Friday Hope: Myricetin: Broad Spike Binding Inhibition and Strong Anti-Inflammatory Properties
Myricetin is yet another super-flavonoid with cytoprotective, antioxidant, antimicrobial, antiviral, and antiplatelet properties.
This week I would like to discuss another superb ally Nature has provided for us. This ally is a flavonoid known as Myricetin. So, let’s take a look at it.
Although myricetin occurs throughout the Plant Kingdom, it is produced mainly by members of the families Myricaceae [1,2], Anacardiaceae [3], Polygonaceae [4], Pinaceae [5] and Primulaceae [6]. This phenolic compound is very common in berries, vegetables, and in teas and wines produced from various plants.
The history of myricetin (1) extends back to more than a hundred years. It was first isolated in the late eighteenth century from the bark of Myrica nagi Thunb. (Myricaceae), harvested in India, as light yellow-coloured crystals [10].
Myricetin: A Dietary Molecule with Diverse Biological Activities
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772053/
When it comes to dealing with the pathogenic Spike Protein of SARS-CoV-2, Myricetin addresses its deleterious effects in a number of ways.
AMELIORATES SPIKE INDUCED INFLAMMATION
Myricetin significantly reduces the levels of TNFa and IL-6, which the Spike is widely known to dramatically increase.
The results showed that myricetin significantly suppressed the extensive edema formation in the dermis (Suppl. Figs. 5B, C) without immune organ toxicity (Suppl. Fig. 5D). In the rat model of carrageenan-induced paw edema, myricetin could significantly reduce inflammatory activity at the 2nd-5th h after injection (Figs. 5C, D, E). Moreover, we established LPS-induced acute lung injury model in mice, and found that pre-treatment with myricetin (200, 300, and 400 mg/kg body weight) not only alleviated lung edema but also decreased the alveolar inflammation in the ALI mice (Fig. 5E). Consistent with the in vitro results, the mRNA levels of TNFα, IL-6 and NF-κBp65 in the lung tissues were significantly downregulated by myricetin.
SUPPRESSES RIPK1 EXPRESSION LEVELS AND INHIBITS NF-κB SIGNALING
It was reported that SARS-CoV-2 had a strong capability of inhibiting the receptor-interacting serine/threonine protein kinase 1 (RIPK1) -mediated host defense response to promote its propagation. Inhibition of RIPK1 may be a therapeutic option for treating COVID-19 (Xu et al., 2021). We first established an LPS-induced hyperinflammatory cell model in THP1 macrophages to simulate a state with high RIPK1 levels. The results showed that myricetin significantly reduced RIPK1 expression levels, as well as the mRNA levels of NF-κBp65, RIPK3, RIPK1, MLKL, FADD, Caspase8 and JNK.
Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice
https://pmc.ncbi.nlm.nih.gov/articles/PMC10162847/
In addition to the above discussed benefits, Myricetin has the ability to significantly reduce the ability of the Spike Protein to bind ACE2.
SARS-CoV-2 enters into the host cells via the S-protein and engages ACE2 as the host cell-entry receptor (Hoffmann et al., 2020). We firstly used immunocytochemistry to detect the expression of human ACE2 on HEK293 cells with fluorescence. By applying ELISA, we found that myricetin significantly inhibited the interactions between the RBDWT and ACE2 protein (Suppl. Fig. 2). In addition, we visualized these interactions in HEK293-hACE2-EGFP cells and found that the binding of SARS-CoV-2 S protein to HEK293-hACE2-EGFP cell membranes was blocked by myricetin (Fig. 3 A and Suppl. Fig. 3). The SARS-CoV-2 RBDWT and mutant proteins (RBDN501Y, RBDN439K, RBDY453F, and S-D614G) on HEK293-hACE2-EGFP cell surfaces showed a dose-dependent decrease in immunoreactive signal after myricetin treatment (Fig. 3B), indicating that myricetin might engage in a crosstalk between the host cells and wide-type and mutant SARS-CoV-2.
This also held true for Spike variants, which is splendid news, indeed.
These results above suggest that myricetin was able to inhibit wild-type SARS-CoV-2 and its variants.
Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice
https://pmc.ncbi.nlm.nih.gov/articles/PMC10162847/
Where may we find Myricetin, other than in supplements? Fortunately, it happens to be in some of my favorite foods and beverages. Perhaps they are yours, too.
Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications
https://pmc.ncbi.nlm.nih.gov/articles/PMC7395214/
And, of course, Red Red Wine.
Background and aims: Moderate red wine consumption associates with lower incidence of cardiovascular diseases. Attention to the source of this cardioprotection was focused on flavonoids, the non-alcoholic component of the red wine, whose intake inversely correlates with adverse cardiovascular events. We analysed whether two red wine flavonoids, quercetin and myricetin, affect mammalian basal myocardial and coronary function.
Conclusions: The cardiomodulation elicited on basal mechanical performance by quercetin and the selective vasodilation induced by myricetin point to these flavonoids as potent cardioactive principles, able to protect the heart in the presence of cardiovascular diseases.
Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols
https://pubmed.ncbi.nlm.nih.gov/20096547/
I am absolutely certain that I will be enjoying my Myricetin this weekend! I hope everyone else will, as well. It is very chilly up here in Nothern Vermont, so some lamb stew paired with a nice Cabernet will fit the bill this evening.
Thank you, always as always, for your readership, dialogue and support. I wish everyone a joyous welcoming weekend to the newly arrived Winter Holiday season!
Myricetin is a brand new term for me. Thank you, Walter! These magical flavanoids can be found in so many fruits including Gogi Berries and also beet root...the more pigment the better! If you're searching for foods with massive amounts of flavanoids...look to the amount of pigment they have...it's usually a good indicator of flavanoids up the kazoo.
I think prunes are rich in flavanoids too? They are darker when dried but they are so good for the gut microbiome too. I've been making homemade kefir for years now which is naturally full of vitmamin K and Vitamin B and tons and tons of probiotic microorganisms. The trick to really make happy and healthy grains is screw the whole milk and go right for the half and half. My kefir grains make the most amazing kefir with half-n-half and it comes out so creamy and rich just like a supercharged full fat greek yogurt. I've even made amazing Tzatziki with my kefir.
Seriously, ya'll need to get you some kefir grains and start making your own kefir! It heals the gut and is delish! Just be sure to sterilize all of your utensils and vessels and you're good to go.
Well, Walter, your lamb stew sounds wonderful. This week-end I'll be making Jacque Pepin's mother's beef stew. She doesn't use any beef stock and just a full bottle of red wine!! ??!! If the wine concoction is too "thin" in taste, I'll add some coconut amino acids and organic soy sauce.
Looks like homemade cranberry juice would be a good way to get lots of cranberries. Most start with 2 quarts of cranberries. Many add oj or other juices. Just boil and strain. Use your own sweetener + whatever flavorings (citrus, cinnamon, etc.) you like.