Cardiovascular Effect of Diosgenin in Ovariectomized Rats.

Diosgenin is a phytoestrogen and a constituent of Dioscorea. It has several biological effects, and some of them are anti-inflammatory, antidiabetic, antitumor, and vasodilatory. The present study investigated both the vasorelaxing and antioxidant mechanisms of diosgenin in isolated rat aortic rings. Female rats weighing 200-220 g were subjected to sham or OVX operations at 8 weeks of age. Ovariectomy was performed for menopause induction after anesthesia. Diosgenin (10-9 M-3 × 10-4 M) produced a concentration-dependent relaxation in aortic rings precontracted with phenylephrine (1 µM), exhibiting Emax value of 55.34% ± 7.7% (in endothelium-intact rings) and Emax value of 30.30% ± 5.7% (in endothelium-denuded rings). In the endothelium-intact rings, the vasorelaxing effect of diosgenin was reduced by NG-nitro-l-arginine methyl ester (L-NAME) (100 µM), atropine (1 µM), indomethacin (10 µM), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (10 µM), 4-aminopyridine (1 mM), tetraethylammonium (3 mM), glibenclamide (10 µM), apamin (10 µM), and Tiron (1 µM). Diosgenin (10-5 M) inhibited the contractions induced by cumulative addition of phenylephrine (10-9-10-5 M). The 28-days treatment with diosgenin (50 mg/kg, v.o.) did not imply changes in the myeloperoxidase parameter, but increased significantly, levels of glutathione, superoxide dismutase, and nitric oxide, as well as reduced the concentration of malondialdehyde related to lipid peroxidation. Our results suggest that diosgenin induced relaxation in aortic rings via an endothelium-dependent pathway, which involves the EDRF, the opening of potassium channels and antioxidant action.

Vasorelaxant activity and acute toxicity of the ethanolic extract of Zanthoxylum rhoifolium Lam leaves

The study evaluated the vasorelaxant effect induced by the ethanolic extract of the leaves of Zanthoxylum rhoifolium Lam (EEtOH-Zr/leaves). Wistar rats were treated with the leaf extract containing a single dose of 2,000 mg / kg, v.o. After 14 days, the animals were anesthetized for blood collection and subsequent analysis of the biochemical parameters; they were then euthanized (sodium pentobarbital-100 mg/kg, i.p.) for the removal and morphological analysis of the heart, lung, liver and kidney. The vasorelaxation activity the and vascular reactivity of EEtOH-Zr/leaves were evaluated on artery mesenteric rings isolated from rats. The extract showed no signs of toxicity and no significant difference in the values of the biochemical parameters between the control group and the group of treated animals. In the evaluation of pharmacological activity in the smooth muscle, the EEtOH-Zr/leaves caused vasorelaxant effect on the tonic contraction induced by phenylephrine in mesenteric artery preparations in the presence (pD2=2.17±0.05 µg/mL; Emax=99.8±5.2%) and absence (pD2=2.14±0.05 µg/mL; Emax=95.3±6.4%) of the vascular endothelium. Oral administration of EEtOH-Zr/leaves reduced the contraction induced by the cumulative addition of PHE. It is concluded that the EEtOH-Zr/leaves promote vasorelaxation and reduce vascular reactivity of adrenergic alpha-1 agonist in the mesenteric artery. The results did not show toxic effects of the extract.

Pharmaceutical development of tablets containing a spray-dried optimized extract from Lippia origanoides H. B. K.: influence of excipients and toxicological assessment

ABSTRACT Lippia origanoides is a honey shrub which has showed hypotensive potential assessed by in vivo studies. The aim of this work is the development of a pharmaceutical formulation composed by an optimized extract obtained from aerial parts of L. origanoides. The quantification of the naringenin marker in the dry extract and tablets developed was performed, as well as the assessment of the oral acute toxicity in rats. The hydroalcoholic extract of L. origanoides was spray-dried with the addition of colloidal silicon dioxide (Lo-HAE/CSD), and then applied in the preparation of eight different lots of tablets. The influence of the diluent (cellulose or babassu mesocarp), the presence of binder, and the percentage of lubricant, as well as organoleptic and physicochemical characteristics were screened. For the quantification of the marker content both in Lo-HAE/CSD and in the tablets, an analytical curve of the naringenin standard was fitted, and the samples were then analyzed in UFLC. The toxicological assessment was performed in female Wistar rats according to the Acute Toxic Class Method from OECD. The developed tablets produced meet acceptable macroscopic characteristics, and the presence of babassu as diluent provided improved physicochemical properties. The best content of Lo-HAE/CSD in the tablet (100.27%) was identified for the lot containing babassu, composed by 1.0% magnesium stearate, without PVP binder in its formulation. Moreover, Lo-HAE/CSD showed no signs of toxicity. Therefore, the babassu mesocarp powder is a promising pharmaceutical excipient for the development of herbal tablets containing the Lippia origanoides extract.