摘要Ulcerative colitis(UC)is a chronic and non-specific inflammatory bowel disease(IBD).Huanglian Ganjiang decoction(HGD),derived from ancient book Beiji Qianjin Yao Fang,has demonstrated efficacy in treating UC patients traditionally.Previous research established that the compatibility of cold herb Coptidis Rhizoma+Phellodendri Chinensis Cortex(CP)and hot herb Angelicae Sinensis Radix+Zingiberis Rhizoma(AZ)in HGD synergistically improved colitis mice.This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice.The experimental colitis model was estab-lished by administering 3％dextran sulphate sodium(DSS)to mice for 7 days,followed by CP,AZ and CPAZ treatment for an additional 7 days.M1/M2 macrophage polarization levels,gluc-ose metabolites levels and pyruvate dehydrogenase kinase 4(PDK4)expression were ana-lyzed using flow cytometry,Western blot,immunofluorescence and targeted glucose meta-bolomics.The findings indicated that CP inhibited M1 macrophage polarization,decreased in-flammatory metabolites associated with tricarboxylic acid(TCA)cycle,and suppressed PDK4 expression and pyruvate dehydrogenase(PDH)(Ser-293)phosphorylation level.AZ en-hanced M2 macrophage polarization,increased lactate axis metabolite lactate levels,and up-regulated PDK4 expression and PDH(Ser-293)phosphorylation level.TCA cycle blocker AG-221 and adeno-associated virus(AAV)-PDK4 partially negated CP's inhibition of M1 macro-phage polarization.Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate(DCA)partially reduced AZ's activation of M2 macrophage polarization.In conclusion,the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macro-phage polarization balance via PDK4-mediated glucose metabolism reprogramming.Specific-ally,CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition,while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.