{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:29:41Z","timestamp":1791847781547,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874404"],"award-info":[{"award-number":["81874404"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274294"],"award-info":[{"award-number":["82274294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK\u2010242 and JSH23 were administered to RSC96 and GMI\u2010R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA sequencing showed that TLR4\/NF\u2010\u03baB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, IL\u20108, and TGF\u2010\u03b2 protein levels and IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, TGF\u2010\u03b2, TLR4, and IBA\u20101 mRNA levels; and decreased IL\u201010 and INF\u2010\u03b3 protein levels and IL\u20104 mRNA levels. Immunohistochemistry showed that IBA\u20101, CD32, IL\u20101\u03b2, iNOS, nNOS, COX2, and TLR4 expression was increased while S100\u03b2 and Arg\u20101 decreased. CCI increased TLR4, IBA\u20101, IL\u20101\u03b2, iNOS, Myd88, p\u2010NF\u2010\u03baB, and p\u2010p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl\u20102 and Bcl\u2010xl protein and mRNA levels and increasing Bax and Bad mRNA and IL\u20101\u03b2, TLR4, Myd88, p\u2010NF\u2010\u03baB, and p\u2010p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL\u20101\u03b2, TLR4, Myd88, p\u2010NF\u2010\u03baB, and p\u2010p38MAPK levels and increasing Bcl\u20102 and Bcl\u2010xl levels. In GMI\u2010R1 cells, Ferulic acid attenuated LPS\u2010induced M1 polarization by decreasing the M1 polarization markers IL\u20101\u03b2, IL\u20106, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL\u20104, IL\u201010 and Arg\u20101. After LPS treatment, IL\u20101\u03b2, iNOS, TLR4, Myd88, p\u2010p38MAPK, and p\u2010NF\u2010\u03baB levels were obviously increased, and Arg\u20101 expression was reduced, while ferulic acid reversed these changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4\/NF\u2010\u03baB pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14060","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T07:29:42Z","timestamp":1672903782000},"page":"1000-1011","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Ferulic acid alleviates sciatica by inhibiting neuroinflammation and promoting nerve repair via the TLR4\/NF\u2010\u03baB 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