
Mus musculus
|
61.2
%
|
|
Journal : J. Nat. Prod.
Title : Quadranosides I-V, new triterpene glucosides from the seeds of Combretum quadrangulare.
Year : 2000
Volume : 63
Issue : 4
First Page : 496
Last Page : 500
Authors : Adnyana IK, Tezuka Y, Banskota AH, Xiong Q, Tran KQ, Kadota S.
Abstract : Five new triterpene glucosides, quadranosides I-V (1-5), have been isolated from a MeOH extract of the seeds of Combretum quadrangulare, together with 13 known compounds. The structures of compounds 1-5 were elucidated on the basis of spectroscopic analysis. Among the new triterpene glucosides, three compounds (1, 2, 5) showed significant hepatoprotective effects against D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes.
|
Hepatoprotective activity against mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cell death at 100 uM after 18 hrs by MTT assay
|
Mus musculus
|
96.5
%
|
|
Journal : J. Nat. Prod.
Title : Quadranosides I-V, new triterpene glucosides from the seeds of Combretum quadrangulare.
Year : 2000
Volume : 63
Issue : 4
First Page : 496
Last Page : 500
Authors : Adnyana IK, Tezuka Y, Banskota AH, Xiong Q, Tran KQ, Kadota S.
Abstract : Five new triterpene glucosides, quadranosides I-V (1-5), have been isolated from a MeOH extract of the seeds of Combretum quadrangulare, together with 13 known compounds. The structures of compounds 1-5 were elucidated on the basis of spectroscopic analysis. Among the new triterpene glucosides, three compounds (1, 2, 5) showed significant hepatoprotective effects against D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes.
|
Hepatoprotective activity against mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cell death at 200 uM after 18 hrs by MTT assay
|
Mus musculus
|
70.8
%
|
|
Journal : J. Nat. Prod.
Title : Quadranosides I-V, new triterpene glucosides from the seeds of Combretum quadrangulare.
Year : 2000
Volume : 63
Issue : 4
First Page : 496
Last Page : 500
Authors : Adnyana IK, Tezuka Y, Banskota AH, Xiong Q, Tran KQ, Kadota S.
Abstract : Five new triterpene glucosides, quadranosides I-V (1-5), have been isolated from a MeOH extract of the seeds of Combretum quadrangulare, together with 13 known compounds. The structures of compounds 1-5 were elucidated on the basis of spectroscopic analysis. Among the new triterpene glucosides, three compounds (1, 2, 5) showed significant hepatoprotective effects against D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 3 uM after 44 hrs by MTT assay relative to control
|
Mus musculus
|
4.8
%
|
|
Journal : J. Nat. Prod.
Title : Structures of new sesquiterpenes and hepatoprotective constituents from the Egyptian herbal medicine Cyperus longus.
Year : 2004
Volume : 67
Issue : 4
First Page : 569
Last Page : 576
Authors : Xu F, Morikawa T, Matsuda H, Ninomiya K, Yoshikawa M.
Abstract : Six new sesquiterpenes, cyperusols A(1) (1), A(2) (2), B(1) (3), B(2) (4), C (5), and D (6), together with two monoterpenes and 13 sesquiterpenes were isolated from an Egyptian herbal medicine, the whole plants of Cyperus longus. The stereostructures of the new sesquiterpenes were determined on the basis of chemical and physicochemical evidence. In addition, the principal constituents were found to exhibit inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 10 uM after 44 hrs by MTT assay relative to control
|
Mus musculus
|
7.7
%
|
|
Journal : J. Nat. Prod.
Title : Structures of new sesquiterpenes and hepatoprotective constituents from the Egyptian herbal medicine Cyperus longus.
Year : 2004
Volume : 67
Issue : 4
First Page : 569
Last Page : 576
Authors : Xu F, Morikawa T, Matsuda H, Ninomiya K, Yoshikawa M.
Abstract : Six new sesquiterpenes, cyperusols A(1) (1), A(2) (2), B(1) (3), B(2) (4), C (5), and D (6), together with two monoterpenes and 13 sesquiterpenes were isolated from an Egyptian herbal medicine, the whole plants of Cyperus longus. The stereostructures of the new sesquiterpenes were determined on the basis of chemical and physicochemical evidence. In addition, the principal constituents were found to exhibit inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 30 uM after 44 hrs by MTT assay relative to control
|
Mus musculus
|
45.2
%
|
|
Journal : J. Nat. Prod.
Title : Structures of new sesquiterpenes and hepatoprotective constituents from the Egyptian herbal medicine Cyperus longus.
Year : 2004
Volume : 67
Issue : 4
First Page : 569
Last Page : 576
Authors : Xu F, Morikawa T, Matsuda H, Ninomiya K, Yoshikawa M.
Abstract : Six new sesquiterpenes, cyperusols A(1) (1), A(2) (2), B(1) (3), B(2) (4), C (5), and D (6), together with two monoterpenes and 13 sesquiterpenes were isolated from an Egyptian herbal medicine, the whole plants of Cyperus longus. The stereostructures of the new sesquiterpenes were determined on the basis of chemical and physicochemical evidence. In addition, the principal constituents were found to exhibit inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 100 uM after 44 hrs by MTT assay relative to control
|
Mus musculus
|
77.0
%
|
|
Journal : J. Nat. Prod.
