Calenduloside E inhibits lipopolysaccharide-induced inflammatory response by inhibiting activation of ROS-mediated JAK1-stat3 signaling pathway in RAW264.7 cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of calenduloside E on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and explore the underlying molecular mechanism.@*METHODS@#CCK-8 assay was used to examine the effect of different concentrations of calenduloside E (0-30 μg/mL) on the viability of RAW264.7 cells. The release of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in RAW264.7 cells in response to pretreatment with 6, 8, and 10 μg/mL calenduloside E for 2 h followed by stimulation with 100 ng/mL LPS was detected using enzyme-linked immunosorbent assay (ELISA). The expression levels of iNOS and COX-2 and the activation of JAK-stats, MAPKs and NF-кB signaling pathways in the treated cells were determined using Western blotting. A reactive oxygen species (ROS) detection kit was used to detect ROS production in the cells, and the nuclear translocation of the transcription factor stat3 was observed by laser confocal microscopy.@*RESULTS@#Calenduloside E below 20 μg/mL did not significantly affect the viability of RAW264.7 cells. Calenduloside E dose-dependently decreased the expression levels of iNOS and COX-2 induced by LPS, inhibited LPS-induced release of TNF-α and IL-1β, and suppressed LPS-induced JAK1-stat3 signaling pathway activation and stat3 nuclear translocation. Calenduloside E also significantly reduced ROS production induced by LPS in RAW264.7 cells.@*CONCLUSIONS@#Calenduloside E inhibits LPS-induced inflammatory response by blocking ROS-mediated activation of JAK1-stat3 signaling pathway in RAW264.7 cells.

Structural modification and anti-inflammatory biological evaluation of monomeric compounds from Aralia elata / 中草药

Objective: Based on structural modification of monomeric compound calenduloside E from Aralia elata, to evaluate anti-inflammatory activity of the analogues. Methods: Applying oleanolic acid as starting material, the target compounds were prepared by seven steps reactions and evaluated for anti-inflammatory effects by RAW264. 7 cells in vitro. Results: Ten analogues G1-G5 and H1-H5 were synthesized. The structures of the target compounds were identified by spectrum. Pharmacological results showed that all of the compounds had different levels potency of anti-inflammatory effects in cells. In particular, compounds G1-G4 and H1-H3 showed significant anti-inflammatory activity comparing wiht lead compounds. Conclusion: The new compounds G1-G5 and H1-H5 which showed potential of anti-inflammatory biological activity, had not been reported in any literatures and deserved further research.