The Experts below are selected from a list of 2676 Experts worldwide ranked by ideXlab platform
Hyeun Wook Chang - One of the best experts on this subject based on the ideXlab platform.
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New anti-inflammatory synthetic Biflavonoid with C-C (6-6″) linkage: Differential effects on cyclooxygenase-2 and inducible nitric oxide synthase
Archives of Pharmacal Research, 2009Co-Authors: Haeil Park, Hyeun Wook ChangAbstract:Previously, a synthetic biflavone having a C-C (6–6″) linkage ([6,6″]biflavone, BF6-6) was shown to possess considerable anti-inflammatory activity. The present investigation was conducted to develop more active anti-inflammatory Biflavonoids having unique mechanisms of action based on the BF6-6 molecule. For this purpose, 5,7-dihydroxy[6,6″]biflavone (G168) was synthesized using Suzuki-Miyaura C-C cross coupling reaction. The anti-inflammatory activities of G168 were then examined on lipopolysaccharide-treated RAW 264.7 cells, carrageenaninduced paw edema and acetic acid-induced writhing in mice. It was found that G168 showed much stronger inhibition against cyclooxygenase-2-mediated PGE_2 production than the original molecule, BF6-6. It also demonstrated inhibitory activity against inducible nitric oxide synthase (iNOS)-mediated NO production at least partly by the down-regulation of iNOS. Furthermore, G168, administered intraperitoneally at a dosage of 1–5 mg/kg, showed a potent in vivo anti-inflammatory activity on carrageenan-induced paw edema and analgesic activity on acetic acid-induced writhing in mice. Therefore, the newly synthesized Biflavonoid, G168, may be used as a synthetic lead for new anti-inflammatory drug development.
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new anti inflammatory synthetic Biflavonoid with c c 6 6 linkage differential effects on cyclooxygenase 2 and inducible nitric oxide synthase
Archives of Pharmacal Research, 2009Co-Authors: Hyun Lim, Hyeun Wook Chang, Haeil Park, Soo Bae Kim, Hyun Pyo KimAbstract:Previously, a synthetic biflavone having a C-C (6–6″) linkage ([6,6″]biflavone, BF6-6) was shown to possess considerable anti-inflammatory activity. The present investigation was conducted to develop more active anti-inflammatory Biflavonoids having unique mechanisms of action based on the BF6-6 molecule. For this purpose, 5,7-dihydroxy[6,6″]biflavone (G168) was synthesized using Suzuki-Miyaura C-C cross coupling reaction. The anti-inflammatory activities of G168 were then examined on lipopolysaccharide-treated RAW 264.7 cells, carrageenaninduced paw edema and acetic acid-induced writhing in mice. It was found that G168 showed much stronger inhibition against cyclooxygenase-2-mediated PGE2 production than the original molecule, BF6-6. It also demonstrated inhibitory activity against inducible nitric oxide synthase (iNOS)-mediated NO production at least partly by the down-regulation of iNOS. Furthermore, G168, administered intraperitoneally at a dosage of 1–5 mg/kg, showed a potent in vivo anti-inflammatory activity on carrageenan-induced paw edema and analgesic activity on acetic acid-induced writhing in mice. Therefore, the newly synthesized Biflavonoid, G168, may be used as a synthetic lead for new anti-inflammatory drug development.
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Biochemical pharmacology of Biflavonoids: Implications for anti-inflammatory action
Archives of Pharmacal Research, 2008Co-Authors: Haeil Park, Hyeun Wook Chang, Sam-sik KangAbstract:Biflavonoids belong to a subclass of the plant flavonoid family. Distribution of Biflavonoids in the plant kingdom is limited to several species. Previously, some pharmacological activities of Biflavonoids were described such as inhibition of histamine release from mast cells and inhibition of lymphocyte proliferation, suggesting the anti-inflammatory/antiallergic potential of the Biflavonoids. Furthermore, several natural Biflavonoids including ochnaflavone and ginkgetin inhibit phospholipase A_2. Most importantly, certain Biflavonoids exhibit anti-inflammatory activity through the regulation of proinflammatory gene expression in vitro and in vivo . Recently, several synthetic approaches yielded new Biflavonoid molecules with anti-inflammatory potential. These molecules also exhibit phospholipase A_2 and cyclooxygenase-2 inhibitory activity. Although the bioavailability needs be improved, certain Biflavonoids may have potential as new anti-inflammatory agents. This is the first review of Biflavonoid pharmacology to date.
