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Genkwanin Inhibits Proinflammatory Mediators Mainly through the Regulation of miR-101/MKP-1/MAPK Pathway in LPS-Activated Macrophages
Open accessAbstract
Genkwanin is one of the major non-glycosylated flavonoids in many herbs with anti-inflammatory activities. Although its anti-inflammatory activity in vivo has been reported, the potential molecular mechanisms remain obscure. In this study, by pharmacological and genetic approaches, we explore the anti-inflammatory effects of genkwanin in LPS-activated RAW264.7 macrophages. Genkwanin potently decreases the proinflammatory mediators, such as iNOS, TNF-α, IL-1β and IL-6, at the transcriptional and translational levels without cytotoxicity, indicating the excellent anti-inflammatory potency of genkwanin in vitro. Mechanism study shows that genkwanin significantly suppresses the p38- and JNK-mediated AP-1 signaling pathway and increases the mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression at the posttranscriptional level. We also confirmed that microRNA-101 (miR-101) is a negative regulator of MKP-1 expression. Moreover, regardless of miR-101-deficient cells or miR-101-abundant cells, the suppression effects of genkwanin on supernatant proinflammatory mediators' levels are far less than that in respective negative control cells, suggesting that genkwanin exerts anti-inflammatory effect mainly through reducing miR-101 production. However, genkwanin can't affect the level of phospho-Akt (p-Akt), indicating that the phosphorylation of Akt may be not responsible for the effect of genkwanin on miR-101 production. We conclude that genkwanin exerts its anti-inflammatory effect mainly through the regulation of the miR-101/MKP-1/MAPK pathway.
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“The absolute level of IL6 we detected fell in the middle range of reported levels (50 pg/mL to 200 ng/mL) in inflammatory contexts and above reported ranges post-exercise and diet-induced obesity (30-100 pg/mL) (Chowdhury et al.; Gao et al., 2014; Greenhill et al., 2011; Masuda et al., 2013; Osuchowski et al., 2006; Remick et al., 2005; Vida et al.; Wang et al., 2017; Yan et al., 2015).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Gao et al., 2014
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“Kaempferol-3-O-rhamnoside ( 1 ) is commonly reported as inactive [45], and although genkwanin ( 6 ), siegeskaurolic acid ( 7 ), and lupeol ( 11 ) have shown anti-inflammatory effects in some macrophage assays [46–48], they were weak under our experimental conditions.”
Metadata
- Authors
- Gao, Y., Liu, F., Fang, L., Cai, R., Zong, C., & Qi, Y.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Qi, Yun
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-05-06
- Volume
- 9
- Issue
- 5
- Pages
- e96741
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4011752
- OpenAlex
- W2035643839
- Cited by
- 110
- References
- 61
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 15 · 2023: 15 · 2022: 14 · 2021: 16 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 5 · 2015: 4
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (81173645, 2014ZX09201022-006, 81274163, 2012ZX09301002-001)
- Ministry of Science and Technology of the People's Republic of China (81274163, 2012ZX09301-002, 2014ZX09201022-006, 2012ZX09301-002-001)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Bioactive natural compounds
- Keywords
- genkwanin, anti-inflammatory activity, macrophages, lipopolysaccharide stimulation, miR-101, MKP-1, MAPK signaling, AP-1 signaling, p38 MAPK, JNK, inflammatory cytokines, inducible nitric oxide synthase, post-transcriptional regulation, Akt
- MeSH terms
- Animals, Anti-Inflammatory Agents, Cell Line, Lipopolysaccharides, Macrophages, Nitric Oxide, Phosphorylation, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Up-Regulation, Oligonucleotides, Antisense, Inflammation Mediators, Mitogen-Activated Protein Kinases, MicroRNAs, Flavones, Mice, Nitric Oxide Synthase Type II, Interleukin-1beta, Dual Specificity Phosphatase 1
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