Specific Ginsenosides Improve Cardiac Function in Rodent Heart Failure Models

In a systematic review and network meta-analysis evaluating preclinical cardiovascular interventions, researchers found that specific ginsenosides significantly improved key hemodynamic and cardiac functional measurements in rodent models of heart failure. The comprehensive analysis, conducted by Chang Su, Zhixi Hu, and colleagues, synthesized experimental findings from twenty-nine animal studies examining ten distinct ginsenoside interventions. The investigation focused strictly on laboratory rodent experiments designed to model cardiac dysfunction, comparing compound actions against untreated model controls.

By systematically aggregating these functional, hemodynamic, and biochemical endpoints across independent preclinical laboratories, the study sought to determine whether particular ginsenoside variants offer distinct pharmacological advantages over others in experimental heart failure models.

Methodologically, the researchers employed a random-effects network meta-analysis model to calculate pooled effect estimates alongside corresponding ninety-five percent confidence intervals and ninety-five percent prediction intervals relative to model controls. Because of this absence of closed treatment loops, the authors could not conduct statistical inconsistency testing between direct and indirect experimental evidence. To evaluate the methodological rigor of the underlying animal literature, the review team applied the SYRCLE risk-of-bias assessment tool. This systematic quality appraisal highlighted prevalent methodological limitations across the primary literature, underscoring the necessity of exercising substantial caution when interpreting aggregated preclinical effect sizes.

Assessments of systolic cardiac pumping efficiency revealed notable improvements across several ginsenoside interventions when compared directly against untreated heart failure controls. In evaluations of left ventricular ejection fraction, total ginsenosides produced the largest mean increase, demonstrating a mean difference of 17.56 with a ninety-five percent confidence interval ranging from 7.65 to 27.48. Significant increases were likewise recorded for ginsenoside Re with a mean difference of 17.31, ginsenoside Rg3 with a mean difference of 16.09, ginsenoside Rg1 with a mean difference of 13.68, and ginsenoside Rb1 with a mean difference of 12.09. Similarly, left ventricular fractional shortening was significantly higher following treatment with multiple active interventions, including ginsenoside Rg1 with a mean difference of 11.72 and ginsenoside Rb1 with a mean difference of 8.95, alongside gains documented for total secondary ginsenosides, Rg3, Re, and Rd.

Hemodynamic parameters measuring intracardiac filling pressures and contractile kinetics also demonstrated statistically significant alterations in response to select ginsenoside therapies. For left ventricular end-diastolic pressure, total ginsenosides achieved the greatest reduction, yielding a mean difference of −3.97 with a ninety-five percent confidence interval of −4.39 to −3.55. Statistically significant reductions in end-diastolic filling pressure were additionally documented for ginsenoside Re with a mean difference of −1.65, ginsenoside Rb1 with a mean difference of −1.49, and ginsenoside Rb2 with a mean difference of −1.40. In parallel, myocardial contractile kinetics were evaluated via the maximum rate of left ventricular pressure rise, denoted as +dP/dtmax. Total ginsenosides increased this kinetic parameter by a mean difference of 1374.00, while purified ginsenoside Rb1 generated a significant mean difference of 1200.74 with a confidence interval spanning from 718.89 to 1682.60.

Biochemical markers of myocardial stress demonstrated favorable reductions under certain treatment regimens, although structural cardiac remodeling outcomes remained inconclusive. Circulating levels of B-type natriuretic peptide and its amino-terminal counterpart decreased significantly following administration of ginsenoside Rb1, displaying a standardized mean difference of −2.60, while total ginsenosides yielded a standardized mean difference of −1.94. Although ginsenoside Rg1 initially exhibited a significant biomarker reduction with a standardized mean difference of −2.38, this effect lost statistical significance during sensitivity analyses that excluded mixture nodes. The investigators concluded that the available preclinical evidence was insufficient to determine whether ginsenoside interventions meaningfully modify gross cardiac hypertrophy or organ weight ratios in these animal models.

To explore potential sources of variation across the twenty-nine evaluated studies, the researchers conducted exploratory subgroup analyses examining the influence of model induction types, animal species, administration routes, and treatment durations. In their concluding assessment, the authors stressed that while specific ginsenosides demonstrate measurable capacity to enhance ventricular mechanics and hemodynamics in rodent models, existing methodological weaknesses across the primary animal studies require cautious interpretation. Consequently, the researchers emphasized that these laboratory observations must be thoroughly corroborated through rigorously designed, high-quality preclinical investigations before any definitive conclusions can be drawn regarding therapeutic utility.

Subject of Research: Network meta-analysis of ginsenoside efficacy in rodent heart failure models

Article Title: Comparing the pharmacological effects of different ginsenosides in rodent models of heart failure: a systematic review and network meta-analysis

Article References: Su, C., Tian, P., Chen, B., Lian, K., Wu, Z., Wu, L., Li, W., & Hu, Z. (2026). Comparing the pharmacological effects of different ginsenosides in rodent models of heart failure: a systematic review and network meta-analysis. Frontiers in Pharmacology, 17, Article 1939723. https://doi.org/10.3389/fphar.2026.1939723

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1939723

Keywords: ginsenosides, heart failure, rodent models, network meta-analysis, systematic review, left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic pressure, B-type natriuretic peptide, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Rg3, ginsenoside Re, ginsenoside Rd, total ginsenosides, SYRCLE risk of bias, preclinical pharmacology, cardiac hemodynamics