Title : Structures of new sesquiterpenes and hepatoprotective constituents from the Egyptian herbal medicine Cyperus longus.
Year : 2004
Volume : 67
Issue : 4
First Page : 569
Last Page : 576
Authors : Xu F, Morikawa T, Matsuda H, Ninomiya K, Yoshikawa M.
Abstract : Six new sesquiterpenes, cyperusols A(1) (1), A(2) (2), B(1) (3), B(2) (4), C (5), and D (6), together with two monoterpenes and 13 sesquiterpenes were isolated from an Egyptian herbal medicine, the whole plants of Cyperus longus. The stereostructures of the new sesquiterpenes were determined on the basis of chemical and physicochemical evidence. In addition, the principal constituents were found to exhibit inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.
|
Inhibition of bovine xanthine oxidase assessed as reduction in xanthine turnover at 10 uM
|
Bos taurus
|
50.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin.
Year : 2009
Volume : 72
Issue : 4
First Page : 725
Last Page : 731
Authors : Pauff JM, Hille R.
Abstract : Xanthine oxidoreductase (XOR) is a molybdenum-containing enzyme that under physiological conditions catalyzes the final two steps in purine catabolism, ultimately generating uric acid for excretion. Here we have investigated four naturally occurring compounds that have been reported to be inhibitors of XOR in order to examine the nature of their inhibition utilizing in vitro steady-state kinetic studies. We find that luteolin and quercetin are competitive inhibitors and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike allopurinol, the inhibition is not time-dependent. These three natural products also decrease the production of superoxide by the enzyme. In contrast, and contrary to previous reports in the literature based on in vivo and other nonmechanistic studies, we find that curcumin did not inhibit the activity of purified XO nor its superoxide production in vitro.
|
Inhibition of bovine xanthine oxidase assessed as reduction in xanthine turnover at 25 uM
|
Bos taurus
|
50.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin.
Year : 2009
Volume : 72
Issue : 4
First Page : 725
Last Page : 731
Authors : Pauff JM, Hille R.
Abstract : Xanthine oxidoreductase (XOR) is a molybdenum-containing enzyme that under physiological conditions catalyzes the final two steps in purine catabolism, ultimately generating uric acid for excretion. Here we have investigated four naturally occurring compounds that have been reported to be inhibitors of XOR in order to examine the nature of their inhibition utilizing in vitro steady-state kinetic studies. We find that luteolin and quercetin are competitive inhibitors and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike allopurinol, the inhibition is not time-dependent. These three natural products also decrease the production of superoxide by the enzyme. In contrast, and contrary to previous reports in the literature based on in vivo and other nonmechanistic studies, we find that curcumin did not inhibit the activity of purified XO nor its superoxide production in vitro.
|
Inhibition of bovine xanthine oxidase assessed as reduction in xanthine turnover at 50 uM
|
Bos taurus
|
50.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin.
Year : 2009
Volume : 72
Issue : 4
First Page : 725
Last Page : 731
Authors : Pauff JM, Hille R.
Abstract : Xanthine oxidoreductase (XOR) is a molybdenum-containing enzyme that under physiological conditions catalyzes the final two steps in purine catabolism, ultimately generating uric acid for excretion. Here we have investigated four naturally occurring compounds that have been reported to be inhibitors of XOR in order to examine the nature of their inhibition utilizing in vitro steady-state kinetic studies. We find that luteolin and quercetin are competitive inhibitors and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike allopurinol, the inhibition is not time-dependent. These three natural products also decrease the production of superoxide by the enzyme. In contrast, and contrary to previous reports in the literature based on in vivo and other nonmechanistic studies, we find that curcumin did not inhibit the activity of purified XO nor its superoxide production in vitro.
|
Inhibition of bovine xanthine oxidase assessed as decrease in production of superoxide at 50 uM relative to control
|
Bos taurus
|
20.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin.
Year : 2009
Volume : 72
Issue : 4
First Page : 725
Last Page : 731
Authors : Pauff JM, Hille R.
Abstract : Xanthine oxidoreductase (XOR) is a molybdenum-containing enzyme that under physiological conditions catalyzes the final two steps in purine catabolism, ultimately generating uric acid for excretion. Here we have investigated four naturally occurring compounds that have been reported to be inhibitors of XOR in order to examine the nature of their inhibition utilizing in vitro steady-state kinetic studies. We find that luteolin and quercetin are competitive inhibitors and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike allopurinol, the inhibition is not time-dependent. These three natural products also decrease the production of superoxide by the enzyme. In contrast, and contrary to previous reports in the literature based on in vivo and other nonmechanistic studies, we find that curcumin did not inhibit the activity of purified XO nor its superoxide production in vitro.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 3 uM after 44 hrs by MTT assay relative to untreated control
|
Mus musculus
|
5.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 10 uM after 44 hrs by MTT assay relative to untreated control
|
Mus musculus
|
8.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 30 uM after 44 hrs by MTT assay relative to untreated control
|
Mus musculus
|
45.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 100 uM after 44 hrs by MTT assay relative to untreated control
|
Mus musculus
|
77.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cytotoxicity at 1 uM after 20 hrs by MTT assay relative to untreated control
|
Mus musculus
|
11.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cytotoxicity at 3 uM after 20 hrs by MTT assay relative to untreated control
|
Mus musculus
|
19.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cytotoxicity at 10 uM after 20 hrs by MTT assay relative to untreated control
|
Mus musculus
|
37.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse hepatocytes assessed as inhibition of D-galactosamine/TNFalpha-induced cytotoxicity at 30 uM after 20 hrs by MTT assay relative to untreated control
|
Mus musculus
|
93.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.
