Toxicological Evaluation of the Hydroethanolic Seed Extract of Randia aculeata (Rubiaceae) in Acute and Sub-acute Oral Toxicity Models

Randia aculeata (Rubiaceae), commonly known as “crucetillo,” is widely used in Mexican folk medicine, particularly its seeds, yet systematic toxicological evaluations remain scarce. This study assessed the safety of the hydroethanolic seed extract (EHRA) in Wistar rats through acute and subacute oral toxicity assays. In the acute model, a single oral dose of 2000 mg/kg produced no mortality (LD₅₀ > 5000 mg/kg), but increases in hepatic enzyme activity, reduced erythrocyte and hemoglobin levels, and focal hepatocellular necrosis suggested liver injury. In the 28-day repeated-dose study, animals receiving 250, 500, or 1000 mg/kg/day displayed progressive alterations in biochemical and hematological parameters, including elevated AST, ALT, ALP, bilirubin, urea, and creatinine, along with reduced red blood cell counts and hemoglobin levels. Histopathological analyses confirmed hepatocellular necrosis and acute tubular necrosis in the kidneys. Collectively, these findings indicate that while EHRA exhibits low acute lethality, repeated administration induces significant hepatic and renal toxicity. Considering the widespread traditional consumption of R. aculeata seeds, these results underscore the need for careful dosage considerations, evidence-based safety guidelines, and further mechanistic studies before the potential therapeutic application of this plant can be recommended.