Poriferast-5-en-3β-ol improves pelvic inflammatory disease via reducing GADD45A-induced inflammation

Pelvic inflammatory disease (PID), often triggered by pathogens like Chlamydia, is a major cause of female infertility. This study investigated molecular mechanisms in PID and the therapeutic potential of DanZhiYin (DZY) and its components.

Bioinformatic analysis of dataset GSE110106 identified differentially expressed genes in PID, validated clinically. A Chlamydia infection model in OE-E6/E7 cells was used. siRNA knockdown and overexpression revealed GADD45A's role. Anti-inflammatory effects of DZY, Salvia miltiorrhiza, and Poriferast-5-en-3β-ol were tested via quantitative reverse transcription polymerase Chain Reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Molecular dynamics and rescue experiments clarified the mechanism, and a PID mouse model assessed efficacy.

MAPK signaling was upregulated in PID. GADD45A was identified as a key diagnostic marker, with an area under the curve (AUC) of 0.747. Chlamydia infection increased GADD45A and cytokines; its silencing reduced inflammation, while overexpression exacerbated it. DZY, Salvia miltiorrhiza, and Poriferast-5-en-3β-ol inhibited inflammation dose-dependently. Poriferast-5-en-3β-ol directly binds to GADD45A, thereby suppressing the production of IL-1β and TNF-α by inhibiting p38 MAPK and its phosphorylated form (p-p38). In vivo, all treatments reduced bacterial load and inflammation, with DZY being most effective.

GADD45A is a central inflammatory regulator in PID. DZY and Poriferast-5-en-3β-ol attenuate inflammation by targeting GADD45A, providing new mechanistic and therapeutic insights for PID.