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Inhibition of nuclear factor-kappaB activation by 2',8''-biapigenin
Eun-Rhan Woo1, Yuba Raj Pokharel, Jin Won Yang
1College of Pharmacy, Chosun University, Gwangju, South Korea.
Abstract:
Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) play a key role in the inflammatory processes. Improper overproduction of NO and prostaglandins by both enzymes are also believed to be involved in the pathogenesis of certain human cancers. Crude extracts of Selaginella tamariscina are used as an oriental medicine, which has been reported to inhibit the production of proinflammatory cytokines and cause cell cycle arrest. We isolated 2',8''-biapigenin from S. tamariscina and investigated whether it modulates iNOS and COX-2 expressions in Raw264.7 macrophages stimulated with lipopolysaccharide (LPS). We found that 2',8''-biapigenin blocked the transactivations of iNOS and COX-2 genes via the inactivation of nuclear factor-kappaB by preventing the nuclear translocation of p65. Hence, it may be possible to develop S. tamariscina extracts or 2',8''-biapigenin as a useful agent for cancer chemoprevention or for the treatment of inflammatory diseases.
Insights
2
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are key enzymes in inflammation and cancer pathogenesis.
- Overproduction of nitric oxide (NO) and prostaglandins by iNOS and COX-2 contributes to human cancer development.
- Selaginella tamariscina extracts are traditionally used in oriental medicine and show anti-inflammatory and anti-cancer properties.
Purpose of the Study:
- To investigate the effects of 2',8''-biapigenin, isolated from S. tamariscina, on iNOS and COX-2 expression.
- To determine the molecular mechanisms by which 2',8''-biapigenin modulates inflammatory gene expression.
- To explore the potential of S. tamariscina and its compounds in cancer chemoprevention and inflammatory disease treatment.
Main Methods:
- Isolation of 2',8''-biapigenin from Selaginella tamariscina.
- Stimulation of Raw264.7 macrophages with lipopolysaccharide (LPS).
- Assessment of iNOS and COX-2 gene expression and nuclear factor-kappaB (NF-κB) pathway activation.
Main Results:
- 2',8''-biapigenin significantly inhibited the gene transactivation of iNOS and COX-2.
- The compound effectively blocked the nuclear translocation of the p65 subunit of NF-κB.
- This inactivation of NF-κB by 2',8''-biapigenin suppressed LPS-induced inflammatory responses.
Conclusions:
- 2',8''-biapigenin from S. tamariscina effectively inhibits iNOS and COX-2 expression by blocking NF-κB activation.
- This compound demonstrates potential as a therapeutic agent for inflammatory diseases.
- S. tamariscina extracts and 2',8''-biapigenin may serve as valuable agents for cancer chemoprevention.
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