Tier 4 — mechanistic

Fisetin: A Dietary Antioxidant for Health Promotion

Khan N, Syed DN, Ahmad N, Mukhtar H
Antioxidants & Redox Signaling 2013 Volume 19, issue 2, pages 151-162

Bibliography

PubMed
PMID 23121441
PubMed Central
PMC3689181
DOI
10.1089/ars.2012.4901
Funding
United States National Institutes of Health, National Cancer Institute grants R01CA120451 (to H. Mukhtar) and R03CA153961 (to N. Khan).
Competing interests
No competing interests were declared in the manuscript. The review is authored by the University of Wisconsin dermatology laboratory whose own work forms much of the anticancer evidence discussed.

Study snapshot

DesignNarrative review of fisetin's dietary sources, antioxidant chemistry, anticancer mechanisms (lung, colon, prostate, pancreatic cancer, melanoma), neuroprotective effects, and pharmacokinetics/bioavailability.
ModelSynthesis of in vitro cancer cell line studies, rodent xenograft and disease models (including stroke and Huntington's disease models), and rodent pharmacokinetic studies; no original human data.
SampleNarrative review synthesising dozens of published in vitro and animal studies; no human data.
InterventionVaries by reviewed study; representative rodent pharmacokinetic data cited an intraperitoneal dose of 223 mg/kg.
DurationNot applicable — narrative review of the literature to date of publication (2013).
EndpointsDietary fisetin content across fruits and vegetables; Antioxidant/free-radical scavenging mechanism; Anticarcinogenic activity across cancer types (lung, colon, prostate, pancreatic, melanoma); Neuroprotective and cognitive effects; Oral bioavailability and pharmacokinetics

What the study showed, in plain terms

This is a broad scientific review, not a new experiment. It was written by the same University of Wisconsin dermatology laboratory responsible for several of the mechanistic prostate-cancer and lung-cancer fisetin papers in this Data Center, pulling together what was known about fisetin's antioxidant chemistry, cancer biology, and nervous-system effects as of 2013.

The review documents where fisetin is found in the diet (strawberries have by far the highest concentration, at roughly 160 micrograms per gram, followed by much smaller amounts in apple, persimmon, grape, onion and cucumber), and explains its basic antioxidant chemistry — the way its multiple hydroxyl groups let it neutralise free radicals directly and also activate the body's own antioxidant defence systems.

Most of the review summarises anticancer laboratory and animal evidence across several cancer types, and separately covers early evidence of neuroprotective effects, including improved memory in animal models and protection in stroke and Huntington's disease models. A pharmacokinetics section notes fisetin's core practical problem: after an oral or injected dose, most of it is rapidly broken down (sulfated and glucuronidated) by the body, leaving genuinely low levels of the active, unmodified compound in the bloodstream.

As a review, it does not add new experimental evidence beyond what its cited primary papers show; treat it as a helpful map of the field circa 2013 and cross-reference the primary studies it summarises (several of which are separately catalogued in this Data Center) rather than citing it for any specific numeric claim.

Key findings

  • Fisetin is present at markedly higher concentrations in strawberries (about 160 µg/g) than in other dietary sources such as apple (26.9 µg/g), persimmon (10.6 µg/g), grape, onion, or cucumber.
  • Fisetin's antioxidant activity stems from multiple hydroxyl groups on its flavone structure, enabling both direct free-radical scavenging and activation of endogenous antioxidant response pathways.
  • The review summarises evidence that fisetin inhibits proliferation and induces apoptosis across multiple cancer types in vitro and in rodent models, including lung, colon, prostate and pancreatic cancer and melanoma, largely via modulation of PI3K/Akt/mTOR and related signalling pathways.
  • Neuroprotective evidence reviewed includes fisetin's ability to enhance memory and long-term potentiation in animal models, and to reduce injury in rodent stroke and Huntington's disease models.
  • Pharmacokinetic data cited in the review show fisetin has low oral bioavailability, with extensive first-pass sulfation and glucuronidation; peak plasma concentration after a 223 mg/kg intraperitoneal dose in mice was reached within about 15 minutes and was rapidly cleared.

What this study can and cannot tell us

This is a narrative (non-systematic) review, not a primary study; it carries no new data of its own; and it summarises no human clinical trial evidence — every anticancer and neuroprotective finding it discusses comes from in vitro or animal work.

The review is authored by the same laboratory group responsible for a substantial share of the primary fisetin-cancer literature it discusses, so its framing and emphasis should be read as an expert case for the field's promise rather than an independent, systematic appraisal.

Being published in 2013, it predates more than a decade of subsequent fisetin research (including the senolytic literature and later human pharmacokinetic and clinical trial work) and should not be treated as the current state of evidence on its own.

Related papers in the corpus

Tier 4
Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management
Adhami VM et al. · Biochemical Pharmacology · 2012
Tier 4
Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells
Mukhtar E et al. · Cancer Letters · 2015
Tier 4
Anti-cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies
Sun X et al. · International Journal of Molecular Medicine · 2018

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology