The antihypertensive and diuretic effect of crude root extract and saponins from Solanum sisymbriifolium Lam., in L-NAME-induced hypertension in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum sisymbriifolium Lam., is used in Paraguayan folk medicine claiming antihypertensive and diuretic properties. AIM OF THE STUDY: This study aimed to determine the influence of chronic oral administration of the crude root extract and saponins obtained from S. sisymbriifolium Lam., on the blood pressure of male and female rats with hypertension induced by L-NAME, and its consequences on diuresis, the body weight, blood glucose, and level of serum parameters of liver and kidney functionality. MATERIALS AND METHODS: Wistar rats were randomly divided into seven male, and seven female groups (8 animals each), which received as 6-week pretreatment, 0.9% saline solution (two groups; 0.1mL/10 g of b.w.), L-arginine (100.0 mg/kg/day), enalapril (15.0 mg/kg/day), crude extract (CESs 100.0 mg/kg/day), and saponin purified fraction (1.0, and 10.0 mg/kg/day), and treated with L-NAME (20 mg/kg/day/i.p.) twice, 1, and 6 h after pre-treatment. The animals' body weight, glycemia, and blood pressure were recorded weekly, while serum, hepatic, renal, and histological parameters were analyzed at the end of 6-week of treatment. RESULTS: A protective effect of CESs (100.0 mg/kg/day), and saponins (1.0, and 10.0 mg/kg/day) against hypertension induced by L-NAME was verified in the systolic, diastolic, and mean blood pressure values, which were significantly lower than the positive L-NAME-hypertensive control group (male and female) at the end of the 6-week treatment. Also, pretreatment with enalapril (15.0 mg/kg/day) induced an efficient protective activity, which validates the method used. Likewise, the volume of urine, creatinine, uric acid, urea, and electrolyte excretion was enhanced at the end of 6-week of treatment in concordance with the reduction in serum level of the same parameters, compatible with the improvement of the diuretic activity. The glycemia, body weight, heart rate, and functional hepato-renal parameters were not modified after a 6-week of treatment, in comparison to the control group, indicating relatively acceptable harmless properties of CESs and saponins. Interestingly, the HDL level in females was increased in contrast to male rats by chronic saponins treatment when compared with the negative control group. CONCLUSIONS: It can be concluded that either the increment in blood pressure (systolic, diastolic, and median) or cardiorenal remodeling effects in male and female rats submitted to L-NAME-induced hypertensive condition, were prevented and well-preserved without a significant variation during a period of 6-week of pretreatment with CESs and saponins pretreatments. Likewise, an important diuretic effect was revealed after this period of treatment.

Coupling biological detection to liquid chromatography: a new tool in drug discovery.

Procedures to characterize drugs that can be obtained from plant extracts or combinatorial chemistry are tedious, and they consume considerable resources (e.g., animals) and time. Thus, we have looked for a way to streamline this process. We describe here a novel system for the pre-characterization of drugs based on liquid chromatography coupled to biological detection using perifused or perfused organs. This novel system allows the on-line detection of pharmacologically active substances in hydrosoluble mixtures from vegetal extracts or combinatorial chemistry libraries. Depending on the volume of drug solution and concentration of the samples, the procedure can work through either medium pressure liquid chromatography or HPLC, and it enables the fingerprints of drugs to be assessed based on their contractile activity on combinations of different isolated tissues. As an example, we show how the system can identify active fractions from an extract of Stevia rebaudiana Bertoni, an activity that was later associated with rebaudioside N. Coupling liquid chromatography to biological detection offers a rapid way to focus attention on active products in complex samples, mostly from hydrosoluble species, helping to considerably reduce the time and cost of the pre-characterization of drugs.