Protective effects of nordalbergin against LPS-induced endotoxemia through inhibiting MAPK/NF-κB signaling pathway, NLRP3 inflammasome activation, and ROS production

• Published in: Inflammation research 2024-10, Vol.73 (10), p.1657-1670
• Main Authors: Chen, Pin-Rong, Li, Chia-Yang, Yazal, Taha, Chen, I-Chen, Liu, Po-Len, Chen, Yi-Ting, Liu, Ching-Chih, Lo, Jung, Lin, Tzu-Chieh, Chang, Ching-Tang, Wu, Hsin-En, Chen, Yuan-Ru, Cheng, Wei-Chung, Chiu, Chien-Chih, Chen, Chi-Shuo, Wang, Shu-Chi
• Format: Article
• Language: English
• Subjects: Activation analysis; Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biological effects; Biomedical and Life Sciences; Biomedicine; Caspase-1; Cell activation; Cell Line; Coumarin; Coumarins - pharmacology; Coumarins - therapeutic use; Cyclooxygenase-2; Cytokines; Cytokines - metabolism; Damage; Dermatology; Endotoxemia; Endotoxemia - chemically induced; Endotoxemia - drug therapy; IL-1β; Immunology; Inflammasomes; Inflammasomes - drug effects; Inflammasomes - metabolism; Inflammation; Innate immunity; Lipopolysaccharides; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; MAP kinase; MAP Kinase Signaling System - drug effects; Metastases; Mice; Mice, Inbred C57BL; Neurology; NF-kappa B - metabolism; NF-κB protein; Nigericin; Nitric Oxide - metabolism; Nitric-oxide synthase; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Original Research Paper; Oxidants; Oxidizing agents; Pharmacology/Toxicology; Phosphorylation; Prostaglandin E2; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rheumatology; Sepsis; Signal transduction; Signal Transduction - drug effects; Tumor necrosis factor-TNF
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-024-01922-4

Objective Nordalbergin is a coumarin extracted from Dalbergia sissoo DC. To date, the biological effects of nordalbergin have not been well investigated. To investigate the anti-inflammatory responses and the anti-oxidant abilities of nordalbergin using lipopolysaccharide (LPS)-activated macrophages and LPS-induced sepsis mouse model. Materials and methods Production of nitrite oxide (NO), prostaglandin E2 (PGE 2 ), pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β), reactive oxygen species (ROS), tissue damage and serum inflammatory markers, and the activation of the NLRP3 inflammasome were examined. Results Our results indicated that nordalbergin reduced the production of NO and pro-inflammatory cytokines in vitro and ex vivo. Nordalbergin also suppressed iNOS and cyclooxygenase-2 expressions, decreased NF-κB activity, and attenuated MAPKs signaling pathway activation by decreasing JNK and p38 phosphorylation by LPS-activated J774A.1 macrophages. Notably, nordalbergin diminished NLRP3 inflammasome activation via repressing the maturation of IL-1β and caspase-1 and suppressing ROS production by LPS/ATP- and LPS/nigericin-activated J774A.1 macrophages. Furthermore, nordalbergin exhibited protective effects against the infiltration of inflammatory cells and also inhibited the levels of organ damage markers (AST, ALT, BUN) by LPS-challenged mice. Conclusion Nordalbergin possesses anti-inflammatory effects in macrophage-mediated innate immune responses, alleviates ROS production, decreases NLRP3 activation, and exhibits protective effects against LPS-induced tissue damage in mice.