Do endogenous ligands of peripheral μ- and δ-opiate receptors mediate antiarrhythmic and cardioprotective effects ofRhodiola rosea?

Abstract

Oral administration of Rhodiola rosea extract to rats (3.5 ml/kg, 8 days) prevents reperfusion arrhythmias and elicits a protective effect in experiments on isolated heart. Experiments with naloxone and ICI 174,864 suggest that the antiarrhythmic effect of R. rosea extract is mediated through activation of ~t-opiate receptors in the myocardium. The cardioprotective effect of this extract is not associated with opiate receptors.Key Words: Ix-and 8-opiate receptors; arrhythmias; isolated heart; adaptogens It has been previously shown that extract of RhodioIa rosea, a natural adaptogen, exhibits cardioprotective and antiarrhythmic activity in vivo [2,4]. Moreover, we showed that repeated administration of this preparation induces accumulation of opioid peptides in tissues [2][3][4], while preliminary injection of the nonselective opiate receptor (OR) blocker naloxone abolishes the antiarrhythmic effects of R. rosea [3]. These data suggest that the above-mentioned effects of R. rosea are mediated through activation of cardiac OR of their endogenous ligands.In light of the above and because the search for new means for preventing ischemic and reperfusion damage to the myocardium is an important medical problem, we studied opiatergic mechanisms of the antiarrhythmic and cardioprotective effects of R. rosea on isolated perfused rat heart. MATERIALS AND METHODSExperiments were carried out on 94 Wistar rats weighing 200-250 g and adapted by repeated oral administration (3.5 ml/kg for 8 days) of an officinal Department of Experimental Cardiology, Institute of Cardiology, Siberian Division of the Russian Academy of Medical Sciences, Tomsk R. rosea extract. The dose and the schelne of administration were chosen on the basis of our previous data on antiarrhythlnic effect of the preparation in vivo [2]. In some experimental series, 15 rain prior to heart isolation the rats were intravenously injected with naloxone (Sigma) in a dose of 0.5 mg/kg (sufficient for blockade of ~t-and 8-OR [5]) or ICI 174,864 (Chiron Mimotopes Peptide System), a blocker of 8-OR, in a dose of 2.5 mg/kg [5]. Intact animals served as the control.The heart was isolated and perfused by Langendorff as described previously 11,7]. The heaJ~t was adapted to perfusion conditions for 20 rain and then, after recording the initial parameters, total normothermal ischelnia was modeled by interrupting the perfusion with Krebs--Henseleit solution for 45 rain followed by 60-min reperfusion. Electrodes for electrocardiogram recording were positioned on the right atrium and left ventricle. Recording and computerassisted processing of ECG were performed using an UBF 4-03 biopotential amplifier (Pushchino). The total percentage of ventricular arrhythmias and the percentage of ventricular fibrillations were estimated in each group of isolated hearts for a 60-min reperfusion period. Damage to cardiomyocytes was assessed by creatine phosphokinase (CPK) activity in the perfusate measured with NAC-activated C K 47-

Anti‐inflammatory activity of Rhodiola rosea – “a second‐generation adaptogen”

“…This plant indigenous to the high-altitude Arctic regions has been used in Russian and Chinese folk medicine (Rege et al, 1999). Many biological activities have been reported on this versatile phytoadaptogen: anti-oxidant (Anilakumar et al, 2006); anti-arrhythmic (Maslov et al, 1998); antistress (Darbiyan et al, 2000;Spasov et al, 2000); anticancer and antibacterial properties (Udintsev and Shakov, 1991;Ming et al, 2005); besides its cardio protective effect (Maslov et al, 1997). Our recent work also established a significant antioxidant activity associated with this plant (Anilakumar et al, 2006).…”

Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity

“… HPA- axis, including cortisol and glucocorticoid receptors [ 21 , 123 , 124 ]. Beta-endorphin [ 125 , 126 , 127 ]. Nitric oxide [ 21 , 128 , 129 , 130 , 131 ].…”

Bioactive compounds fromRhodiola rosea (Crassulaceae)

“…Rhodiola species have been prescribed for hemostatic, antibechic and tonic purposes in Chinese traditional preparations and have been used as an endermic liniment for burns and contusions for thousands of years (Ip et al, 2001;Yoshikawa et al, 1996). In recent years, many biological activities have been reported for Rhodiola species such as adaptogenic (Spasov et al, 2000;Rege et al, 1999), antihypoxia (Kurmukov et al, 1986), antifatigue (Azizov and Seifulla, 1998;Darbinyan et al, 2002), antioxidant (Furmanowa et al, 1998), antiarrhythmic (Maslov et al, 1998), cardioprotection (Maslov et al, 1997), anticancer (Udintsev and Shakhov, 1991), and enhancement in learning and memory Fan et al, 1999).…”