Friday Hope: Isoquercetin: A Strong Cancer Antiproliferative, SARS-CoV-2 Therapeutic

This glycoside of Quercetin exhibits greater bioavailability than Quercetin while providing multiple benefits.

Molecular and physiological targets of quercetin and isoquercetin in Covid-19. SARS-CoV-2 infection and life cycle are graphically represented. Potential targets for inhibition by the flavonols are written in red and highlighted in yellow. Their full identity and the role in Covid-19 pathogenesis are described in the text. NSPs stand for non-structural proteins, and SPs for structural proteins.

For years we have known how beneficial Quercetin is in treating SARS-CoV-2/Spike Protein disease/injury. Today I would like to discuss another voice in the Quercetin chorus. That is its glycoside, Isoquercetin. Isoqercetin is similar, yet different from Quercetin, Please note that you will find this glycoside spelled in many ways. However, they all refer to the same substance.

Isoquercitrin (quercetin-3-O-β-d-glucopyranoside; Fig. 1, Table 1) is, together with rutin (quercetin-3-O-rutinoside), one of the major glycosidic forms of the natural flavonol quercetin (3,5,7,3′,4′-pentahydroxyflavone; Fig. 1). In recent decades, quercetin has been the subject of a large number of biological studies (Boots et al., 2008, Dajas, 2012, Gibellini et al., 2011, Harwood et al., 2007, Okamoto, 2005, Russo et al., 2012). In contrast, the biological activity of quercetin glycosides has been studied to a lesser extent. For instance, in 2012, the Web of Science database shows 1489 records on quercetin, 482 records on rutin and only 49 records on isoquercitrin. However, isoquercitrin has been attracting increasing research attention (Fig. 2) due to its presence in plant-derived food and a growing array of its biological activities.

Isoquercitrin: Pharmacology, toxicology, and metabolism
https://www.sciencedirect.com/science/article/abs/pii/S0278691514001471

What I particularly like about Isoquercetin is its immense advantage in bioavailability over Quercetin.

A HPLC-FD method with in-line post-column complexation was employed to quantify the quercetin metabolites (QM) in plasma and tissues. Compared to the quercetin gavage the isoquercitrin gavage consistently produced higher levels of QM in tissues (double to five-fold) as well as in plasma (double to three-fold). In body tissues, the highest amounts of QM were observed in the lung. In brain tissue, the highest levels of QM were found in the cerebellum, while the striatum contained the lowest levels of QM. In conclusion, this study clearly demonstrates that orally given isoquercitrin leads to higher levels in plasma and in all investigated tissue than quercetin aglycone.

Isoquercitrin provides better bioavailability than quercetin: comparison of quercetin metabolites in body tissue and brain sections after six days administration of isoquercitrin and quercetin
https://pubmed.ncbi.nlm.nih.gov/23346761/

And here, perhaps, we have another clue as to why Quercetin is so effective against all things Spike. Notice where it distributes the most: The Lung.

Isoquercetin (IQ) is effective at inhibiting the spread of certain cancers. With the advent of Turbocancers, Isoquercetin appears to apply this inhibition to many of the more commonly reported types of Turbocancers.

The antiproliferative activities of quercetin derivatives and rutin were compared using different cancer cell lines and the results demonstrated that IQ had more potent antiproliferative effects than the other flavonoids did, especially in colon, breast, and hepatocellular cancers[71]. Similar studies demonstrated that hydrolyzed rutin, which is obtained following the enzymatic hydrolysis of rutin by an hesperidinase and mainly composed of IQ (70%), exerted markedly potent antiproliferative effect in vitro compared to the effects of quercetin and rutin in various cancer cell lines including ovarian adenocarcinoma (OVCAR-3), breast adenocarcinoma (MCF-7), and glioma (U-251). It is suggested that the most potent antiproliferative effect induced by IQ mixtures might be related to its specific glucose transport carrier SGLT-1[7].

Review of anticancer mechanisms of isoquercitin
https://pmc.ncbi.nlm.nih.gov/articles/PMC4826964/

Once again, it is the greater bioavailability of Isoquercetin that warrants its inclusion in a COVID/Spike Protein protocol. It is important to note that we are not talking about using one at the expense of the other. They are both valuable and deserving of inclusion. Given the aforementioned anti-cancer effects that are unique to Isoquercetin, especially so.

In this review, we presume that, as a potential anti-SARS-CoV-2 drug, isoquercetin represents a better choice than quercetin aglycone because it is a more absorbable precursor of quercetin, allowing greater bioavailability of the aglycone. Together, these two flavonols represent potentially effective medications for the treatment of COVID-19 patients, the reasons being: 1) their broad-spectrum antiviral activities; 2) their potent activities against SARS-CoV-2-induced symptoms as an antioxidant, anti-inflammatory, immunomodulatory, anticoagulant agent; 3) in silico analyses by molecular docking and molecular dynamics simulations, indicating that several proteins involved in SARS-CoV-2 entry and replication exhibit strong affinity for these flavonols; 4) their safety when orally administered in phase 1 clinical trials. Experiments in vitro and in animals should corroborate this presumption and elucidate their mechanisms of their action.

Isoquercetin as an Anti-Covid-19 Medication: A Potential to Realize
https://pmc.ncbi.nlm.nih.gov/articles/PMC8924057/

I hope clinicians and research institutes will study Isoquercetin further, not only in its ability to treat COVID/Spike related disease but also its ability to curb the spread of cancers. Of course, as with all medicines and supplements, always consult your primary care provider before use.

Happiest of Fouths to all! It is full-on glorious summer here in northern Vermont. One could not ask for a more perfect day. Calm breezes, mostly sunny skies and highs in the seventies. Thank you, as always, for your readership, dialogue and support. Wherever you live, please have a blessed and hopeful weekend.