Novel Antiplatelet Naphthalene from Rhamnus nakaharai

Lin, Chun‐Nan; Lu, Chai-Ming; Lin, Hsien-Cheng; Ko, Feng‐Nien; Chen, Teng

doi:10.1021/np50126a023

Cited by 28 publications

(25 citation statements)

References 5 publications

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“…The IC 50 values of ayanin (3) and QPME (5) were similar to that of quercetin (1), suggesting that substitution of neither the C-3, -7, and -4′ nor of the C-3, -5, -7, -3′, and -4′ hydroxyl groups with methoxy groups significantly altered the effect on PDE3 inhibition. Interestingly, the IC 50 values of QPA (6) and QMTA (7) were significantly lower than that of quercetin (1), suggesting that substitution of all the hydroxyl groups of quercetin (1) or 3-MQ (2) with acetyl groups increased the effect on PDE3 inhibition when compared to that of quercetin (1).…”

Section: Inhibitory Effects Of Quercetin Derivatives On Pde3mentioning

confidence: 96%

“…In our laboratory, quercetin-3-O-methylether (3-MQ, 2) was isolated from Rhamnus nakaharai Hayata [7]. However, quercetin-3,7,4′-O-trimethylether (ayanin, 3) and quercetin-3,7,3′,4′-O-tetramethylether (QTME, 4) were synthesized according to the method described by Gomm and Nierenstein [8], and quercetin-3,5,7,3′,4′-O-pentamethylether (QPME, 5) was synthesized according to the method described by Kupchan and Bauerschmidt [9].…”

Section: Reagents and Drugsmentioning

confidence: 99%

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Inhibitory effects of quercetin derivatives on phosphodiesterase isozymes and high-affinity [3 H]-rolipram binding in guinea pig tissues

et al. 2008

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Rolipram has high (PDE4(H)) and low (PDE4(L)) affinities for phosphodiesterase (PDE)-4, respectively. In general, it is believed that inhibitions by PDE4(H) and PDE4(L) are respectively associated with an adverse response and with anti-inflammatory and bronchodilating effects. This has provided a rational basis for designing new compounds with high PDE4(H)/PDE4(L) ratios. In the present study, we attempted to determine the PDE4(H)/PDE4(L) ratios of quercetin (1), qercetin-3-O-methylether (3-MQ, 2), quercetin-3,7,4'-O-trimethylether (ayanin, 3), quercetin-3,7,3',4'-O- tetramethylether (QTME, 4), quercetin-3,5,7,3',4'-O-petamethylether (QPME, 5), quercetin-3,5,7,3',4'-O-pentaacetate (QPA, 6), and quercetin-3-O-methyl-5,7,3',4'-O-tetraacetate (QMTA, 7). The activities of PDE1 approximately 5, which were partially separated from homogenates of guinea pig lungs and hearts, were measured by a two-step procedure using adenosine 3',5'-cyclic monophosphate (cAMP) with [(3) H]-cAMP or guanosine 3',5'-cyclic monophosphate (cGMP) with [(3) H]-cGMP as substrates. The IC(50) values of all of these compounds except quercetin (1), 3-MQ (2), and QMTA (7) on PDE1 approximately 5 inhibition were determined. The anti-inflammatory effects of PDE4 inhibitors were reported to be associated with inhibition of PDE4 catalytic activity. Therefore, these IC(50) values for PDE4 inhibition were taken as the PDE4(L) values. The effective concentration (EC(50)), at which one half of the [(3) H]-rolipram bound to high-affinity rolipram binding sites (HARBSs) of brain cell membranes was replaced, was defined as the PDE4(H) value. In the present results, the PDE4(H)/PDE4(L) ratios of quercetin (1), ayanin (3), and QPME (5) were >30, >19, and 11, respectively (Table 1), which are higher than or equal to that of AWD12-281, the selective PDE4 inhibitor with the greatest potential currently undergoing clinical trials for treating asthma and chronic obstructive pulmonary disease.

