Hypericum perforatum L.: a legacy of herbal medicine in light of modern scientific evidence.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum perforatum L. has been used for centuries in traditional medicine, with core therapeutic applications including alleviation of emotional, wound and burn healing and neurological disorders, and antiparasitic treatments. AIM OF THE STUDY: This review summarizes and interprets current knowledge on the traditional use, phytochemistry, pharmacology, quality control, safety, and herb-drug interactions of H. perforatum, with particular attention to the relationships between major constituents, proposed mechanisms, and clinical relevance. MATERIALS AND METHODS: Relevant literature on H. perforatum was identified through major scientific databases, including CNKI, Web of Science, and PubMed, together with complementary sources such as Flora of China, classical herbal literature, and academic dissertations. RESULTS: H. perforatum contains diverse bioactive constituents, notably PPAPs, naphthodianthrones, and flavonoids. The strongest clinical evidence supports its use in mild-to-moderate depression and menopausal symptoms, with efficacy comparable to SSRIs and superiority over placebo. Preliminary case reports also suggest potential benefits in diabetic complications, though these findings are limited. Beyond depression, most pharmacological activities, including neuroprotective, anticancer, antiviral, antimicrobial, wound healing, and metabolic effects, remain preclinical. Recent advances in nanoformulation strategies (e.g., nanostructured lipid carriers, plant-derived exosome-like nanovesicles) have enhanced the performance of key constituents such as hypericin and hyperforin in photodynamic therapy and antimicrobial applications. Quality control has evolved from single-marker assays to holistic approaches integrating non-targeted metabolomics, machine learning, and fingerprinting, addressing compositional variability and heavy metal contamination. However, heterogeneity in plant material, extraction procedures, constituent standardization, and experimental design still complicates data interpretation. Clinically relevant herb-drug interactions, especially those associated with CYP enzyme and P-gp induction, remain a major safety concern. CONCLUSION: This narrative review indicates that H. perforatum has established efficacy in depression and broader but uneven pharmacological potential elsewhere. Emerging formulation technologies and multi-component quality control offer promising ways to improve consistency and efficacy. Future progress requires better extract standardization, clearer constituent-mechanism links, higher-quality clinical trials (especially for non-psychiatric uses), and continued attention to safety and drug interactions.