Hypericum perforatum (St John's wort) beyond depression: A therapeutic perspective for pain conditions

Ethnopharmacological relevance: Hypericum perforatum L. (Hypericaceae), popularly called St. John's wort (SJW), has a rich historical background being one of the oldest used and most extensively investigated medicinal herbs. Many bioactivities and applications of SJW are listed in popular and in scientific literature, including antibacterial, antiviral, anti-inflammatory. In the last three decades many studies focused on the antidepressant activity of SJW extracts. However, several studies in recent years also described the antinociceptive and analgesic properties of SJW that validate the traditional uses of the plant in pain conditions. Aim of the review: This review provides up-to-date information on the traditional uses, pre-clinical and clinical evidence on the pain relieving activity of SJW and its active ingredients, and focuses on the possible exploitation of this plant for the management of pain. Materials and methods: Historical ethnobotanical publications from 1597 were reviewed for finding local and traditional uses. The relevant data on the preclinical and clinical effects of SJW were searched using various databases such as PubMed, Science Direct, Scopus, and Google Scholar. Plant taxonomy was validated by the database Plantlist.org. Results: Preclinical animal studies demonstrated the ability of low doses of SJW dry extracts (0.3% hypericins; 3-5% hyperforins) to induce antinociception, to relieve from acute and chronic hyperalgesic states and to augment opioid analgesia. Clinical studies (homeopathic remedies, dry extracts) highlighted dental pain conditions as a promising SJW application. In vivo and in vitro studies showed that the main components responsible for the pain relieving activity are hyperforin and hypericin. SJW analgesia appears at low doses (5100 mg/kg), minimizing the risk of herbal-drug interactions produced by hyperforin, a potent inducer of CYP enzymes. Conclusion: Preclinical studies indicate a potential use of SJW in medical pain management. However, clinical research in this field is still scarce and the few studies available on chronic pain produced negative results. Prospective randomized controlled clinical trials performed at low doses are needed to validate its potential efficacy in humans.