A New Class of Hybrid Anti-inflammatory Agents of Silibinin A Modified Using Gamma Irradiation.

Abstract

Silibinin is the major active constituent of the medicinal plant milk thistle seeds and possesses hepatoprotective functions. In this study, silibinin A was irradiated with gamma rays to produce 2 novel flavonolignans, silibinosins A (2) and B (3). The structures of these compounds were determined using spectroscopy and spectrometry. The anti-inflammatory effects of the flavonolignan derivatives were assessed using lipopolysaccharide (LPS)-stimulated RAW264.7 and DH82 macrophages. Silibinosin A (2) effectively suppressed the LPS-induced overproduction of pro-inflammatory mediators and cytokines in murine RAW264.7 cells. Western blot analysis revealed that compound 2 decreased the LPS-induced expression of inducible nitric oxide synthase, cyclooxygenase, and phosphorylated nuclear factor-κB and inhibitor-κBα compared to the original silibinin. Furthermore, the inhibitory effects on nitric oxide and prostaglandin E₂ production were observed in LPS-stimulated DH82 canine macrophages. Our results suggest that the newly generated flavonolignans can be novel anti-inflammatory agents for use as therapeutics or ingredients in functional foods.