Acute and subacute toxicological evaluation of the alkaloid-rich fraction from Smyrnium olusatrum L. seeds in mice.
Smyrnium olusatrum L. (Apiaceae) is a medicinal plant traditionally used in Mediterranean ethnomedicine to treat gastrointestinal disorders, as well as inflammatory conditions, urinary tract disorders, gynecological ailments, and respiratory diseases. Alkaloids constitute an important class of bioactive constituents in medicinal plants and may contribute to their pharmacological effects; however, their biological activities may also be associated with dose-dependent toxicity. Despite the pharmacological potential of S. olusatrum alkaloids, their toxicological profile remains insufficiently characterized, which may limit their further pharmacological investigation and development.
This study aimed to evaluate the acute and subacute toxicity of the alkaloid-rich fraction isolated from S. olusatrum seeds as part of the preclinical safety assessment to support its further pharmacological investigation.
Acute toxicity was investigated following a single intraperitoneal administration of the alkaloid-rich fraction at doses of 1, 10, 20, 200, and 2000 mg/kg, followed by a 14-day observation period. Subacute toxicity was assessed after daily intraperitoneal (i.p.) administration of 25, 50, 100, and 200 mg/kg for 28 consecutive days. Clinical observations, body and relative organ weights, hematological and biochemical parameters, and histopathological examinations of major organs were performed.
No mortality or treatment-related clinical signs were observed following acute administration, indicating an LD50 greater than 2000 mg/kg (i.p.). Repeated administration for 28 days produced no significant changes in body weight, relative organ weights, hematological indices, or serum biochemical parameters compared with controls. Histopathological examination revealed normal architecture in the kidneys, heart, lungs, and spleen. Mild hepatic histoarchitectural changes, consisting of slight disorganization of hepatocyte cords and sinusoidal dilation, were observed only in male mice at 100 and 200 mg/kg without accompanying biochemical evidence of liver injury. The alkaloid-rich fraction of S. olusatrum seeds exhibited a favorable toxicological profile following acute and repeated i.p. administration in Swiss mice. Under the experimental conditions, the NOAEL was established at 50 mg/kg/day (i.p.) based on the first occurrence of treatment-related hepatic histological changes at 100 mg/kg.
Alkaloid extracts from S. olusatrum seeds showed low acute and subacute toxicity in mice, supporting their further preclinical pharmacological investigation while highlighting the importance of dose optimization and sex-specific hepatic responses.
This study aimed to evaluate the acute and subacute toxicity of the alkaloid-rich fraction isolated from S. olusatrum seeds as part of the preclinical safety assessment to support its further pharmacological investigation.
Acute toxicity was investigated following a single intraperitoneal administration of the alkaloid-rich fraction at doses of 1, 10, 20, 200, and 2000 mg/kg, followed by a 14-day observation period. Subacute toxicity was assessed after daily intraperitoneal (i.p.) administration of 25, 50, 100, and 200 mg/kg for 28 consecutive days. Clinical observations, body and relative organ weights, hematological and biochemical parameters, and histopathological examinations of major organs were performed.
No mortality or treatment-related clinical signs were observed following acute administration, indicating an LD50 greater than 2000 mg/kg (i.p.). Repeated administration for 28 days produced no significant changes in body weight, relative organ weights, hematological indices, or serum biochemical parameters compared with controls. Histopathological examination revealed normal architecture in the kidneys, heart, lungs, and spleen. Mild hepatic histoarchitectural changes, consisting of slight disorganization of hepatocyte cords and sinusoidal dilation, were observed only in male mice at 100 and 200 mg/kg without accompanying biochemical evidence of liver injury. The alkaloid-rich fraction of S. olusatrum seeds exhibited a favorable toxicological profile following acute and repeated i.p. administration in Swiss mice. Under the experimental conditions, the NOAEL was established at 50 mg/kg/day (i.p.) based on the first occurrence of treatment-related hepatic histological changes at 100 mg/kg.
Alkaloid extracts from S. olusatrum seeds showed low acute and subacute toxicity in mice, supporting their further preclinical pharmacological investigation while highlighting the importance of dose optimization and sex-specific hepatic responses.
Authors
Sekkout Sekkout, Boudaia Boudaia, De Palma De Palma, Dopazo Dopazo, Izzo Izzo, Cicala Cicala, Radallah Radallah, Amrani Amrani, Youbi Youbi
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