{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:33:12Z","timestamp":1792099992070,"version":"4.4.0"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Alveolar echinococcosis (AE) is a lethal parasitic disease that leads to progressive liver fibrosis, a process characterized by the dominance of M2 macrophages in advanced stages. While the compound Biejia-Ruangan tablet (CBRT) has demonstrated efficacy in reversing hepatic fibrosis, its underlying mechanisms in the context of AE-induced fibrosis are not fully understood. This study aimed to investigate the therapeutic potential of CBRT against AE-induced liver fibrosis and to elucidate its mechanisms of action. Serum levels of liver fibrosis markers and cytokines were measured by ELISA. Liver histopathology and collagen deposition were assessed using H&amp;E and Masson\u2019s trichrome staining. Apoptosis in GHA1 hepatocytes was evaluated by flow cytometry. Macrophage migration was analyzed via scratch and Transwell invasion assays. The involvement of the STING-TBK1 signaling pathway was examined through western blotting (WB), immunohistochemistry (IHC), immunofluorescence (IF), and quantitative real-time PCR (qRT-PCR). Livers from\n                      <jats:italic toggle=\"yes\">Echinococcus multilocularis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">E.m<\/jats:italic>\n                      .)-infected mice exhibited severe fibrosis accompanied by significant infiltration of M2 macrophages and upregulated expression of STING-TBK1 pathway components (Arg-1, \u03b1-SMA, STING, and TBK1). Treatment with CBRT (1 g\/kg) markedly attenuated liver fibrosis\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01) and inhibited the activation of mouse hepatic stellate cells (mHSCs)\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . CBRT suppressed the activation of HSCs, partly by upregulating IFN-\u03b3, suppressed apoptosis in GHA1 hepatocytes, and improved hepatocyte function. Mechanistically, CBRT activates the STING-TBK1 signaling pathway, which subsequently suppresses the polarization of macrophages toward the M2 phenotype, thereby alleviating fibrogenesis. This study demonstrates that CBRT alleviates hepatic fibrosis by activating the STING-TBK1 signaling pathway. This activation elicits a shift in macrophage polarization from the pro-fibrotic M2 phenotype towards the M1 phenotype, which subsequently suppresses the activation of hepatic stellate cells and alleviates fibrogenesis. These findings reveal a novel immunomodulatory mechanism of CBRT centered on the STING-TBK1 axis, providing both experimental evidence and a theoretical foundation for its potential application in treating hepatic fibrosis associated with AE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that compound Biejia-Ruangan tablet (CBRT) alleviates\n                      <jats:italic toggle=\"yes\">Echinococcus multilocularis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">E.m.<\/jats:italic>\n                      )-induced hepatic fibrosis by reactivating the suppressed STING-TBK1 signaling pathway in the chronic infection stage, thereby reprogramming macrophage polarization from a pro-fibrotic M2 phenotype toward an M1 phenotype. This work identifies CBRT as a promising immunomodulatory agent that can reverse the Th2\/M2-dominated immunosuppressive microenvironment, providing a novel therapeutic strategy for AE and potentially other infection-associated fibrotic diseases. However, further research is required to validate the translational efficacy of CBRT and to define the precise therapeutic window for STING-TBK1 modulation in human fibrotic disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02115-25","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:05:29Z","timestamp":1776776729000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Compound Biejia-Ruangan tablets activate the STING-TBK1 pathway to alleviate hepatic fibrosis in alveolar echinococcosis"],"prefix":"10.1128","volume":"14","author":[{"given":"Yuyu","family":"Ma","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University","place":["Urumqi, 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