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A cohort of 78 male Sprague\u2013Dawley rats was used to develop models of sciatic nerve damage, with an additional 18 rats in the sham surgery group. The rats were randomly assigned to eight groups: Sham, Control, PNI\u2009+\u2009Emodin (20\u2009mg\/kg), PNI\u2009+\u2009Emodin (80\u2009mg\/kg), PNI\u2009+\u2009MCC950 (10\u2009mg\/kg), PNI\u2009+\u2009Rapamycin (2\u2009mg\/kg), PNI\u2009+\u2009Emodin (80\u2009mg\/kg)\u2009+\u20093\u2010MA (15\u2009mg\/kg), and PNI\u2009+\u2009Emodin (80\u2009mg\/kg)\u2009+\u2009NSC 228155 (5\u2009mg\/kg). Emodin was administered intragastrical daily, while the inhibitors or agonist were administered via intraperitoneal injection, as per the respective dosages and schedules. The treatment period included assessments of nerve regeneration and functional recovery, such as histological staining, immunofluorescence for cellular markers, TEM for ultrastructural changes, SFI for functional recovery, and western blot analysis for autophagy and inflammatory proteins. IF and TEM images showed that emodin enhanced axonal and myelin regeneration. Histological analysis revealed emodin reduced muscular atrophy and collagen deposition. Emodin decreased pro\u2010inflammatory macrophage markers (CD68) while increasing M2 markers (CD206), inhibited the NLRP3 inflammasome, and reduced IL\u20101\u03b2 and caspase\u20101. It activated autophagy in Schwann cells, with increased LC3\u2010II levels. Network pharmacology and molecular docking identified EGFR in the PI3K\/AKT\/mTOR pathway as a key target, with emodin inhibiting EGFR activation. This study reveals that emodin promotes early nerve recovery by enhancing functional outcomes, axonal remyelination, and reducing muscle atrophy. It boosts autophagy in Schwann cells, inhibits NLRP3 inflammasome activation, and promotes M2 macrophage polarization. These effects are closely related to the EGFR\/PI3K\/AKT\/mTOR pathway.<\/jats:p>","DOI":"10.1002\/ptr.8469","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T22:07:41Z","timestamp":1743199661000},"page":"2324-2338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Emodin Promotes Peripheral Nerve Repair by Modulating Inflammasome Activation Through Autophagy via the\n                    <scp>EGFR<\/scp>\n                    \/\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>mTOR<\/scp>\n                    Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Zhengyang","family":"Long","sequence":"first","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou 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