Acute toxicity study and prevention of Nω-nitro-L-arginine methyl ester-induced hypertension by Osteopermum imbricatum
Purpose: To determine the phytochemical content, toxicity and hypertension prevention effects of Osteospermum imbricatum leaf and root extracts.
Methods: Phytochemical screening of leaf and root extracts of O. imbricatum was performed by colorimetric procedure. Acute toxicity of leaf and root extracts was conducted in two phases; phase I consisted of three groups of mice (n = 3) for each dose level of 10, 100 and 1000 mg/kg while phase II had three mice that received 1600, 2900 or 5000 mg/kg. Wistar rats were grouped into 7 groups that were co-treated with L-NAME and normal saline or L-NAME and hydroethanolic leaf extract (150 and 300 mg/kg) or L-NAME and hydroethanolic root extract (150 and 300 mg/kg) or L-NAME and amlodipine (5 mg/kg) or normal saline only for 4 weeks. Treatment was carried out via the oral route while blood pressure was measured weekly for 4 weeks by non-invasive tail cuff method.
Results: The phytochemical profile of the leaf and root extracts revealed the presence of phenols, terpenoids, flavonoids, glycosides, tannins, steroids and saponins. Both the leaf and root extracts were toxic at 5000 mg/kg with an LD50 of 3807.89 mg/kg. In the fourth week of the study, only the leaf extract significantly (p < 0.01) prevented the progression of L-NAME induced hypertension; systolic and diastolic blood pressure of the group treated with L-NAME and leaf extract (300 mg/kg) were 183 ± 1 and 140 ± 1 mmHg, respectively, compared to the group that was treated with L-NAME and normal saline which produced systolic and diastolic BP values of 213 ± 3 and 172 ± 4 mmHg, respectively. The extracts, especially OIR300, exhibited diuretic effects in the second and third week of study by promoting excretion of 16 and 19 ml urine, respectively, compared to 11 and 14 ml for LN group.
Conclusion: The results suggest that O. imbricatum is moderately toxic at a high dose and contains a wide range of phytochemicals which offer partial protection against the development of nitric oxide deficiency hypertension.
Keywords: Hypertension, Phytochemicals, Acute toxicity, Nω-Nitro-L-arginine methyl ester (L-NAME), Osteospermum imbricatum