ABSTRACT
ETHNOPHARMACOLOGY RELEVANCE: The plant Senecio nutans SCh. Bip. is used by Andean communities to treat altitude sickness. Recent evidence suggests it may produce vasodilation and negative cardiac inotropy, though the cellular mechanisms have not been elucidated. PURPOSE: To determinate the mechanisms action of S. nutans on cardiovascular function in normotensive animals. METHODS: The effect of the extract on rat blood pressure was measured with a transducer in the carotid artery and intraventricular pressure by a Langendorff system. The effects on sheep ventricular intracellular calcium handling and contractility were evaluated using photometry. Ultra-high-performance liquid-chromatography with diode array detection coupled with heated electrospray-ionization quadrupole-orbitrap mass spectrometric detection (UHPLC-DAD-ESI-Q-OT-MSn) was used for extract chemical characterization. RESULTS: In normotensive rats, S. nutans (10 mg/kg) reduced mean arterial pressure (MAP) by 40% (p < 0.05), causing a dose-dependent coronary artery dilation and decreased left ventricular pressure. In isolated cells, S. nutans extract (1 µg/ml) rapidly reduced the [Ca2+]i transient amplitude and sarcomere shorting by 40 and 49% (p < 0.001), respectively. The amplitude of the caffeine evoked [Ca2+]i transient was reduced by 24% (p < 0.001), indicating reduced sarcoplasmic reticulum (SR) Ca2+ content. Sodium-calcium exchanger (NCX) activity increased by 17% (p < 0.05), while sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) activity was decreased by 21% (p < 0.05). LC-MS results showed the presence of vitamin C, malic acid, and several antioxidant phenolic acids reported for the first time. Dihydroeuparin and 4-hydroxy-3-(3-methylbut-2-enyl) acetophenone were abundant in the extract. CONCLUSION: In normotensive animals, S. nutans partially reduces MAP by decreasing heart rate and cardiac contractility. This negative inotropy is accounted for by decreased SERCA activity and increased NCX activity which reduces SR Ca2+ content. These results highlight the plant's potential as a source of novel cardio-active phytopharmaceuticals or nutraceuticals.
Subject(s)
Senecio , Acetophenones/pharmacology , Animals , Antioxidants/pharmacology , Ascorbic Acid/pharmacology , Caffeine/pharmacology , Calcium/metabolism , Myocardial Contraction , Myocytes, Cardiac , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/pharmacology , Senecio/chemistry , Sheep , Sodium-Calcium Exchanger/pharmacologyABSTRACT
With the realization of faster telecommunication data rates and an expanding interest in ultrafast chemical and physical phenomena, it has become important to develop techniques that enable simple measurements of optical waveforms with subpicosecond resolution. State-of-the-art oscilloscopes with high-speed photodetectors provide single-shot waveform measurement with 30-ps resolution. Although multiple-shot sampling techniques can achieve few-picosecond resolution, single-shot measurements are necessary to analyse events that are rapidly varying in time, asynchronous, or may occur only once. Further improvements in single-shot resolution are challenging, owing to microelectronic bandwidth limitations. To overcome these limitations, researchers have looked towards all-optical techniques because of the large processing bandwidths that photonics allow. This has generated an explosion of interest in the integration of photonics on standard electronics platforms, which has spawned the field of silicon photonics and promises to enable the next generation of computer processing units and advances in high-bandwidth communications. For the success of silicon photonics in these areas, on-chip optical signal-processing for optical performance monitoring will prove critical. Beyond next-generation communications, silicon-compatible ultrafast metrology would be of great utility to many fundamental research fields, as evident from the scientific impact that ultrafast measurement techniques continue to make. Here, using time-to-frequency conversion via the nonlinear process of four-wave mixing on a silicon chip, we demonstrate a waveform measurement technology within a silicon-photonic platform. We measure optical waveforms with 220-fs resolution over lengths greater than 100 ps, which represent the largest record-length-to-resolution ratio (>450) of any single-shot-capable picosecond waveform measurement technique. Our implementation allows for single-shot measurements and uses only highly developed electronic and optical materials of complementary metal-oxide-semiconductor (CMOS)-compatible silicon-on-insulator technology and single-mode optical fibre. The mature silicon-on-insulator platform and the ability to integrate electronics with these CMOS-compatible photonics offer great promise to extend this technology into commonplace bench-top and chip-scale instruments.