{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:18:39Z","timestamp":1790857119211,"version":"4.1.0"},"reference-count":20,"publisher":"Baishideng Publishing Group Inc.","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n                  <jats:p>Liuweiwuling Tablet (LWWL) is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus (HBV) infection. Previous studies have indicated an anti-HBV effect of LWWL, specifically in terms of antigen inhibition, but the underlying mechanism remains unclear.<\/jats:p>\n                  <jats:p>AIM<\/jats:p>\n                  <jats:p>To investigate the potential mechanism of action of LWWL against HBV.<\/jats:p>\n                  <jats:p>METHODS<\/jats:p>\n                  <jats:p>In vitro  experiments utilized three HBV-replicating and three non-HBV-replicating cell lines. The in vivo  experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.<\/jats:p>\n                  <jats:p>RESULTS<\/jats:p>\n                  <jats:p>In HepG2.1403F cells, LWWL (0.8 mg\/mL) exhibited inhibitory effects on HBV DNA, hepatitis B surface antigen and pregenomic RNA (pgRNA) at rates of 51.36%, 24.74% and 50.74%, respectively. The inhibition rates of LWWL (0.8 mg\/mL) on pgRNA\/covalently closed circular DNA in HepG2.1403F, HepG2.2.15 and HepG2.A64 cells were 47.78%, 39.51% and 46.74%, respectively. Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis (PI3K-AKT, CASP8-CASP3 and P53 pathways). Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group (CG) among HBV-replicating cell lines, including HepG2.2.15 (2.92% \u00b1 1.01% vs  6.68% \u00b1 2.04%, P  &lt; 0.05), HepG2.A64 (4.89% \u00b1 1.28% vs  8.52% \u00b1 0.50%, P  &lt; 0.05) and HepG2.1403F (3.76% \u00b1 1.40% vs  7.57% \u00b1 1.35%, P  &lt; 0.05) (CG vs  LWWL-treated group). However, there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells (5.04% \u00b1 0.74% vs  5.51% \u00b1 1.57%, P  &gt; 0.05), L02 cells (5.49% \u00b1 0.80% vs  5.48% \u00b1 1.01%, P  &gt; 0.05) and LX2 cells (6.29% \u00b1 1.54% vs  6.29% \u00b1 0.88%, P  &gt; 0.05). TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBV-replicating mouse model, while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.<\/jats:p>\n                  <jats:p>CONCLUSION<\/jats:p>\n                  <jats:p>Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV, potentially involving selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.<\/jats:p>","DOI":"10.3748\/wjg.v30.i13.1911","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T04:20:41Z","timestamp":1712031641000},"page":"1911-1925","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of hepatitis B virus\n                    <i>via<\/i>\n                    selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet"],"prefix":"10.3748","volume":"30","author":[{"given":"Fei-Lin","family":"Ge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan-Lan","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Zhen","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Fang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Gang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-He","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2024,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30119-0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.733364"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-19"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-023-00861-2"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3947\/ic.2020.52.3.381"},{"key":"B6","unstructured":"Hepatobiliary Specialized Committee of China Association of Chinese Medicine;  Liver Diseases Specialized Committee of China Medical Association of Minorities. 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