Increase of myocardial performance by Rhodiola–ethanol extract in diabetic rats

Abstract

Ethno pharmacological relevance

Rhodiola rosea (also known as golden root or roseroot) is a perennial plant of the Crassulaceae family that grows in the Arctic and in the mountainous regions of Europe, Asia, and North America. The rhizome and roots of this plant have been long used as traditional medicine in Eastern Europe and Asia for enhancing physical and mental performance.

Aim of the study

The present study is designed to investigate the cardiac action of Rhodiola–ethanol extract in streptozotocin-induced diabetic rats (STZ-diabetic rats) with heart failure.

Materials and methods

Diabetes was induced in Wistar rats by injection of streptozotocin. We measured the changes of body weight, water intake, and food intake in three groups of age-matched rats; the normal control received vehicle, STZ-diabetic rat received Rhodiola–ethanol extract or vehicle. Cardiac output, heart rate, blood pressure, and hemodynamic dP/dt in addition to plasma insulin and glucose level were also determined. The mRNA and protein levels of PPARδ were measured using real-time PCR and Western blotting, respectively.

Results

Food intake, water intake and blood glucose were raised in STZ-diabetic rats showing lower body weight and plasma insulin, as compared with the control. Also, cardiac output, heart rate, blood pressure and hemodynamic dP/dt were markedly reduced in STZ-diabetic rats indicating the heart failure physiologically. After a 21-day treatment with Rhodiola–ethanol extract, cardiac output was raised in STZ-rats while the diabetic parameters were not modified. The PPARδ expression of both mRNA and protein was markedly elevated in the heart of STZ-rats receiving treatment with Rhodiola–ethanol extract. Also, the increased phosphorylation level of cardiac troponin-I was restored by this treatment with Rhodiola–ethanol extract. Otherwise, increase of cardiac output by Rhodiola–ethanol extract was blocked by antagonist of PPARδ in STZ-diabetic rats.

Conclusions

Our results suggest that ethanol extract of Rhodiola has an ability to increase the cardiac output in STZ-diabetic rats showing heart failure. Also, increase of PPAR-δ is responsible for this action of Rodiola–ethanol extract.

Introduction

Rhodiola rosea (R. rosea), also known as a golden or rose or arctic root, belongs to the plant family of Crassulaceae, subfamily of sedoideae and genus Rhodiola that is widely distributed in the Arctic and mountainous regions throughout Europe and Asia (Kelly, 2001). It is a popular plant in Eastern Europe and Asia as a traditional medicine used to stimulate the nervous system, decrease depression, enhance work performance, eliminate fatigue, and prevent high altitude sickness (Petkov et al., 1986). The cardioprotective effects of R. rosea were also observed in animals, including the pronounced antiarrhythmic effect (Maslova et al., 1994), prevention of the lowered coronary flow and increase of contractility in the postischemic period (Zhang et al., 1998). Moreover, it lowered blood pressure (Lishmanov Iu et al., 1997) and prevented stress-induced cardiac damage to work as cardioprotective substance in animals (Li et al., 2006).

Diabetes ranks among the main risk factors for the development of heart failure (Kannel et al., 1974, Kannel and McGee, 1979). Many patients with heart failure and hyperglycemic symptoms have accompanying abnormalities including obesity, dyslipidemia and hypertension that also lead to structural and functional abnormalities of heart (Herlitz et al., 1988, Malmberg and Ryden, 1988, An and Rodrigues, 2006, Poornima et al., 2006). A decrease of PPARδ expression in the heart of streptozotocin-induced diabetic rats (STZ-diabetic rats) has been observed (Yu et al., 2008).

PPARs are ligand-activated transcriptional factors that regulate expression of genes involved in lipid metabolism and inflammation (Yang and Li, 2007). Three subtypes of PPARs, PPARα, PPARγ, and PPARδ, modulate expression of different genes and exert various bioactivities (Yang and Li, 2007). PPARα is relatively abundant in tissues with a high oxidative capacity, such as liver and heart. PPARγ expression is confined to a limited number of tissues, primarily adipose tissue (Issemann and Green, 1990, Yang and Li, 2007). The ubiquitously expressed PPARδ enhances lipid catabolism in adipose tissue and muscle (Yang and Li, 2007). PPARδ-dependent maintenance of inotropic function and metabolic effects is crucial for cardiomyocytes (Cheng et al., 2004a, Cheng et al., 2004b, Barish et al., 2006). Deletion of cardiac PPARδ, which is accompanied by decreased contraction, increased left ventricular end-diastolic pressure, and lowered cardiac output, leads to decreased contraction and increased incidence of cardiac failure (Cheng et al., 2004a). Important role of PPARδ in cardiac contraction has thus been established.

Previous studies indicated that impaired relaxation is the prominent cardiac abnormality and it is related to the depressed troponin function in the heart of STZ-diabetic rats (Fein et al., 1980, Fein et al., 1981). Also, we observed that cardiomyopathy in STZ-diabetic rats is associated with a marked decrease in cardiac PPARδ expression (Yu et al., 2008). The effect of Rhodiola on cardiac function has been established (Li et al., 2006), but the role of PPARδ remains unclear. Thus, in the present study, we used STZ-diabetic rats to investigate the role of PPARδ in inotropic action of Rhodiola–ethanol extract.