Antihypoxic Activities of Methanolic Extract of Silybum marianum and Silymarin in Asphyctic, Haemic, and Circulatory Hypoxia Models in Mice

Background and purpose: Hypoxia can lead to impairments in body function and is linked to the pathology of acute mountain sickness, cardiovascular disease, and stroke, all of which are leading causes of death in many countries. Silybum marianum is a plant known for its strong antioxidant properties. This research aims to investigate the anti-hypoxic effects of S. marianum and its major constituent, silymarin, in three experimental models of hypoxia in mice. Materials and methods: The protective effects of the methanolic extract of S. marianum aerial parts and silymarin against hypoxia-induced lethality in mice were evaluated using three experimental models of hypoxia: asphyctic, haemic, and circulatory. In the asphyctic hypoxic model, phenytoin (50 mg/kg, i.p.) was used as the positive control, while in the haemic and circulatory models, propranolol (20 and 30 mg/kg, i.p.) served as the positive control. Normal saline (0.5 ml, i.p.) was used as the negative control. Analysis of variance (ANOVA), followed by Newman-Keuls multiple comparisons (performed using GraphPad Prism 8), was used to determine significant differences in means. Results: The extract and silymarin exhibited significant protective effects by increasing the survival time of male mice, even at their lowest doses, across all tested models. Silymarin was effective in all models and demonstrated a comparable effect to propranolol and phenytoin, which were used as positive controls. Except in the asphyctic model, the extract at a dose of 62.5 mg/kg exhibited the same activity as silymarin at 12.5 mg/kg. Conclusion: The presence of silymarin in the extract may be responsible for the antihypoxic activities observed in the plant extract. Both the methanolic extract and silymarin, when tested separately, demonstrated significant protective effects against hypoxia in all tested models, exhibiting similar activity to the positive controls.