Constituents of Mediterranean Spices Counteracting Vascular Smooth Muscle Cell Proliferation: Identification and Characterization of Rosmarinic Acid Methyl Ester as a Novel Inhibitor

2018 ◽  
Vol 62 (7) ◽  
pp. 1700860 ◽  
Author(s):  
Rongxia Liu ◽  
Elke H. Heiss ◽  
Birgit Waltenberger ◽  
Tina Blažević ◽  
Daniel Schachner ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Methyl Ester ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Rosmarinic Acid ◽  
Acid Methyl Ester ◽  
Acid Methyl ◽  
Identification And Characterization

scholarly journals Short Chain (≤C4) Esterification Increases Bioavailability of Rosmarinic Acid and Its Potency to Inhibit Vascular Smooth Muscle Cell Proliferation

2021 ◽  
Vol 11 ◽  
Author(s):  
Tina Blažević ◽  
Gottfried Reznicek ◽  
Limin Ding ◽  
Gangqiang Yang ◽  
Patricia Haiss ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cell ◽  
Rosmarinic Acid ◽  
Smooth Muscle Cell Proliferation ◽  
Alkyl Chains

Rosmarinic acid is a natural phenolic acid and active compound found in many culinary plants, such as rosemary, mint, basil and perilla. Aiming to improve the pharmacokinetic profile of rosmarinic acid and its activity on vascular smooth muscle cell proliferation, we generated a series of rosmarinic acid esters with increasing alkyl chain length ranging from C1 to C12. UHPLC-MS/MS analysis of rat blood samples revealed the highest increase in bioavailability of rosmarinic acid, up to 10.52%, after oral administration of its butyl ester, compared to only 1.57% after rosmarinic acid had been administered in its original form. When added to vascular smooth muscle cells in vitro, all rosmarinic acid esters were taken up, remained esterified and inhibited vascular smooth muscle cell proliferation with IC50 values declining as the length of alkyl chains increased up to C4, with an IC50 of 2.84 µM for rosmarinic acid butyl ester, as evident in a resazurin assay. Vascular smooth muscle cells were arrested in the G0/G1 phase of the cell cycle and the retinoblastoma protein phosphorylation was blocked. Esterification with longer alkyl chains did not improve absorption and resulted in cytotoxicity in in vitro settings. In this study, we proved that esterification with proper length of alkyl chains (C1–C4) is a promising way to improve in vivo bioavailability of rosmarinic acid in rats and in vitro biological activity in rat vascular smooth muscle cells.

Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

1990 ◽  
Vol 63 (02) ◽  
pp. 291-297 ◽  
Author(s):  
Herm-Jan M Brinkman ◽  
Marijke F van Buul-Worteiboer ◽  
Jan A van Mourik
Keyword(s):  
Cell Proliferation ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Muscle Cells ◽  
Smooth Muscle Cell Proliferation

SummaryWe observed that the growth of human umbilical arterysmooth muscle cells was inhibited by the phospholipase A2 inhibitors p-bromophenacylbromide and mepacrine. Thesefindings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxy-genase pathway. The following metabolites were identified: prostaglandin E2 (PGE2), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE2 was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE2 inhibits the serum-induced [3H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETEexerts this inhibitory property. Thus, our data suggeststhat human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE2 and 11-HETE, may inhibit vascular smooth muscle cell proliferation.

Influence of Endothelium on Cultured Vascular Smooth Muscle Cell Proliferation

Hypertension ◽  
1995 ◽  
Vol 25 (4) ◽  
pp. 748-751 ◽  
Author(s):  
Concepción Peiró ◽  
Juliana Redondo ◽  
M. Angeles Rodríguez-Martínez ◽  
Javier Angulo ◽  
Jesús Marín ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Smooth Muscle Cell Proliferation
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