The anti-inflammatory agent curcumin degrades rapidly, leading to speculations that curcumin’s reported effects stem from its degradation products. Curcumin can degrade via hydrolysis, and more recently it was discovered that curcumin can degrade via oxidation at physiological pH. Additionally, bicyclopentadione is the major degradation product from this oxidation reaction. Evidence from the literature suggests that curcumin degrades primarily through oxidation. However, the biology of the oxidation products is not well characterized, and there is debate on whether oxidation intermediates or curcumin itself is more biologically active. To further elucidate the biology of the oxidation products, their effects on inflammation were examined. RAW264.7 murine macrophage cells were stimulated with E. coli lipopolysaccharide (LPS) and treated with curcumin, curcumin’s total oxidative degradation products, and bicyclopentadione. Curcumin strongly decreased LPS-induced nitric oxide production and iNOS expression in a dose dependent manner; total degradation products slightly decreased nitric oxide production and iNOS expression, while bicyclopentadione failed to decrease either. Additionally, curcumin was significantly more effective than either bicyclopentadione or total degradation products in inhibiting COX-2 expression. iNOS and COX-2 arise from the activation of the NF-kB pathway, which curcumin is known to modulate; thus, the oxidation products’ effect on key proteins in this pathway was also examined. Neither total degradation products nor bicyclopentadione inhibited translocation of NF-kB into the nucleus, prevented degradation of IκBα, nor inhibited phosphorylation of IKK as effectively as curcumin. In conclusion, curcumin is significantly more effective at inhibiting inflammation than the oxidation degradation products.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:masters_theses_2-1382 |
| Date | 13 July 2016 |
| Creators | Zhu, Julia |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Masters Theses |
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