Dual Inhibition of Cyclooxygenases-2 and 5-Lipoxygenase by Deoxypodophyllotoxin in Mouse Bone Marrow-Derived Mast Cells

Lee, Seung Hoo; Son, Min Jung; Ju, Hye Kyung; Lin, Chang Xiu; Moon, Tae Chul; Choi, Hyun Seok; Son, Jong Keun; Chang, Hyeun Wook

doi:10.1248/bpb.27.786

Cited by 78 publications

(52 citation statements)

References 15 publications

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“…The use of BMMCs as a model appears to be suitable for screening of selective COX-1/COX-2 or 5-LOX and COX-2/5-LOX dual inhibitors and degranulation inhibitors from various sources (Moon et al, 1999;Lee et al, 2004;Son et al, 2005;Jin et al, 2009). The generation of COX-2 dependent PGD2 and 5-LOX dependent LTC4 were tested after activation of the BMMCs with a combination of KL, interleukin and LPS in the presence or absence of each compound.…”

Section: Resultsmentioning

confidence: 99%

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

Zheng¹,

Yang²,

Li³

et al. 2010

Biomolecules and Therapeutics

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-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 against 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 D2 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 β-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.

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Section: Resultsmentioning

confidence: 99%

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

Zheng¹,

Yang²,

Li³

et al. 2010

Biomolecules and Therapeutics

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“…Hence, it is reasonable to assume that natural compounds that chelate Ca 2+ or interfere with Ca 2+ mobilization (i. e., by blocking channels, or interaction with signaling molecules such as PLC, IP3 receptors) prevent activation of 5-LO without inhibiting the enzyme directly. For instance, the lignan deoxypodophyllotoxin 55 from Hernandia nymphaeifolia potently impairs the production of LTC 4 (IC 50 = 0.37 mM) in intact cells [49], but a direct effect on 5-LO was not demonstrated. Of interest, it inhibited the increase in [Ca 2+ ] i induced by PAF, LTB 4 , and thapsigargin [50] that is required for activation of 5-LO.…”

Section: Activation Pathways Of 5-lo In the Cellmentioning

confidence: 99%

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Werz¹

2007

Planta Med

155

135

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The biosynthesis of leukotrienes (LTs) is initiated by the transformation of free arachidonic acid to LTA 4 by 5-lipoxygenase (5-LO). Subsequent enzymatic conversion of LTA 4 yields LTB 4 and the cysteinyl-LTs C 4 , D 4 and E 4 . LTs have prominent functions in pathophysiology and are connected to numerous disorders including bronchial asthma, allergic rhinitis, inflammatory bowel and skin diseases, rheumatoid arthritis, cancer, osteoporosis and cardiovascular diseases. Pharmacological and genetic interruption of the 5-LO pathway or blockade of LT receptors, serving as means for intervention with LTs, may be of therapeutic value for certain related disorders. Natural or plant-derived substances were among the first 5-LO inhibitors identified in the early 1980 s. To date, a huge number of diverse plant-derived compounds have been reported to interfere with 5-LO product synthesis. However, many investigations have addressed the efficacy of a given compound solely in cellular test systems and analysis of direct interference with 5-LO has been neglected. In the first part of this review, the biology and molecular pharmacology of the 5-LO pathway is summarized in order to understand its overall regulation and complexity as well as to comprehend the possible points of attack of compounds that eventually lead to inhibition of 5-LO product formation in intact cells. In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structureactivity relationships are discussed.

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“…The roots of A. sylvestris have been used as antitussive, antipyretic, analgesic, diuretic, and cough remedy in Chinese traditional medicine, and the young aerial part of this plant is used for food (Kozawa et al, 1978a;Wang et al, 1982;Yang et al, 2010). This plant has a lignan named deoxypodophyllotoxin (Noguchi et al, 1940), which is known to have many bioactivities such as antitumor activity (Kozawa et al, 1978b;Ayres et al, 1990;Lim et al, 1999), anti-platelet aggregation activity, antiviral activity, antiproliferative activity, broad insecticidal activity, inhibition of passive cutaneous anaphylaxis reactions , liver protective action (Kiso et al, 1982), and anti-inflammatory activity (Lee et al, 2004). A. sylvestris contains highly lignans, phenylpropanoids, flavonoids, coumarins, organic acids, and so on (Tozaburo et al, 1979;Liang et al, 1990;Milovanovic et al, 1996;Ikeda et al, 1998;Bos et al, 2002;Koulman et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Antitumor Constituents from Anthriscus Sylvestris (L.) Hoffm

Chen¹,

Jiang²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Dual Inhibition of Cyclooxygenases-2 and 5-Lipoxygenase by Deoxypodophyllotoxin in Mouse Bone Marrow-Derived Mast Cells

Cited by 78 publications

References 15 publications

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

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

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Antitumor Constituents from Anthriscus Sylvestris (L.) Hoffm

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