QUERCETIN

Quercetin is a dietary flavanoid most associated with capers and red onions but has many sources. Direct clinical evidence of its beneficial actions in patients can be seen in various systemic inflammatory diseases. For instance with tyrosine kinase inhibitor dasatinib, where quercetin combines with the tki to reduce so called senesent cells in the lung disease idiopathic pulmonary fibrosis. These zombie like cellular entities are associated with cancer and its progression, amongst many other disease factors.

A few other studies have been published in systemic inflammatory diseases including rheumatoid arthritis, polycystic ovary syndrome and even early stage covid related virus therapy. These outcomes undoubtedly show suppressive actions on a variety of metabolic and inflammatory mechanisms also associated with with cancer risk and progression rates. Including lowering lactate dehydrogenase levels and insulin resistance whilst raising adiponectin. The latter is a protein hormone with many metabolic health actions, and low levels are linked with progression rates in multiple cancers including breast, kidney , prostate and colorectal.

In glioblastoma, there is recent compelling pre-clinical evidence that suppressing of specific enzymes IRE1 radically reduces so called unfolded protein response driving growth and treatment resistance. Meanwhile, quercetin has also been shown recently to inhibit IRE1. (see Pathfinder). Mulitple cancers including colorectal, lung, kidney and especially multiple myeloma are also known to show this behavior.

Flavanoids such as quercetin are well known for reducing cancer risk, including prostate, gastric, lung and bladder (see Examples)

TYPICAL ABSORPTION LEVELS

20 – 40%

EXAMPLES OF IMPROVED OUTCOMES

PENDING

PRE-DIAGNOSIS OR PREVENTION

YES
ANALYSIS

Highlighted Studies

Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib [a tyrosine kinase inhibitor] and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of...

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After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved . Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406...

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The treatment group received 1 g quercetin (two 500 mg capsules) daily for 12 weeks.. In addition to anthropometric assessments, fasting serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, glucose, insulin, testosterone, LH, and SHBG were also measured at the baseline and at the end of the trial. Quercetin could slightly increase the level of adiponectin by 5.56% and HMW adiponectin by 3.9% .. while it reduced the level of testosterone (0.71 ng/dl in quercetin vs...

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Recently, quercetin has received more attention due to its potential therapeutic effects. Therefore, this review provides insights into the mechanism of action of quercetin for prostate cancer, quercetin patents, commercial products, and clinical trials, which provide a comprehensive review of the beneficial impact of quercetin as an antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and protective agent in cardiovascular diseases risk. It also ameliorates immunity and shows speedy r...

