Tier 3 — preclinical

Fisetin Suppresses the Inflammatory Response and Oxidative Stress in Bronchial Epithelial Cells

Wu SJ, Huang WC, Cheng CY, Wang MC, Cheng SC, Liou CJ
Nutrients 2022 Volume 14, issue 9, article 1841

Bibliography

PubMed
PMID 35565807
PubMed Central
PMC9103812
DOI
10.3390/nu14091841
Funding
Chang Gung Memorial Hospital (CMRPF1H0043, CMRPF1K0082, CMRPF1L0011, CMRPF1K0032) and the Ministry of Science and Technology in Taiwan (109-2320-B-255-002-MY3, 109-2320-B-255-005-MY3, 109-2320-B-255-008-MY3).
Competing interests
The authors declare no conflict of interest.

Study snapshot

DesignIn vitro cell culture study using TNF-alpha- and TNF-alpha/IL-4-stimulated BEAS-2B human bronchial epithelial cells and THP-1 monocyte adhesion assays, plus an in vivo ovalbumin-sensitized BALB/c mouse model of allergic asthma.
ModelHuman bronchial epithelial cell line BEAS-2B and human monocyte cell line THP-1; ovalbumin-sensitized female BALB/c mice (32 mice, 4 groups of 8).
SampleCell experiments performed in triplicate with 8-12 wells per condition for ELISA; 8 mice per group (normal, OVA, Fis 5 mg/kg, Fis 10 mg/kg).
InterventionBEAS-2B cells pretreated with fisetin 0-30 micromolar for 1 hour before TNF-alpha or TNF-alpha/IL-4 stimulation; OVA-sensitized mice treated intraperitoneally with fisetin 5 mg/kg or 10 mg/kg before each OVA challenge.
DurationCell stimulation 24 hours; mouse sensitization/challenge protocol over 28 days with sacrifice on day 29.
EndpointsIL-6, IL-8, CCL5, MCP-1, CCL11 and CCL24 secretion and gene expression (ELISA, RT-PCR); ICAM-1 and MUC5AC expression and THP-1 monocyte adhesion; NF-kB and MAPK (p38, JNK, ERK1/2) pathway activation; Intracellular ROS levels and HO-1/Nrf2 expression; Airway hyperresponsiveness (Penh) to methacholine; Bronchoalveolar lavage fluid eosinophil and cell counts; Lung COX-2, GSH and MDA levels

What the study showed, in plain terms

This Taiwanese group asked whether fisetin can calm the airway lining cells that go into overdrive during an asthma attack, using human bronchial epithelial cells stimulated with the inflammatory signal TNF-alpha, and a mouse model of allergic asthma.

In the cell dish, fisetin dose-dependently reduced the release of several inflammatory chemicals (IL-6, IL-8, CCL5, MCP-1) and the eosinophil-attracting signals CCL11 and CCL24, and it cut down the sticky surface protein ICAM-1 that lets immune cells attach to the airway lining.

In OVA-sensitized asthmatic mice, fisetin injections reduced airway twitchiness on methacholine challenge, lowered the number of eosinophils flooding the lungs, and improved markers of oxidative stress (more glutathione, less malondialdehyde) alongside reduced COX-2.

The mechanistic thread ties back to NF-kB and the MAPK cascade (p38, JNK, ERK), plus activation of the antioxidant Nrf2/HO-1 pathway - the same signalling nodes seen across other fisetin anti-inflammatory papers in this Data Center.

The caveat: fisetin here was given by injection at defined mouse doses, not orally as a supplement, so this is mechanistic support for an anti-inflammatory, antioxidant role in airway disease rather than direct evidence for an oral asthma treatment in people.

Key findings

  • Fisetin reduced TNF-alpha-induced IL-6, IL-8, CCL5 and MCP-1 secretion in bronchial epithelial cells
  • Fisetin suppressed ICAM-1 expression and THP-1 monocyte adhesion to activated epithelial cells
  • Fisetin blocked NF-kB nuclear translocation and MAPK (p38/JNK/ERK) phosphorylation
  • Fisetin reduced eotaxin (CCL11/CCL24) secretion in IL-4/TNF-alpha-stimulated cells
  • In asthmatic mice, fisetin lowered airway hyperresponsiveness and eosinophil counts in BALF
  • Fisetin increased lung glutathione and reduced malondialdehyde and COX-2 in asthmatic mice

What this study can and cannot tell us

All experiments used a single immortalized bronchial epithelial cell line and one mouse strain/allergen model; findings have not been replicated in primary human airway cells or confirmed in human asthma patients.

Fisetin was administered by intraperitoneal injection in the mouse model, so the results do not establish efficacy or an effective dose for oral supplementation in humans.

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