The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms.

The proceeding pandemic of coronavirus disease 2019 is the latest global challenge. Like most other infectious diseases, inflammation, oxidative stress, and immune system dysfunctions play a pivotal role in the pathogenesis of COVID-19. Furthermore, the quest of finding a potential pharmaceutical therapy for preventing and treating COVID-19 is still ongoing. Silymarin, a mixture of flavonolignans extracted from the milk thistle, has exhibited numerous therapeutic benefits. We reviewed the beneficial effects of silymarin on oxidative stress, inflammation, and the immune system, as primary factors involved in the pathogenesis of COVID-19. We searched PubMed/Medline, Web of Science, Scopus, and Science Direct databases up to April 2022 using the relevant keywords. In summary, the current review indicates that silymarin might exert therapeutic effects against COVID-19 by improving the antioxidant system, attenuating inflammatory response and respiratory distress, and enhancing immune system function. Silymarin can also bind to target proteins of SARS-CoV-2, including main protease, spike glycoprotein, and RNA-dependent RNA-polymerase, leading to the inhibition of viral replication. Although multiple lines of evidence suggest the possible promising impacts of silymarin in COVID-19, further clinical trials are encouraged.

Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: A double-blind placebo-controlled clinical trial.

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration (p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group (p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.

Phyto-pharmacological perspective of Silymarin: A potential prophylactic or therapeutic agent for COVID-19, based on its promising immunomodulatory, anti-coagulant and anti-viral property.

Coronavirus disease 2019 (COVID-19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the global community but also spread rapidly via global travel. To date there are no effective vaccines or specific treatments against this highly contagious virus; therefore, there is an urgent need to advocate novel prophylactic or therapeutic interventions for COVID-19. This brief opinion critically discusses the potential of Silymarin, a flavonolignan with diverse pharmacological activity having antiinflammatory, antioxidant, antiplatelet, and antiviral properties, with versatile immune-cytokine regulatory functions, that able to bind with transmembrane protease serine 2 (TMPRSS2) and induce endogenous antiviral cytokine interferon-stimulated gene 15, for the management of COVID-19. Silymarin inhibits the expression of host cell surface receptor TMPRSS2 with a docking binding energy corresponding to -1,350.61 kcal/mol and a full fitness score of -8.11. The binding affinity of silymarin with an impressive virtual score exhibits significant potential to interfere with SARS-CoV-2 replication. We propose in-depth pre-clinical and clinical review studies of silymarin for the development of anti-COVID-19 lead, based on its clinical manifestations of COVID-19 and multifaceted bioactivities.