Flavonoids from Artichoke (Cynara scolymus L.) Up-Regulate Endothelial-Type Nitric-Oxide Synthase Gene Expression in Human Endothelial Cells

Abstract

Nitric oxide (NO) produced by endothelial nitric-oxide synthase (eNOS) represents an antithrombotic and anti-atherosclerotic principle in the vasculature. Hence, an enhanced expression of eNOS in response to pharmacological interventions could provide protection against cardiovascular diseases. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVECs), an artichoke leaf extract (ALE) increased the activity of the human eNOS promoter (determined by luciferase reporter gene assay). An organic subfraction from ALE was more potent in this respect than the crude extract, whereas an aqueous subfraction of ALE was without effect. ALE and the organic subfraction thereof also increased eNOS mRNA expression (measured by an RNase protection assay) and eNOS protein expression (determined by Western blot) both in EA.hy 926 cells and in native HUVECs. NO production (measured by NO-ozone chemiluminescence) was increased by both extracts. In organ chamber experiments, ex vivo incubation (18 h) of rat aortic rings with the organic subfraction of ALE enhanced the NO-mediated vasodilator response to acetylcholine, indicating that the up-regulated eNOS remained functional. Caffeoylquinic acids and flavonoids are two major groups of constituents of ALE. Interestingly, the flavonoids luteolin and cynaroside increased eNOS promoter activity and eNOS mRNA expression, whereas the caffeoylquinic acids cynarin and chlorogenic acid were without effect. Thus, in addition to the lipidlowering and antioxidant properties of artichoke, an increase in eNOS gene transcription may also contribute to its beneficial cardiovascular profile. Artichoke flavonoids are likely to represent the active ingredients mediating eNOS up-regulation.

Antioxidant and Antimicrobial Activities of Ethanol Extracts of <i>Cynara Scolymus (Cynarae folium, Asteraceae</i> Family)

“…Enhancement of extraction from plant materials by the fluidized bed method indicate that the technique promotes the release of various phenolic compounds. The high flavonoid content of the fliuidized bed extracts is significant in view of the claimed vasculoprotector and antiatherosclerotic effects of these compounds [4]. Thus artichoke extracts may be of use in reducing blood lipids, and when taken together with its antioxidant property, the extract could be potentially useful for cardiovascular protection.…”

“…It was reported that artichoke is rich in fiber and low in fat. Thus, its health benefits were due to its high fiber content [2][3][4].…”

Diversity of active constituents inCichorium endiviaandCynara cornigeraextracts

“…The phenolic contents in leaf and seed of Cynara cardunculus were similar and two times higher than those in flower heads [16]. The organic subfraction of artichoke is rich in polyphenolic compounds, with caffeoylquinic acids and flavonoids as the major chemical constituent [32]. In leaf extracts of commercially available artichoke (C. scolymus) a number of compounds were identified, including 8-deoxy-11-hydroxy-13-chlorogrosheimin, cryptochlorogenic acid, chlorogenic acid, neochlorogenic acid, cynarin, cynaratriol (tentatively), grosheimin, 8-deoxy-11,13-dihydroxygrosheimin, luteolin-7-O-rutinoside, luteolin-7-O-glucoside, and cynaropicrin [18].…”

Effects of Vasoactive Chinese Herbs on the Endothelial NO System

“…Importantly, our studies have demonstrated that ursolic acid (also present in Salviae miltiorrhizae radix) [24], betulinic acid (also a constituent of Zizyphi spinosae semen) [24], luteolin and cynaroside (also constituents of artichoke, Cynara scolymus L.) [25] are eNOSupregulating compounds. Ursolic acid and betulinic acid are two of the main PVL triterpenoids; luteolin and cynaroside are two of the main PVL flavonoids [23].…”