• Title/Summary/Keyword: Lipoxygenase

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Effects of Naturally Occurring Flavonoids on Inflammatory Responses and Their Action Mechanisms

  • Kim, Hyun-Pyo;Son, Kun-Ho;Chang, Hyeun-Wook;Kang, Sam-Sik
    • Natural Product Sciences
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    • v.6 no.4
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    • pp.170-178
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    • 2000
  • Flavonoids are natural polyphenolic compounds widely distributed in plant kingdom. Although many flavonoids were found to show anti-inflammatory activity in vitro and in vivo, the potency of anti-inflammatory activity was not enough for a clinical trial. Thus, a search for finding potential flavonoid molecules is continuing. In this review, in vivo anti-inflammatory activity of various flavonoid derivatives is summarized mainly based on the results obtained in authors' laboratories. Among them, several biflavonoids such as amentoflavone and ginkgetin were found to possess anti-inflammatory activity on animal models of acute/chronic inflammation comparable to nonsteroidal and steroidal anti-inflammatory drugs currently used. In respect of their action mechanisms, the effects on arachidonic acid metabolism and nitric oxide production were described. Some flavonoids directly inhibit cyclooxygenase and/or lipoxygenase. Biflavones such as ochnaflavone and ginkgetin are inhibitors of phospholipase $A_2$. In recent studies, certain flavonoids were also found to suppress cyclooxygenase-2 and inducible nitric oxide synthase expression induced by inflammatory stimuli. Therefore, it is suggested that anti-inflammatory activity of the certain flavonoids (mainly flavones, flavonols and biflavonoids) may be mediated by direct inhibition of arachidonic acid metabolizing enzymes as well as suppression of the enzyme expression involved in inflammatory responses.

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lntracellular $Ca^{2+}$ Mediates Lipoxygenase-induced Proliferation of U-373 MG Human Astrocytoma Cells

  • Kim, Jung-Ae;Chung, Young-Ja;Lee, Yong-Soo
    • Archives of Pharmacal Research
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    • v.21 no.6
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    • pp.664-670
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    • 1998
  • The role of intracellular $Ca^{2+}$, in the regulation of tumor cell proliferation by products of arachidonic acid (AA) metabolism was investigated using U-373 MG human as trocytoma cells. Treatment with nordihydroguaiaretic acid (NDGA), a lipoxygenase (LOX) inhibitor, or caffeic acid (CA), a specific 5-LOX inhibitor, suppressed proliferation of the tumor cells in a dose-dependent manner. However, indomethacin (indo), a cyclooxygenase (COX) inhibitor, did not significantly alter proliferation of the tumor cells. At anti-proliferative concentrations, NDGA and CA significantly inhibited intracellular $Ca^{2+}$ release induced by carbachol, a known intracelluar $Ca^{2+}$ agonist in the tumor cells. Exogenous administration of leukotriene $B_4(LTB_4)$, an AA metabolite of LOX pathway, enhanced proliferation of the tumor cells in a concentration-dependent fashion. In addition, $LTB_4$, induced intracelluar $Ca^{2+}$ release. Intracellular $Ca^{2+}$-inhibitors, such as an intracellular $Ca^{2+}$ chelator (BAPTA) and intracellular $Ca^{2+}$-release inhibitors (dantrolene and TMB-8), significantly blocked the LTB4-induced enhancement of cell proliferation and intracellular $Ca^{2+}$ release. These results suggest that LOX activity may be critical for cell proliferation of the human astrocytoma cells and that intracelluar $Ca^{2+}$ may play a major role in the mechanism of action of LOX.

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Lipoxygenase Inhibition and Antioxidative Activity of Flavonoids from Paeonia moutan Seeds

  • Kim, Hyo-Jin;Chung, Shin-Kyo;Park, Sang-won
    • Preventive Nutrition and Food Science
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    • v.3 no.4
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    • pp.315-319
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    • 1998
  • Previously, the methanolic extract of Paeonia moutan seeds was found to potently inhibit soybean lipoxy-genase (SLO). Hence to isolate SLO inhibitor, the defattd methaniolic extract of the seeds was consecutively partitioned wiht ether, ethyl acetate,n-butanol ,adn water. The ether souble fraction showing strong inhibitory activity against SLO was further fractionated into a strongly acidic, a weakly acidic, and a neutral fractions. The strongly acidic components of the ether extract were successively subjected to chromatography on a silica gel, Sephadex LH-20, and preparative HPLC. Four phenolic compounds were isolated , and twio of them showing a strong SLO inhibition activity were identified as luteolin (IC50=2.32$\mu\textrm{g}$/ml) and 5,6,4'-trihydroxy-7,3'- dimethoxylflavone (IC50=0.31$\mu\textrm{g}$/ml) by UV, IR, 1H-& 13C-NMR, and MS spectroscopy. In addition, two flavonoids showed significantly antioxidative activity as strong as that of of $\alpha$-tocopherol (p<0.05) in the autoxidation system of linoleic acid. These results suggest that luteolin and 5,6,4'-trihydroxy-7,3'-dimethoxy-flavone may be used as a potential source of anti-inflammatory agents with antioxidative activity.

