Inhibition of HIF-1α through Suppression of
                        NF-κB Activation by Compounds Isolated from Senecio
                        graveolens

Ticona, Luis Apaza; Cano-Adamuz, Nuria; Serban, Andreea M.; Sánchez, Ángel Rumbero

doi:10.1055/a-1063-6722

Cited by 3 publications

(2 citation statements)

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“…Moreover, chachacoma is used to treat problems associated with acute mountain sickness and to regulate arterial pressure [ 5 ]. Extracts and infusions of S. nutans have shown significant antioxidant, hemolytic, cytotoxic [ 2 , 6 , 7 ], vasodilatory, hypotensive, and antihypertensive activity in in vitro as well as animal models [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…From a phytochemical point of view, analysis of the aerial parts of S. nutans show that p-hydroxyacetophenone and its benzophenone derivatives are the most abundant compounds [ 8 , 10 , 11 ]. Moreover, coumarins (such as scopoletin and scoparone) [ 6 , 7 ], the sesquiterpene lactone damsine, and the spirolactone canrenone and sesquiterpenes γ- and δ-cadinene [ 12 ] have been found in S. nutans .…”

Section: Introductionmentioning

confidence: 99%

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Novel Oxime Synthesized from a Natural Product of Senecio nutans SCh. Bip. (Asteraceae) Enhances Vascular Relaxation in Rats by an Endothelium-Independent Mechanism

et al. 2022

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Senecio nutans Sch. Bip. and its constituents are reported to have antihypertensive effects. We isolated metabolite–1, a natural compound from S. nutans (4-hydroxy-3-(isopenten-2-yl)-acetophenone), and synthesized novel oxime – 1 (4-hydroxy-3-(isopenten-2-yl)-acetophenoxime) to evaluate their effect on vascular reactivity. Compounds were purified (metabolite–1) or synthetized (oxime–1) and characterized using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). Using pharmacological agents such as phenylephrine (PE) and KCl (enhancing contraction), acetylcholine (ACh), L-NAME (nitric oxide (NO) and endothelial function), Bay K8644-induced CaV1.2 channel (calcium channel modulator), and isolated aortic rings in an organ bath setup, the possible mechanisms of vascular action were determined. Pre-incubation of aortic rings with 10−5 M oxime–1 significantly (p < 0.001) decreased the contractile response to 30 mM KCl. EC50 to KCl significantly (p < 0.01) increased in the presence of oxime–1 (37.72 ± 2.10 mM) compared to that obtained under control conditions (22.37 ± 1.40 mM). Oxime–1 significantly reduced (p < 0.001) the contractile response to different concentrations of PE (10−7 to 10−5 M) by a mechanism that decreases Cav1.2-mediated Ca2+ influx from the extracellular space and reduces Ca2+ release from intracellular stores. At a submaximal concentration (10−5 M), oxime–1 caused a significant relaxation in rat aorta even without vascular endothelium or after pre-incubate the tissue with L-NAME. Oxime–1 decreases the contractile response to PE by blunting the release of Ca2+ from intracellular stores and blocking of Ca2+ influx by channels. Metabolite–1 reduces the contractile response to KCl, apparently by reducing the plasma membrane depolarization and Ca2+ influx from the extracellular space. These acetophenone derivates from S. nutans (metabolite–1 and oxime–1) cause vasorelaxation through pathways involving an increase of the endothelial NO generation or a higher bioavailability, further highlighting that structural modification of naturally occurring metabolites can enhance their intended pharmacological functions.

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