{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T20:24:23Z","timestamp":1770323063533,"version":"3.49.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Oxymatrine (OMT) alleviates damage to dopaminergic (DA) neurons and microglia-mediated neuroinflammation in an MPTP mouse model of parkinsonism by inhibiting the High-mobility group protein B1 (HMGB1) pathway. However, the precise mechanism by which OMT inhibits HMGB1 remains unclear. Although miR-141-3p is downregulated in the peripheral blood serum of Parkinson\u2019s disease (PD) patients, its potential relationship with HMGB1 remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      TargetScan software and dual-luciferase reporter gene assays predicted that miR-141-3p binds to the 3\u2019-UTR of HMGB1 mRNA. BV2 cells were transfected with miR-141-3p mimics and stimulated with MPP\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments. C57BL\/6\u202fJ mice received stereotaxic injections of miR-141-3p agomir or miR-141-3p antagomir into the bilateral substantia nigra pars compacta (SNpc). Subsequently, the mice were intraperitoneally injected with MPTP four times within a single day. After miR-141-3p antagomir injection, OMT was administered continuously by injection for 7\u202fdays. Behavioral tests were assessed using the rotarod and open field tests. Real-time PCR, western blot, ELISA, and immunofluorescence staining were performed on BV2 cells and SNpc tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study showed an inverse correlation between HMGB1 and miR-141-3p expression in both BV2 microglia exposed to MPP\n                      <jats:sup>+<\/jats:sup>\n                      and MPTP-treated mice. TargetScan analysis identified complementary binding sites between miR-141-3p and the 3\u2019-UTR of HMGB1 mRNA, which was subsequently confirmed through dual-luciferase reporter assays. Through experiments in BV2 microglia exposed to MPP\n                      <jats:sup>+<\/jats:sup>\n                      and in MPTP-treated mice, miR-141-3p downregulates HMGB1, reduces pro-inflammatory cytokine readouts, and\n                      <jats:italic>in vivo<\/jats:italic>\n                      is associated with improved rotarod and open-field performance and attenuated Tyrosine Hydroxylase (TH)-positive neuronal loss. OMT increases miR-141-3p in the MPTP model, alongside reduced HMGB1 and inflammatory readouts, and these effects are diminished by miR-141-3p inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      miR-141-3p targets HMGB1 to inhibit microglial reaction and mitigate neuroinflammation both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and vitro experiments, reduce TH-positive neuronal loss in the MPTP model. OMT increases miR-141-3p in the MPTP model, alongside reduced HMGB1 and inflammatory readouts, and these effects are diminished by miR-141-3p inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1731850","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T06:45:44Z","timestamp":1770273944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxymatrine-associated protection in an MPTP mouse model is accompanied by increased miR-141-3p and reduced HMGB1"],"prefix":"10.3389","volume":"19","author":[{"given":"Ping","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Affiliated Taizhou Second People\u2019s Hospital of Yangzhou University","place":["Taizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical School, Nantong University","place":["Nantong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Taizhou Second People\u2019s Hospital of Yangzhou University","place":["Taizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ming","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Taizhou Second People\u2019s Hospital of Yangzhou University","place":["Taizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Fang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Taizhou Second People\u2019s Hospital of Yangzhou University","place":["Taizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Mei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Taizhou Second People\u2019s Hospital of Yangzhou University","place":["Taizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Taizhou Second People\u2019s Hospital of Yangzhou University","place":["Taizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical School, Nantong University","place":["Nantong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1476-4598-13-33","article-title":"Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128","volume":"13","author":"Adlakha","year":"2014","journal-title":"Mol. 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