Inhibitory Effects of Methyl Brevifolincarboxylate Isolated from Phyllanthus niruri L. on Platelet Aggregation

Iizuka, Tokio; Nagai, Masahiro; Taniguchi, Akihiro; Moriyama, Hiroyoshi; Hoshi, Keiko

doi:10.1248/bpb.30.382

Cited by 24 publications

(17 citation statements)

References 17 publications

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“…1 Our previous study revealed that 1 is an inhibitor of the aggregation of human platelets, suggesting that 1 is a receptor-binding inhibitor because it exhibits potent inhibition of platelet aggregation induced by both collagen and ADP. 5) Therefore antiplatelet-aggregating effects of 1 may also involve [Ca 2ϩ ] i released into the platelets to inhibit platelet aggregation, based on the present findings, as 1 have ROCs. To elucidate the mechanism of platelet-aggregating inhibition by 1, additional studies are required to confirm whether [Ca 2ϩ ] i play a role in antiplatelet aggregation.…”

Section: When Ne 3ϫ10supporting

confidence: 54%

Vasorelaxant Effects of Methyl Brevifolincarboxylate from the Leaves of Phyllanthus niruri

Iizuka

Moriyama

Nagai

2006

Biological & Pharmaceutical Bulletin

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Members of the genus Phyllanthus (Euphorbiaceae) include some 500 species and are widespread in temperate and tropical climates. Phyllanthus species have attracted the attention of researchers for their hepatoprotective properties; an aqueous extract of Phyllanthus amarus was demonstrated to exert antihepatitis B virus effects to varying degrees. 1,2) In 2003, various constituents isolated from Phyllanthus species were screened for anti-human hepatitis B virus in vitro. 3)However, little or no attention has been paid to constituents isolated from Phyllanthus niruri L. for other biological studies, thus prompting us to isolate constituents that might have antiplatelet aggregatory effects, as previously detected in the crude extract of P. niruri.4) Furthermore, we isolated methyl brevifolincarboxylate (compound 1) as a constituent responsible for the antiplatelet aggregatory effects. 5)Interestingly, 1 (Fig. 1) was also isolated from Phyllanthus urinaria L.6) and other Phyllanthus species, although no mention was made of its biological activities.7) Therefore, we investigated the vasorelaxant effects of 1 on rat aortic rings in connection with the receptor-operated Ca 2ϩ channel. MATERIALS AND METHODSPlant Material Dried P. niruri leaves were obtained from PT Haldin Pacific Semesta (Jakarta, Indonesia).Chemicals Norepinephrine hydrochloride (NE), nicardipine, ethyleneglycol-bis-(b-aminoethyl ether)-tetraacetic acid (EGTA), and acetylcholine chloride (Ach) were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.).Compound 1 (Methyl Brevifolincarboxylate) The extraction, isolation and confirmation of 1 was described in our previous study. 5)Isolation of Rat Aortic Strips Male Wistar rats weighing 240-300 g were killed by bleeding from the carotid arteries under anesthetization. A section of the thoracic aorta between the aortic arch and the diaphragm was removed and placed in oxygenated, modified Krebs-Henseleit solution (KHS) composed of (mM): NaCl 118.0; KCl, 4.7; NaHCO 3 , 25.0; CaCl 2 , 1.8; NaH 2 PO 4 , 1.2; MgSO 4 , 1.2; and glucose, 11.0. The aorta was cleaned by removing loosely attached fat and connective tissue and cut into 3-mm lengths. To detach the endothelium, endothelial cells on each strip were removed by gentle rubbing of the endothelial surface with a disposable cotton applicator. The tissue was placed in a welloxygenated (95% O 2 , 5% CO 2 ) bath of KHS 10 ml at 37°C with the ringed aorta connected to a tissue holder and to a force-displacement transducer (Nihon Kohden, TB-611T). The tissue was equilibrated for 60 min under a resting tension of 1.0 g. During this time the KHS in the tissue bath was replaced every 20 min.Experimental Protocol Experiments were performed according to method in the previous studies.8-10) After equilibration, each aortic ring was contracted by treatment with 3ϫ10 Ϫ7 M NE. The presence of functional endothelial cells was confirmed by demonstrating relaxation with response to 10 Ϫ5 M Ach, and tissues indicating 80% relaxation of the aortic ring were regarded as tiss...

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Section: When Ne 3ϫ10supporting

confidence: 54%

Vasorelaxant Effects of Methyl Brevifolincarboxylate from the Leaves of Phyllanthus niruri

Iizuka

Moriyama

Nagai

2006

Biological & Pharmaceutical Bulletin

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“…It would also be interesting to investigate coumarinolignans for their antiplatelet effects, since our previous study of methyl brevifolincarboxylate isolated from the leaves of P. niruri revealed that the constituent had both ef- fects, suggesting the presence of a similar pharmacologic action. 2,14) In conclusion, the organic extract of A. nikoense and 1-3 as major constituents of the extract relaxed NE-precontracted rat aortic rings. The extract showed vasorelaxant effects on aortic rings with or without endothelium.…”

Section: Resultsmentioning

confidence: 82%

Vasorelaxant Effects of Acer nikoense Extract and Isolated Coumarinolignans on Rat Aortic Rings

