Out With The Old…

Fisetin is a flavonoid (specifically, a flavonol), but it’s a little different than most. While it has the usual antioxidant, anti-inflammatory, and anti-cancer properties you might reasonably expect from flavonoids, it has an extra anti-aging trick up its sleeve that most don’t.

❝Fisetin is a flavonol that shares distinct antioxidant properties with a plethora of other plant polyphenols. Additionally, it exhibits a specific biological activity of considerable interest as regards the protection of functional macromolecules against stress which results in the sustenance of normal cells cytoprotection. Moreover, it shows potential as an anti-inflammatory, chemopreventive, chemotherapeutic and recently also senotherapeutic agent❞

~ Dr. Grynkiewicz & Dr. Demchuk

Let’s briefly do some due diligence on its expected properties, and then we’ll take a look at its bonus anti-aging effects.

The flavonol that does-it-ol

Because of the similar mechanisms involved, there are three things that often come together, which are:

• Antioxidant
• Anti-inflammatory
• Anticancer

This list often gets expanded to also include:

• Anti-aging

…although that is usually the last thing to get tested out of that list.

In today’s case, let’s kick it off with…

❝Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a dietary flavonoid found in various fruits (strawberries, apples, mangoes, persimmons, kiwis, and grapes), vegetables (tomatoes, onions, and cucumbers), nuts, and wine that has shown strong anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic, anti-diabetic, neuroprotective, and cardioprotective effects❞

~ Dr. Harish Pal et al.

Read more: Fisetin and Its Role in Chronic Diseases

Understanding its anticancer mechanisms

The way that fisetin fights cancer is basically “all the ways”, and this will be important when we get to its special abilities shortly:

❝Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion),prevent cell cycle progression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage, and modulate the expressions of Bcl‐2 family proteins in different cancer cell lines (HT‐29, U266, MDA‐MB‐231, BT549, and PC‐3M‐luc‐6), respectively. Further, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF‐κB activation, and down‐regulates the level of the oncoprotein securin. Fisetin also inhibited cell division and proliferation and invasion as well as lowered the TET1 expression levels. ❞

~ Dr. Muhammad Imran et al.

Read more: Fisetin: An anticancer perspective

There’s also more about it than we even have room to quote, here:

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

Now For What’s New And Exciting: Senolysis

All that selectivity that fisetin exhibits when it comes to “this cell gets to live, and this one doesn’t” actions?

It makes a difference when it comes to aging, too. Because aging and cancer happen by quite similar mechanisms; they’re both DNA-copying errors that get copied forward, to our detriment.

• In the case of cancer, it’s a cell line that accidentally became immortal and so we end up with too many of them multiplying in one place (a tumor)
• In the case of aging, it’s the cellular equivalent of “a photocopy of a photocopy of a photocopy” gradually losing information as it goes

In both cases…

The cell must die if we want to live

Critically, and which quality differentiates it from a lot of other flavonoids, fisetin has the ability to selectively kill senescent cells.

To labor the photocopying metaphor, this means there’s an office worker whose job it is to say “this photocopy is barely legible, I’m going to toss this, and then copy directly from the clearest copy we have instead”, thus keeping the documents (your DNA) in pristine condition.

In fisetin’s case, this was first tested in mouse (in vivo) studies, and in human tissue (in vitro) studies, before moving to human clinical studies:

❝Of the 10 flavonoids tested, fisetin was the most potent senolytic.

The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit.❞

~ Dr. Matthew Yousefzadeh et al.

Read in full: Fisetin is a senotherapeutic that extends health and lifespan

There’s lots more science that’s been done to it since that first groundbreaking study though; here’s a more recent example:

Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection

Want some?

We don’t sell it, but here for your convenience is an example product on Amazon

Enjoy!

Let’s Get Fruity

Bromelain is an enzyme* found in pineapple (and only in pineapple), that has many very healthful properties, some of them unique to bromelain.

*actually a combination of enzymes, but most often referred to collectively in the singular. But when you do see it referred to as “they”, that’s what that means.

