Friday Hope: Silymarin (Milk Thistle) Inhibits Binding of Spike Protein to ACE2

Silymarin also restores endothelial function and vascular tone in aging.

Graphic depiction of the binding site between human ACE2 and 11 molecules of silymarin.

One of the most important actions that can be taken against the Spike Protein of SARS-Cov-2 is to prevent its binding to cells. Although other receptors have been discovered, the main receptor for the Spike Protein is ACE2. Silymarin molecules bind to ACE2, preventing the Spike Protein from doing so. Silymarin is found in Milk Thistle. It also has other anti-Spike and anti-aging properties.

What is Milk Thistle?

Milk thistle is an upright herb that can grow to be 30 to 200 cm (12 to 79 in) tall and has an overall conical shape.[3] The approximate maximum base diameter is 160 cm (63 in). The stem is grooved and may be covered in a light cottony fuzz.[4] The largest specimens have hollow stems.

The leaves are oblong to lanceolate and 15–60 cm long and typically pinnately lobed, with spiny edges like most thistles.[3] They are hairless, shiny green, with milk-white veins.[3]

The flower heads are 4 to 12 cm long and wide, of red-purple colour. They flower from June to August in the North or December to February in the Southern Hemisphere (summer through autumn).[4] The flower head is surround by bracts which are hairless, with triangular, spine-edged appendages, tipped with a stout yellow spine.

The fruits are black achenes with a simple long white pappus, surrounded by a yellow basal ring.[5][3] A long pappus acts as a "parachute", supporting seed dispersal by wind.[6]

Silybum marianum
https://en.wikipedia.org/wiki/Silybum_marianum

Milk Thistle has long been used in the treatment of digestive issues, liver disease and diabetes.

Research on milk thistle use for specific conditions shows:

·         Diabetes. Milk thistle might lower blood sugar in people who have type 2 diabetes, but more studies are needed to confirm its benefits.

·         Indigestion (dyspepsia). Milk thistle, in combination with other supplements, might improve the symptoms of indigestion.

·         Liver disease. Research on the effects of milk thistle on liver disease, such as cirrhosis and hepatitis C, has shown mixed results.

Milk thistle
https://www.mayoclinic.org/drugs-supplements-milk-thistle/art-20362885

When Silymarin was studied for potential use against SARS-CoV-2, interesting discoveries were made. It was found that Silymarin molecules bind to ACE2, preventing the Spike Protein from doing so.

Firstly, we found that silymarin bioactive compounds had high binding affinities with viral host receptor ACE2 (Table 1). Human ACE2 is expressed in many cell surfaces (e.g., heart and lungs), which is recognized and well-known as the binding receptor of SARS-CoV-2, mediating virus entry into the host cells to trigger virus replication and proliferation cycle [82,83]. The intervention of virus-ACE2 receptor binding can reduce the entry of viruses to host cells to decrease the subsequent viral infection. Therefore, targeting ACE2 is one of the best strategies for exploring treatment agents against SARS-CoV-2 infection [84,85]. Our study showed that silymarin compounds have a higher binding affinity with ACE2 compared to viral proteins. Among these compounds, silybin A and silybin B showed the highest binding affinity (−10.2 kcal/mol for both) in complexes with ACE2 (Table 1).

Anti-Viral Activity of Bioactive Molecules of Silymarin against COVID-19 via In Silico Studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610370/
(Also the source of the above graphic.)

What makes Silymarin (SM) especially attractive from my research perspective, is that it restores endothelial dysfunction and vascular tone in aging. This is an extremely beneficial property. As I have stated from the beginning that the Spike Protein damages the endothelium by what I have called Spike Protein Endothelial Disease (SPED). To find a nutraceutical which can both inhibit the Spike Protein and ameliorate its damage is clearly a wonderful find. Again, nature provides us with safe and effective answers.

The important findings of this study are SM partially restored endothelial dysfunction and blocked NOS enzyme preventing SM action. On the other hand, when synthesis and liberation of prostaglandins from arachidonic acid are inhibited by COX enzyme inhibitor, SM could exert its effect on the vessels. It is clear that the effect SM has on vasculature is not associated with prostaglandins and its action could be mediated on the NO pathway. ROS play a critical role in initiating the process of cellular senescence and limiting the lifespan of cells (Cau et al., Citation2012). If ROS are elevated, they react with existing NO, decrease NO functions and participate in the inflammatory process of aging vasculature (Ungvari et al., Citation2010). It results in increased contractility of the vessel. A large number of studies have established that SM and its compounds possess cell-protective antioxidant properties in vitro and in vivo. Silybin has been found to be protective on human umbilical vein endothelial cell (HUVEC) against H2O2 injury through its antioxidant activity, by increasing the NO content and the activity of glutathione peroxidase and inhibiting the caspase-3 apoptotic pathway (Wang et al., Citation2005). Additionally, SM has been found to be effective in improving Ach responses in obese diabetic mice vessel by reducing in both circulating and vascular asymmetric nG,nG-dimethyl-l-arginine (ADMA) level which is an inhibitor of all forms of NOS activity (Volti et al., Citation2011).

Conclusion

The results of this study indicate that SM is a potential candidate for preventing and treating oxidative stress-induced damage of endothelial cells in aging. The possible immediate mechanisms for the reversal of endothelial dysfunction by SM in aging might be associated with its effect on the NO pathway, calcium antagonistic and antioxidant features. Moreover, this study will be helpful for researchers who consider SM’s potential value and safety for future chemotherapeutic or liver protectant trials.

Treated effect of silymarin on vascular function of aged rats: Dependant on nitric oxide pathway
https://www.tandfonline.com/doi/full/10.3109/13880209.2013.842597

Please remember that the above is a work of medical research and not medical advice. Though rare, Milk Thistle can generate an allergic response and it does interact negatively with certain medications. As with all medications and supplements, please consult your Primary Care Provider before using.

I wish all another beautiful Spring weekend! I intend to enjoy some Milk Thistle tea. I am often surprised at the additional benefits of so many nutraceuticals that we may gloss over when shopping online or at our favorite local supplement merchant. As always, thank you for your continued support, readership and dialog.