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Section: Inhibitory Effects Of Quercetin Derivatives On Pde3mentioning

confidence: 96%

Section: Reagents and Drugsmentioning

confidence: 99%

Inhibitory effects of quercetin derivatives on phosphodiesterase isozymes and high-affinity [3 H]-rolipram binding in guinea pig tissues

et al. 2008

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“…8,9,18,19) To date, bioactivities of 6-methoxysorigenin and its derivatives remain largely unknown. This is the first report on their antioxidant activities.…”

Section: Resultsmentioning

confidence: 99%

“…6) It was also demonstrated a selective and competitive inhibitor of phosphosdiesterase subtype 3/subtype 4. 5) Isotorachrysone (1), an acetonaphthone isolated from R. nakaharai, showed antioxidant 7) and platelet aggregation inhibitory 8) activities. 6-Methoxysorigenin (2), isolated from the wood of R. nakaharai, possesses a structure closely analogous to 1 ( Fig.…”

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confidence: 99%

Antioxidative Effects of 6-Methoxysorigenin and Its Derivatives from Rhamnus nakaharai

Lin

2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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Oxidative stress is well known as a major cause of various chronic diseases, namely cardiovascular diseases, rheumatism, diabetes mellitus, and cancer.1,2) Reactive oxygen species (ROS) are generated in vivo during shock, inflammation, and ischemia/reperfusion injury.3) Antioxidant therapy has been clinically demonstrated to be valuable in the prevention of certain chronic diseases. 3,4) Antioxidants also play an important role in the food industry, because excessive formation of free radicals can accelerate oxidation of lipids in foods and thereby decreases food quality.Rhamnus nakaharai HAYATA (Rhamnaceae) is traditionally used as a folk medicine in Taiwan for treating constipation, inflammation, malignant tumors, and asthma. 5) 3-O-Methyquercetin, the main constituent of the plant, has been reported to inhibit cAMP-and cGMP-phosphodiesterase activity of guinea pig trachealis.6) It was also demonstrated a selective and competitive inhibitor of phosphosdiesterase subtype 3/subtype 4. 5) Isotorachrysone (1), an acetonaphthone isolated from R. nakaharai, showed antioxidant 7) and platelet aggregation inhibitory 8) activities. 6-Methoxysorigenin (2), isolated from the wood of R. nakaharai, possesses a structure closely analogous to 1 (Fig. 1) and is rich in glycosides. 9)To evaluate the antioxidant effect of 2 and its derivatives, glycosides from the wood of R. nakaharai were isolated and characterized. They were 6-methoxysorigenin-8-O-glucoside (3), a-sorinin (4), 6-methoxysorigenin-8-O-rutinoside (5). In addition, peracylates 2a and 2b, and 2 were prepared and evaluated for antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), metal chelating, and electron spin resonance (ESR) assays as well as FeCl 2 -ascorbic acid-induced lipid peroxidation assay in rat liver homogenates in vitro. Their antioxidant activities were compared with those of trolox and with EDTA for results of metal chelating assay. Results and DiscussionDPPH · is a stable free radical that accepts an electron or hydrogen radical to become a stable diamagnetic molecule. 10)In this assay, all test compounds effectively reduced the stable radical DPPH to the yellow-colored diphenylpicrylhydrazine and their scavenging effect was dose-dependent. It was found that compound 2 possesses the most potent DPPH radical-scavenging activity, with an IC 50 value of 3.48 mg/ml, which is close to that of trolox (IC 50 : 3.18 mg/ml) ( Table 1).Chelating agents, which form s-bonds with a metal, are effective as secondary antioxidants because they reduce the redox potential thereby stabilizing the oxidized form of the metal ion.11) Chelation may inhibit lipid oxidation by stabilizing transition metals. In this study, all test compounds including trolox and EDTA interfered with the formation of ferrous and ferrozine complexes, suggesting that they have chelating activity and are able to capture ferrous ion before ferrozine. Compound 2 (IC 50 : 615.90 mg/ml) showed a stronger iron-binding capacity than trolox (IC 50 : 1848.83 mg/ In the search for potentia...

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“…1) was isolated from Rhamnus nakaharai Hayata (Lin et al, 1995), and identified by spectral methods, including UV, IR, MS, and NMR spectroscopic techniques. The purity of 3-MQ was 99%.…”

Section: Reagents and Drugsmentioning

confidence: 99%

Mechanisms of suppression of nitric oxide production by 3-O-methylquercetin in RAW 264.7 cells

Jiang

Shih

Wang

et al. 2006

Journal of Ethnopharmacology

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Novel Antiplatelet Naphthalene from Rhamnus nakaharai

Cited by 28 publications

References 5 publications

Inhibitory effects of quercetin derivatives on phosphodiesterase isozymes and high-affinity [3 H]-rolipram binding in guinea pig tissues

Inhibitory effects of quercetin derivatives on phosphodiesterase isozymes and high-affinity [3 H]-rolipram binding in guinea pig tissues

Antioxidative Effects of 6-Methoxysorigenin and Its Derivatives from Rhamnus nakaharai

Mechanisms of suppression of nitric oxide production by 3-O-methylquercetin in RAW 264.7 cells

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