Australian Herbal Insight
Advances in Herbal Research | online ISSN 2209-1890
  1. You are here:
  2. Home
  3. Journals
  4. Plant Sciences
REVIEWS   (Open Access)
Contents Vol 4 (1)

St. John's Wort (Hypericum perforatum): A Review of its Potential Antidepressant Efficacy and Safety

Mohsin Ahmed 1, Rownak Jahan 2, Mohammed Rahmatullah 2*

+ Author Affiliations

Australian Herbal Insight 4 (1) 1-6 https://doi.org/10.25163/ahi.4110003

Submitted: 12 April 2021 Revised: 18 June 2021  Published: 19 June 2021 

Abstract

Background: St. John's Wort (SJW), scientifically known as Hypericum perforatum, is widely utilized as an over-the-counter remedy for various ailments, particularly depression, despite lacking FDA approval. The active compounds in SJW, including hypericin, hyperforin, and flavonoids, are believed to alleviate depressive symptoms by inhibiting neurotransmitter reuptake. However, concerns regarding its safety arise from extensive drug-drug interactions, pointing to deficiencies in quality control and regulation of SJW distribution. Methods: This narrative review synthesizes existing literature on the therapeutic effects, safety profile, indications, and adverse effects of SJW in treating depression. It also examines the regulatory landscape surrounding SJW and highlights the necessity for standardized practices and comprehensive clinical trials. Results: SJW has shown efficacy in managing mild to moderate depression, with some studies suggesting it may offer benefits comparable to conventional antidepressants while exhibiting a more favorable side effect profile. However, significant safety concerns persist due to potential interactions with other medications, leading to adverse reactions such as serotonin syndrome. Current regulatory frameworks vary globally, with SJW classified as a dietary supplement in the U.S. and subjected to stricter regulations in Europe. Conclusion: Despite its widespread use and potential therapeutic benefits, the safety and efficacy of SJW in treating depression remain inadequately substantiated by clinical evidence. Enhanced regulatory measures and rigorous clinical research are imperative to clarify SJW's role in depression treatment and ensure its safe application in clinical practice. Inclusion in pharmacopeias and adherence to good manufacturing practices could further improve the quality and safety of SJW products.

Keywords: St. John's Wort, Hypericums, Hypericum perforatum, Johnswort, Emotional Depression, Major Depressive Disorder.

References

Ahmet Yildirim, Aksoy, T., Hüsniye Kayalar, & Ibrahim Cüneyt Balcioglu. (2024). Semen Cannabis and Oleum Hyperici: Antileishmanial activity against Leishmania tropica promastigotes and intracellular amastigotes. Parasitology International, 103, 102950–102950. https://doi.org/10.1016/j.parint.2024.102950

Allaire, A. (2000). Complementary and alternative medicine in pregnancy: a survey of North Carolina certified nurse-midwives. Obstetrics & Gynecology, 95(1), 19–23. https://doi.org/10.1016/s0029-7844(99)00481-0

Benitez, J. S. C., Hernandez, T. E., Sundararajan, R., Sarwar, S., Arriaga, A. J., Khan, A. T., Matayoshi, A., Quintanilla, H. A., Kochhar, H., Alam, M., Mago, A., Hans, A., & Benitez, G. A. (2022). Advantages and Disadvantages of Using St. John’s Wort as a Treatment for Depression. Cureus, 14(9). https://doi.org/10.7759/cureus.29468

Bladt, S., & Wagner, H. (1994). Inhibition of MAO by Fractions and Constituents of Hypericum Extract. Journal of Geriatric Psychiatry and Neurology, 7(1), 57–59. https://doi.org/10.1177/089198879400700115

Butterweck, V. (2003). Mechanism of Action of St John’s Wort in Depression. CNS Drugs, 17(8), 539–562. https://doi.org/10.2165/00023210-200317080-00001

Caccia, S., & Gobbi, M. (2009). St. Johns Wort Components and the Brain: Uptake, Concentrations Reached and the Mechanisms Underlying Pharmacological Effects. Current Drug Metabolism, 10(9), 1055–1065. https://doi.org/10.2174/138920009790711878