Year : 2009
Volume : 17
Issue : 20
First Page : 7313
Last Page : 7323
Authors : Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M.
Abstract : The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
|
Hepatoprotective activity in ddY mouse primary cultured hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 3 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
4.8
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Hepatoprotective activity in ddY mouse primary cultured hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 10 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
7.7
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Hepatoprotective activity in ddY mouse primary cultured hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 30 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
45.2
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Hepatoprotective activity in ddY mouse primary cultured hepatocytes assessed as inhibition of D-galactosamine-induced cytotoxicity at 100 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
77.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Cytoprotective activity in mouse L929 cells assessed as inhibition of TNF-alpha-induced cytotoxicity at 3 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
5.3
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Cytoprotective activity in mouse L929 cells assessed as inhibition of TNF-alpha-induced cytotoxicity at 10 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
22.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Cytoprotective activity in mouse L929 cells assessed as inhibition of TNF-alpha-induced cytotoxicity at 30 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
48.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Cytoprotective activity in mouse L929 cells assessed as inhibition of TNF-alpha-induced cytotoxicity at 100 ug/mL after 44 hrs by MTT assay
|
Mus musculus
|
50.8
%
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Cytoprotective activity in mouse L929 cells assessed as inhibition of TNF-alpha-induced cytotoxicity after 44 hrs by MTT assay
|
Mus musculus
|
60.4
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa.
Year : 2010
Volume : 18
Issue : 5
First Page : 1882
Last Page : 1890
Authors : Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O.
Abstract : The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.
|
Cytoprotective activity in human embryo L02 cells assessed as inhibition of D-galactosamine-induced cytotoxicity at 6.25 ug/ml treated for 1 hr prior to D-galactosamine challenge measured after 48 hrs by MTT assay relative to control
|
Homo sapiens
|
28.2
%
|
|
Journal : J. Nat. Prod.
Title : Bioactive dammarane-type saponins from Operculina turpethum.
Year : 2011
Volume : 74
Issue : 9
First Page : 1868
Last Page : 1874
Authors : Ding W, Zeng F, Xu L, Chen Y, Wang Y, Wei X.
Abstract : Four new dammarane-type saponins, operculinosides A-D (1-4), were isolated from the aerial parts of Operculina turpethum, of which 1 and 2 are the first two dammarane-type triterpenoids having an oxymethyl group at C-24. Their structures were determined by spectroscopic analysis and acid hydrolysis. The absolute configuration of operculinoside A (1) was confirmed by X-ray crystallography. Compounds 1 and 3 showed significant protective activities against d-galactosamine-induced toxicity in L-02 human hepatic cells.
|
Cytoprotective activity in human embryo L02 cells assessed as inhibition of D-galactosamine-induced cytotoxicity at 3.13 ug/ml treated for 1 hr prior to D-galactosamine challenge measured after 48 hrs by MTT assay relative to control
|
Homo sapiens
|
33.4
%
|
|
Journal : J. Nat. Prod.
Title : Bioactive dammarane-type saponins from Operculina turpethum.
Year : 2011
Volume : 74
Issue : 9
First Page : 1868
Last Page : 1874
Authors : Ding W, Zeng F, Xu L, Chen Y, Wang Y, Wei X.
Abstract : Four new dammarane-type saponins, operculinosides A-D (1-4), were isolated from the aerial parts of Operculina turpethum, of which 1 and 2 are the first two dammarane-type triterpenoids having an oxymethyl group at C-24. Their structures were determined by spectroscopic analysis and acid hydrolysis. The absolute configuration of operculinoside A (1) was confirmed by X-ray crystallography. Compounds 1 and 3 showed significant protective activities against d-galactosamine-induced toxicity in L-02 human hepatic cells.
|
Cytoprotective activity in human embryo L02 cells assessed as inhibition of D-galactosamine-induced cytotoxicity at 1.56 ug/ml treated for 1 hr prior to D-galactosamine challenge measured after 48 hrs by MTT assay relative to control
|
Homo sapiens
|
10.1
%
|
|
Journal : J. Nat. Prod.
Title : Bioactive dammarane-type saponins from Operculina turpethum.
Year : 2011
Volume : 74
Issue : 9
First Page : 1868
Last Page : 1874
Authors : Ding W, Zeng F, Xu L, Chen Y, Wang Y, Wei X.
