Bigel formulations of St. John’s wort extract in wound healing: toxicological aspects

Abstract

This study aimed to investigate the toxicological profile of hyperforin (HP) in silico and to assess it in vivo after topical application of an HP-rich St. John’s wort (SJW) extract. The former analysis predicted low toxicity because of HP’s inability to bind DNA or proteins, but structural alerts for skin irritation/corrosion, carcinogenicity, and mutagenicity were found. Animal studies involved the treatment of excision wounds in Wistar rats with poloxamer 407/borage oil formulations (bigels; Bs) containing HP-rich SJW extract previously developed by us. The effects of semisolids comprising ‘free’ extract (B/SJW) or extract loaded in nanostructured lipid carriers (B/NLC-SJW) were compared to positive (commercial herbal product) and negative (untreated) controls after 2-, 7-, 14-, and 21-day applications. Malondialdehyde (MDA) and ABTS assays evaluated the degree of oxidative stress—treatment with bigels did not affect MDA favorably but led to an increased radical-cation scavenging capacity (compared to controls). Gamma-glutamyl transferase (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lactate dehydrogenase (LDH) enzyme levels were measured as indicators for liver/tissue damage. Treatment with both B/SJW and B/NLC-SJW for 21 days resulted in lower GGT and ASAT levels than those in controls. Two-day application of the biphasic semisolids contributed to normalized ALAT levels (lower than in both negative and positive controls), and the same trends were observed in LDH levels after a 7-day treatment. The promising results obtained after the B/NLC-SJW application suggest that this drug delivery system may not only preserve HP in SJW extract effectively but also ‘expose’ its cyto-/hepatoprotective potential.

Keywords:

• Bigels
• hyperforin
• QSAR
• Hypericum perforatum
• in vivo toxicity
• wounds

Authors’ contributions

Conceptualization: Y.K.-K. and V.A.; collection of biological material: O.T., S.S., M.H., Y.K.-K., and V.A.; experimental work and data acquisition: Y.S., D.V., and S.S.; formal analysis: D.V. and I.I.; data analysis: Y.S., D.V., O.T., S.G., M.H., Y.K.-K., and V.A.; literature research and original draft preparation: Y.S., D.V., O.T., and I.I.; visualization: O.T., I.I. and Y.K.-K.; writing—review and editing: Y.S., D.V., O.T., S.G., Y.K.-K., and V.A.; funding acquisition: V.A.; supervision: V.A. All authors have read and approved the final version of the manuscript and agree to be responsible and accountable for all aspects of the reported work.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

All data are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was funded by Fund ‘Nauka’ at the Medical University of Varna, Bulgaria, through Project No. 18027, ‘Lipid nanoparticles—a modern technological approach for the inclusion of hyperforin with improved chemical stability in topical formulations for accelerated wound healing,’ Competition-Based Session for Scientific Research Projects, 2018.