Chakraborty, S., Piyush Baindara, Sharma, P., Austin Jose T, Kumaravel V, Manoharan, R., & Mandal, S. M. (2024). Anti-Biofilm Action of Cineole and Hypericum perforatum to Combat Pneumonia-Causing Drug-Resistant P. aeruginosa. Antibiotics, 13(8), 689–689. https://doi.org/10.3390/antibiotics13080689

Chand, S., & Arif, H. (2023, July 17). Depression. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK430847/

Dennehy, C., Tsourounis, C., Bui, L., & King, T. L. (2010). The Use of Herbs by California Midwives. Journal of Obstetric, Gynecologic & Neonatal Nursing, 39(6), 684–693. https://doi.org/10.1111/j.1552-6909.2010.01193.x

Di Carlo, G., Borrelli, F., Ernst, E., & Izzo, A. A. (2001). St John’s wort: Prozac from the plant kingdom. Trends in Pharmacological Sciences, 22(6), 292–297. https://doi.org/10.1016/s0165-6147(00)01716-8

Eich-Höchli, D., Oppliger, R., Golay, K. P., Baumann, P., & Eap, C. B. (2003). Methadone Maintenance Treatment and St. John’s Wort. Pharmacopsychiatry, 36(1), 35–37. https://doi.org/10.1055/s-2003-38090

Gaster, B., & Holroyd, J. (2000). St John’s Wort for Depression. Archives of Internal Medicine, 160(2), 152. https://doi.org/10.1001/archinte.160.2.152

Greeson, J. M., Sanford, B., & Monti, D. A. (2001). St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology, 153(4), 402–414. https://doi.org/10.1007/s002130000625

Josey ES;Tackett RL. (2017). St. John’s wort: a new alternative for depression? International Journal of Clinical Pharmacology and Therapeutics, 37(3). https://pubmed.ncbi.nlm.nih.gov/10190758/

Kasper, S., Dienel, A., & Kieser, M. (2004). Continuation and long-term maintenance treatment with Hypericum extract WS® 5570 after successful acute treatment of mild to moderate depression – rationale and study design. International Journal of Methods in Psychiatric Research, 13(3), 176–183. https://doi.org/10.1002/mpr.173

Kholghi, G., Arjmandi-Rad, S., Zarrindast, M.-R., & Vaseghi, S. (2022). St. John's wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems? Naunyn-Schmiedeberg’s Archives of Pharmacology, 395(6). https://doi.org/10.1007/s00210-022-02229-z

Klemow, K. M., Bartlow, A., Crawford, J., Kocher, N., Shah, J., & Ritsick, M. (2014). Medical Attributes of St. John’s Wort (Hypericum perforatum). Nih.gov; CRC Press/Taylor & Francis. https://www.ncbi.nlm.nih.gov/books/NBK92750/#:~:text=Worldwide%20annual%20sales%20of%20products

Kupfer, D. J. (2005). The pharmacological management of depression. Dialogues in Clinical Neuroscience, 7(3), 191–205. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181740/

Lei, C., Li, N., Chen, J., & Wang, Q. (2023). Hypericin Ameliorates Depression-like Behaviors via Neurotrophin Signaling Pathway Mediating m6A Epitranscriptome Modification. Molecules, 28(9), 3859. https://doi.org/10.3390/molecules28093859

Li, J.-D., He, S.-L., Wang, G., Chen, J., Liu, X., Wang, T., Zhou, M., Du, C., Chen, H.-F., & Tian, W.-J. (2024). Filicinic acid based meroterpenoids from Hypericum elodeoides and their anti-Alzheimer’s disease effects. Bioorganic Chemistry, 107787–107787. https://doi.org/10.1016/j.bioorg.2024.107787

Maher, A. R., Hempel, S., Apaydin, E., Shanman, R. M., Booth, M., Miles, J. N. V., & Sorbero, M. E. (2016). St. John’s Wort for Major Depressive Disorder. Rand Health Quarterly, 5(4). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158227/

