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This study investigated the therapeutic effects of leflunomide, a STAT1 inhibitor on dystrophic muscles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Design<\/jats:title>\n                    <jats:p>\n                      The characterization of M1 macrophage polarization and the level of STAT1\/\n                      <jats:italic>p<\/jats:italic>\n                      \u2010STAT1 were measured in DMD patients. Lipopolysaccharide (LPS)\/IFN\u2010\u03b3 and RO8191 were selected to stimulate STAT1 for evaluating the inhibitory effect of A771726 on M1 polarization and STAT1. Conditionally cocultured M1 RAW264.7 cells and differentiated C2C12 myoblasts were used to explore the differentiation of A771726 to myopathy in inflammatory environments. After 4\u2010week treatment with leflunomide, the protein levels of STAT1 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2010STAT1 were evaluated in mdx mice. CD86 and CD68 were selected for evaluating inflammation event. The proinflammatory cytokines were measured by RT\u2010PCR and ELISA. Muscle function and myofibre damage were examined by behavioural experiments and serum CK and LDH level, respectively. The muscle regeneration event was demonstrated by myosin heavy chain, myogenic differentiation (MyOD) protein levels and eMyHC immunofluorescence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      STAT1 was remarkably upregulated in mdx mice and DMD patients compared with control groups. A771726 restrained LPS\/IFN\u2010\u03b3\u2010induced M1 macrophage polarization via inhibiting\n                      <jats:italic>p<\/jats:italic>\n                      \u2010STAT1 and STAT1. Specific activation of STAT1 by RO8191 promoted macrophage polarize towards M1 type, which was partially counteracted by A771726. Leflunomide\u2010inhibited inflammation infiltration mediated by M1 macrophage and exerted promising therapeutic effect on muscle repair in mdx mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      Leflunomide relieved M1 macrophage infiltration and improved muscle regeneration by downregulating STAT1 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2010STAT1. STAT1 may merge as a promising target for the therapy of DMD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70518","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T03:46:24Z","timestamp":1782531984000},"page":"5496-5515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leflunomide\u2010inhibited STAT1 activity ameliorates intramuscular M1 macrophage infiltration and promotes muscle regeneration in Duchenne muscular dystrophy"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9821-7191","authenticated-orcid":false,"given":"Wanting","family":"Hu","sequence":"first","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 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