Esberg Lucy B, Wang Guei-Jane, Lin Yun-Lian, Ren Jun
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks, ND 58203, USA.
J Pharm Pharmacol. 2003 Jan;55(1):103-7. doi: 10.1211/002235702577.
Petasites formosanus is an indigenous species of the medicinal plant Petasites which has been used to treat hypertension. Both S-petasin and its isoform iso-S-petasin have been shown to be the effective ingredients in P. formosanus. However, their effect on heart function has not been revealed. This study was to examine the effect of iso-S-petasin on cardiac contractile function at the myocyte level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz under 1.0 mM extracellular Ca(2+). Contractile properties were evaluated using an IonOptix MyoCam system including peak shortening (PS), time to PS (TPS), time to 90% re-lengthening (TR(90)) and maximal velocity of shortening/re-lengthening (+/-dL/dt). Intracellular Ca(2+) properties were assessed by fura-2 and presented as Ca(2+)-induced Ca(2+) release (CICR) and intracellular Ca(2+) decay. Acute application of iso-S-petasin (10(-7) to 10(-4) M) elicited a concentration-dependent inhibition in PS and CICR, with maximal inhibitions of 51.0% and 31.0%, respectively. Iso-S-petasin also induced a concentration-dependent inhibition of+/-dL/dt without affecting TPS, TR(90), baseline intracellular Ca(2+) level or intracellular Ca(2+) decay. Elevation of extracellular Ca(2+) from 1.0 mM to 2.7 mM significantly antagonized the iso-S-petasin-induced depression in PS and CICR. These results demonstrated a direct depressant action of iso-S-petasin on ventricular contraction, which may work in concert with its antihypertensive action to reduce the cardiac load. The iso-S-petasin-induced decrease in CICR may play a role in its cardiac depressant effect.
台湾蜂斗菜是药用植物蜂斗菜属的本土物种，一直被用于治疗高血压。S-蜂斗菜素及其异构体异-S-蜂斗菜素均已被证明是台湾蜂斗菜中的有效成分。然而，它们对心脏功能的影响尚未明确。本研究旨在从心肌细胞水平研究异-S-蜂斗菜素对心脏收缩功能的影响。从成年大鼠心脏分离出心室肌细胞，并在1.0 mM细胞外Ca(2+) 条件下以0.5 Hz频率刺激其收缩。使用IonOptix MyoCam系统评估收缩特性，包括峰值缩短（PS）、达到PS的时间（TPS）、达到90%再延长的时间（TR(90)）以及缩短/再延长的最大速度（+/-dL/dt）。通过fura-2评估细胞内Ca(2+) 特性，并以Ca(2+) 诱导的Ca(2+) 释放（CICR）和细胞内Ca(2+) 衰减表示。急性应用异-S-蜂斗菜素（10(-7) 至10(-4) M）引起PS和CICR的浓度依赖性抑制，最大抑制率分别为51.0%和31.0%。异-S-蜂斗菜素还诱导+/-dL/dt的浓度依赖性抑制，而不影响TPS、TR(90)、细胞内Ca(2+) 基线水平或细胞内Ca(2+) 衰减。将细胞外Ca(2+) 从1.0 mM升高至2.7 mM可显著拮抗异-S-蜂斗菜素诱导的PS和CICR降低。这些结果表明异-S-蜂斗菜素对心室收缩具有直接抑制作用，这可能与其降压作用协同发挥作用以减轻心脏负荷。异-S-蜂斗菜素诱导的CICR降低可能在其心脏抑制作用中发挥作用。
