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Traditional chemical immunomodulators often have toxic side effects; for example, long\u2010term use of cyclophosphamide (CTX) can lead to severe adverse consequences.\n                      <jats:italic>Stropharia rugosoannulata<\/jats:italic>\n                      , a flavorful edible mushroom native to China, exhibits antioxidant, immunomodulatory, and antibacterial activity, with its polysaccharides being the key active components responsible for its immunomodulatory effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Polysaccharides were extracted from\n                      <jats:italic>S. rugosoannulata<\/jats:italic>\n                      using a three\u2010phase method to investigate their immunomodulatory activity and hepatoprotective effects in cyclophosphamide\u2010induced mice.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments showed that these polysaccharides significantly increased body weight, spleen index, and phagocytic index, regulated the CD4+\/CD8+ ratio, and promoted secretion of tumor necrosis factor\u2010\n                      <jats:italic>\u03b1<\/jats:italic>\n                      (TNF\u2010\n                      <jats:italic>\u03b1<\/jats:italic>\n                      ), interleukin\u20101\n                      <jats:italic>\u03b2<\/jats:italic>\n                      (IL\u20101\n                      <jats:italic>\u03b2<\/jats:italic>\n                      ), interleukin\u20106 (IL\u20106), immunoglobulin A (IgA), and immunoglobulin G (IgG). The mechanism involved activation of the TLR4\/MyD88\/NF\u2010\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B signaling pathway, effectively enhancing immune function.\n                    <\/jats:p>\n                    <jats:p>\n                      Regarding hepatic protection,\n                      <jats:italic>S. rugosoannulata<\/jats:italic>\n                      polysaccharides (SRP) increased serum malondialdehyde (MDA) and decreased superoxide dismutase (SOD), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in immunosuppressed mice, reversing CTX\u2010induced liver injury. Histopathological analysis confirmed that SRP ameliorated CTX\u2010induced pathological changes, including single\u2010cell necrosis in the jejunal mucosa and insufficient hematopoietic compensation, and reduced lymphocytes in splenic white pulp.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>This study provides a theoretical basis for developing and applying SRP as an immunomodulator or hepatoprotective agent, with potential value in functional food and pharmaceutical applications. \u00a9 2025 Society of Chemical Industry.<\/jats:p>\n                  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