Inhibition of Phospholipase Cγ<sub>1</sub>by the Prenylated Flavonoids from<i>Sophora flavescens</i>

Lee, Hyun Sun; Ko, Hack Ryong; Ryu, Shi Yong; Oh, Won Keun; Kim, Bo Yeon; Ahn, Soon Cheol; Mheen, Tae Ick; Ahn, Jong Seog

doi:10.1055/s-2006-957670

Cited by 31 publications

(13 citation statements)

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“…In vitro , diverse mechanisms of inhibition of platelet signaling pathways have been hypothesized, and some studies have related the flavonoid structure to their inhibitory potential. Thus, flavonoids have been shown to impair enzymes involved in cellular signaling as cyclo‐oxygenases and lypoxygenases [7,8], phosphodiesterases [7], tyrosine kinases [9], and phospholipases [10,11]. They have also been postulated to have anticoagulant activity by inhibition of NAD(P)H:quinine acceptor oxidoreductase [12], an enzyme inhibited by oral anticoagulants, or by interfering with phosphatidylserine exposure [13].…”

Section: Introductionmentioning

confidence: 99%

Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor

Guerrero

Lozano

Castillo

et al. 2005

Journal of Thrombosis and Haemostasis

174

149

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Summary. Background: Dietary flavonoids are known for their antiplatelet activity resulting in cardiovascular protection, although the specific mechanisms by which this inhibition occurs has not been fully established. Objective: The aim of this study was to investigate the interaction of nine flavonoids representative of various chemical classes, with platelet responses dependent on thromboxane A 2 (TxA 2 ) generation and on receptor antagonism, and to analyze the structural requirements for such effects. Methods: The effect of several types of flavonoids on platelet aggregation, serotonin release, and TxA 2 generation was investigated. Competitive radioligand binding assays were used to screen for affinity of these compounds to TxA 2 receptors. Results: Flavones (apigenin and luteolin) and isoflavones (genistein) abrogated arachidonic acid and collagen-induced platelet responses, such as aggregation and secretion, with a less substantial effect on TxA 2 synthesis. These compounds were identified as specific ligands of the TxA 2 receptor in the lmol L )1 range, this effect accounting for antiplatelet effects related to stimulation with those agonists. Tight binding of flavonoids to the human TxA 2 receptor relies on structural features such as the presence of the double bond in C2-C3, and a keto group in C4. Conclusions: The inhibition by specific flavonoids of in vitro platelet responses induced by collagen or arachidonic acid seems to be related, to a great extent, to their ability to compete for binding to the TxA 2 receptor. Therefore, antagonism of this TxA 2 receptor may represent an additional mechanism for the inhibitory effect of these compounds in platelet function.

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Section: Introductionmentioning

confidence: 99%

Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor

Guerrero

Lozano

Castillo

et al. 2005

Journal of Thrombosis and Haemostasis

174

149

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“…9) Lavandulylated (C 10 ) or prenylated (C 5 ) flavanones, lavandulyl chalcones, pterocarpanes, and quinolizidine alkaloids were isolated from S. flavescens. [10][11][12][13][14] They possess various biological activities such as anticancer, antioxidant, antibacterial, antifungal, antiviral, and anti-inflammatory activities. [15][16][17] Although the anti-inflammatory activities of flavonoids from S. flavesens have been reported, the mechanism of kurarinone (1), lavandulyl flavanone and kuraridin (2), lavandulyl chalcone on anti-inflammatory activity remains unclear in macrophages.…”

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confidence: 99%

Lavandulyl Flavonoids from Sophora flavescens Suppress Lipopolysaccharide-Induced Activation of Nuclear Factor-.KAPPA.B and Mitogen-Activated Protein Kinases in RAW264.7 Cells

