The Spanish Agency for Medicines and Health Products (AEMPS) has just approved the clinical trial SilCOVID19 with this substance in oncohematological patients with coronavirus. Euromed S.A. is known internationally for its leadership in manufacturing standardised botanical extracts, and its milk thistle extract has been clinically studied during the past few decades in thousands of patients worldwide.
Milk thistle (Silybum marianum) is a herbaceous plant that’s usually adorned with a purple-pink flower. Milk thistle seed extracts have validated benefits for liver health. They also have been used both preventively and curatively to protect the liver from toxins, including alcohol, aspirin, acetaminophen, heavy metals and the death cap mushroom. The active constituent of milk thistle seeds (fruits) is a flavonoid called silymarin, the key component of which is silibinin. Recent investigation suggests that it may have further benefits that go beyond liver support. For instance, silibinin has a recognized antitumor activity, and could also be effective in the fight against COVID-19. This is the conclusion of a study by the Catalan Institute of Oncology (ICO) and the Girona Biomedical Research Institute (IDIBGI), recently published in the Journal of Clinical Medicine, presenting the reasons for an evaluation of its possible use as a treatment for the coronavirus SARS-CoV-2 2019, which is causing a global pandemic with hundreds of thousands of infections and deaths worldwide.
The study is led by Dr. Joaquim Bosch, oncologist of the Medical Oncology Service of the ICO Girona, and Dr. Javier Menéndez, head of the Metabolism and Cancer Laboratory and member of the ProCURE program (Program Against Therapeutic Resistance to Cancer) of the ICO-IDIBGI. Both researchers have already published several previous studies showing the antitumor ability of silibinin in cancer patients.
Triple function of silibinin against COVID-19
According to this study, the clinical-molecular evidence of silibinin as a possible treatment for COVID-19 is presented in three parts:
- As an immunodulator of the “cytokine storm”: it analyzes the ability of silibinin to act as an immunomodulator of the so-called “cytokine storm”, one of the key mechanisms in the poor prognosis of patients COVID-19 with acute respiratory distress syndrome. This mechanism would depend on the STAT3 protein, a molecular target of silibinin that the same researchers had already described in patients with brain metastases. Thus, this first level of action would take place in the “host / patient” area.
- As an antiviral: it is also presented, for the first time, a comprehensive computational analysis of a new mechanism of silibinin against RNA polymerase of SARS-CoV-2, the main component of the virus replication / transcription machinery. This computational study, developed in collaboration with Dr. José Antonio Encinar (University of Elche), predicts a pharmacological behavior of silibinin very similar to that known with Remdesivir, which has recently been the first drug approved by the European Agency for Drug (EMA) against COVID-19. This second level of action would take place in the virus itself.
This dual nature of silibinin, capable of acting both in the systemic environment via STAT3 – controlling the exacerbated and uncontrolled response of the immune system against lung epithelial cells damaged by infection – and in the virus by directly blocking RNA polymerase from SARS-CoV-2, provides a good reason for the development of clinical studies.
- Proposed clinical trial for the treatment of oncohematological patients with COVID-19: Based on this evidence, the authors present the design of a phase II multicenter clinical trial. The study, with the acronym SilCOVID19, will evaluate the therapeutic efficacy of silibinin in the prevention of acute respiratory distress syndrome in oncohematological patients with COVID-19, who require admission, of which the ICO is the promoter. SilCOVID19 has just received approval from the AEMPS and will begin shortly with Dr. Joaquim Bosch as principal investigator and Dr. Javier Menéndez as scientific coordinator. In this study, silibinin, from milk thistle extract, will be administered to patients in the study through the drug Legalon®, which is processed at Euromed S.A.
With this work, the researchers bring to the society and the scientific community the potential of this natural molecule, and propose a randomized clinical trial with a multicenter, phase II control group. The result of this study will determine whether silibinin may be helpful in fighting COVID-19.
Euromed S.A. has committed a donation to IDIBGI, a not-for-profit organization, as a support towards the fundraising campaign for this study. Donations to IDIBGI projects can also be done at: https://www.idibgi.org/en/content/donations
 Bosch-Barrera, J.; Martin-Castillo, B.; Buxó, M.; Brunet, J.; Encinar, J.A.; Menendez, J.A. Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients. J. Clin. Med. 2020, 9, 1770.