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Anti-inflammatory activity of the synthetic C-C Biflavonoids.
Journal of Pharmacy and Pharmacology, 2006Co-Authors: Haeil Park, Hyeun Wook Chang, Young Hoon Kim, Hyun Pyo KimAbstract:To find anti-inflammatory agents based on plant constituents, the effects of six synthetic C-C Biflavonoids connecting with different positions of C-C bond between flavone monomers (a: 4'-4', b: 4'-3', c: 4'-6, d: 3'-6, e: 6-6, f: 4'-3) were examined on PGE(2) and nitric oxide (NO) production from lipopolysaccharide (LPS)-treated macrophages, RAW 264.7. Among the compounds tested, the Biflavonoids d, e, and f showed a considerable inhibition of cyclooxygenase-2 (COX-2)-mediated PGE(2) production at concentrations up to 50 microM, while the derivative c exerted cytotoxic effects on RAW cells. Especially, the Biflavonoid e possessed the most potent inhibitory activity of PGE(2) production with an IC50 of 3.7 microM, compared with an IC50 of 8.2-20.7 microM by ginkgetin (natural Biflavonoid). Western blot and reverse transcriptase-polymerase chain reaction analyses have shown that the inhibition of PGE(2) production by these synthetic derivatives was mediated at least in part by COX-2 inhibition, but not by COX-2 down-regulation. Meanwhile, these synthetic Biflavonoids did not considerably inhibit inducible nitric oxide synthase-mediated NO production at concentrations up to 50 microM. When intraperitoneally administered, the Biflavonoid e showed a significant anti-inflammatory activity (22.2% inhibition) against rat carrageenan-induced paw oedema at 5 mg kg(-1). The Biflavonoid e may be used as a synthetic lead for developing new anti-inflammatory agents.
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Synthesis of phospholipase A2 inhibitory Biflavonoids.
Bioorganic & Medicinal Chemistry Letters, 2006Co-Authors: Jianjun Chen, Hyeun Wook Chang, Hyun Pyo Kim, Haeil ParkAbstract:Abstract A series of C–C biflavones was designed to investigate the relationship between structural array of different flavone–flavone subunit linkage and the inhibitory activity against phospholipase A2 (PLA2). Among six classes of C–C biflavones designed, four classes of C–C biflavones, which have flavone–flavone subunit linkages at A ring–A ring, A ring–B ring, B ring–B ring, and B ring–C ring, were synthesized. The synthetic biflavones exhibited somewhat different inhibitory activities against sPLA2-IIA. Among them, the biflavone a having a C–C 4′–4′ linkage showed comparable inhibitory activity with that of the natural Biflavonoid, ochnaflavone, and 7-fold stronger activity than that of amentoflavone. Further chemical modification is being carried out in order to obtain the chemically optimized Biflavonoids.
Joseph J Karchesy - One of the best experts on this subject based on the ideXlab platform.
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[5′,5′]-bisdihydroquercetin: A B-ring linked Biflavonoid from Pseudotsuga menziesii
Phytochemistry, 1992Co-Authors: Richard F Helm, Joseph J KarchesyAbstract:Abstract The isolation of [5′,5′]-bisdihydroquercetin from the outer bark of Douglas-fir, as the first example of a true Biflavonoid linked exclusively via the B-rings, broadens the known heterogeneity of interflavonoid- linkage modes among natural Biflavonoids, and supports the concept that the constitution of phlobaphenes is primarily derived by oxidative coupling of dihydroquercetin and other co-occurring components.
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5 5 bisdihydroquercetin a b ring linked Biflavonoid from pseudotsuga menziesii
Phytochemistry, 1992Co-Authors: Yeap Foo Lai, Richard F Helm, Joseph J KarchesyAbstract:Abstract The isolation of [5′,5′]-bisdihydroquercetin from the outer bark of Douglas-fir, as the first example of a true Biflavonoid linked exclusively via the B-rings, broadens the known heterogeneity of interflavonoid- linkage modes among natural Biflavonoids, and supports the concept that the constitution of phlobaphenes is primarily derived by oxidative coupling of dihydroquercetin and other co-occurring components.
Haeil Park - One of the best experts on this subject based on the ideXlab platform.