Abstract : Four new dammarane-type saponins, operculinosides A-D (1-4), were isolated from the aerial parts of Operculina turpethum, of which 1 and 2 are the first two dammarane-type triterpenoids having an oxymethyl group at C-24. Their structures were determined by spectroscopic analysis and acid hydrolysis. The absolute configuration of operculinoside A (1) was confirmed by X-ray crystallography. Compounds 1 and 3 showed significant protective activities against d-galactosamine-induced toxicity in L-02 human hepatic cells.
|
Inhibition of electric eel AChE at 2 mg/ml by Ellman's method
|
Electrophorus electricus
|
7.08
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Inhibition of horse BChE at 2 mg/ml by Ellman's method
|
Equus caballus
|
-7.94
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Inhibition of electric eel AChE at 100 uM by colorimetric Ellman assay
|
Electrophorus electricus
|
5.5
%
|
|
Journal : J. Med. Chem.
Title : Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and pro-cognitive and hepatoprotective effects in vivo.
Year : 2012
Volume : 55
Issue : 11
First Page : 5231
Last Page : 5242
Authors : Chen X, Zenger K, Lupp A, Kling B, Heilmann J, Fleck C, Kraus B, Decker M.
Abstract : A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, analyzing the influence on viability and mitochondria of hepatic stellate cells (HSC), the toxicity of the codrug was markedly reduced in comparison to that of tacrine. Using a neuronal cell line (HT-22), a neuroprotective effect against glutamate-induced toxicity could be observed that was absent for the 1:1 mixture of components. In subsequent in vivo experiments in rats, in contrast to the effects seen after tacrine treatment, after administration of the codrug no hepatotoxicity and no induction of the cytochrome P450 system were noticed. In a scopolamine-induced cognitive impairment model using Wistar rats, the codrug was as potent as tacrine in reversing memory dysfunction. The tacrine-silibinin codrug shows high AChE and BChE inhibition, neuroprotective effects, lacks tacrine's hepatotoxicity in vitro and in vivo, and shows the same pro-cognitive effects in vivo as tacrine, being superior to the physical mixture of tacrine and silibinin in all these regards.
|
Inhibition of horse AChE at 100 uM by colorimetric Ellman assay
|
Equus caballus
|
3.1
%
|
|
Journal : J. Med. Chem.
Title : Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and pro-cognitive and hepatoprotective effects in vivo.
Year : 2012
Volume : 55
Issue : 11
First Page : 5231
Last Page : 5242
Authors : Chen X, Zenger K, Lupp A, Kling B, Heilmann J, Fleck C, Kraus B, Decker M.
Abstract : A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, analyzing the influence on viability and mitochondria of hepatic stellate cells (HSC), the toxicity of the codrug was markedly reduced in comparison to that of tacrine. Using a neuronal cell line (HT-22), a neuroprotective effect against glutamate-induced toxicity could be observed that was absent for the 1:1 mixture of components. In subsequent in vivo experiments in rats, in contrast to the effects seen after tacrine treatment, after administration of the codrug no hepatotoxicity and no induction of the cytochrome P450 system were noticed. In a scopolamine-induced cognitive impairment model using Wistar rats, the codrug was as potent as tacrine in reversing memory dysfunction. The tacrine-silibinin codrug shows high AChE and BChE inhibition, neuroprotective effects, lacks tacrine's hepatotoxicity in vitro and in vivo, and shows the same pro-cognitive effects in vivo as tacrine, being superior to the physical mixture of tacrine and silibinin in all these regards.
|
Inhibition of human thrombin assessed as decrease in platelet aggregation at 1000 uM preincubated for 10 mins measured for 10 mins by dual channel chrono-log aggregometric analysis relative to control
|
Homo sapiens
|
43.0
%
|
|
Journal : Med Chem Res
Title : Thrombin inhibitory activity of some polyphenolic compounds.
Year : 2013
First Page : 1
Last Page : 14
Authors : Bijak M, Ziewiecki R, Saluk J, Ponczek M, Pawlaczyk I, Krotkiewski H, Wachowicz B, Nowak P.
Abstract : Thrombin, also known as an active plasma coagulation factor II, belongs to the family of serine proteases and plays a crucial role in blood coagulation process. The process of thrombin generation is the central event of the hemostatic process and regulates blood coagulant activity. For this reason, thrombin inhibition is key to successful novel antithrombotic pharmacotherapy. The aim of our present study was to examine the effects of the well-known polyphenolic compounds on the activity of thrombin, by characterization of its interaction with selected polyphenols using different biochemical methods and biosensor BIAcore analyses. Only six compounds, cyanidin, quercetin, silybin, cyanin, (+)-catechin and (-)-epicatechin, of all examined in this study polyphenols caused the inhibition of thrombin amidolytic activity. But only three of the six compounds (cyanidin, quercetin and silybin) changed thrombin proteolytic activity. BIAcore analyses demonstrated that cyanidin and quercetin caused a strong response in the interaction with immobilized thrombin, while cyanin and (-)-epicatechin induced a low response. Lineweaver-Burk curves show that used polyphenol aglycones act as competitive thrombin inhibitors. Our results suggest that polyphenolic compounds might be potential structural bases and source to find and project nature-based, safe, orally bioavailable direct thrombin inhibitors.
|
Inhibition of Wnt/beta-catenin signaling pathway in human HEK293 cells at 20 uM after 24 hrs by dual luciferase reporter gene assay relative to vehicle-treated control
|
Homo sapiens
|
8.3
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the suppression of Wnt/β-catenin signaling pathway in colon cancer cells.
