Fisetin

 Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells, 2017

Fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

Fisetin Suppresses the Proliferation and Metastasis of Renal Cell Carcinoma through Upregulation of MEK/ERK-Targeting CTSS and ADAM9, 2019

 Fisetin inhibits proliferation and metastasis of RCC cells by downregulating CTSS and ADAM9 through the MEK/ERK signaling pathway. These findings indicate that fisetin is a promising antitumor agent against RCC.

Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients

A growing body of evidence indicates that inflammation is associated with tumorigenesis, metastasis and chemotherapeutic resistance in patients with colorectal cancer (CRC). Natural flavonoids are promising agents for inflammation-related tumor progression in patients with CRC. This study aimed to assess the efficacy of flavonoid fisetin supplementation on the inflammatory status and matrix metalloproteinase (MMP) levels in these patients. In this double-blind, randomized placebo-controlled clinical trial, 37 CRC patients undergoing chemotherapy were assigned to receive either 100 mg fisetin (n = 18) or placebo (n = 19) for seven consecutive weeks. The supplementation began one week before chemotherapy and continued until the end of the second chemotherapy cycle. Levels of interleukin (IL)-8, IL-10, high-sensitivity C-reactive protein (hs-CRP), MMP-7, and MMP-9 were measured in plasma using ELISA, before and after the intervention. The trial was registered at http://www.irct.ir (code: IRCT2015110511288N9). The participants were 55.59 ± 15.46 years old with 62.16% being male. After the intervention, the plasma levels of IL-8 and hs-CRP reduced significantly in the fisetin group (p < 0.04 and p < 0.01, respectively). Additionally, fisetin supplementation suppressed the values of MMP-7 levels (p < 0.02). However, significant changes were observed only in IL-8 concentrations in the fisetin group when compared with the placebo group (p < 0.03). The changes in the levels of other metabolic factors were not statistically significant. According to the results, fisetin could improve the inflammatory status in CRC patients, suggesting it as a novel complementary antitumor agent for these patients and warranting further studies.

Dietary flavonoid fisetin for cancer prevention and treatment, 2016

Dietary flavonoid fisetin found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through alteration of cell cycle, inducing apoptosis, angiogenesis, invasion, and metastasis without causing any toxicity to normal cells. 

Cancer chemopreventive role of fisetin: Regulation of cell signaling pathways in different cancers, 2021

In this review, we have focused on the available evidence related to regulation of PI3K/AKT/mTOR, Wnt/β-catenin, NF-κB and TRAIL/TRAIL-R by fisetin in different cancers. Fisetin has also been shown to inhibit the metastatic spread of cancer cells in tumor-bearing mice. We have also summarized how fisetin regulated autophagy in different cancers. In addition, this review also covers fisetin-mediated regulation of VEGF/VEGFR, EGFR, necroptosis and Hippo pathway.

• Fisetin alleviates hepatic and adipocyte fibrosis and insulin resistance in diet-induced obese mice, 2020

• Fisetin protects against hepatic steatosis through regulation of the Sirt1/AMPK and fatty acid β-oxidation signaling pathway in high-fat diet-induced obese mice, 2018

• Fisetin inhibited growth and metastasis of triple-negative breast cancer by reversing epithelial-to-mesenchymal transition via PTEN/Akt/GSK3β signal pathway, 2018

Fisetin is a senotherapeutic that extends health and lifespan (full text)

Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan. The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit. These characteristics suggest the feasibility to translation to human clinical studies.

To determine if fisetin-mediated clearance of senescent cells impacts the health or lifespan of mice, WT f1 C57BL/6:FVB mice were fed a diet containing 500 ppm fisetin  (500 mg/kg) beginning at 85 wks of age, roughly equivalent to age 75 years in humans. This resulted in an extension of median as well as maximal lifespan (Fig. 5A-B). Amylase and alanine aminotransferase (ALT) were significantly lower in serum of aged WT mice fed the diet supplemented with fisetin, consistent with improved pancreatic and liver homeostasis (Fig. 5C). Brain, kidney, liver, lung, and forepaw tissue sections were stained with hematoxylin and eosin and evaluated by a veterinary pathologist. Using the Geropathology Grading Platform to score age-related lesions [63], several tissues had reduced age-related pathology in the fisetin diet group compared to the control diet (Fig. 5D). An example of this is illustrated in a representative image from renal sections in Fig. 5E. Similar to the progeroid mice, fisetin reduced the expression of senescence and SASP markers in multiple tissues of aged WT mice exposed to oral fisetin (Fig. 5F-I). Furthermore, there was a reduction in senescence and SASP factor expression in peripheral CD3+ T cells (Fig. 5J). There was also a reduction in levels of circulating MCP-1 (Fig. 5K), a SASP factor [51]. Finally, fisetin reduced oxidative stress in the liver of old WT mice (Fig. 5L-M).

