Friday Hope: Sulforaphane: Remarkable Radical Scavenging Ability and SARS-CoV-2 Inhibition

Sulforaphane is the most potent natural Nrf2 (oxidative stress resistance) activator known at this time.

Comparison of capacity to induce NQO1 by a range of phytochemicals, indicating that SFN exhibits many-fold greater inducer ability (data compiled from Yang and Liu [168] and Fahey and Kensler, 2008). 

Now that we know that SARS-CoV-2 and its Spike Protein are significant generators of ROS (Reactive Oxygen Species), it is necessary to find safe, effective and preferably natural solutions to address this phenomenon. Fortunately, nature does have such a therapeutic available to us. It is called Sulforaphane – and it is found in Broccoli and other cruciferous vegetables. 

Please see my previous post discussing the ROS-producing abilities of the Spike Protein. 

It is interesting to note that COVID infection is, not surprisingly, a ROS geyser. (Note our good friend Vitamin C referenced in the paper below.) 

SARS-CoV-2 starts a pathogenic cascade because it evades the IFN-I/III response (Schönrich et al., 2020). This results in prolonged and extensive replication of the virus in lung epithelial cells and in endothelial cells of the vessels. As a consequence, immune cells are massively recruited to the inflamed tissue and produce large amounts of ROS thereby creating an imbalanced oxidative stress response. This leads to damage-associated molecular patterns that trigger pro-inflammatory cytokine secretion through Toll-like receptors (TLR) signaling thereby activating the redox-sensitive transcription factor NF-κB. ROS and TLR also drive NET formation. Because of several positive feedback loops between cytokines (TNF-α, IL-1β) and ROS production as well as between cytokines and NET formation, a pathogenic cascade may result which contributes to organ damage, intravasal blood clotting, and immunosuppression. 

Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100929/ 

Enter the Hero of this story, Sulforaphane. Let’s take a look at our new best friend: 

Sulforaphane (SFN), which is a hydrolysis product from glucoraphanin, a compound found in cruciferous vegetables, has been studied for its potential health benefits, particularly in disease prevention and treatment. SFN has proven to be effective in combating different types of cancer by inhibiting the proliferation of tumors and triggering apoptosis. This dual action has been demonstrated to result in a reduction in tumor size and an enhancement of survival rates in animal models. SFN has also shown antidiabetic and anti-obesity effects, improving glucose tolerance and reducing fat accumulation. SFN’s ability to activate Nrf2, a transcription factor regulating oxidative stress and inflammation in cells, is a primary mechanism behind its anticancerogenic and antidiabetic effects. Its antioxidant, anti-inflammatory, and anti-apoptotic properties are also suggested to provide beneficial effects against neurodegenerative diseases. 

Sulforaphane—A Compound with Potential Health Benefits for Disease Prevention and Treatment: Insights from Pharmacological and Toxicological Experimental Studies 
https://www.mdpi.com/2076-3921/13/2/147 

Now, in the context of the Spike Protein and COVID/Long COVID disease, let’s look at how Sulforaphane addresses the significant generation of ROS. 

Our investigation into the effect of SFN on total neutrophil ROS production yield the observation that SFN attenuated ROS in a concentration-dependent manner. Previous studies have demonstrated that SFN suppresses oxidative stress by interacting with the classic regulator of redox balance, nuclear factor erythroid 2-related factor 2 (Nrf2) [21,22,23,24]. In mice, intraperitoneal administration of SFN reduces neutrophil ROS production [25]. Additionally, in mouse neutrophils and macrophage-like RAW264.7 cells, SFN exposure increases the expression of antioxidant-related genes, such as Nrf2, heme oxygenase (HO)-1, and catalase [21]. Therefore, we initially presumed that the ROS suppression effect of SFN obtained in this study was due to this “endogenous” antioxidant activity of SFN. 

However, as shown in the deferoxamine addition experiments, SFN suppressed ROS in whole blood, even when HOCl generation was inhibited by MPO inhibition. This prompted us to further investigate the effects of SFN on stimulated cells before the “endogenous” action, and again SFN inhibited ROS. In addition to its “endogenous” antioxidant activity, we measured the scavenging capacity of HOCl in the cell-free system and found that SFN was capable of scavenging ROS, including at least HCIO, and its antioxidant capacity was higher than that of L-ascorbic acid. Thus, our results suggest that SFN is capable of scavenging ROS “exogenously”. An in silico study has also shown that SFN is capable of scavenging O2−, H2O2, and HOCl in the presence of Fe-superoxide dismutase (SOD) [26], which is consistent with our results. Based on the above results, SFN is expected to exert a strong antioxidant effect in vivo through both “endogenous” and “exogenous” antioxidant effects. 

Sulforaphane Attenuates Neutrophil ROS Production, MPO Degranulation and Phagocytosis, but Does Not Affect NET Formation Ex Vivo and In Vitro 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217910/ 

Additionally, Sulforaphane has the ability to stop SARS-CoV-2 in its tracks. It inhibits the virus from replicating. 

Our results demonstrate that pharmacologically relevant micromolar concentrations of SFN inhibited viral replication and virus-induced cell death in vitro. Consumption of SFN-rich broccoli sprouts (single oral daily dose equivalent to 200 µmol of SFN) results in a peak plasma concentration (Cmax) of 1.9 µM at 2–3 h65,66, and higher steady-state levels could be achieved by administering the same dose in two divided doses10,65,67. By comparison, SFN inhibited in vitro SARS-CoV-2 replication in human cells with an IC50 of 2.4 µM. It is important to note that the bioavailability of SFN in humans is dependent on many factors including amount consumed, dietary form and preparation technique, and the individual’s gastrointestinal microflora10,68,69. Studies using SFN-rich broccoli sprouts corresponding to 50–400 μmol SFN daily have shown that SFN is well tolerated without clinically significant adverse effects10,32,70,71. Additionally, while SFN is rapidly eliminated from plasma, it reportedly exerts a sustained effect on gene expression72. A daily dose of SFN-rich broccoli sprouts corresponding to 400 μmol (70 mg) of SFN in humans is not equivalent to the 30 mg/kg of SFN used in the current mouse studies. Thus, while our results are promising, additional studies in humans are needed to determine the efficacy of SFN as a therapy for COVID-19. 

Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice 
https://www.nature.com/articles/s42003-022-03189-z 

I will admit, I love Broccoli. I look forward to having time tomorrow to prepare a Boursin filled chicken breast, wrapped in Prosciutto and served on a bed of pureed Broccoli. A meal well suited to the beautiful late summer weather we are currently experiencing here in Vermont. 

Of course, please remember that this is a work of medical research and not medical advice. Please always consult your Primary Care Provider before using any medication or supplement.  

As always, Thank you! Your support allows my research. I will continue to work and report my findings to you. Please have a beautiful, blessed and wonderful weekend - filled with much Broccoli!