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TABLE OF REFERENCES

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https://www.thelancet.com/article/S2352-3964(19)30591-2/fulltext3Our findings provide support for the likelihood that the beneficial effects of intermittent D + Q on cellular senescence-related phenotypes in IPF, which we reported in the first clinical trial of senolytics [40], were indeed due to reduction in senescent cell burden. Over and above the trends we noted for circulating SASP factors to be lower after than before D + Q in that first clinical trial, in the second clinical trial to examine senolytics, others documented a decrease of 53 out of 66 SASP factors, as well as decreases in a DNA damage/telomere stress-induced senescence gene set. These changes were found in comparing skin biopsies from a subset of patients with systemic sclerosis who had an initially high senescent cell burden before being treated with D (no Q) continuously for ~6 months vs. after treatment [41]. Now, in the third peer-reviewed clinical trial of senolytics reported here, we provide direct evidence for a decrease in both adipose tissue and skin epidermal senescent cell abundance and circulating SASP factors 11 days following a single 3-day course of D + Q.We tested if key circulating SASP factors were decreased by the short course of senolytics. Plasma IL-1α, −2, −6, and − 9 and Matrix Metalloproteinases (MMP)-2, −9, and −12 were significantly lower 11 days after than before the 3 days of D + Q administration (Fig. 5) and IL1-RA, Fibroblast Growth Factor (FGF)-2, and Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) tended to be lower (all p = 0·06). Abundance of adipose tissue p16INK4A+ cells (relative to adipocytes) correlated significantly with plasma IL-6, IL-9, IL-1α, IL1-RA, MMP12, MMP9, and MMP-2 (R2 = 0·34*, 0·25*, 0·56***, 0·24*, 0·51**, 0·36**, and 0·25*, respectively; * p < 0·05, ** p < 0·005, and ***p < 0·001). These circulating SASP factor data are consistent with a systemic decrease in senescent cell abundance that remained apparent well beyond the 4 to 11 h elimination half-lives of D + Q
https://www.thieme-connect.de/products/ejournals/html/10.1055/s-0042-118705#N10E6B3The treatment group received 1 g quercetin (two 500 mg capsules) daily for 12 weeks, and the control group received placebo. In addition to anthropometric assessments, fasting serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, glucose, insulin, testosterone, LH, and SHBG were also measured at the baseline and at the end of the trial. Quercetin could slightly increase the level of adiponectin by 5.56% as compared to placebo (adjusted p-value=0.001) and HMW adiponectin by 3.9% as compared to placebo (adjusted p-value=0.017), while it reduced the level of testosterone (0.71 ng/dl in quercetin vs. 0.77 ng/dl in placebo; p<0.001) and LH (8.42 IU/l in quercetin vs. 8.68 IU/l in placebo; p=0.009). HOMA-IR levels were also significantly (p<0.001) lower in quercetin (1.84) group compared to placebo group (2.21). Oral quercetin supplementation was effective in improving the adiponectin-mediated insulin resistance and hormonal profile of women with PCOS.Our findings showed that supplementation with quercetin have slightly beneficial effects on testosterone and LH level, which are the important hormones in the pathogenesis of PCOS. It has been shown that adiponectin modulates the reproductive system by inhibiting LH and GnRH secretion [37]. Adiponectin receptors are expressed in oocytes and animal studies have demonstrated that this protein exerts its protective functions on oocytes through AMPK pathway [38]. Quercetin administration did not have a significant influence on SHBG levels, indicating that the effect of quercetin on testosterone is not secondary to the changes in SHBG levels. To date, the effects of quercetin on testosterone levels have not been addressed; this study, for the first time, reveals slightly decreased testosterone levels in serum after quercetin supplementation
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1096853/full2.5The present study also revealed significant improvement in the patients serum LDH levels, supporting the possible anti-inflammatory therapeutic effect of quercetin in COVID-19. Serum LDH level is an important severity marker in patients with COVID-19 (Szarpak et al., 2021). In a metanalysis study by Henry et al. (2020) elevated LDH levels were associated with a ∼6-fold increase in odds of developing severe disease and a ∼16-fold increase in odds of mortality in patients with COVID-19. Quercetin exhibits diverse anti-inflammatory mechanisms including the inhibition of lipid-peroxidation, lipoxygenase and phospholipase A2, the nucleotide-binding oligomerization domain leucine rich repeat and pyrine domain containing protein 3 (NLRP3) inflmmasome-mediated IL-1ß productionThe results of quercetin complementary therapy revealed in this study are also in line with those reported by other randomized clinical trials in hospitalised COVID-19 patients. In study by Shohan et al. (2022) a daily 1000 mg quercetin supplementation with antivirals (remdesivir or favipiravir) for 7 days was significantly associated with partial earlier hospital discharge, reduction in the serum levels of LDH, alkaline phosphatase (ALP), and q-CRP, as well as significant increase in the patients hemoglobin level and respiratory rate as compared to the antiviral treatment alone. In study by Onal et al. (2021) a daily 1000 mg of quercetin (in combination with 1000 mg vitamin C and 100 mg bromelain) resulted in significant reduction in CRP, ferritin levels, and increase in platelet and lymphocyte counts.
