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Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental
L O Somova1, A Nadar, P Rammanan
1Department of Human Physiology, University of Durban-Westville, Durban, South Africa. somova@pixie.udw.ac.za
Insights
Oleanolic acid (OA) and ursolic acid (UA) prevented severe hypertension in rats by acting as diuretics and antioxidants. These triterpenoids also reduced heart rate, lipids, and blood glucose levels.
Area of Science:
- Pharmacology and Toxicology
- Cardiovascular Research
- Natural Product Chemistry
Background:
- Genetic hypertension models, like Dahl salt-sensitive (DSS) rats, are crucial for studying cardiovascular diseases.
- Insulin resistance is a common comorbidity in genetic hypertension, complicating treatment strategies.
- Triterpenoids, such as oleanolic acid (OA) and ursolic acid (UA), are natural compounds with potential therapeutic benefits.
Purpose of the Study:
- To investigate the cardiovascular, antihyperlipidemic, antioxidant, diuretic/saluretic, and hypoglycemic activities of oleanolic acid (OA) and ursolic acid (UA).
- To evaluate the efficacy of OA and UA in preventing the development of severe hypertension in a rat model.
Main Methods:
- Assessed the toxicity of OA and UA using LC50 measurements.
- Administered daily doses of OA and UA (60 mg/kg b.w., i.p.) to Dahl salt-sensitive (DSS) rats for 6 weeks.
- Monitored cardiovascular parameters (blood pressure, heart rate), lipid profiles, antioxidant enzyme activity (GPx, SOD), and blood glucose levels.
Main Results:
- OA and UA demonstrated low toxicity (LC50 0.10 and 0.95 mg/ml).
- Both compounds prevented severe hypertension development, attributed to diuretic, natriuretic, and saluretic effects.
- Observed significant reductions in heart rate, LDL, triglycerides, and blood glucose, alongside increased antioxidant enzyme activity (GPx, SOD).
Conclusions:
- Oleanolic acid and ursolic acid exhibit multifaceted pharmacological effects beneficial for managing hypertension.
- The antihypertensive effects are linked to diuretic, cardiac, lipid-lowering, antioxidant, and hypoglycemic actions.
- These findings represent novel in vivo antihypertensive effects of OA and UA, warranting further mechanistic investigation.
Abstract:
Cardiovascular (systolic and diastolic blood pressure, heart rate), antihyperlipidemic (tryglycerides, total cholesterol and lipoprotein fractions), antioxidant (glutathione peroxidase--GPx, and superoxide dismutase--SOD), diuretic/saluretic and hypoglycemic activity of 98% pure oleanolic (OA) and ursolic (UA) acid were studied in Dahl salt-sensitive (DSS), insulin resistant rat model of genetic hypertension. Both OA and UA displayed low toxicity, with LC50 0.10 and 0.95 mg/ml, respectively. Although both triterpenoids did not have direct hypotensive effect, after 6-week application in a daily dose 60 mg/kg b.w., i.p., they prevented the development of severe hypertension. The antihypertensive effect was attributed to their potent diuretic-natriuretic-saluretic activity; direct cardiac effect (heart rate decrease by 34% and 32%, respectively); antihyperlipidemic (more than two times decrease of LDL and triglycerides); antioxidant (GPx increase by 12% and 10%, respectively; SOD increase by 12% and 22%, respectively), and hypoglycemic (blood glucose decrease by 20% and 50%, respectively) effects on the DSS rats. Except for the antihyperlipidemic effects, the other described above in vivo antihypertensive effects of OA and UA are reported for the first time and the underlying mechanisms are currently under investigation.
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