Research Article Journal of Pharmacy and Pharmacology JPP 2002, 54: 1–4  2002 The Authors Received July 7, 2002 Accepted August 20, 2002 DOI 10.1211/002235702577 ISSN 0022-3573 Iso-S-petasin, a hypotensive sesquiterpene from Petasites formosanus, depresses cardiac contraction and intracellular Ca 2M transients in adult rat ventricular myocytes Lucy B. Esberg, Guei-Jane Wang, Yun-Lian Lin and Jun Ren Abstract Petasites formosanus is an indigenous species of the medicinal plant Petasites, which 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0mM 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0mM to 27mM 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. Introduction Herbal medicine is complementary to mainstream medicine, especially when the latter is ineffective or inadequate (Marshall 1994). However, many herbal medicinal compounds are empirical with multiple unidentified components, thus making it difficult to define their pharmacology and mechanism of action. It is therefore crucial to isolate and purify the active ingredients of these medicinal plants and characterize their pharmacological properties. Petasites is a medicinal herb with a long history in the treatment of respiratory (Ziolo & Samochowiec 1998), gastrointestinal and urogenital disorders (Brune et al 1993). P. formosanus, an indigenous species of Petasites found in Taiwan, has been used to treat hypertension. However, the effective ingredients and pharmacological action of P. formosanus remain obscure. Among the sesquiterpene compounds extracted from the aerial part of P. formosanus (Lin et al 1998) are S- petasin, of which the pharmacological properties have recently been reported (Wang et al 2001), and iso-S-petasin (Figure 1), an isomer of S-petasin with an isopropenyl group at position 7. The aim of this study was to elucidate the effect of iso-S-petasin on cardiac contractile function by evaluating cell shortening and intracellular Ca 2 + properties in isolated ventricular myocytes. Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks, ND 58203, USA Lucy B. Esberg, Jun Ren National Research Institute of Chinese Medicine, Taipei, Republic of China Guei-Jane Wang, Yun-Lian Lin Correspondence : J. Ren, Division of Pharmaceutical Sciences, University of Wyoming College of Health Sciences, School of Pharmacy, 16 Gibbon, Laramie, WY 82071, USA. E-mail: jrenmedicine.nodak.edu Acknowledgment and funding : The authors would like to acknowledge Mr Kadon K. Hintz for his technical assistance. LBE is a Ronald McNair Scholar at the University of North Dakota. 1