https://pubmed.ncbi.nlm.nih.gov/19402938/2.5 Our major finding was that quercetin supplementation significantly reduced SBP. This effect was most pronounced in subjects aged 25–50 years. In addition, quercetin caused a significant reduction in plasma concentrations of atherogenic oxidised LDL. In contrast, there were no effects of quercetin on biomarkers of inflammation and metabolism including body composition. We used a moderate supranutritional but non-pharmacological dose of quercetin, since these data should provide a rational basis for the development of functional foodsIn contrast to placebo, quercetin decreased systolic blood pressure (SBP) by 2·6 mmHg (P < 0·01) in the entire study group, by 2·9 mmHg (P < 0·01) in the subgroup of hypertensive subjects and by 3·7 mmHg (P < 0·001) in the subgroup of younger adults aged 25–50 years. Quercetin decreased serum HDL-cholesterol concentrations (P < 0·001), while total cholesterol, TAG and the LDL:HDL-cholesterol and TAG:HDL-cholesterol ratios were unaltered. Quercetin significantly decreased plasma concentrations of atherogenic oxidised LDL, but did not affect TNF-α and C-reactive protein when compared with placebo.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6204471/2.5unlike statins (atorvastatin), the application of quercetin basic therapy in patients with stable coronary artery disease reveals a positive impact on the indicators of chronic systemic inflammation during a two-month treatment period. Quercetin reduces the levels of IL-1β and, to a lesser extent, TNF-α in blood, in addition to reducing the levels of IkBα mRNA, thereby indicating a decrease in the transcriptional activity of NF-kB. Arguably, the anti-inflammatory effects of quercetin may be due to its impact on the different levels of signal transduction. The results obtained in our study substantiate the relevance of further studies on the molecular mechanisms underlying the anti-inflammatory activities of quercetin and its widespread useTaken together, these effects confirm the anti-inflammatory activity of this polyphenol at different levels of signal transduction. IL-1β is of immense pathogenetic importance in the inflammatory activation of ET. IL-1β is related to TNF receptor-associated factor 6 (TRAF6) action on IkB kinase-α (IKKα), which destroys the relationship of the dimer NF-kB p50/p65 with IkBα, thereby leading to the translocation of the p65 subunit into the nucleus with the transcription of the genes of various inflammatory molecules, including the very same IL-1β.
https://www.jfda-online.com/cgi/viewcontent.cgi?article=3090&context=journal1Quercetin also increased the secretion of IGF-binding protein-3 in the conditioned medium of MDA-MB-231 cells while reducing the secretion of IGF1; thus, quercetin interrupted the autocrine or paracrine loop of IGF1 signaling.These findings suggest that TNBC can ac- quire stem cell-like and invasive features by IGF1R signaling-dependent EMT; thus, its resis- tance to drug treatment is increased. Here, we observed that the protein expression of Sox2, Oct4, and Nanog, the well-identified transcription fac- tors that maintain the pluripotency of CSCL cells, was dose-dependently downregulated by quer- cetin in MDA-MB-231 cells (Fig. 3C), similar to the inhibition of mesenchymal-like and invasive phe- notypes. Thus, we suggest that EMT reversion by quercetin could make MDA-MB-231 cells well- differentiatedScreenshot from 2024-02-05 15-26-46
https://ar.iiarjournals.org/content/36/12/6367#abstract-11Our present data suggest that Lu and Qu are promising and prospective candidates that function as anti-CSC and anti-metastasis agents. Together with the JNK inhibitor SP600125, they may provide a new approach for therapeutic treatment in the future. In addition, our selective Du145-III prostate cancer cell model system could serve as a useful tool to develop and establish effective therapies that target CSCs.We found that Lu and Qu lowered the expression of CSC markers CD44, ABCG2, Sox2 and Nanog and substantively attenuated cancer stem cell associated spheroid formation. Lu and Qu inhibited the JNK signaling pathway, which explains their effects on stemness, VM and metastatic potential. Previous studies have indicated that JNK kinase activity plays an important role in maintaining the stemness of glioblastoma and other cells
https://www.ijbs.com/v16p1121.htm1As shown by in-vivo study, xenograft tumors treated by docetaxel with quercetin had poorest growth. Then, to investigate the underlying mechanisms, the differences among parental cells, docetaxel-resistant subclones and quercetin treated resistant subclones were evaluated. It was found that docetaxel-resistant subclones had stronger activation of androgen receptor and PI3K/Akt pathway, more remarkable mesenchymal and stem-like cell phenotypes, and more P-gp expression than that of parental cells. Interestingly, quercetin could reverse these transformations. Our data revealed that quercetin had docetaxel-resistance reversal effect both in vitro and in vivo and provided in-depth support for clinical use of quercetin in docetaxel-resistant prostate cancer The combined therapy could considerably inhibit cell migration, invasion, colony formation and reduce cell viability. It was also associated with increased apoptosis and inhibition of PI3K/Akt signal pathway. In-vivo study showed that combined use of quercetin and docetaxel could inhibit docetaxel-resistant xenograft tumor growth to the largest extent and lead to the least Ki67 expression. These results suggested that resistant cells could become sensitive to docetaxel again after being treated by quercetin. In the CCK-8 proliferation assay (Figure 1e & f), 20 μM Quer + 5 nM Doc could achieved improved efficacy compared 20 nM Doc alone. So, it was suggested to add quercetin to the original chemotherapy regimen rather than increasing docetaxel dosage. Furthermore, combining quercetin with docetaxel might be more cost-effective and cause fewer side effects than docetaxel aloneScreenshot from 2024-02-05 15-32-56
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249127/1Accumulating evidences show that quercetin has beneficial effects on these three metabolic diseases through various mechanisms. It can improve diabetes by promoting insulin secretion, improving insulin resistance, regulating glucose homeostasis, and inhibiting inflammation, oxidative stress, and apoptosis. The therapeutic mechanisms of quercetin on hyperlipidemia also involve multiple aspects. It can inhibit the absorption of intestinal cholesterol, reduce oxidative stress, downregulate the expression of some adipogenic genes (e.g., FAS and SREBP-1c), and promote the expression of PPARα, PPARγ, and LXRα. In addition, the therapeutic effect of quercetin on NAFLD can be attributed to its ability to ameliorate liver lipid accumulation, alleviate inflammation and oxidative stress, and regulate serum metabolic disorders.Up to now, clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. The beneficial effects of quercetin on these three diseases have been observed in some human clinical trials. However, some studies have also reported inconsistent or conflicting results, especially for diabetes. The dosage and duration of treatment may be the key factors affecting the clinical effectiveness of quercetin. Therefore, definitive conclusions cannot be drawn until more clinical data are obtained. Overall, although many animal studies have reported the therapeutic effects of quercetin on the three metabolic diseases, its clinical application in humans still has a long way to go

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