Anti-Inflammatory Activities of Isogosferol, a Furanocoumarin Isolated from Citrus junos Seed Shells through Bioactivity-Guided Fractionation

Citrus junos Tanaka is a traditional medicine for treating coughs, dyspepsia, diabetes, asthma, neuralgia, and inflammatory disorders, and is distributed in Asia, especially in Korea, Japan, and China. This study aimed to use bioactivity-guided fractionation to find therapeutic phytochemicals from C. junos seeds, which can attenuate inflammatory responses. Nine coumarins (1–9) were isolated from the methanolic extract of C. junos seed shells and the inhibitory effects against inflammatory mediators were investigated using murine macrophages. Among the coumarins, compound 3, isogosferol (ISO), more potently attenuated the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. ISO also inhibited the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Additionally, the phosphorylation of extracellular-regulated kinases (pERK)1/2 was reduced by ISO. We confirmed that ISO attenuated the release of interleukin-1 beta (IL-1β), which is a central mediator of the inflammatory response. These results demonstrate that ISO from C. junos seed shells may be a potent therapeutic candidate for the treatment of inflammatory diseases.

• Publication year

  2019

• Venue

  Molecules

• Publication date

  2019-11-01

• Fields of study

  Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.3390/molecules24224088PMID 31726781PMCID 6891542
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2017cited by this paper
• GYF-17, a chloride substituted 2-(2-phenethyl)-chromone, suppresses LPS-induced inflammatory mediator production in RAW264.7 cells by inhibiting STAT1/3 and ERK1/2 signaling pathways.

  2016influential reference
• Chemical Composition of Clausena lansium (Lour.) Skeels Leaves and Antifungal Activity

  2016cited by this paper
• The Chemistry and Pharmacology of Citrus Limonoids

  2016cited by this paper
• 13C-NMR Data from Coumarins from Moraceae Family

  2015cited by this paper
• Lycojaponicuminol A-F: cytotoxic serratene triterpenoids from Lycopodium japonicum.

  2014cited by this paper
• Capillarisin inhibits iNOS, COX-2 expression, and proinflammatory cytokines in LPS-induced RAW 264.7 macrophages via the suppression of ERK, JNK, and NF-κB activation

  2013cited by this paper
• 국내 시판 경옥고 제품의 품질 특성 및 항염증 활성

  2013cited by this paper
• Antioxidant Capacity of Selected Plant Extracts and Their Essential Oils

  2013cited by this paper
• Antioxidant and Anti-inflammatory Effect of Extracts from Flammulina velutipes (Curtis) Singer

  2012cited by this paper
• Anti-inflammatory activity of bark of Dioscorea batatas DECNE through the inhibition of iNOS and COX-2 expressions in RAW264.7 cells via NF-κB and ERK1/2 inactivation.

  2010influential reference
• Oxidative stress, inflammation, and cancer: how are they linked?

  2010cited by this paper
• Osthol and isopimpinellin from Fructus cnidii for the control of Dactylogyrus intermedius in Carassius auratus.

  2008cited by this paper
• Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-kappaB in RAW 264.7 macrophages.

  2008cited by this paper
• Inhibitory effect of 2'-hydroxycinnamaldehyde on nitric oxide production through inhibition of NF-kappa B activation in RAW 264.7 cells.

  2005cited by this paper
• MAP kinase pathways

  2005cited by this paper
• Preparative isolation and purification of coumarins from Cnidium monnieri (L.) Cusson by high-speed counter-current chromatography.

  2004cited by this paper
• Diabetes, oxidative stress, and antioxidants: A review

  2003cited by this paper
• Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.

  2003cited by this paper
• Effect of flavone derivatives on interleukin-1beta (IL-1beta) mRNA expression and IL-1beta protein synthesis in stimulated RAW 264.7 macrophages.

  2003cited by this paper
• HPLC-NMR/HPLC-MS analysis of the bark extract of Stauranthus perforatus.

  2003cited by this paper
• Nitric oxide modulates pro- and anti-inflammatory cytokines in lipopolysaccharide-activated macrophages.

  2003cited by this paper
• Effect of Flavone Derivatives on Interleukin‐1β (IL‐1β) mRNA Expression and IL‐1β Protein Synthesis in Stimulated RAW 264.7 Macrophages

  2003cited by this paper
• NF-κB: arresting a major culprit in cancer

  2002cited by this paper
• NF-kappa B: arresting a major culprit in cancer.

  2002cited by this paper
• Signal transduction pathways of IL-1β-mediated iNOS in pulmonary vascular smooth muscle cells

  2001cited by this paper
• Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase‐2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages

  2001cited by this paper
• Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia.

  2001cited by this paper
• Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer.

  2001cited by this paper
• Signal transduction pathways of IL-1beta-mediated iNOS in pulmonary vascular smooth muscle cells.

  2001cited by this paper
• Antiproliferative constituents from umbelliferae plants. V. A new furanocoumarin and falcarindiol furanocoumarin ethers from the root of Angelica japonica.

  1999cited by this paper
• Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships.

  1999cited by this paper
• Stimulation of inducible nitric oxide synthase in rat liver by hyaluronan fragments

  1998cited by this paper
• Prostaglandin H synthases, nonsteroidal antiinflammatory drugs, and colon cancer

  1997cited by this paper
• Biologic basis for interleukin-1 in disease.

  1996cited by this paper
• Nitric oxide as a secretory product of mammalian cells

  1992cited by this paper
• The inducible transcription activator NF-kappa B: regulation by distinct protein subunits.

  1991cited by this paper
• The inducible transcription activator NF-κB: regulation by distinct protein subunits

  1991cited by this paper
• Constituents of Yuzu (Citrus junos) Oil

  1970cited by this paper
• Antioxidant Determinations by the Use of a Stable Free Radical

  1958cited by this paper

• Linear furanocoumarins: Bridging natural wisdom and synthetic ingenuity in drug discovery

  2025cites this paper
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  2025cites this paper
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  2024cites this paper
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  2023cites this paper
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  2022cites this paper
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  2022cites this paper
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