Journal of Ethnopharmacology 105 (2006) 441–448 Hypolipidemic effects of acute and sub-chronic administration of an aqueous extract of Ajuga iva L. whole plant in normal and diabetic rats Jaouad El-Hilaly a , Adil Tahraoui a , Zafar H. Israili b , Badiˆ aa Lyoussi a,∗ a UFR Physiology-Pharmacology, Universit´ e Sidi Mohamed Ben Abdellah, Laboratory of Animal Physiology, Department of Biology, Faculty of Sciences Dhar El Mehraz, BP 1796 Atlas, Fez 30000, Morocco b Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Received 19 May 2005; received in revised form 25 October 2005; accepted 24 November 2005 Available online 18 January 2006 Abstract Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular (CV) morbidity and mortality in diabetic patients. The plant Ajuga iva (L.) Schreiber (Labiatea) is used in the treatment of diabetes in Moroccan folk medicine. Previously, we have demonstrated potent hypoglycemic activity and relatively non-toxic nature of a lyophilized aqueous extract of the whole plant (AI-extract) in normal (normoglycemic) and streptozotocin (STZ)-diabetic rats. In this study, we examined the AI-extract for its possible lipid-lowering activity in normal and STZ-diabetic rats. Taurine (TR) and glibenclamide (GLB) were used as reference substances. As shown previously, the AI-extract (10 mg/kg; oral) reduced plasma glucose levels after acute (single) and sub-chronic (3 weeks) dosing both in normal and diabetic rats. In normal rats, single and repeated oral administration of the AI-extract, at a dose of 10 mg/kg produced a small but significant decrease in plasma CHL levels (P < 0.05). A single dose of the AI-extract did not produce a significant change in plasma TG, but sub-chronic dosing (for up to 21 days) caused a significant decrease in plasma TG (P < 0.05). In STZ-diabetic rats, a single dose as well as repeated (3 weeks) treatment with the AI-extract produced a significant decrease in plasma CHL (P < 0.01), and triglyceride (P < 0.01) levels. The AI-extract also prevented weight loss in the diabetic animals. In summary, an aqueous extract of the Ajuga iva whole plant showed hypolipidemic activity, in addition to its hypoglycemic effect in normoglycemic and diabetic rats. In view of the hypoglycemic and hypolipidemic activity, and its relatively non-toxic nature (shown previously), Ajuga iva may be a candidate for development as an anti-diabetic agent in humans. Further studies are warranted to confirm our results and fractionate the AI-extract to isolate and identify the active principle(s), and to determine the exact mechanism(s) of action. © 2005 Published by Elsevier Ireland Ltd. Keywords: Ajuga iva (L.) Schreiber (Labiatea); Streptozotocin-diabetic rats; Cholesterol; Triglycerides; Lyophilized aqueous extract; Hypolipidemic effect 1. Introduction The number of people with diabetes mellitus worldwide is increasing rapidly. Presently, there are more than 150 million people with diagnosed disease and another 314 million with impaired glucose tolerance, a prediabetic state (International Diabetes and Federation, 2005). Among the diabetics, about 10% have type 1 diabetes (IDDM; insulin deficient), while 90% have type 2 diabetes (NIDDM; insulin resistant) (American Diabetes Association, 2005). Diabetes and its complications [acute metabolic (ketoacidosis and hyperosmolar non-ketotic syndrome), macrovascular (coronary, cerebrovascular and ∗ Corresponding author. peripheral vascular disease) and microvascular (peripheral neuropathy, retinopathy and nephropathy)] are the major cause of disability and hospitalization and together they also pose a significant financial burden. The oxidative stress caused by chronic elevation of glucose levels in diabetes causes oxidative stress (Mohamed et al., 1999), and together they lead to protein oxidation and glycation (King and Loeken, 2004), and dyslipi- demia [elevated plasma levels of total cholesterol (CHL), low density lipoprotein-cholesterol (LDL-c) and triglycerides (TG) and low concentration of high density lipoprotein cholesterol (HDL-c)]. Dyslipidemia, in both types 1 and 2 diabetes, plays a significant role in the manifestation and development of premature atherosclerosis leading to cardiovascular (CV) disease, and together, they are the major cause of CV morbidity and mortality in diabetic patients (Nathan et al., 1997; Feher, 0378-8741/$ – see front matter © 2005 Published by Elsevier Ireland Ltd. doi:10.1016/j.jep.2005.11.023