Year : 2013
Volume : 23
Issue : 20
First Page : 5511
Last Page : 5514
Authors : Lee MA, Kim WK, Park HJ, Kang SS, Lee SK.
Abstract : Based on the Wnt inhibitors as potential targets in the development of anticancer agents, natural compounds were evaluated for β-catenin-mediated transcriptional activity. A natural lignan hydnocarpin isolated from Lonicera japonica was considered a potential inhibitor for Wnt/β-catenin signalings. The anti-proliferative activity of hydnocarpin was also found to be associated with the suppression of Wnt/β-catenin-mediated signaling pathway in human colon cancer cells. These data suggest that hydnocarpin might be a novel Wnt inhibitor and has a potential of signaling regulator in β-catenin-mediated signaling pathways.
|
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
54.77
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
46.89
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Inhibition of biofilm formation in Staphylococcus aureus 8325-4 after 24 hrs by microtiter plate assay
|
Staphylococcus aureus
|
64.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Hydnocarpin-Type Flavonolignans: Semisynthesis and Inhibitory Effects on Staphylococcus aureus Biofilm Formation.
Year : 2015
Volume : 78
Issue : 8
First Page : 2095
Last Page : 2103
Authors : Vimberg V, Kuzma M, Stodůlková E, Novák P, Bednárová L, Šulc M, Gažák R.
Abstract : A new, efficient, and general semisynthesis of hydnocarpin-type flavonolignans was developed and optimized, enabling gram-scale production of hydnocarpin D (2). Moreover, the syntheses of optically pure hydnocarpin isomers [(10R,11R)-hydnocarpin (1a), (10R,11R)-hydnocarpin D (2a), and (10S,11S)-hydnocarpin D (2b)], as well as the synthesis of isohydnocarpin (8), were achieved for the first time utilizing this new method. The synthesis is based on the two-step transformation of the readily available flavonolignans from milk thistle (Silybum marianum), accessible by isolation from the commercial extract silymarin. The first step relies on the regioselective formylation of the C-3 hydroxy group of the dihydroflavonol-type precursor using the Vilsmeier-Haack reagent, followed by formic acid elimination by triethylamine in the second step. The synthesized compounds were effective inhibitors of Staphylococcus aureus biofilm formation, with (10S,11S)-hydnocarpin D (2b) being the most potent inhibitor. Furthermore, the effect of glucose on biofilm formation was tested, and glucose decreased the biofilm inhibitory activity of 2b. Moreover, 2b increased the susceptibility of Staph. aureus to enrofloxacin.
|
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of LPS-induced TNFalpha production at 1 uM after 24 hrs by ELISA relative to control
|
Mus musculus
|
10.3
%
|
|
Journal : Bioorg Med Chem Lett
Title : Antioxidant and anti-inflammatory neolignans from the seeds of hawthorn.
Year : 2016
Volume : 26
Issue : 22
First Page : 5501
Last Page : 5506
Authors : Peng Y, Lou LL, Liu SF, Zhou L, Huang XX, Song SJ.
Abstract : Seven new neolignans (1-2, 7-11) and five known compounds (3-6, 12) were isolated from the 70% EtOH extract of hawthorn seeds. Their structures were determined by spectroscopic analyses. The antioxidant and anti-inflammatory activities of all the isolates were investigated. Most of the isolates showed moderate radical scavenging activity in the DPPH assay and significant activities in the ABTS and FRAP assays. Furthermore, compounds 7-12 exhibited marked nitric oxide (NO) inhibition and compounds 1-4 had a potent necrosis factor-α (TNF-α) inhibitory effect. The results we obtained showed that hawthorn seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors.
|
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of LPS-induced TNFalpha production at 10 uM after 24 hrs by ELISA relative to control
|
Mus musculus
|
27.0
%
|
|
Journal : Bioorg Med Chem Lett
Title : Antioxidant and anti-inflammatory neolignans from the seeds of hawthorn.
Year : 2016
Volume : 26
Issue : 22
First Page : 5501
Last Page : 5506
Authors : Peng Y, Lou LL, Liu SF, Zhou L, Huang XX, Song SJ.
Abstract : Seven new neolignans (1-2, 7-11) and five known compounds (3-6, 12) were isolated from the 70% EtOH extract of hawthorn seeds. Their structures were determined by spectroscopic analyses. The antioxidant and anti-inflammatory activities of all the isolates were investigated. Most of the isolates showed moderate radical scavenging activity in the DPPH assay and significant activities in the ABTS and FRAP assays. Furthermore, compounds 7-12 exhibited marked nitric oxide (NO) inhibition and compounds 1-4 had a potent necrosis factor-α (TNF-α) inhibitory effect. The results we obtained showed that hawthorn seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors.
|
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of LPS-induced TNFalpha production at 50 uM after 24 hrs by ELISA relative to control
|
Mus musculus
|
47.0
%
|
|
Journal : Bioorg Med Chem Lett
Title : Antioxidant and anti-inflammatory neolignans from the seeds of hawthorn.
