{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:40Z","timestamp":1789625020803,"version":"build-2803163510"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study systematically evaluated the antidepressant-like effects of individual ginsenoside monomers and total ginsenosides in animal models of depression, compared pooled behavioral profiles across components, and summarized the principal mechanisms proposed in the included studies. The comparative analyses were intended to identify patterns within the existing evidence base rather than to establish a definitive hierarchy of antidepressant potency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Animal studies comparing a ginsenoside intervention with a vehicle-treated depression-model control were synthesized using random-effects meta-analysis. Standardized mean differences (SMDs) were calculated for the sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST), and open field test (OFT) outcomes. Interaction analyses were used to explore component-by-behavior differences, and dose-stratified analyses of ginsenoside Rb1 (GRb1) were considered exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-five animal studies evaluating 10 individual ginsenoside monomers and total ginsenosides were included. Ginsenoside treatment increased sucrose consumption in the SPT (SMD: 3.20, 95% CI: 2.61\u20133.80; Z = 10.52;\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.00001) and reduced immobility time in the FST (SMD: \u22122.21, 95% CI: \u22122.66 to \u22121.76; Z = 9.72;\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.00001) and TST (SMD: \u22122.07, 95% CI: \u22122.45 to \u22121.68; Z = 10.44;\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.00001). GRb1 showed comparatively large pooled effects in the SPT and FST, whereas GRh2 showed strong effects in behavioral-despair paradigms. Other monomers showed notable effects in selected behavioral domains. Interaction analyses suggested that the observed effects varied according to ginsenoside component and behavioral outcome. However, these comparisons were predominantly indirect and were based on heterogeneous experiments. Several pooled SMDs were very large and should be interpreted in the context of small samples, methodological limitations, and possible small-study or reporting effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ginsenosides were associated with improvements across several depression-related behavioral domains in animal models. The evidence supports further investigation of GRb1 and other active monomers in standardized, adequately powered, head-to-head preclinical studies. It does not establish the superiority of one ginsenoside, clinical antidepressant efficacy, clinical safety, or an optimal therapeutic dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD420251273532<\/jats:ext-link>\n                      ; Idetifier: CRD420251273532.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1833994","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:38Z","timestamp":1789623098000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic review and meta-analysis of the antidepressant-like effects of ginsenosides in animal models: comparative behavioral profiles and exploratory dose-stratified analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuhua","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","place":["Yiwu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuancheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","place":["Yiwu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","place":["Yiwu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University","place":["Yiwu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta5330","article-title":"Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives","volume":"5","author":"Brookes","year":"2001","journal-title":"Health Technol. 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