Potential Inhibitors of Platelet Aggregation from Plant Sources, III

Yun‐Choi, Hye Sook; Kim, Jae-Hoon; Lee, Jong Ran

doi:10.1021/np50054a008

Cited by 25 publications

(14 citation statements)

References 11 publications

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“…Previous studies have reported that PCA blocked agonistinduced platelet change such as ADP-, arachidonic acid-, or collagen-induced platelet aggregation (Yun-Choi et al, 1987;Chang and Hsu, 1992), which was not observed in our study. The effective concentration of PCA in those studies was 10 Ϫ4 to 10 Ϫ3 M, which is much higher than in our experimental system, and this high concentration range might not be easily achieved in an in vivo system.…”

Section: Discussioncontrasting

confidence: 84%

Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation

Kim

Bae

Lim

et al. 2012

J Pharmacol Exp Ther

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Bleeding is the most common and serious adverse effect of currently available antiplatelet drugs. Many efforts are being made to develop novel antithrombotic agents without bleeding risks. Shear stress-induced platelet aggregation (SIPA), which occurs under abnormally high shear stress, plays a crucial role in the development of arterial thrombotic diseases. Here, we demonstrate that protocatechuic acid (PCA), a bioactive phytochemical from Lonicera (honeysuckle) flowers, selectively and potently inhibits high shear (Ͼ10,000 s Ϫ1 )-induced platelet aggregation. In isolated human platelets, PCA decreased SIPA and attenuated accompanying platelet activation, including intracellular calcium mobilization, granule secretion, and adhesion receptor expression. The anti-SIPA effect of PCA was mediated through blockade of von Willebrand factor binding to activated glycoprotein Ib, a primary and initial event for the accomplishment of SIPA. Conspicuously, PCA did not inhibit platelet aggregation induced by other endogenous agonists like collagen, thrombin, or ADP that are important in both pathological thrombosis and normal hemostasis. Antithrombotic effects of PCA were confirmed in vivo in a rat arterial thrombosis model, where PCA significantly delayed the arterial occlusion induced by FeCl 3 . Of particular note, PCA did not increase bleeding times in a rat tail transection model, whereas conventional antiplatelet drugs, aspirin, and clopidogrel substantially prolonged it. Collectively, these results suggest that PCA may be a novel antiplatelet agent that can prevent thrombosis without increasing bleeding risks.

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Section: Discussioncontrasting

confidence: 84%

Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation

Kim

Bae

Lim

et al. 2012

J Pharmacol Exp Ther

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“…Of those, we determined that MV is as the most effective active ingredient that increases osteoblast differentiation with activation of the Wnt/β-catenin pathway. MV is present in many plants, including the stem bark of Zanthoxylum scandens and HDT, and has been reported to have anti-platelet and anti-oxidant activity [36], [41]–[43]. Here, we showed that MV induces osteoblast differentiation in vitro and the oral administration of MV rescues femoral trabecular and cortical bone loss caused by OVX.…”

Section: Discussionmentioning

confidence: 60%

Hovenia dulcis Thunb Extract and Its Ingredient Methyl Vanillate Activate Wnt/β-Catenin Pathway and Increase Bone Mass in Growing or Ovariectomized Mice

et al. 2014

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The Wnt/β-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/β-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT) extract as a Wnt/β-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial osteoblasts without cytotoxicity. In addition, HDT extract increased femoral bone mass without inducing significant weight changes in normal mice. In addition, thickness and area of femoral cortical bone were also significantly increased by the HDT extract. Methyl vanillate (MV), one of the ingredients in HDT, also activated the Wnt/β-catenin pathway and induced osteoblast differentiation in vitro. MV rescued trabecular or cortical femoral bone loss in the ovariectomized mice without inducing any significant weight changes or abnormality in liver tissue when administrated orally. Thus, natural HDT extract and its ingredient MV are potential anabolic agents for treating osteoporosis.

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“…It had been reported that hot water extract of E. senticosus reduced the levels of aspartate transaminase and alanine transaminase in serum and improved histological changes of liver in carbon tetrachloride‐or acetaminophen‐induced liver injury in rats (Lin & Huang 2000). Since E. senticosus have been reported to inhibit tumour necrosis factor‐α production (Yi et al 2002) and inhibit platelet aggregation (Yun‐Choi et al 1987) it was suggested that E. senticosus may be effective in suppressing liver injury induced by D‐galactosamine/lipopolysaccharide, because tumour necrosis factor‐α and platelet activating factor are important in D‐galactosamine/lipopolysaccharide‐induced fulminant hepatic failure (Komatsu et al 1996).…”

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confidence: 99%

Water‐Soluble Polysaccharide from Eleutherococcus senticosus Stems Attenuates Fulminant Hepatic Failure Induced by D‐Galactosamine and Lipopolysaccharide in Mice

Park

Nan

Zhao

et al. 2004

Basic Clin Pharma Tox

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The aim of this study was to investigate whether Eleutherococcus senticosus stems could attenuate D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. E. senticosus, known as Siberian ginseng, is a popular folk medicine used as a tonic in Asia. Preparations of E. senticosus used in this study were as follows; (i) 70% ethanol extract (ii) water extract (iii) ethanol-soluble part of the water extract (iv) polysaccharide obtained as an 80% ethanol insoluble of the water extract. Preparations were given by intraperitoneal (300 mg/kg and 50 mg/kg) or oral (300 mg/kg) injection at 12 hr and 1 hr before a D-galactosamine/lipopolysaccharide injection. The intraperitoneal injection of water extract and polysaccharide significantly lowered serum levels of tumour necrosis factor-alpha, aspartate transaminase and alanine transaminase, improved the histologic changes in liver, inhibited hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay, and suppressed the lethality induced by D-galactosamine/lipopolysaccharide. The oral administration of water extract and polysaccharide also reduced serum aspartate transaminase, alanine transaminase and tumour necrosis factor-alpha levels. In contrast 70% ethanol extract and ethanol-soluble part of the water extract had no protective effect when treated intraperitoneally or orally. These results indicate E. senticosus stems attenuate fulminant hepatic failure induced by D-galactosamine/lipopolysaccharide in mice and the protective effect is due to water-soluble polysaccharides in E. senticosus stems.

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Potential Inhibitors of Platelet Aggregation from Plant Sources, III

Cited by 25 publications

References 11 publications

Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation

Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation

Hovenia dulcis Thunb Extract and Its Ingredient Methyl Vanillate Activate Wnt/β-Catenin Pathway and Increase Bone Mass in Growing or Ovariectomized Mice

Water‐Soluble Polysaccharide from Eleutherococcus senticosus Stems Attenuates Fulminant Hepatic Failure Induced by D‐Galactosamine and Lipopolysaccharide in Mice

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