Year : 2016
Volume : 26
Issue : 22
First Page : 5501
Last Page : 5506
Authors : Peng Y, Lou LL, Liu SF, Zhou L, Huang XX, Song SJ.
Abstract : Seven new neolignans (1-2, 7-11) and five known compounds (3-6, 12) were isolated from the 70% EtOH extract of hawthorn seeds. Their structures were determined by spectroscopic analyses. The antioxidant and anti-inflammatory activities of all the isolates were investigated. Most of the isolates showed moderate radical scavenging activity in the DPPH assay and significant activities in the ABTS and FRAP assays. Furthermore, compounds 7-12 exhibited marked nitric oxide (NO) inhibition and compounds 1-4 had a potent necrosis factor-α (TNF-α) inhibitory effect. The results we obtained showed that hawthorn seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors.
|
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of LPS-induced TNFalpha production at 100 uM after 24 hrs by ELISA relative to control
|
Mus musculus
|
53.8
%
|
|
Journal : Bioorg Med Chem Lett
Title : Antioxidant and anti-inflammatory neolignans from the seeds of hawthorn.
Year : 2016
Volume : 26
Issue : 22
First Page : 5501
Last Page : 5506
Authors : Peng Y, Lou LL, Liu SF, Zhou L, Huang XX, Song SJ.
Abstract : Seven new neolignans (1-2, 7-11) and five known compounds (3-6, 12) were isolated from the 70% EtOH extract of hawthorn seeds. Their structures were determined by spectroscopic analyses. The antioxidant and anti-inflammatory activities of all the isolates were investigated. Most of the isolates showed moderate radical scavenging activity in the DPPH assay and significant activities in the ABTS and FRAP assays. Furthermore, compounds 7-12 exhibited marked nitric oxide (NO) inhibition and compounds 1-4 had a potent necrosis factor-α (TNF-α) inhibitory effect. The results we obtained showed that hawthorn seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors.
|
Inhibition of amyloid beta 42 (unknown origin) expressed in Escherichia coli BL21 (DE3) aggregation at 10 uM incubated for overnight by Th-S fluorescence staining based UV-Vis spectrophotometer (Rvb = 0 +/- 1%)
|
Homo sapiens
|
4.8
%
|
|
Journal : Eur J Med Chem
Title : Regioselective synthesis of 7-O-esters of the flavonolignan silibinin and SARs lead to compounds with overadditive neuroprotective effects.
Year : 2018
Volume : 146
First Page : 93
Last Page : 107
Authors : Schramm S, Huang G, Gunesch S, Lang F, Roa J, Högger P, Sabaté R, Maher P, Decker M.
Abstract : A series of neuroprotective hybrid compounds was synthesized by conjugation of the flavonolignan silibinin with natural phenolic acids, such as ferulic, cinnamic and syringic acid. Selective 7-O-esterfication without protection groups was achieved by applying the respective acyl chlorides. Sixteen compounds were obtained and SARs were established by evaluating antioxidative properties in the physicochemical FRAP assay, as well as in a cell-based neuroprotection assay using murine hippocampal HT-22 cells. Despite weak activities in the FRAP assay, esters of the α,β-unsaturated acids showed pronounced overadditive effects at low concentrations greatly exceeding the effects of equimolar mixtures of silibinin and the respective acids in the neuroprotection assay. Cinnamic and ferulic acid esters (5a and 6a) also showed overadditive effects regarding inhibition of microglial activation, PC12 cell differentiation, in vitro ischemia as well as anti-aggregating abilities against Aβ42 peptide and τ protein. Remarkably, the esters of ferulic acid with silybin A and silybin B (11a and 11b) showed a moderate but significant difference in both neuroprotection and in their anti-aggregating capacities. The results demonstrate that non-toxic natural antioxidants can be regioselectively connected as esters with medium-term stability exhibiting very pronounced overadditive effects in a portfolio of biological assays.
|
Inhibition of amyloid beta 42 (unknown origin) expressed in Escherichia coli BL21 (DE3) aggregation at 100 uM incubated for overnight by Th-S fluorescence staining based UV-Vis spectrophotometer (Rvb = 0 +/- 4.4%)
|
Homo sapiens
|
16.0
%
|
|
Journal : Eur J Med Chem
Title : Regioselective synthesis of 7-O-esters of the flavonolignan silibinin and SARs lead to compounds with overadditive neuroprotective effects.
Year : 2018
Volume : 146
First Page : 93
Last Page : 107
Authors : Schramm S, Huang G, Gunesch S, Lang F, Roa J, Högger P, Sabaté R, Maher P, Decker M.
