OVA Inhalation and Baicalin Intervention: Unraveling Their Impact on Hepatic Function and the Involvement of Bitter Taste Signaling

Particulate matter (PM) inhalation induces systemic toxicity including liver injury. Here, aerosolized ovalbumin (OVA) was employed to establish a mouse model mimicking PM-induced injury. OVA exposure notably affected hepatic cord architecture, inflammation, and alanine and aspartate aminotransferase activities. Hepatic hydrogen peroxide and malondialdehyde contents significantly increased by 1.74- and 1.37-fold, with markedly reduced superoxide dismutase activity and glutathione content (<i>p</i> < 0.05). The expression of inflammatory cytokines (IL-1β/IL-6/<i>IFN</i>-γ/<i>IL</i>-<i>4</i>/<i>IL</i>-<i>5</i>/<i>IL</i>-<i>4R</i>α) and key signaling molecules (<i>JAK1</i>/<i>JAK2</i>/<i>JAK3</i>/<i>STAT3</i>/p-STAT3) were significantly upregulated, while bitter taste receptor (T2R) 108/129/137 and downstream α-<i>gustducin</i> and <i>TRPM5</i> were significantly downregulated. Conversely, baicalin alleviated the inflammatory effects of OVA-induced liver inflammation and injury, while restoring the expression of bitter signaling genes T2R108/T2R129/α-gustducin/TRPM5. Molecular docking/dynamics confirmed a stable binding between baicalin and T2R108 (Δ<i>G</i> = -7.58 kcal/mol). These findings provide the first evidence that reactivation of the bitter taste signaling pathway facilitates hepatic recovery from PM-induced injury, highlighting this pathway as a novel therapeutic target for PM-associated liver damage.