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

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 (p < 0.05). The expression of inflammatory cytokines (IL-1β/IL-6/IFN-γ/IL-4/IL-5/IL-4Rα) and key signaling molecules (JAK1/JAK2/JAK3/STAT3/p-STAT3) were significantly upregulated, while bitter taste receptor (T2R) 108/129/137 and downstream α-gustducin and TRPM5 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 (ΔG = -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.