1 Scandoside exerts anti - inflammatory effect via 2 suppressing NF - κ B and MAPK signaling pathways in 3 LPS - induced RAW 264 . 7 macrophages 4

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the 17 specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid 18 compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect 19 was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory 20 mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA 21 significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor 22 necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide 23 synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced 24 RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear 25 transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and 26 c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to 27 COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of 28 SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear 29 transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling 30 pathways, which provided useful information for its application and development. 31