In the present study, we demonstrate that: 1) mice with PF develop cardiac dysfunction and myocardial fibrosis; 2) wogonin attenuates both lung fibrosis and cardiac fibrosis, effectively mitigating the progression of cardiac dysfunction; 3) the Sirt1/γ-H2AX pathway is critically involved in DNA damage and cardiomyocyte apoptosis, key contributors to cardiac fibrosis and dysfunction; 4) wogonin directly interacts with Sirt1, reducing DNA damage and apoptosis. Here, H2AX is linked to pemphigus foliaceus.