Identification of Ostruthin from <i>Peucedanum ostruthium</i> Rhizomes as an Inhibitor of Vascular Smooth Muscle Cell Proliferation

Joa, Helge; Vogl, Sylvia; Atanasov, Atanas G.; Zehl, Martin; Nakel, Thomas; Fakhrudin, Nanang; Heiss, Elke H.; Picker, Paolo; Urban, Ernst; Wawrosch, Christoph; Saukel, Johannes; Reznicek, Gottfried; Kopp, Brigitte; Dirsch, Verena M.

doi:10.1021/np200072a

Cited by 30 publications

(26 citation statements)

References 15 publications

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“… 2012 ), this compound was shown to inhibit vascular smooth muscle cell proliferation (Joa et al. 2011 ), inhibit acetylcholinesterase activity (Urbain et al. 2005 ), and display antimycobacterial activity (Schinkovitz et al.…”

Section: Resultsmentioning

confidence: 99%

Anti-inflammatory coumarins from Paramignya trimera

Anh

Kim

et al. 2017

Pharmaceutical Biology

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Context:Paramignya trimera (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated.Objective: This study investigated chemical constituents of the P. trimera stems and evaluated anti-inflammatory effects of isolated compounds.Materials and methods: Cytotoxicity of isolated compounds (5–40 μM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24 h. Inhibitory effects of isolated compounds (5-40 μM) on nitrite and PGE2 concentrations were determined using Griess reaction and PGE2 ELISA kit, respectively (pretreated with the compounds for 3 h and then stimulated for 18 h with LPS). Inhibitory effects of compounds (5-40 μM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3 h and then stimulated for 24 h with LPS).Results: Seven coumarins were isolated and identified as: ostruthin (1), ninhvanin (2), 8-geranyl-7-hydroxycoumarin (3), 6-(6′,7′-dihydroxy-3′,7′-dimethylocta-2′-enyl)-7-hydroxycoumarin (4), 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin (5), 6-(2-hydroxyethyl)-2,2-dimethyl-2H-1-benzopyran (6), and luvangetin (7). Compounds 1–4 and 7 inhibited NO and PGE2 production in LPS-stimulated BV2 cells, with IC50 values ranging from 9.8 to 46.8 and from 9.4 to 52.8 μM, respectively. Ostruthin (1) and ninhvanin (2) were shown to suppress LPS-induced iNOS and COX-2 protein expression.Discussion and conclusion: The present study provides a scientific rationale for the use of P. trimera in the prevention and treatment of neuroinflammatory diseases. Ostruthin and ninhvanin might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.

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Section: Resultsmentioning

confidence: 99%

Anti-inflammatory coumarins from Paramignya trimera

Anh

Kim

et al. 2017

Pharmaceutical Biology

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“…For evaluating whether ginger contains compounds able to inhibit PDGF‐induced proliferation of VSMC, a dichloromethane extract of Z. officinale roots was applied at different concentrations (0.3–30 μg/mL; Fig. ), and the total amount of metabolically active cells was measured after 48 h by the resazurin conversion method . The extract suppressed VSMC proliferation concentration dependently with an IC 50 of 2.5 μg/mL.…”

Section: Resultsmentioning

confidence: 99%

Identification and characterization of [6]‐shogaol from ginger as inhibitor of vascular smooth muscle cell proliferation

Liu

Heiss

Sider

et al. 2015

Molecular Nutrition Food Res

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ScopeVascular smooth muscle cell (VSMC) proliferation is involved in the pathogenesis of cardiovascular disease, making the identification of new counteracting agents and their mechanisms of action relevant. Ginger and its constituents have been reported to improve cardiovascular health, but no studies exist addressing a potential interference with VSMC proliferation.Methods and resultsThe dichloromethane extract of ginger inhibited VSMC proliferation when monitored by resazurin metabolic conversion (IC50 = 2.5 μg/mL). The examination of major constituents from ginger yielded [6]-shogaol as the most active compound (IC50 = 2.7 μM). In the tested concentration range [6]-shogaol did not exhibit cytotoxicity toward VSMC and did not interfere with endothelial cell proliferation. [6]-shogaol inhibited DNA synthesis and induced accumulation of the VSMC in the G0/G1 cell-cycle phase accompanied with activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Since [6]-shogaol lost its antiproliferative activity in the presence of the heme oxygenase-1 (HO-1) inhibitor tin protoporphyrin IX, HO-1 induction appears to contribute to the antiproliferative effect.ConclusionThis study demonstrates for the first time inhibitory potential of ginger constituents on VSMC proliferation. The presented data suggest that [6]-shogaol exerts its antiproliferative effect through accumulation of cells in the G0/G1 cell-cycle phase associated with activation of the Nrf2/HO-1 pathway.

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“…A sensitive and specific HPLC–DAD–MS method was developed for the simultaneous identification and quantification of the main coumarin constituents of this herbal drug [ 56 ]. A dichloromethane extract of the rhizome of P. ostruthium was found to inhibit VSMC proliferation, and bioassay-guided fractionation led to the identification of ostruthin ( 19 ) as the active component mediating this effect [ 57 ] (Fig. 11 ).…”

Section: Selected Findings Of the Dnti Projectmentioning

confidence: 99%

Drugs from nature targeting inflammation (DNTI): a successful Austrian interdisciplinary network project

et al. 2016

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Inflammation is part of numerous pathological conditions, which are lacking satisfying treatment and effective concepts of prevention. A national research network project, DNTI, involving scientists from six Austrian universities as well as several external partners aimed to identify and characterize natural products capable of combating inflammatory processes specifically in the cardiovascular system. The combined use of computational techniques with traditional knowledge, high-tech chemical analysis and synthesis, and a broad range of in vitro, cell-based, and in vivo pharmacological models led to the identification of a series of promising anti-inflammatory drug lead candidates. Mechanistic studies contributed to a better understanding of their mechanism of action and delivered new knowledge on the molecular level of inflammatory processes. Herein, the used approaches and selected highlights of the results of this interdisciplinary project are presented.Graphical abstract

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Identification of Ostruthin from Peucedanum ostruthium Rhizomes as an Inhibitor of Vascular Smooth Muscle Cell Proliferation

Cited by 30 publications

References 15 publications

Anti-inflammatory coumarins from Paramignya trimera

Anti-inflammatory coumarins from Paramignya trimera

Identification and characterization of [6]‐shogaol from ginger as inhibitor of vascular smooth muscle cell proliferation

Drugs from nature targeting inflammation (DNTI): a successful Austrian interdisciplinary network project

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