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Leukotriene Synthesis in Response to A23187 Is Inhibited by Methyl-β-Cyclodextrin in RBL-2H3 Cells

  • You, Hye Jin;Seo, Ji-Min;Moon, Ji-Young;Han, Sung-Sik;Ko, Young-Gyu;Kim, Jae-Hong
    • Molecules and Cells
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    • v.23 no.1
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    • pp.57-63
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    • 2007
  • Leukotrienes (LTs) are produced by several biosynthetic enzymes including cytosolic phospholipase $A_2$ ($cPLA_2$), 5-lipoxygenase (5-LO), and 5-lipoxygenase activating protein (FLAP) in the perinuclear area. In the present study, we showed that pretreatment with methyl-${\beta}$-cyclodextrin (MβCD), a cholesterol-depleting agent, dramatically reduced the synthesis of LTs in response to A23187 in mast cells. A23187-induced LT synthesis was inhibited by pretreatment with M${\beta}$CD, and this effect was reversed when cholesterol was added. In an approach to identifying the $M{\beta}CD$-sensitive protein(s), we observed that FLAP co-localized with flotillin-1, a lipid raft marker protein, in the lipid raft-rich low-density region of sucrose gradients. In addition, electron microscopic analysis revealed that FLAP co-localized with flotillin-1. Together, these results suggest that FLAP is present in cholesterol-rich lipid raft-like domains and that its localization in these domains is critical for LT synthesis.

Anti-Inflammatory Activity of Constituents Isolated from Ulmus davidiana var. japonica

  • Zheng, Ming Shan;Yang, Ju-Hye;Li, Ying;Li, Xian;Chang, Hyeun-Wook;Son, Jong-Keun
    • Biomolecules & Therapeutics
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    • v.18 no.3
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    • pp.321-328
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    • 2010
  • Twenty six compounds (1-26) were isolated from the root barks of Ulmus davidiana var. japonica. The anti-inflammatory activity of the isolated compounds were evaluated agai nst the generation of inflammatory chemical mediators in bone marrow-derived mast cells. Among them, compounds 10, 11, 13, 15 and 19 inhibited not only cyclooxygenase-2 dependent prostaglandin $D_2$ generation but also 5-lipoxygenase dependent leukotrien $C_4$ generation in a concentration-dependent manner. In addition, compounds 11, 12, 13, 15 and 19 also inhibited $\beta$-hexosaminidase release, a marker of mast cell degranulation reaction, from bone marrow-derived mast cell. These results suggest that the anti-inflammatory activity of U. davidiana might in part occur by both the inhibition of eicosanoid generations and the degranulation reaction of mast cells.

Quality Characteristics of Cheese Analogs Containing Lipoxygenase-Defected Soymilk and ${\alpha}$-Chymotrypsin Modified Soy Protein Isolate

  • Ahn Tae-Hyun;Lee Sook-Young
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.51 no.2
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    • pp.154-162
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    • 2006
  • Cheese analogs using lipoxygenase-defected soymilk and ${\alpha}$-chymotrypsin modified soy protein isolate (SPI) were prepared. Color, textural properties, sensory attributes and melting spreadability of cheese analogs were evaluated and compared with mozzarella cheese, and relationships between textural properties, sensory attributes and melting spreadability of cheese analogs were analyzed. Off-flavors were not mostly discriminated. Cheese analogs containing 10% SPI untreated and containing 6% and 8% SPI treated by ${\alpha}$-chymotrypsin in ${\Delta}E$ value of color were the most similar to mozzarella cheese. Quality characteristics and melting spreadability of cheese analogs were highly affected and improved by ${\alpha}$-chymotrypsin modification. Sensory attributes and melting spreadability of cheese analogs containing 6% SPI treated by ${\alpha}$-chymotrypsin were the most similar to mozzarella cheese, while in textural properties, cheese analogs containing 10% SPI were the most similar with mozzarella cheese. Hardness in sensory attributes was highly positively correlated with hardness (r>0.65), adhesiveness (r>0.56), chewiness (r>0.77) and gumminess (r>0.76) in textural properties, while it was highly negatively correlated with melting spreadability (r>-0.68).