1. Indole derivative XCR-5a alleviates LPS-induced inflammation in vitro and in vivo .
- Author
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Zhao J, Roy P, Tang H, Ma X, Di Q, Quan J, Guan Y, Li X, Xiao W, and Chen W
- Subjects
- Animals, Anti-Inflammatory Agents therapeutic use, Cytokines metabolism, Indoles pharmacology, Mice, NF-kappa B metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type II metabolism, Inflammation chemically induced, Inflammation drug therapy, Inflammation metabolism, Lipopolysaccharides toxicity
- Abstract
Context: 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 ., Objective: This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms., Materials and Methods: 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., Results: 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., Conclusions: 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.
- Published
- 2022
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