α-Ecdysone suppresses inflammatory responses via the Nrf2 pathway in lipopolysaccharide-stimulated RAW 264.7 cells
Abstract
The search for new biologically active compounds is a topic of current research because of their ubiquitous availability and low toxicity. Plants of the Silene genus contain secondary metabolites known as phytoecdysteroids that reportedly have various biological activities. α-Ecdysone is a phytoecdysteroid with biological activity that has not been thoroughly investigated to date. Therefore, we investigated the immunomodulatory and anti-inflammatory effects of α-ecdysone on LPS-treated RAW264.7macrophage cells and in a zebrafish model. To explore these activities, RAW264.7 cells were pretreated with α-ecdysone (0.1-10 μM) for 24 h and then with LPS to induce inflammation. We assayed membrane fluidity, lysosomal enzyme activity, and superoxide generation to determine the immunomodulatory activity. Using ELISA, we examined the levels of the pro-inflammatory cytokines prostaglandin (PGE 2) and interleukin-1β (IL-1β), as well as the protein expression of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α) and heme‑oxygenase-1 (HO-1) by immunoblotting. We also investigated the subcellular localization of the nuclear transcription factor (NF-κB) subunits and expression of the mitogen-activated protein kinase (MAPK) pathway. We found that α-ecdysone is a potent immunostimulator that enhances membrane fluidity and lysosomal enzyme activity and generates superoxide anions. Simultaneously, α-ecdysone inhibited nitric oxide levels and suppressed the levels of pro-inflammatory mediators and cytokines. Furthermore, α-ecdysone increased HO-1 and nuclear factor erythroid 2-related factor (Nrf2) production, mitigated NF-κB subunit proteins in the nucleus and decreased MAPKs and Akt activation. These results suggest that α-ecdysone is a good immunostimulator with anti-inflammatory effects that occur via inhibition of pro-inflammatory mediators and cytokines through stimulation of HO-1 and Nrf-2 production.
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α-Ecdysone showed potent immunostimulatory effects by enhancing membrane fluidity and lysosomal enzyme activity, inhibited NO, suppressed pro-inflammatory mediators and cytokines, increased HO-1 and Nrf-2, mitigated NF-κB activity, and reduced MAPK and Akt activation.
“The compound showed potent immunostimulatory effects by enhancing membrane fluidity and lysosomal enzyme activity. α-Ecdysone simultaneously inhibited the levels of NO and suppressed the levels of pro-inflammatory mediators and cytokines. An intriguing mechanism of the action involved increased heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) production and mit”
From The Phytochemical, Biological, and Medicinal Attributes of Phytoecdysteroids: An Updated Review (2021) · cites this paper as [155]
α-Ecdysone acts as an immunomodulator and anti-inflammasome.
“α-Ecdysone acts as an immunomodulator and anti-inflammasome [159].”
From Phytoecdysteroids: Distribution, Structural Diversity, Biosynthesis, Activity, and Crosstalk with Phytohormones (2022) · cites this paper as [159]
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- Authors
- Bhardwaj, M., Mamadalieva, N. Z., Chauhan, A. K., & Kang, S. C.
- Affiliations
- Daegu Gyeongbuk Institute of Science and Technology (KR)
- Yunusov Institute of the Chemistry of Plant Substances (UZ)
- Konkuk University (KR)
- Daegu University (KR)
- Corresponding author
- Kang, Sun Chul
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 73
- Pages
- 405-413
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W2946945322
- Cited by
- 18
- References
- 24
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 3 · 2014: 1
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Keywords
- alpha-ecdysone, phytoecdysteroids, anti-inflammatory activity, Nrf2 signaling, heme oxygenase-1, lipopolysaccharide, macrophages, RAW 264.7 macrophages, NF-κB, MAPK signaling, Akt signaling, inflammatory cytokines, prostaglandin E2, IL-1β, nitric oxide, immunomodulation, zebrafish model, membrane fluidity, lysosomal enzyme activity, superoxide production
- MeSH terms
- RAW 264.7 Cells, Animals, Anti-Inflammatory Agents, Ecdysone, Larva, Lipopolysaccharides, Membrane Proteins, Spine, Zebrafish, Signal Transduction, NF-kappa B, Mitogen-Activated Protein Kinases, NF-E2-Related Factor 2, Mice, Heme Oxygenase-1
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