Isochlorogenic Acid A Attenuated Periodontitis by Inhibiting Inflammation via ACE/PGK1/STAT1 Signaling

The purpose of the present study was to evaluate the effect of isochlorogenic acid A (IAA) on periodontitis and explore its potential mechanism. A ligature/LPS procedure was employed to induce periodontitis in rats. LPS-induced HPDLF was used as the in vitro model. Bioinformatic analyses indicated that angiotensin-converting enzyme (ACE) might be the target of IAA in periodontitis. PGK1/STAT1 might be the related molecules of ACE. Treatment with IAA inhibited inflammatory cytokines, inflammatory molecule transcriptions in gingival tissues and HPDLFs. MicroCT, H&E, TRAP and Runx2 staining showed that IAA relieved periodontitis. Immunofluorescence observation and WB revealed that IAA inhibited ACE/PGK1/STAT1 in dental papilla, parodontium, gingival tissues and HPDLFs. IAA suppressed glycolysis, mitochondrial fission, oxidative stress and promoted oxidative phosphorylation, mitochondrial fusion. The application of the ACE-overexpression plasmid, PGK1 SiRNA, the ACE inhibitor captopril, the PGK1 inhibitor NG52 suggested that ACE and PGK1 were involved in IAA-mediated anti-inflammatory response. Molecular docking, molecular dynamics, DARTS and CETSA indicated that IAA might combine with ACE. It was also found that MYC governed ACE transcription. The Y195 residue of PGK1 was conservative and critical for the combination between PGK1 and ACE. ACE and PGK1 were also upregulated in gingival tissues of periodontitis patients. In conclusion, IAA ameliorated periodontitis by inhibiting inflammation via ACE/PGK1/STAT1 signaling.