Spatial metabolomics revealed multi-organ toxicity and visualize metabolite changes induced by borneol in zebrafish.

Summary

Using zebrafish and MALDI-MSI spatial metabolomics, the study shows that high-dose borneol induces multi-organ toxicity (cardiac, hepatic, neurologic) and broad metabolic dysregulation without evident renal toxicity. Perturbations in phospholipids, fatty acids, and amino acids and transcriptional changes in lipid/choline/amino acid metabolism pathways suggest mechanism-based safety concerns for borneol used in cosmetics and medicines.

Key Findings

• High-concentration borneol (500 μM) caused morphological abnormalities, cardiotoxicity, hepatotoxicity, and neurotoxicity in zebrafish, with no evident renal toxicity.
• MALDI-MSI revealed significant increases in PC-34:1/34:2, PI-36:4, PE-36:1, LysoPE-22:5, LysoPC-18:1, FA-18:2, phenylalanine, lysine, and glutathione, and decreases in PC-38:6 and PC-40:6.
• mRNA levels of genes involved in phospholipid, fatty acid, choline, and amino acid metabolism (e.g., elovl5, chpt1, chka, setd7, hgd) were significantly altered.

Clinical Implications

While preclinical, the data support cautious use of borneol in topical and inhalational products and motivate dose-limit justification, alternative excipient consideration, and targeted safety testing (e.g., cardiotoxicity and neurobehavioral assays) in product development.

Limitations

• High exposure concentration relative to likely human cosmetic exposure; external validity uncertain
• Zebrafish model lacks human pharmacokinetic and dermal penetration data; no dose–response across lower concentrations reported

Future Directions

Quantify human-relevant exposure ranges, perform dermal exposure models and dose–response studies, and integrate in vitro human cardiomyocyte/neuronal assays to refine risk assessment.