What does it do?

It does a lot of things, for starters:

❝Various in vivo and in vitro studies have shown that they are anti-edematous, anti-inflammatory, anti-cancerous, anti-thrombotic, fibrinolytic, and facilitate the death of apoptotic cells. The pharmacological properties of bromelain are, in part, related to its arachidonate cascade modulation, inhibition of platelet aggregation, such as interference with malignant cell growth; anti-inflammatory action; fibrinolytic activity; skin debridement properties, and reduction of the severe effects of SARS-Cov-2❞

~ Dr. Carolina Varilla et al.

Some quick notes:

• “facilitate the death of apoptotic cells” may sound alarming, but it’s actually good; those cells need to be killed quickly; see for example: Fisetin: The Anti-Aging Assassin
• If you’re wondering what arachidonate cascade modulation means, that’s the modulation of the cascade reaction of arachidonic acid, which plays a part in providing energy for body functions, and has a role in cell structure formation, and is the precursor of assorted inflammatory mediators and cell-signalling chemicals.
• Its skin debridement properties (getting rid of dead skin) are most clearly seen when using bromelain topically (one can literally just make a pineapple poultice), but do occur from ingestion also (because of what it can do from the inside).
• As for being anti-thrombotic and fibrinolytic, let’s touch on that before we get to the main item, its anti-inflammatory properties.

If you want to read more of the above before moving on, though, here’s the full text:

Bromelain, a Group of Pineapple Proteolytic Complex Enzymes (Ananas comosus) and Their Possible Therapeutic and Clinical Effects. A Summary

Anti-thrombotic and fibrinolytic

While it does have anti-thrombotic effects, largely by its fibrinolytic action (i.e., it dissolves the fibrin mesh holding clots together), it can have a paradoxically beneficial effect on wound healing, too:

Stem Bromelain Proteolytic Machinery: Study of the Effects of its Components on Fibrin (ogen) and Blood Coagulation

For more specifically on its wound-healing benefits:

In Vitro Effect of Bromelain on the Regenerative Properties of Mesenchymal Stem Cells

Anti-inflammatory

Bromelain is perhaps most well-known for its anti-inflammatory powers, which are so diverse that it can be a challenge to pin them all down, as it has many mechanisms of action, and there’s a large heterogeneity of studies because it’s often studied in the context of specific diseases. But, for example:

❝Bromelain reduced IL-1β, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process❞

~ Dr. Taline Alves Nobre et al.

Read in full:

Bromelain as a natural anti-inflammatory drug: a systematic review

Or if you want a more specific example, here’s how it stacks up against arthritis:

❝The results demonstrated the chondroprotective effects of bromelain on cartilage degradation and the downregulation of inflammatory cytokine (tumor necrosis factor (TNF)-α, IL-1β, IL-6, IL-8) expression in TNF-α–induced synovial fibroblasts by suppressing NF-κB and MAPK signaling❞

~ Dr. Perephan Pothacharoen et al.

Read in full:

Bromelain Extract Exerts Antiarthritic Effects via Chondroprotection and the Suppression of TNF-α–Induced NF-κB and MAPK Signaling

More?

Yes more! You’ll remember from the first paper we quoted today, that it has a long laundry list of benefits. However, there’s only so much we can cover in one edition, so that’s it for today

Is it safe?

It is generally recognized as safe. However, its blood-thinning effect means it should be avoided if you’re already on blood-thinners, have some sort of bleeding disorder, or are about to have a surgery.

Additionally, if you have a pineapple allergy, this one may not be for you.

Aside from that, anything can have drug interactions, so do check with your doctor/pharmacist to be sure (with the pharmacist usually being the more knowledgeable of the two, when it comes to drug interactions).

Want to try some?

You can just eat pineapples, but if you don’t enjoy that and/or wouldn’t want it every day, bromelain is available in supplement form too.

We don’t sell it, but here for your convenience is an example product on Amazon

Enjoy!