Aloifol I Derived from Dendrobium senile Attenuates Sickness Behaviors in Mice via Regulating Peripheral and Central Immune Responses

Abstract

Sickness behaviors are a natural response to inflammation and pathogenic shocks. However, current treatments have limitations, highlighting the need for novel anti-inflammatory agents. Aloifol I, which is a dihydrostilbenoid, was investigated as a potential candidate. Its anti-inflammatory properties were first evaluated in vitro using lipopolysaccharide (LPS)-induced RAW 264.7 macrophage and BV-2 microglial cells, followed by proteomic analysis to elucidate underlying mechanisms. In vivo efficacy was then evaluated in a mouse model of LPS-induced sickness behaviors at 12.5, 25, and 50 mg/kg doses. Central nervous system (CNS) safety was evaluated at 50 mg/kg by assessing the general behavior and motor coordination of mice. Results demonstrated that aloifol I significantly suppressed the LPS-induced IL-6 and TNF-α release in both macrophage and microglia. Proteomic analysis revealed that aloifol I downregulated proteins involved in translation, glycolysis, and cytoskeletal organization while upregulating proteins related to mitochondrial function, stress response, and inflammation resolution, suggesting its multifaceted anti-inflammatory mechanism. In vivo, aloifol I attenuated LPS-induced fever from 38.3 °C to the basal temperature of 36 °C, confirming its antipyretic effect. It also improved LPS-induced locomotor impairments in a dose-dependent manner, reflecting its ability to alleviate inflammation-associated behavioral impairments. Additionally, aloifol I significantly reduced LPS-induced pro-inflammatory cytokine levels of IL-6 and TNF-α in both plasma and brain tissues, suggesting peripheral and central anti-inflammatory effects. Importantly, no adverse effects on motor coordination or general behaviors were observed, supporting a favorable CNS safety profile. These findings collectively highlight the promising therapeutic potential of aloifol I as a potential anti-inflammatory agent for the treatment of inflammation-related sickness conditions.