Abstract : A series of neuroprotective hybrid compounds was synthesized by conjugation of the flavonolignan silibinin with natural phenolic acids, such as ferulic, cinnamic and syringic acid. Selective 7-O-esterfication without protection groups was achieved by applying the respective acyl chlorides. Sixteen compounds were obtained and SARs were established by evaluating antioxidative properties in the physicochemical FRAP assay, as well as in a cell-based neuroprotection assay using murine hippocampal HT-22 cells. Despite weak activities in the FRAP assay, esters of the α,β-unsaturated acids showed pronounced overadditive effects at low concentrations greatly exceeding the effects of equimolar mixtures of silibinin and the respective acids in the neuroprotection assay. Cinnamic and ferulic acid esters (5a and 6a) also showed overadditive effects regarding inhibition of microglial activation, PC12 cell differentiation, in vitro ischemia as well as anti-aggregating abilities against Aβ42 peptide and τ protein. Remarkably, the esters of ferulic acid with silybin A and silybin B (11a and 11b) showed a moderate but significant difference in both neuroprotection and in their anti-aggregating capacities. The results demonstrate that non-toxic natural antioxidants can be regioselectively connected as esters with medium-term stability exhibiting very pronounced overadditive effects in a portfolio of biological assays.
|
Inhibition of tau (unknown origin) aggregation expressed in Escherichia coli (DE3) at 10 uM incubated for overnight by Th-S fluorescence staining based UV-Vis spectrophotometer (Rvb = 0.0 +/- 1.4%)
|
Homo sapiens
|
2.0
%
|
|
Journal : Eur J Med Chem
Title : Regioselective synthesis of 7-O-esters of the flavonolignan silibinin and SARs lead to compounds with overadditive neuroprotective effects.
Year : 2018
Volume : 146
First Page : 93
Last Page : 107
Authors : Schramm S, Huang G, Gunesch S, Lang F, Roa J, Högger P, Sabaté R, Maher P, Decker M.
Abstract : A series of neuroprotective hybrid compounds was synthesized by conjugation of the flavonolignan silibinin with natural phenolic acids, such as ferulic, cinnamic and syringic acid. Selective 7-O-esterfication without protection groups was achieved by applying the respective acyl chlorides. Sixteen compounds were obtained and SARs were established by evaluating antioxidative properties in the physicochemical FRAP assay, as well as in a cell-based neuroprotection assay using murine hippocampal HT-22 cells. Despite weak activities in the FRAP assay, esters of the α,β-unsaturated acids showed pronounced overadditive effects at low concentrations greatly exceeding the effects of equimolar mixtures of silibinin and the respective acids in the neuroprotection assay. Cinnamic and ferulic acid esters (5a and 6a) also showed overadditive effects regarding inhibition of microglial activation, PC12 cell differentiation, in vitro ischemia as well as anti-aggregating abilities against Aβ42 peptide and τ protein. Remarkably, the esters of ferulic acid with silybin A and silybin B (11a and 11b) showed a moderate but significant difference in both neuroprotection and in their anti-aggregating capacities. The results demonstrate that non-toxic natural antioxidants can be regioselectively connected as esters with medium-term stability exhibiting very pronounced overadditive effects in a portfolio of biological assays.
|
Inhibition of tau (unknown origin) aggregation expressed in Escherichia coli (DE3) at 100 uM incubated for overnight by Th-S fluorescence staining based UV-Vis spectrophotometer (Rvb = 0.0 +/- 2.4%)
|
Homo sapiens
|
10.1
%
|
|
Journal : Eur J Med Chem
Title : Regioselective synthesis of 7-O-esters of the flavonolignan silibinin and SARs lead to compounds with overadditive neuroprotective effects.
Year : 2018
Volume : 146
First Page : 93
Last Page : 107
Authors : Schramm S, Huang G, Gunesch S, Lang F, Roa J, Högger P, Sabaté R, Maher P, Decker M.
Abstract : A series of neuroprotective hybrid compounds was synthesized by conjugation of the flavonolignan silibinin with natural phenolic acids, such as ferulic, cinnamic and syringic acid. Selective 7-O-esterfication without protection groups was achieved by applying the respective acyl chlorides. Sixteen compounds were obtained and SARs were established by evaluating antioxidative properties in the physicochemical FRAP assay, as well as in a cell-based neuroprotection assay using murine hippocampal HT-22 cells. Despite weak activities in the FRAP assay, esters of the α,β-unsaturated acids showed pronounced overadditive effects at low concentrations greatly exceeding the effects of equimolar mixtures of silibinin and the respective acids in the neuroprotection assay. Cinnamic and ferulic acid esters (5a and 6a) also showed overadditive effects regarding inhibition of microglial activation, PC12 cell differentiation, in vitro ischemia as well as anti-aggregating abilities against Aβ42 peptide and τ protein. Remarkably, the esters of ferulic acid with silybin A and silybin B (11a and 11b) showed a moderate but significant difference in both neuroprotection and in their anti-aggregating capacities. The results demonstrate that non-toxic natural antioxidants can be regioselectively connected as esters with medium-term stability exhibiting very pronounced overadditive effects in a portfolio of biological assays.
|
Mixed type inhibition of monophenolase activity of mushroom tyrosinase assessed as reduction in dopachrome formation using L-Tyrosine substrate by UV-Vis spectrophotometry based Dixon plot analysis
|
Agaricus bisporus
|
700.0
nM
|
|
Journal : Bioorg Med Chem
Title : Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle).
Year : 2019
Volume : 27
Issue : 12
First Page : 2499
Last Page : 2507
Authors : Kim JY, Kim JY, Jenis J, Li ZP, Ban YJ, Baiseitova A, Park KH.
