Mass spectrometry-based major phytochemicals and dose dependent cytotoxic and nephrotoxic effects of Commiphora leptophloeos stem bark extract in preclinical in vitro and in vivo models.

ETHNOPHARMACOLOGICAL RELEVANCE: Commiphora leptophloeos (Mart). J.B. Gillet. (Burseraceae family), a plant native to Brazil, has been traditionally used by indigenous and local communities in the treatment of inflammatory and infectious diseases. Despite its extensive ethnopharmacological use, there is a notable lack of studies assessing its safety profile, especially through in vivo repeated-dose oral toxicity models.

OBJECTIVE OF THE STUDY: To evaluate the dose-dependent cytotoxic and toxicological effects of the hydroethanolic extract of the stem bark of C. leptophloeos (HECL) using in vitro and in vivo models.

MATERIALS AND

METHODS

Phytochemical analysis was performed by direct injection of HECL into the mass spectrometer. Cytotoxicity was assessed in RAW 264.7 macrophages exposed to HECL (1-200 μg/mL) via MTT assay and flow cytometry. Acute oral toxicity (2000 mg/kg) was evaluated over 14 days (OECD 423), while sub-acute toxicity was assessed after daily oral administration (200, 400, and 800 mg/kg) for 28 days (OECD 407), including behavioral, hematological, biochemical, and histopathological evaluations.

RESULTS

The major secondary metabolites of HECL were identified as quinic acid and B-type oligomeric procyanidins. HECL at 200 μg/mL reduced cell proliferation by inducing cell cycle arrest at the G2/M phase and promoted DNA fragmentation in approximately 21 % of the cells. No signs of acute toxicity were observed. Sub-acute exposure up to 400 mg/kg caused no adverse effects. However, the 800 mg/kg dose led to elevated serum urea and creatinine and histopathological evidence of nephrotoxicity, including inflammatory infiltrates, vascular congestion, and glomerular atrophy.

CONCLUSION

HECL demonstrated dose-dependent cytotoxic effects in vitro. In vivo, HECL did not cause acute toxicity and was well tolerated at doses up to 400 mg/kg in sub-acute exposure. However, the 800 mg/kg dose induced signs of nephrotoxicity. These effects may be, at least in part, attributed to the high abundance of B-type oligomeric procyanidins, which represent the main metabolites of the extract. Nevertheless, synergistic interactions with other constituents cannot be excluded. Therefore, caution is recommended when using C. leptophloeos extract at high doses or over extended periods.