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New anti-inflammatory synthetic Biflavonoid with C-C (6-6″) linkage: Differential effects on cyclooxygenase-2 and inducible nitric oxide synthase
Archives of Pharmacal Research, 2009Co-Authors: Haeil Park, Hyeun Wook ChangAbstract:Previously, a synthetic biflavone having a C-C (6–6″) linkage ([6,6″]biflavone, BF6-6) was shown to possess considerable anti-inflammatory activity. The present investigation was conducted to develop more active anti-inflammatory Biflavonoids having unique mechanisms of action based on the BF6-6 molecule. For this purpose, 5,7-dihydroxy[6,6″]biflavone (G168) was synthesized using Suzuki-Miyaura C-C cross coupling reaction. The anti-inflammatory activities of G168 were then examined on lipopolysaccharide-treated RAW 264.7 cells, carrageenaninduced paw edema and acetic acid-induced writhing in mice. It was found that G168 showed much stronger inhibition against cyclooxygenase-2-mediated PGE_2 production than the original molecule, BF6-6. It also demonstrated inhibitory activity against inducible nitric oxide synthase (iNOS)-mediated NO production at least partly by the down-regulation of iNOS. Furthermore, G168, administered intraperitoneally at a dosage of 1–5 mg/kg, showed a potent in vivo anti-inflammatory activity on carrageenan-induced paw edema and analgesic activity on acetic acid-induced writhing in mice. Therefore, the newly synthesized Biflavonoid, G168, may be used as a synthetic lead for new anti-inflammatory drug development.
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new anti inflammatory synthetic Biflavonoid with c c 6 6 linkage differential effects on cyclooxygenase 2 and inducible nitric oxide synthase
Archives of Pharmacal Research, 2009Co-Authors: Hyun Lim, Hyeun Wook Chang, Haeil Park, Soo Bae Kim, Hyun Pyo KimAbstract:Previously, a synthetic biflavone having a C-C (6–6″) linkage ([6,6″]biflavone, BF6-6) was shown to possess considerable anti-inflammatory activity. The present investigation was conducted to develop more active anti-inflammatory Biflavonoids having unique mechanisms of action based on the BF6-6 molecule. For this purpose, 5,7-dihydroxy[6,6″]biflavone (G168) was synthesized using Suzuki-Miyaura C-C cross coupling reaction. The anti-inflammatory activities of G168 were then examined on lipopolysaccharide-treated RAW 264.7 cells, carrageenaninduced paw edema and acetic acid-induced writhing in mice. It was found that G168 showed much stronger inhibition against cyclooxygenase-2-mediated PGE2 production than the original molecule, BF6-6. It also demonstrated inhibitory activity against inducible nitric oxide synthase (iNOS)-mediated NO production at least partly by the down-regulation of iNOS. Furthermore, G168, administered intraperitoneally at a dosage of 1–5 mg/kg, showed a potent in vivo anti-inflammatory activity on carrageenan-induced paw edema and analgesic activity on acetic acid-induced writhing in mice. Therefore, the newly synthesized Biflavonoid, G168, may be used as a synthetic lead for new anti-inflammatory drug development.
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Biochemical pharmacology of Biflavonoids: Implications for anti-inflammatory action
Archives of Pharmacal Research, 2008Co-Authors: Haeil Park, Hyeun Wook Chang, Sam-sik KangAbstract:Biflavonoids belong to a subclass of the plant flavonoid family. Distribution of Biflavonoids in the plant kingdom is limited to several species. Previously, some pharmacological activities of Biflavonoids were described such as inhibition of histamine release from mast cells and inhibition of lymphocyte proliferation, suggesting the anti-inflammatory/antiallergic potential of the Biflavonoids. Furthermore, several natural Biflavonoids including ochnaflavone and ginkgetin inhibit phospholipase A_2. Most importantly, certain Biflavonoids exhibit anti-inflammatory activity through the regulation of proinflammatory gene expression in vitro and in vivo . Recently, several synthetic approaches yielded new Biflavonoid molecules with anti-inflammatory potential. These molecules also exhibit phospholipase A_2 and cyclooxygenase-2 inhibitory activity. Although the bioavailability needs be improved, certain Biflavonoids may have potential as new anti-inflammatory agents. This is the first review of Biflavonoid pharmacology to date.
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Anti-inflammatory activity of the synthetic C-C Biflavonoids.
