Abstract: Objective To investigate the regulatory effects of Jinmaitong on glycolysis and histone lactylation in high glucose-induced rat Schwann cell line RSC96, and its impact on macrophage polarization. Methods A high-glucose metabolic stress model was established using RSC96 cells, followed by treatment with different concentrations of Jinmaitong. Cell proliferation, lactate levels, and the expression of glycolytic enzymes (PKM2, LDHA) and histone lactylation marker H3K18la were assessed to evaluate metabolic and epigenetic changes. In addition, conditioned media from high-glucose-treated RSC96 cells were applied to RAW264.7 macrophages to examine changes in polarization-related phenotypic markers. Results High-glucose stimulation enhanced glycolytic activity and lactate accumulation in RSC96 cells, accompanied by upregulation of H3K18la modification, indicating a state of metabolic stress. Jinmaitong treatment led to a dose-dependent reduction in glycolytic enzyme expression and lactate levels, and significantly suppressed H3K18la expression. Conditioned media from high-glucose-treated Schwann cells promoted M1 polarization of RAW264.7 cells, whereas Jinmaitong intervention reversed this trend, promoting M2 polarization and alleviating the pro-inflammatory microenvironment. Conclusions High-glucose conditions induce glycolytic reprogramming and histone lactylation in Schwann cells, which may contribute to macrophage polarization and neural injury.

Key words: glycolytic reprogramming, histone lactylation, macrophage polarization, Jinmaitong (JMT), diabetic peripheral neuropathy