Artesunate Alleviates Apical Periodontitis Macrophage Glycolysis Via Jak2/Stat3 Pathway

Macrophage (Mφ) glycolysis has emerged as a critical regulator of apical periodontitis (AP) progression. Based on this glycolytic mechanism, our study investigates the therapeutic potential and underlying mechanisms of artesunate (ART) in modulating AP outcomes. The current study was approved by our Medical University Stomatological Hospital. Clinical specimens were used to determine the involvement of hexokinase (HXK-I/II) mediated Mφ glycolysis in periapical tissues. Next, network pharmacology, molecular docking, western blot analysis, and extracellular acidification rate (ECAR) were employed to investigate ART’s regulatory effects on HXK-I/II mediated Mφ glycolysis. Then, JAK agonist and chromatin immunoprecipitation were applied to elucidate transcriptional regulation mechanism of ART on HXK-I/II. To gain a better understanding of ART in Mφ glycolysis linked AP, ART-treated rat (200-220g males) AP models were established. Both clinical and experimental evidence demonstrated that HXK-I/II mediated Mφ glycolysis significantly contributes to AP pathogenesis. ART effectively alleviated AP progression through suppression of Mφ glycolysis, evidenced by reduced ECAR levels, downregulated HXK-I/II expression, and modulated inflammatory cytokine profiles (decreased IL-1β and increased IL-10). Mechanistically, ART inhibited HXK-I/II transcriptional activation via JAK2/STAT3 signaling pathway modulation. This study identifies ART as a promising therapeutic agent for AP through its novel anti-glycolysis mediated by JAK2/STAT3 pathway inhibition. These findings provide a scientific basis for developing ART-based adjunctive therapies to mitigate inflammatory tissue destruction in AP.