Solidagenone from Solidago chilensis Meyen Protects against Acute Peritonitis and Lipopolysaccharide-Induced Shock by Regulating NF-κB Signaling Pathway

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 17; no. 3; p. 273
• Main Authors: Santos, Ivanilson Pimenta, Silva, Laís Peres, Silva, Dahara Keyse Carvalho, Dos Reis, Bruna Padilha Zurita Claro, de Oliveira, Temistocles Barroso, Kelly, Andressa Maia, Dos Santos Rodrigues, Edivaldo, de Souza, Claudia Valeria Campos, Oliveira-Costa, José Fernando, Valverde, Simone Sacramento, Santos-Filho, Osvaldo Andrade, Soares, Milena Botelho Pereira, Meira, Cássio Santana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.02.2024; MDPI
• Subjects: Antidepressants; Drug dosages; endotoxic shock; Gene expression; Herbal medicine; Inflammation; Investigations; Kinases; Leukocytes; Neutrophils; NF-κB; Nitric oxide; Peritonitis; Physiology; solidagenone; Thrombocytopenia; Toxicity; Transcription factors; solidagenone; NF-κB; endotoxic shock; inflammation
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17030273

Anti-inflammatory agents are widely used for the treatment of inflammatory diseases. Nevertheless, the associated side effects of the available drugs make it necessary to search for new anti-inflammatory drugs. Here, we investigated the anti-inflammatory activity of solidagenone. Initially, we observed that a single dose of 30, 60, or 90 mg/kg of solidagenone did not result in mortality or elicit any discernible signs of toxicity in mice. At the same doses, solidagenone promoted a significant reduction in the migration of neutrophils in an acute peritonitis model and decreased mortality in a lipopolysaccharide-induced endotoxic shock model. Interestingly, treatment with solidagenone conferred a protective effect against leukopenia and thrombocytopenia, hematological disorders commonly observed in sepsis conditions. In addition, treatment with all the doses of solidagenone promoted a significant reduction in nitric oxide, TNF-α, and IL-1β levels relative to the LPS-stimulated vehicle-treated cultures. Furthermore, gene expression and in silico analyses also supported the modulation of the NF- B pathway by solidagenone. Finally, in silico pharmacokinetics predictions indicated a favorable drugability profile for solidagenone. Taken together, the findings of the present investigation show that solidagenone exhibits significant anti-inflammatory properties in acute experimental models, potentially through the modulation of the NF-κB signaling pathway.