Objective: To evaluate anti-dyslipidemic, antioxidant and anti-atherosclerogenic properties of this extract in diet-induced hypercholesterolemic rat, a model of metabolic syndrome-induced atherosclerosis and associated cardiovascular diseases. Methods: Normocholesterolemic (NC) male rats were divided into six groups (n=10) and fed a high-cholesterol (HC) diet for 30 days (5 groups), or normal rat chow (normal control group). Rats given a HC diet also received distilled water (disease control), the potent hypocholesterolemic agent with anti-atherosclerotic activity atorvastatin (2 mg/kg, positive control), or one of the three doses of Zanthoxylum heitzii stem bark aqueous extract tested (225, 300 and 375 mg/kg) concomitantly for four months. Signs of general toxicity, body temperature and weight, and water and food intake were monitored in live animals. After sacrifice, lipid profiles and oxidative stress markers were assessed in the blood and liver, aorta, and feces, and histopathological analysis of aorta was performed. Results: Plant extract prevented the elevation of aortic total cholesterol and triglycerides, and hepatic low density lipoprotein, very low density lipoprotein, and total cholesterol. Lipid peroxidation (TBARS) was decreased and aortic atherosclerotic plaque formation prevented. Conclusions: These observations strongly suggest that stem bark aqueous extract of Zanthoxylum heitzii has anti-atherosclerogenic properties, at least partly mediated by antioxidant and hypolipidemic effects.

OBJECTIVEZanthoxylum heitzii is a medicinal plant widely used in central Africa for the treatment of many diseases, especially cardiovascular diseases and hypertension. The diuretic effects of crude stem bark extraction were determined and its safety in rats was evaluated.

METHODSThe diuretic effects of crude stem bark extraction of Z. heitzii 250 g ± 10 g) of both sexes. The crude stem bark extraction of Z. heitzii at the doses of 225, 300 and 375 mg/kg was administered to rats at 5 mL/kg body weight. Urine volume was determined 1, 2, 3, 4, 5, 6 and 24 h after administration of the extract. Kinetics of electrolyte elimination in response to a single oral administration dose of acute treatment was measured. The experiments were performed under the same conditions with two synthetic pharmacological diuretics considered as reference (furosemide and hydrochlorothiazide). Urinary and plasma concentrations of sodium and potassium ions were determined using flame photometry. Concentrations of creatinine, urea, glucose, albumin and electrolytes in the plasma and urine samples were evaluated using a two-way digital bidirectional spectrophotometer. The osmolarity of plasma and urine samples was measured by cytometry using an osmometer. Aldosterone was measured by radioimmunoassay.

RESULTSThe plant extract accelerated the elimination of overloaded fluid and increased urine volume and the excretion of Na+, K+ and Cl- 24 h after administration (P<0.05). The increase in elimination of Na+, K+, and Cl- induced by caused alkalinization of the urine, and showed a strong inhibitory effect on carbonic anhydrase and saluretic. These effects were mainly observed at the dose of 375 mg/kg. At the maximum diuretic response, urinary osmolarity decreased significantly (P<0.05) when compared to controls. The stability of aldosterone level, the absence of correlation with the plasma levels of Na+, and increased clearance of free water in the animals treated with indicated that increased diuresis and natriuresis were tubular in origin. No significant (P>0.05) changes were observed in the body temperature of the animals.

CONCLUSIONThe significant increase in urine volume 24 h after treatment followed a dose-response pattern. The excretion of Na+, K+ and Cl- caused a decrease in urine osmolarity. The stability of aldosterone, the absence of correlation with the plasma levels of sodium, and increased clearance of free water in animals treated with aqueous extract suggest that increased diuresis and moderate natriuresis elevation were of tubular origin.

Animals ; Carbonic Anhydrase Inhibitors ; pharmacology ; Diuretics ; pharmacology ; Electrolytes ; metabolism ; Female ; Furosemide ; pharmacology ; Hydrochlorothiazide ; pharmacology ; Kidney ; drug effects ; physiology ; Male ; Plant Bark ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Zanthoxylum ; chemistry