Reviews:

• I have seasonal allergy's, I was using 2-3 bottles of sinus spray a month for years, not good at all. I read about fiestin helping with this issue. I ordered a bottle, when it arrived I took one 100mg capsule and 20 minutes later I had no more allergy's I could breath again without nose spray. It has been 4 months I still have no allergy's and have not needed nose spray to breath since my first dose. I do not know about the longevity claim but it has eliminated any and all allergy issues for me.

•  I felt a marked decrease in arthritic pain.

• I have been taking Fisetin supplement for a couple of months and have noticed a vast improvement in my age-related brain fog.

• After taking this supplement, I feel more energetic.

• I'm a Type 1 diabetic, 40+ years. After taking Fisetin for a couple days, I noticed my insulin does were more effective, so I didn't have to take as much as before. It's been over a month since I've started, and the necessary amount of insulin I need has reduced about 10-20%.

•  Brain fog gone. I'm on my third bottle.as I can say is wow,night and day difference.

•  My memory appears to be improving, and I seem to be more alert, even when I haven't had a sufficient amount of sleep. However, I've only been taking the product for about a month, and it's going to take more time before I can make a final assessment. One very positive thing that I can report is the fact that I've had absolutely no side effects.

•  I have had a brutal sleep disorder for over a year - waking up every night after about 2 hours of sleep with inability to return to sleep. My mind was turning into a shambles, and my ability to focus and remember things was laughable. I'd pretty much made peace with this, but then I stumbled across Fisetin, and I can't believe the impact it had. I won't go so far as to say everybody will be wowed, but for me personally the impact was life changing and just about straightened me back out, at least a huge difference versus where I'd ended up at. Now to keep this real, I take quite a few supplements and experiment with all kinds of different stuff, especially with this sleep problem. From neurotropic hacks to Ashgwanda root, and berberine and everything else under the sun. And frankly, while I waste a good fistful of dollars every month, I can't tell that any of them really do anything. So I stepped into this one with a bit of skepticism, but the impact was almost instant, and seems to last.

• I've also experienced a gradual increase in mental clarity and overall sense of well-being with no apparent side effects. 

• It has helped me focus more on my work and it has helped me as an antioxidant (I can tell the difference when I don't take it) I take it early in the morning.

• My energy levels are greatly improved.

• Blue Rice: I started taking 100mg of Fisetin maybe 6 months ago. I added it to my routine of resveratrol, NAD and a few others. Thought nothing of it. Expected nothing out of it. I mean 100mg orally is clinically insignificant.

I have genital herpes and nothing has ever really cut down the outbreaks. I get them regularly - along with pretty bad nerve pain all down my legs, feet, butt etc. That's life.

After taking Fisetin I had zero outbreaks. For 6 months. This had never happened for the last 12+ years, in addition I had some occasions when it SHOULD have happened (stress, damage to skin etc).. I wrote earlier about this as a one-off.. Isn't that odd kind of thing.

This last month I ran out of Fisetin and didn't re-order in a hurry. I was off it for 11 days. All I can say is I experienced a total immune system collapse. I got a herpes outbreak on my lip (something almost never happens - twice in 12 years) had a constant outbreak on genitals that lasted for 9 of those 11 days, my shoulder injury started hurting again (it stopped after fisetin) and just 4 days ago I got an earache.. Rare.

Again, could all be non-related.. But it's weird.

Fisetin came in mail. I took 500mg two days in row, and back to 100mg - after two days the shoulder stopped hurting, the herpes outbreak just flat out stopped - as in just stopped out of nowhere, and earache stopped as well. Normally I would be on antibiotics.

Nothing changed that I'm aware of during this time, same diet, no stress. Only variable was the tiny amount of Fisetin.