TNF/NF-κB Signaling Pathway is Involved in Mechanisms of Tongluo Decoction on Rat Models with Sequelae of Pelvic Inflammatory Disease

Purpose: Traditional Chinese medicine can produce strong therapeutic activities for sequelae of pelvic inflammatory disease (SPID). This study aimed to investigate the efficacy and protective mechanisms of Tongluo Decoction (TLD) in the treatment of SPID.

Patients and methods: The damage-protective and inflammation-inhibitory effects of TLD on SPID were investigated in rat models. The possible targets of TLD against SPID were predicted using network pharmacology. The hub targets were tested in SPID rat models. Rescue experiments were conducted in human endometrial epithelial cells (HEECs). Detection of Necroptosis was used the flow cytometry. ELISA was used for the quantification of inflammatory cytokines. Protein levels were detected using a Western blot assay.

Results: TLD had a protective effect against uterus tissue damage caused during SPID. TLD inhibited the levels of adhesion cytokines (VEGF and TGF-β1), the tight junction proteins (ZO-1 and occludin), and inflammatory cytokines (TNF-α and IL-6). TNF, IKBKB, and NFKB1 were predicted as hub targets for TLD against SPID. TLD inhibited Necroptosis of HEECs via TNF, IKBKB, and NFKB1. TLD inhibited the ratio of CD86+ M1 macrophages after differentiation induction of THP-1.

Conclusion: The therapeutic effects of TLD for SPID may be the result of a dual action on inflammation and Necroptosis, via TNF, IKBKB, and NFKB1.

formula; herb; inflammation; necroptosis; uterus.