Antiplatelet mechanism of an herbal mixture prepared from the extracts of Phyllostachys pubescens leaves and Prunus mume fruits

Abstract

BackgroundBamboo (Phyllostachys pubescens) leaves and Japanese apricot (Mume fructus) fruit are traditionally recognized to be safe herbs broadly used for food and medicinal purposes in Southeast Asia. Our group previously explored their antiplatelet effects. This study was designed to confirm inhibition effects of PM21 (a 2:1 mixture of bamboo leaf extract and Japanese apricot fruit extract) on platelet aggregation and evaluate its potency to use as an herbal remedy to prevent and/or treat the diseases caused by platelet aggregation and thrombus formation.MethodsWashed platelets were prepared and platelet aggregation was induced by adding 5 μg/mL collagen. Anti-platelet effects of PM21 (75 mg/kg, 150 mg/kg, and 300 mg/kg for ex vivo and in vivo assays, and 50, 100, 200 μg/mL for in vitro assays) were evaluated. In ex vivo assays, PM21 was orally administered to rats daily after overnight fasting for 3 days and blood was collected 1 h after the final treatment. In vivo antithrombotic effect of PM21 was observed from a carrageenan induced mouse tail thrombosis model.ResultsIn ex vivo assay, PM21 inhibited platelet aggregation significantly. PM21 showed a strong antithrombotic effect by reducing significantly the length of mouse tail thrombus. PM21 increased intracellular cAMP level and reduced the release of ATP, TXA2, and serotonin. PM21 also reduced intracellular concentration of calcium ion, fibrinogen binding to integrin αIIbβ3, and phosphorylation of ERK2, p38, PLCγ2, and PI3 K.ConclusionsPM21 showed remarkable inhibitory effects on platelet aggregation and thrombus formation. Its inhibitory function seems to influence on GPVI binding to its ligand and subsequent initiation of a signaling cascade that involves activation of effector proteins and secretion of effector molecules, such as ATP, TXA2, serotonin, and Ca2+. PM21 also appears to exert its anti-platelet effect by deactivation of ERKs activation pathway as well as inhibition of fibrinogen binding to integrin αIIbβ3.

A novel di‐peptide Met‐Glu from collagen hydrolysates inhibits platelet aggregation and thrombus formation via regulation of Gq‐mediated signaling

“…The platelet was isolated from SD rat aorta blood and mixed with sodium citrate (1:9, v/v) as previously described with some modifications (Son, Kim, Yang, Kim, & Cha, 2017). Briefly, anticoagulated blood was centrifuged (50 × g , 10 min) to obtain platelet‐rich plasma (PRP).…”

Comprehensive Review of Phytochemical Constituents, Pharmacological Properties, and Clinical Applications of Prunus mume

“…The polyacylated sucrose, citric acid, and mumefural derivatives of P. mume showed inhibitory effects on collagen-, arachidonic acid-, and ADP-induced platelet aggregation in vitro (Yoshikawa et al, 2002;Kubo et al, 2005). An herbal mixture of Phyllostachys pubescens leaves and P. mume fruits also showed inhibitory effects on platelet aggregation in vitro (Dong-Seon et al, 2013;Son et al, 2017). In the arteriovenous shunt thrombosis rat model and the carrageenan-induced mice tail thrombosis model, the mixture dose-dependently reduced the weight or length of tail thrombosis, respectively.…”

“…The mechanism study showed that the mixture upregulated intracellular cAMP levels, inhibited the release of granule contents containing serotonin, platelet-activating factor (PAF), and thromboxane A2 (TXA 2 ), and decreased the intracellular concentration of calcium ion. The mixture also exerted inhibitory effects by deactivating the collagen receptor glycoprotein VI (GPVI), blocking ligand binding to the receptor, inhibiting the downstream signaling pathway and the ERK activation pathway, and inhibiting the conversion of fibrinogen to fibrin (Dong- Seon et al, 2013;Son et al, 2017). Utsunomiya et al (2002) found that a fruit juice concentrate of P. mume markedly inhibited angiotensin II and H 2 O 2 -induced epidermal growth factor (EGF) receptor transactivation, inhibited ERK activation, and mitigated angiotensin II-induced vascular remodeling.…”

Extracts of Phyllostachys pubescens Leaves Represses Human Steroid 5-Alpha Reductase Type 2 Promoter Activity in BHP-1 Cells and Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rat Model

“…Bamboo is known to be effective against obesity, and it also relaxes the mind and helps relieve stress, insomnia, and forgetfulness [ 18 , 19 ]. It is also known for its anti-inflammatory, antioxidant, anti-osteoporosis, and anti-wrinkle effects, and it is helpful for hypertension, arteriosclerosis, and activating innate immunity [ 20 , 21 ].…”