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Morroniside (Mor), an iridoid glycoside compound in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Cornus officinalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    , is one of the effective active components. The effects of Mor on antioxidant stress, antiapoptosis, and nerve repair function have been widely studied, but the mechanism of Mor in AD treatment remains unclear. To study the neuroprotective effects of Mor and elucidate the molecular mechanisms underlying its improvement of AD symptoms, we used\n                    <jats:italic>ApoE4<\/jats:italic>\n                    transgenic mice and\n                    <jats:italic>ApoE4<\/jats:italic>\n                    \u2010transfected BV2 cells as models of AD, focusing on microglia phenotype, function, and neuroinflammation. The 10\u2010month\u2010old mice were randomly divided into the\n                    <jats:italic>ApoE3<\/jats:italic>\n                    control group (\n                    <jats:italic>ApoE3<\/jats:italic>\n                    \u2009+\u2009Veh), the\n                    <jats:italic>ApoE4<\/jats:italic>\n                    model group (\n                    <jats:italic>ApoE4<\/jats:italic>\n                    \u2009+\u2009Veh), and the\n                    <jats:italic>ApoE4<\/jats:italic>\n                    \u2009+\u2009Mor 10, 20, and 40\u2009mg\/kg groups as in\u00a0vivo models. The in\u00a0vitro BV2\u2010\n                    <jats:italic>ApoE<\/jats:italic>\n                    model was constructed via lentiviral transfection. The effects of Mor on cognitive function of AD models were assessed through behavioral tests, western blot, immunofluorescence staining, and ELISA to measure changes of related pathological and inflammatory factors. Mor improved the cognitive function of\n                    <jats:italic>ApoE4<\/jats:italic>\n                    transgenic mice by reducing A\u03b2 plaques in the brain, improving the structural lesions of hippocampal neurons, and increasing synaptic plasticity in the brain of AD mice. In addition, Mor promoted the transformation of microglia from the M1 to the M2 phenotype, inhibited the activation of the CX3CR1\/PU.1 signaling axis, and alleviated the dysfunction of microglia both in\u00a0vitro and in\u00a0vivo. CX3CR1 siRNA and PU.1 siRNA were used further to verify the regulatory effect of Mor on microglia phenotype. Our findings indicate that Mor can inhibit neuroinflammation, reduce A\u03b2 accumulation, and improve synaptic damage in\n                    <jats:italic>ApoE4<\/jats:italic>\n                    mice via the CX3CL1\/CX3CR1\/PU.1 pathway regulating the phenotype and function of microglia. This study provides a new therapeutic candidate for the prevention and treatment of AD.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70177","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:35:51Z","timestamp":1767861351000},"page":"783-799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Morroniside Modulates Microglia Polarization via the CX3CL1\/CX3CR1\/PU.1 Axis in\n                    <i>ApoE4<\/i>\n                    Transgenic Mice"],"prefix":"10.1002","volume":"40","author":[{"given":"Ying\u2010Yan","family":"Chang","sequence":"first","affiliation":[{"name":"School of Pharmacy Henan University  Kaifeng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu\u2010Hui","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Henan University  Kaifeng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Henan University  Kaifeng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Henan University  Kaifeng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Tong","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Henan University  Kaifeng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue\u2010Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Henan University  Kaifeng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy Henan University  Kaifeng 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