Abstract : Anti-melanogenesis effects of silymarin from milk thistle have been reported recently, but detailed tyrosinase inhibition properties of individual components have not been investigated. This study purported to substantiate tyrosinase inhibition and its mechanism based on a single metabolite. The responsible components for tyrosinase inhibition of target source were found out as flavonolignans which consist of isosilybin A (1), isosilybin B (2), silydianin (3), 2,3-dihydrosilychristin (4), silychristin A (5), silychristin B (6) and silybin (7), respectively. The isolated flavonolignans (1-7) inhibited both monophenolase (IC<sub>50</sub> = 1.7-7.6 µM) and diphenolase (IC<sub>50</sub> = 12.1-44.9 µM) of tyrosinase significantly. Their inhibitions were 10-fold effective in comparison with their mother skeletons (8-10). Inhibitory functions were also proved by HPLC analysis using N-acetyl-l-tyrosine as substrate. The predominant formation of E<sub>met</sub>·I was confirmed from a long prolongation of lag time and a decrease of the static state activity of the enzyme. All tested compounds had a significant binding affinity to tyrosinase with K<sub>SV</sub> values of 0.06-0.27 × 10<sup>4</sup> L·mol<sup>-1</sup>, which are well correlated with IC<sub>50</sub>s. In kinetic study, all flavonolignan (1-7) were mixed type I (K<sub>I</sub> < K<sub>IS</sub>) inhibitors, whereas their mother skeletons (8-10) were competitive ones. The UPLC-ESI-TOF/MS analysis showed that the isolated inhibitors are the most abundant metabolites in the target plant.
|
Inhibition of monophenolase activity of mushroom tyrosinase assessed as inhibition constant for free enzyme-inhibitor complex by measuring reduction in dopachrome formation using L-Tyrosine substrate by UV-Vis spectrophotometry
|
Agaricus bisporus
|
700.0
nM
|
|
Journal : Bioorg Med Chem
Title : Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle).
Year : 2019
Volume : 27
Issue : 12
First Page : 2499
Last Page : 2507
Authors : Kim JY, Kim JY, Jenis J, Li ZP, Ban YJ, Baiseitova A, Park KH.
Abstract : Anti-melanogenesis effects of silymarin from milk thistle have been reported recently, but detailed tyrosinase inhibition properties of individual components have not been investigated. This study purported to substantiate tyrosinase inhibition and its mechanism based on a single metabolite. The responsible components for tyrosinase inhibition of target source were found out as flavonolignans which consist of isosilybin A (1), isosilybin B (2), silydianin (3), 2,3-dihydrosilychristin (4), silychristin A (5), silychristin B (6) and silybin (7), respectively. The isolated flavonolignans (1-7) inhibited both monophenolase (IC<sub>50</sub> = 1.7-7.6 µM) and diphenolase (IC<sub>50</sub> = 12.1-44.9 µM) of tyrosinase significantly. Their inhibitions were 10-fold effective in comparison with their mother skeletons (8-10). Inhibitory functions were also proved by HPLC analysis using N-acetyl-l-tyrosine as substrate. The predominant formation of E<sub>met</sub>·I was confirmed from a long prolongation of lag time and a decrease of the static state activity of the enzyme. All tested compounds had a significant binding affinity to tyrosinase with K<sub>SV</sub> values of 0.06-0.27 × 10<sup>4</sup> L·mol<sup>-1</sup>, which are well correlated with IC<sub>50</sub>s. In kinetic study, all flavonolignan (1-7) were mixed type I (K<sub>I</sub> < K<sub>IS</sub>) inhibitors, whereas their mother skeletons (8-10) were competitive ones. The UPLC-ESI-TOF/MS analysis showed that the isolated inhibitors are the most abundant metabolites in the target plant.
|
Inhibition of F1F0-ATP synthase in Escherichia coli after 60 mins relative to control
|
Escherichia coli
|
100.0
%
|
|
Journal : Eur J Med Chem
Title : Recent advancements in mechanistic studies and structure activity relationship of FoF1 ATP synthase inhibitor as antimicrobial agent.
Year : 2019
Volume : 182
First Page : 111644
Last Page : 111644
Authors : Narang R, Kumar R, Kalra S, Nayak SK, Khatik GL, Kumar GN, Sudhakar K, Singh SK.
Abstract : The emergence of drug resistance in infectious microbial strains can be overcome by development of novel drug molecules against unexploited microbial target. The success of Bedaquiline in recent years, as FoF1 ATP synthase inhibitor against XDR and MDR mycobacterium strains, has resulted in further exploration to identify more potent and safe drug molecules against resistant strains. FoF1 ATP synthase is the main energy production enzyme in almost all eukaryotes and prokaryotes. Development of bacterial ATP synthase inhibitors is a safe approach, without causing harm to mammalian cells due to structural difference between bacterial and mammalian ATP synthase target sites. This review emphasizes on providing the structural insights for FoF1 ATP synthase of different prokaryotes and will help in the design of new potent antimicrobial agents with better efficacy. Further, applications of synthetic and natural active antimicrobial ATP synthase inhibitors, reported by different research groups are summarized. Their SAR and mode of actions are also analysed.
