Abstract
Oxidative stress and Th2-type immune responses play pivotal roles in asthma pathogenesis. Falcarindiol (FAD), a natural polyacetylene compound, exhibits promising anti-inflammatory and antioxidant properties, yet its therapeutic mechanism and efficacy in asthma treatment remain to be explored. An ovalbumin (OVA)-induced murine asthma model and IL-13-stimulated human bronchial epithelial cells (BEAS-2B) were employed to investigate FAD’s therapeutic mechanisms. Airway inflammation, oxidative stress markers, and Nrf2 pathway activation were comprehensively evaluated through hematoxylin and eosin (H&E) staining, ELISA, flow cytometry, and Western blotting. To establish mechanistic causality, the Nrf2 inhibitor ML385 and targeted shRNA knockdown approaches were used to validate the essential role of Nrf2 activation in mediating FAD’s protective effects. In OVA-induced asthmatic mice, FAD (100 or 200 mg/kg) produced dose-dependent therapeutic benefits, significantly reducing inflammatory scores, decreasing airway wall and smooth muscle thickness, substantially lowering serum IgE levels, and diminishing eosinophil infiltration in bronchoalveolar lavage fluid (BALF). Additionally, FAD effectively ameliorated oxidative stress, while simultaneously suppressing pro-inflammatory cytokine release. In IL-13-stimulated BEAS-2B cells, FAD dose-dependently protected against apoptosis and restored proliferation capacity while robustly activating the Nrf2/HO-1/NQO1 pathway. Mechanistic validation studies revealed that both ML385-mediated Nrf2 inhibition and Nrf2 shRNA knockdown largely abrogated FAD’s protective effects. FAD exerts anti-asthmatic effects through Nrf2 pathway activation, effectively mitigating airway inflammation, oxidative stress, and epithelial injury, establishing it as a promising therapeutic candidate for asthma.
Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Abbreviations
- ANOVA:
-
Analysis of variance
- ARE:
-
Antioxidant response element
- BALF:
-
Bronchoalveolar lavage fluid
- BCA:
-
Bicinchoninic acid
- BSA:
-
Bovine serum albumin
- CAT:
-
Catalase
- CCK:
-
8-cell counting Kit-8
- DAPI:
-
4′,6-diamidino-2-phenylindole
- DEX:
-
Dexamethasone
- ECL:
-
Enhanced chemiluminescence
- EdU:
-
5-ethynyl-2′-deoxyuridine
- ELISA:
-
Enzyme-linked immunosorbent assay
- FAD:
-
Falcarindiol
- FBS:
-
Fetal bovine serum
- FITC:
-
Fluorescein isothiocyanate
- GSH:
-
Px-Glutathione peroxidase
- H&E:
-
Hematoxylin and eosin
- HO:
-
1-Heme oxygenase-1
- HRP:
-
Horseradish peroxidase
- HSD:
-
Honest significant difference
- IgE:
-
Immunoglobulin E
- IL:
-
Interleukin
- Keap1:
-
Kelch-like ECH-associated protein 1
- MDA:
-
Malondialdehyde
- NQO1:
-
NAD(P)H quinone dehydrogenase 1
- Nrf2/NRF2:
-
Nuclear factor erythroid 2-related factor 2
- OVA:
-
Ovalbumin
- Pbm:
-
Perimeter of basement membrane
- PBS:
-
Phosphate-buffered saline
- PI:
-
Propidium iodide
- PVDF:
-
Polyvinylidene fluoride
- RIPA:
-
Radioimmunoprecipitation assay
- SD:
-
Standard deviation
- SDS:
-
PAGE-Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- shRNA:
-
Short hairpin RNA
- SOD:
-
Superoxide dismutase
- TCM:
-
Traditional Chinese medicine
- TdT:
-
Terminal deoxynucleotidyl transferase
- TNF:
-
α-tumor necrosis factor alpha
- TUNEL:
-
Terminal deoxynucleotidyl transferase dUTP nick end labeling
- Wall/Pbm:
-
Airway wall thickness to perimeter ratio
- Wasm/Pbm:
-
Airway smooth muscle thickness to perimeter ratio
- WHO:
-
World Health Organization
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XH Jiang, SX Lai and HF Wu contributed to literature review, study design, manuscript writing and critical reversion, and preparation of Figs. 1–7. Z Lin, and FH Lai were in charge of data extraction, analysis and interpretation. All authors read and agreed to this eventual version for publication.
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This study was reviewed and approved by the Ethics Committee of Longyan First Hospital. Each experiment was performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals. The study was carried out in compliance with the ARRIVE guidelines (https://arriveguidelines.org).
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Jiang, X., Lai, S., Lin, Z. et al. Falcarindiol alleviates airway inflammation and oxidative stress in asthma through Nrf2 pathway activation. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37962-5
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DOI: https://doi.org/10.1038/s41598-026-37962-5
