In silico study of the toxicity of hyperforin and its metabolites

Abstract

St. John’s wort is a medicinal herb well-known for its antidepressant, anti-inflammatory, antimycotic, and wound-healing properties. Hyperforin, the major phloroglucinol derivative, has been implicated as one of the main contributors to these therapeutic effects. Because of its high reactivity, this phytochemical can cause various adverse effects, such as allergic reactions, dizziness, dry mouth, and fatigue. To predict critical parameters of hyperforin’s possible behavior after oral administration, in silico methods were applied. The pharmacokinetic profile, bioactivity, and toxicity of the phytochemical were analyzed by applying Molinspiration cheminformatics, SwissADME, PreADME/Tox, and OECD QSAR Toolbox software. The results showed adequate absorption, a high affinity for plasma proteins, and a prolonged renal excretion of the acylphloroglucinol. The high metabolic activity, a reason for potential cyto- and genotoxicity, and the predicted carcinogenicity and mutagenicity of hyperforin, necessitate further in vitro and in vivo tests.