Beyond Efficacy, Integrated toxicological profiling reveals the preclinical safety of Berberis lycium Royle and its principal alkaloid, Berberine.

Berberis lycium Royle has been widely used in traditional medicine for the treatment of infectious, inflammatory, gastrointestinal, and metabolic disorders. Berberine, its principal isoquinoline alkaloid, is considered an important bioactive constituent associated with several of its pharmacological effects. Despite its ethnomedicinal use, further toxicological assessment is needed to characterize the safety of the crude extract and berberine under defined experimental conditions. The present study evaluated the acute oral toxicity of the crude methanolic extract (CME) of Berberis lycium root bark and berberine in Wistar rats, and investigated the concentration-dependent effects of berberine on the viability of human embryonic kidney cells (HEK-293). Acute oral toxicity was assessed according to OECD Test Guideline 425. Male and female Wistar rats received oral administration of CME (300 mg/kg body weight) or berberine (100 mg/kg body weight). Clinical observations, body weight, food and water consumption, haematological parameters, and serum biochemical markers of hepatic, renal, and metabolic function were evaluated. The in-vitro effects of berberine were assessed using the MTT assay following 24 h exposure of HEK-293 cells to concentrations ranging from 0 to 100 μM. Neither berberine nor CME produced mortality or clinically significant signs of toxicity during the observation period. The oral LD50 of both preparations was reported to exceed 2000 mg/kg body weight. Body weight gain, feed intake, water consumption, haematological indices, and biochemical parameters remained comparable to untreated controls. Berberine produced a concentration-dependent reduction in HEK-293 cell viability, with a marked decline observed up to 40 μM, after which the response approached saturation. Under the conditions tested, CME and berberine were well tolerated in the acute oral toxicity assessment in Wistar rats, while berberine showed concentration-dependent effects on HEK-293 cell viability in vitro. These findings provide evidence regarding acute oral safety at the tested doses, but do not establish overall preclinical safety. The assessment was limited to acute exposure and selected in-vivo endpoints, alongside an in-vitro MTT assay; therefore, it does not address potential effects of repeated or long-term exposure, reproductive toxicity, or other unexamined toxicological outcomes. Further repeated-dose, chronic, reproductive, and mechanistic studies are required to more fully characterize their safety.