Han

Jin

Kim

et al. 2010

Biological & Pharmaceutical Bulletin

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Oxidative stress, which is commonly defined as an imbalance between oxidants and antioxidants at the cellular level, has shown a deep interest constantly as the cause of cardiovascular events and a variety of vascular diseases. 1) One of the crucial steps in oxidative stress augmentation is the overproduction of reactive oxygen species (ROS).2) ROS encompass a variety of diverse chemical species including hydroxyl radical, nitric oxide (NO), and superoxide anion. In particular, the interaction between the superoxide anion and NO is important because it leads to the formation of the peroxynitrite. The peroxynitrite activates a variety of signaling pathways 3,4) and works deleteriously through its pro-atherosclerotic properties. 1)In general, NO and ROS are responsible for the regulation of the transcriptional pathways of nuclear factor-kB (NF-kB) that regulates expression of various inflammatory cytokines, chemokines, and adhesion molecules. 5) After activation by inflammatory cytokines and cellular stresses including tumor necrosis factor (TNF)-a and lipopolysaccharide (LPS), NF-kB proteins to translocate to the nucleus and bind their cognate DNA binding sites to regulate the transcription of a large number of genes including antimicrobial peptides, cytokines, chemokines, stress-response proteins, and antiapoptotic proteins.6) In addition to NF-kB, mitogen-activated protein kinases (MAPKs) have also been implicated in cytokine production in macrophages.7) Three MAPK families (extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK)) are signaling molecules that react to extracellular stimuli (mitogens) and regulate immune responses including proinflammatory cytokine production, mitosis, differentiation, and cell survival/apoptosis. 7,8)Sophora flavescens has long been traditionally used in asthma, bronchitis, bacterial, fungal infections, and skin disorders, and as an antipyretic, analgesic, anthelmintic, and remedy for stomach ailments.9) Lavandulylated (C 10 ) or prenylated (C 5 ) flavanones, lavandulyl chalcones, pterocarpanes, and quinolizidine alkaloids were isolated from S. flavescens. [10][11][12][13][14] They possess various biological activities such as anticancer, antioxidant, antibacterial, antifungal, antiviral, and anti-inflammatory activities. [15][16][17] Although the anti-inflammatory activities of flavonoids from S. flavesens have been reported, the mechanism of kurarinone (1), lavandulyl flavanone and kuraridin (2), lavandulyl chalcone on anti-inflammatory activity remains unclear in macrophages.In this study, we examined the effects of compounds 1 and 2 on LPS-mediated NO production, ROS generation, and expression of inflammatory cytokines, NF-kB activity, and phosphorylation of MAP kinases in murine RAW264.7 macrophages. MATERIALS AND METHODS General Experimental Materials and Cell CultureDulbecco's modified Eagle's medium (DMEM), fetal bovine serum (FBS), penicillin, and streptomycin were obtained from Cambrex (Verviers, Belgium). LPS was obtained from Sigma-Aldr...

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“…[10][11][12][13] S. flavescens contains alkaloids, triterpenoids, and flavonoids 11) that have shown various biological activities such as the inhibition of phospholipase Cg1, melanogenesis, and cytotoxicity against human myeloid leukemia HL-60 cells. [14][15][16] In particular, a large number of flavonoids, including formononetin, kushenol E, kushenol B, sophoraflavanone G, kushenol L, kushenol M, kuraridin, kurarinone, kushenol N, and kushenol F, have been isolated and reported. [10][11][12][13]16) Among the flavonoids, kurarinone was reported to have potent cytotoxic activity against human MCF-7/6 breast cancer cells.…”

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confidence: 99%

Hypolipidemic Effects of Sophora flavescens and Its Constituents in Poloxamer 407-Induced Hyperlipidemic and Cholesterol-Fed Rats

Kim

Jeong

Jung

et al. 2008

Biological & Pharmaceutical Bulletin

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In this study, we investigated the hypolipidemic effects of Sophora flavescens in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. The MeOH extract and 4 fractions of S. flavescens were administered at doses of 250 and 100 mg/kg body weight, respectively, once a day for 3 d to the poloxamer 407-induced hyperlipidemic rats. Serum lipid levels such as total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) were markedly elevated in the poloxamer 407-induced hyperlipidemic control rats, while lipid levels were significantly decreased in the rats administered the MeOH extract or 4 fractions of S. flavescens. In addition, serum high-density lipoprotein-cholesterol (HDL-C) was reduced in the poloxamer 407-induced hyperlipidemic control rats. However, oral administration of both the MeOH extract and 4 fractions significantly increased HDL-C levels. Of the tested fractions, the EtOAc fraction showed the strongest lipid-lowering effect, as well as a high antiatherogenic potential with atherogenic index (A.I.) values of less than 1.92. We also investigated the hypolipidemic effects of the main compounds of the EtOAc fraction, kurarinol and kuraridinol, using the hyperlipidemic and hypercholesterolemic animal models. Here, elevated TC, TG, and LDL-C levels in the poloxamer 407-induced hyperlipidemic and cholesterol-fed rats were significantly reduced after oral administration of the compounds, and HDL-C levels had a significant increase. Furthermore, A.I. values were lowered by administering kurarinol and kuraridinol. In particular, kuraridinol exhibited stronger protective activities against hyperlipidemia than kurarinol. These results suggest that S. flavescens and its constituents may be effective cholesterol-lowering agents and useful for preventing hypercholesterolemic atherosclerosis.

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Inhibition of Phospholipase Cγ₁by the Prenylated Flavonoids fromSophora flavescens

Cited by 31 publications

References 1 publication

Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor

Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor

Lavandulyl Flavonoids from Sophora flavescens Suppress Lipopolysaccharide-Induced Activation of Nuclear Factor-.KAPPA.B and Mitogen-Activated Protein Kinases in RAW264.7 Cells

Hypolipidemic Effects of Sophora flavescens and Its Constituents in Poloxamer 407-Induced Hyperlipidemic and Cholesterol-Fed Rats

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Inhibition of Phospholipase Cγ1by the Prenylated Flavonoids fromSophora flavescens

Cited by 31 publications

References 1 publication

Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor

Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor

Lavandulyl Flavonoids from Sophora flavescens Suppress Lipopolysaccharide-Induced Activation of Nuclear Factor-.KAPPA.B and Mitogen-Activated Protein Kinases in RAW264.7 Cells

Hypolipidemic Effects of Sophora flavescens and Its Constituents in Poloxamer 407-Induced Hyperlipidemic and Cholesterol-Fed Rats

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Inhibition of Phospholipase Cγ₁by the Prenylated Flavonoids fromSophora flavescens