Iizuka

Nagumo

Yotsumoto

et al. 2007

Biological & Pharmaceutical Bulletin

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We previously detected compounds with vasorelaxant effects, such as methyl brevifolincarboxylate, from the leaves of Phyllanthus niruri, 2) ebricoic acid from the extract of Phellinus givus, 3) and forsythiaside from the fruit of Forsythia suspensa. 4) In our attempts to search for compounds with vasorelaxant effects from various plants, in the present study we isolated three constituents from the heartwood of Acer nikoense (Aceraceae): A. nikoense is a Japanese folk medicine used as a remedy primarily for hepatic disorders. Constituents previously isolated from the bark and leaves are diarylheptanoids, phenolic compounds, and tannin, 5) and their bioactivities such as antiinflammatory effects 6) and protective effects against hepatic injury 7) were also reported. First, we found that the organic extract from the heartwood of A. nikoense showed vasorelaxant effects on rat aorta with or without endothelium. Second, scopoletin (1), cleomiscosin A (2), and aquillochin (3) were isolated as major constituents using SiO 2 chromatography. 8) Moreover, the results of our literature search revealed that 1 had vasorelaxant effects by inhibiting intracellular calcium mobilization from norepinephrine (NE)-sensitive stores.9) Consequently, we focused on the vasorelaxant effects of 2 and 3 isolated from the organic extract of the heartwood of A. nikoense and investigated their effects in comparison with that of 1, which was used as a positive control in the present study. MATERIALS AND METHODSPlant Material Dried A. nikoense heartwood was obtained from the Medicinal Plant Garden of Hoshi University, and identified by one of the authors (S.N.).Chemicals NE, nicardipine, ethyleneglycol-bis-(b-aminoethyl ether)-tetraacetic acid (EGTA), and acetylcholine chloride (Ach) were purchased from Sigma Chemical (St. Louis, MO, U.S.A.). Authentic samples of 1-3 were obtained from one of the authors (S.N.) (Fig. 1).Extraction and Isolation Dried A. nikoense heartwood (62.5 g) was extracted with MeOH, and the extract solution was evaporated in vacuo. The residual extract (5.0 g) was further extracted successively with diethyl ether, ethyl acetate, and water. Then the extracts were evaporated in vacuo to obtain extracts of 0.51 g, 0.82 g, and 2.07 g from the successivesolvents. Among the extracts tested for vasorelaxant effects on rat aorta, the ether extract exhibited the most potent relaxant effects on NE-induced aortic contraction. Compounds 1, 2, and 3 of A. nikoense were found in the diethyl ether fraction. 8)Assay for Vasorelaxation Experimental studies using animals were conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals, Hoshi University, and under the supervision of the Committee on Animal Research of Hoshi University, which is accredited by the Ministry of Education, Science, Sports Culture and Technology of Japan. Isolation of Rat Aortic StripsThe preparation of aortic rings and measurement of tension were performed as previously described.2-4) In brief, male Wistar rats weighing 240-340...

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“…Although DMSO was reported as a platelet-aggregatory inhibitor when used at high concentrations, 13) concentrations of DMSO at less than 0.5% showed little or no effect on platelet aggregation. 14) Moreover, the inhibitory effects of adenosine on different solvents such as DMSO and saline at various concentrations were further examined by monitoring the percent distribution of platelet aggregates according to size and changes in T with the laser-light scattering method (Fig. 4, Tables 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

Assay-guided Informatory Screening Method for Antiplatelet Effect of Adenosine Isolated from Malbranchea filamentosa IFM 41300: Inhibitory Behaviors of Adenosine in Different Solvents

Moriyama

Hosoe

Wakana

et al. 2009

JOURNAL OF HEALTH SCIENCE

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A particle-counting aggregometer employing laser-light scattering was used in systematic manners to screen and to detect inhibitor(s) of platelet aggregation from the extract of Malbranchea filamentosa (M. filamentosa) IFM 41300. The inhibitor was determined as adenosine on the basis of the 13 C-and 1 H-NMR spectral data. Although adenosine was previously reported as an inhibitor of platelet aggregation, we isolated the compound from the fungus for the first time. Because the method was able to provide us with information on the developmental formation of platelet aggregates in different sizes with incubation time, we further elaborated the inhibitory behaviors of adenosine, as an example, at varied concentrations in different solvents such as dimethyl sulfoxide (DMSO) and saline. We found that DMSO could facilitate to dissolve less water soluble materials from herbs and fungi by using the present assay method.

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Inhibitory Effects of Methyl Brevifolincarboxylate Isolated from Phyllanthus niruri L. on Platelet Aggregation

Cited by 24 publications

References 17 publications

Vasorelaxant Effects of Methyl Brevifolincarboxylate from the Leaves of Phyllanthus niruri

Vasorelaxant Effects of Methyl Brevifolincarboxylate from the Leaves of Phyllanthus niruri

Vasorelaxant Effects of Acer nikoense Extract and Isolated Coumarinolignans on Rat Aortic Rings

Assay-guided Informatory Screening Method for Antiplatelet Effect of Adenosine Isolated from Malbranchea filamentosa IFM 41300: Inhibitory Behaviors of Adenosine in Different Solvents

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