Journal of Pharmacy and Pharmacology, 2006Co-Authors: Haeil Park, Hyeun Wook Chang, Young Hoon Kim, Hyun Pyo KimAbstract:To find anti-inflammatory agents based on plant constituents, the effects of six synthetic C-C Biflavonoids connecting with different positions of C-C bond between flavone monomers (a: 4'-4', b: 4'-3', c: 4'-6, d: 3'-6, e: 6-6, f: 4'-3) were examined on PGE(2) and nitric oxide (NO) production from lipopolysaccharide (LPS)-treated macrophages, RAW 264.7. Among the compounds tested, the Biflavonoids d, e, and f showed a considerable inhibition of cyclooxygenase-2 (COX-2)-mediated PGE(2) production at concentrations up to 50 microM, while the derivative c exerted cytotoxic effects on RAW cells. Especially, the Biflavonoid e possessed the most potent inhibitory activity of PGE(2) production with an IC50 of 3.7 microM, compared with an IC50 of 8.2-20.7 microM by ginkgetin (natural Biflavonoid). Western blot and reverse transcriptase-polymerase chain reaction analyses have shown that the inhibition of PGE(2) production by these synthetic derivatives was mediated at least in part by COX-2 inhibition, but not by COX-2 down-regulation. Meanwhile, these synthetic Biflavonoids did not considerably inhibit inducible nitric oxide synthase-mediated NO production at concentrations up to 50 microM. When intraperitoneally administered, the Biflavonoid e showed a significant anti-inflammatory activity (22.2% inhibition) against rat carrageenan-induced paw oedema at 5 mg kg(-1). The Biflavonoid e may be used as a synthetic lead for developing new anti-inflammatory agents.
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Synthesis of phospholipase A2 inhibitory Biflavonoids.
Bioorganic & Medicinal Chemistry Letters, 2006Co-Authors: Jianjun Chen, Hyeun Wook Chang, Hyun Pyo Kim, Haeil ParkAbstract:Abstract A series of C–C biflavones was designed to investigate the relationship between structural array of different flavone–flavone subunit linkage and the inhibitory activity against phospholipase A2 (PLA2). Among six classes of C–C biflavones designed, four classes of C–C biflavones, which have flavone–flavone subunit linkages at A ring–A ring, A ring–B ring, B ring–B ring, and B ring–C ring, were synthesized. The synthetic biflavones exhibited somewhat different inhibitory activities against sPLA2-IIA. Among them, the biflavone a having a C–C 4′–4′ linkage showed comparable inhibitory activity with that of the natural Biflavonoid, ochnaflavone, and 7-fold stronger activity than that of amentoflavone. Further chemical modification is being carried out in order to obtain the chemically optimized Biflavonoids.
Sam-sik Kang - One of the best experts on this subject based on the ideXlab platform.
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Biochemical pharmacology of Biflavonoids: Implications for anti-inflammatory action
Archives of Pharmacal Research, 2008Co-Authors: Haeil Park, Hyeun Wook Chang, Sam-sik KangAbstract:Biflavonoids belong to a subclass of the plant flavonoid family. Distribution of Biflavonoids in the plant kingdom is limited to several species. Previously, some pharmacological activities of Biflavonoids were described such as inhibition of histamine release from mast cells and inhibition of lymphocyte proliferation, suggesting the anti-inflammatory/antiallergic potential of the Biflavonoids. Furthermore, several natural Biflavonoids including ochnaflavone and ginkgetin inhibit phospholipase A_2. Most importantly, certain Biflavonoids exhibit anti-inflammatory activity through the regulation of proinflammatory gene expression in vitro and in vivo . Recently, several synthetic approaches yielded new Biflavonoid molecules with anti-inflammatory potential. These molecules also exhibit phospholipase A_2 and cyclooxygenase-2 inhibitory activity. Although the bioavailability needs be improved, certain Biflavonoids may have potential as new anti-inflammatory agents. This is the first review of Biflavonoid pharmacology to date.
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Amentoflavone, a plant biflavone: A new potential anti-inflammatory agent
Archives of Pharmacal Research, 1998Co-Authors: Hyeun Wook Chang, Sam-sik KangAbstract:Biflavonoid is one of unique classes of naturally-occurring bioflavonoids. Certain Biflavonoids including amentoflavone were previously reported to have inhibitory effect on the group II phospholipase A_2 activity. Amentoflavone was also found to inhibit cyclooxygenase from guinea-pig epidermis without affecting lipoxygenase. In this study, anti-inflammatory and analgesic activities of amentoflavone were evaluated. When amentoflavone was administered intraperitoneally, it showed a potent anti-inflammatory activity as determined by amelioration of croton-oil induced mouse ear edema. It also showed a potent anti-inflammatory activity in the rat carrageenan paw edema model (ED_50=42 mg/kg) compared to the activity of prednisolone (35 mg/kg) and indomethacin (10 mg/kg). However, amentoflavone did not show a significant inhibitory activity against rat adjuvant-induced arthritis, a chronic inflammatory model. In addition, amentoflavone was found to possess a potent analgesic activity in the acetic acid writhing test (ED_50=9.6 mg/kg) compared to the activity of indomethacin (3.8 mg/kg). These results suggest that amentoflavone may be a potential lead for a new type of anti-inflammatory agents having dual inhibitory activity of group II phospholipase A_2 and cyclooxygenase.
