Abstract:

[Abstract] Objective  To evaluate the inhibitory effects of a novel tertiary alkaloids small molecule fromSolanum cathayanum , SCE-1，on interleukin (IL-6)，IL-1β and tumor necrosis factor (TNF)-αin vitro . Methods  The inflammation modelin vitro was established by lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage. The cytotoxicity of SCE-1 was determined by the mitochondrial-respiration-dependent3-(4,5-dimethylthiazol -2-yl) -2,5-diphenyltetrazolium (MTT) reduction method. The antagonism activity on proinflammatory cytokine such as IL-6, IL-1β and TNF-α in cell culture medium were determined by enzyme-linked immunosorbent assay (ELISA) method. The inhibitory effect on proinflammatory cytokine of compounds SCE-1 was evaluated. Results  Compared with the control group，(1) the SCE-1(12.5~800 mg/L) showed a significant inhibitory effect in dose- and time-dependent manner on the production of IL-6 (P < 0.01) with an IC50 of 11.82 mg/L; (2) the SCE-1 (200~800 mg/L) decreased the production of TNF-α (P < 0.05 or P < 0.01), and the inhibition rate was 53.13% at a concentration of 800 mg/L and for 2-h treatment; (3) the SCE-1 (400~800 mg/L) significantly increased the production of IL-1β (P < 0.01). Conclusion  The discovery of this com pound provided a potential lead compound for the development of small molecule IL-6 inhibitor with high efficiency and low toxicity.

Key words: IL-6, small antagonists, SCE-1