Market, P. (2024). Herbal Supplements Market Size, Share & Report 2024-2032. Polaris. https://www.polarismarketresearch.com/industry-analysis/herbal-supplements-market

National Center for Complementary and Integrative Health. (2020). St. John’s wort. NCCIH. https://www.nccih.nih.gov/health/st-johns-wort

NCCIH. (2017, December). St. John’s Wort and Depression: In Depth. NCCIH. https://www.nccih.nih.gov/health/st-johns-wort-and-depression-in-depth

Ng, Q. X., Venkatanarayanan, N., & Ho, C. Y. X. (2017). Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. Journal of Affective Disorders, 210, 211–221. https://doi.org/10.1016/j.jad.2016.12.048

Nutrition, C. for F. S. and A. (2021, July 21). Blossom Nature, LLC - 612263 - 02/18/2021. FDA. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/blossom-nature-llc-612263-02182021

Oliveira, A. I., Pinho, C., Sarmento, B., & Dias, A. C. P. (2016). Neuroprotective Activity of Hypericum perforatum and Its Major Components. Frontiers in Plant Science, 7. https://doi.org/10.3389/fpls.2016.01004

Pannu, A., Sharma, P. C., Thakur, V. K., & Goyal, R. K. (2021). Emerging Role of Flavonoids as the Treatment of Depression. Biomolecules, 11(12), 1825. https://doi.org/10.3390/biom11121825

Peterson, B., & Nguyen, H. (2023, May 16). St. John’s Wort. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557465/

Raczkiewicz, I., Céline Rivière, Bouquet, P., Lowiese Desmarets, Tarricone, A., Camuzet, C., François, N., Lefèvre, G., Fabiola Silva Angulo, Robil, C., François Trottein, Sevser Sahpaz, Dubuisson, J., Sandrine Belouzard, Goffard, A., & Séron, K. (2024). Hyperforin, the major metabolite of St. John’s wort, exhibits pan-coronavirus antiviral activity. Frontiers in Microbiology, 15. https://doi.org/10.3389/fmicb.2024.1443183

Saller, R., Melzer, J., & Reichling, J. (2003). Johanniskraut (Hypericum perforatum): Ein plurivalenter Rohstoff für traditionelle und moderne Therapien. Complementary Medicine Research, 10(1), 33–40. https://doi.org/10.1159/000071690

Saller, R., & Rostock, M. (2012). Multimorbidität und Multi-Target-Therapie in der Phytotherapie. Praxis, 101(25), 1637–1642. https://doi.org/10.1024/1661-8157/a001149

Shelton, R. C. (2009). St John’s Wort (Hypericum perforatum) in Major Depression. The Journal of Clinical Psychiatry, 70(suppl 5), 23–27. https://doi.org/10.4088/jcp.8157su1c.05

Singer, A., Wonnemann, M., & Müller, W. E. (1999). Hyperforin, a major antidepressant constituent of St. John’s Wort, inhibits serotonin uptake by elevating free intracellular Na+1. The Journal of Pharmacology and Experimental Therapeutics, 290(3), 1363–1368. https://pubmed.ncbi.nlm.nih.gov/10454515/

St. John’s Wort Extract Market, Report Size, Worth, Revenue, Growth, Industry Value, Share 2024. (2024). Valuates Reports. https://reports.valuates.com/market-reports/QYRE-Auto-19T9546/global-st-john-s-wort-extract

St. John’s Wort (Hypericum perforatum) - Search Results - PubMed. (2014). PubMed. https://pubmed.ncbi.nlm.nih.gov/?term=St.+John%27s+Wort+%28Hypericum+perforatum%29&size=200

World Health Organization. (2023, March 31). Depressive disorder (depression). World Health Organization. https://www.who.int/news-room/fact-sheets/detail/depression

Wu, S., & Tatsis, E. C. (2024). Specialized metabolism in St John’s wort. Current Opinion in Plant Biology, 82, 102625–102625. https://doi.org/10.1016/j.pbi.2024.102625

PDF
Abstract
Export Citation

View Dimensions


View Plumx


View Altmetric




Save
0
Citation
387
View

Share