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Amentoflavone, a plant biflavone: A new potential anti-inflammatory agent
Archives of Pharmacal Research, 1998Co-Authors: Hyeun Wook Chang, Sam-sik KangAbstract:Biflavonoid is one of unique classes of naturally-occurring bioflavonoids. Certain Biflavonoids including amentoflavone were previously reported to have inhibitory effect on the group II phospholipase A_2 activity. Amentoflavone was also found to inhibit cyclooxygenase from guinea-pig epidermis without affecting lipoxygenase. In this study, anti-inflammatory and analgesic activities of amentoflavone were evaluated. When amentoflavone was administered intraperitoneally, it showed a potent anti-inflammatory activity as determined by amelioration of croton-oil induced mouse ear edema. It also showed a potent anti-inflammatory activity in the rat carrageenan paw edema model (ED_50=42 mg/kg) compared to the activity of prednisolone (35 mg/kg) and indomethacin (10 mg/kg). However, amentoflavone did not show a significant inhibitory activity against rat adjuvant-induced arthritis, a chronic inflammatory model. In addition, amentoflavone was found to possess a potent analgesic activity in the acetic acid writhing test (ED_50=9.6 mg/kg) compared to the activity of indomethacin (3.8 mg/kg). These results suggest that amentoflavone may be a potential lead for a new type of anti-inflammatory agents having dual inhibitory activity of group II phospholipase A_2 and cyclooxygenase.
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Inhibition of arachidonate release from rat peritoneal macrophage by Biflavonoids
Archives of Pharmacal Research, 1997Co-Authors: Hyeun Wook Chang, Sam-sik KangAbstract:Biflavonoid is one of unique classes of naturally-occurring bioflavonoid. Previously, certain Biflavonoids were found to possess the inhibitory effects on phospholipase A_2 activity and lymphocytes proliferation^1 suggesting their anti-inflammatory/immunoregulatory potential. In this study, effects of several Biflavonoids on arachidonic acid release from rat peritoneal macrophages were investigated, because arachidonic acid released from the activated macrophages is one of the indices of inflammatory conditions. When resident peritoneal macrophages labeled with [^3H]arachidonic acid were activated by phorbol 12-myristate 13-acetate (PMA) or calcium ionophore, A23187, radioactivity released in the medium was increased approximately 4.1∼7.3 fold after 120 min incubation compared to the spontaneous release in the control incubation. In this condition, Biflavonoids (10 uM) such as ochnaflavone, ginkgetin and isoginkgetin, showed inhibition of arachidonate release from macrophages activated by PMA (32.5∼40.0% inhibition) or A23187 (21.7∼41.7% inhibition). Amentoflavone showed protection only against PMA-induced arachidonate release, while apigenin, a monomer of these Biflavonoids, did not show the significant inhibition up to 10 uM. Staurosporin (1 uM), a protein kinase C inhibitor, showed an inhibitory effect only against PMA-induced arachidonate release (96.8% inhibition). Inhibition of arachidonate release from the activated macrophages may contribute to an anti-inflammatory potential of Biflavonoids in vivo .
Yeap Foo Lai - One of the best experts on this subject based on the ideXlab platform.
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5 5 bisdihydroquercetin a b ring linked Biflavonoid from pseudotsuga menziesii
Phytochemistry, 1992Co-Authors: Yeap Foo Lai, Richard F Helm, Joseph J KarchesyAbstract:Abstract The isolation of [5′,5′]-bisdihydroquercetin from the outer bark of Douglas-fir, as the first example of a true Biflavonoid linked exclusively via the B-rings, broadens the known heterogeneity of interflavonoid- linkage modes among natural Biflavonoids, and supports the concept that the constitution of phlobaphenes is primarily derived by oxidative coupling of dihydroquercetin and other co-occurring components.
