Indole derivative XCR-5a alleviates LPS-induced inflammation in vitro and in vivo

Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo.

This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms.

First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1β, IL-6, and TNF-α was determined and H&E staining was performed.

Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1β, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway.

XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases.