The efficacy and safety of ginseng berry saponin for heart failure: a systematic review and meta-analysis

Background: C.A. Mey (known as "Renshen" in Chinese) berries, exhibits cardioprotective properties, including anti-inflammatory, antioxidant, and anti-fibrotic effects. In traditional Chinese medicine, they are widely used to treat various cardiovascular diseases. Several randomized controlled trials (RCTs) have shown its efficacy for heart failure (HF). Objective: To assess the clinical efficacy and safety of GBS as an adjunct therapy for HF through systematic review and meta-analysis. Methods: A comprehensive and systematic literature search was conducted across seven electronic databases, with no language restrictions, from their respective inception dates through 31 March 2025. These databases included PubMed, the Cochrane Library, EMBASE, Web of Science China National Knowledge Infrastructure China Science and Technology Journal Database (VIP), and Wanfang Data. For quality assessment, the Cochrane Risk of Bias (ROB 2.0) tool was employed, and meta-analyses were performed using Review Manager (RevMan, version 5.4). Under a random-effects model, mean differences and their corresponding 95% confidence intervals (CI) were calculated. Additionally, the certainty of evidence for each outcome was systematically assessed using the GRADE methodology (GRADEpro software v3.6). The study has been registered in PROSPERO, with the registration number CRD420251003193. Results: The final analysis integrated 32 RCTs, comprising 3,476 HF patients for efficacy and safety assessment. Meta-analysis results indicated that adjunctive GBS therapy significantly improved the following outcomes compared with the control group (all P < 0.01): LVEF (MD = 8.91, 95%CI [6.78, 11.04]), 6MWTD (MD = 63.11, 95%CI [43.27, 82.95]), FS (MD = 2.63, 95%CI [2.04, 3.22]), SV (MD = 6.68, 95%CI [5.56, 7.80]), Cardiac Index (MD = 0.51, 95%CI [0.33, 0.70]), CO (MD = 0.68, 95%CI [0.38, 0.99]), NO (MD = 10.82, 95%CI [7.49, 14.15]), FMD (MD = 2.42, 95%CI [1.45, 3.39]), and NMD (MD = 2.13, 95%CI [1.04, 3.21]). Conversely, adjunctive GBS therapy significantly reduced the following parameters (all P < 0.01): LVEDD (MD = -5.71, 95%CI [-7.59, -3.82]), LVESD (MD = -6.30, 95%CI [-10.00, -2.59]), BNP (MD = -159.86, 95%CI [-199.17, -120.56]), NT-proBNP (MD = -529.13, 95%CI [-673.92, -384.33]), CRP (MD = -1.98, 95%CI [-2.25, -1.71]), hs-CRP (MD = -1.61, 95%CI [-2.66, -0.56]), TNF-α (MD = -20.42, 95%CI [-32.58, -8.26]), MMP-9 (MD = -34.76, 95%CI [-54.96, -14.56]), ET-1 (MD = -20.08, 95%CI [-30.18, -9.98]), SAS score (MD = -7.49, 95%CI [-11.43, -3.55]), SDS score (MD = -14.53, 95%CI [-17.26, -11.80]), HAMA score (MD = -4.48, 95%CI [-6.77, -2.20]), and HAMD score (MD = -5.79, 95%CI [-8.89, -2.68]). Conclusion: This systematic review suggests that adjunctive GBS therapy may be associated with improvements in surrogate cardiac function measures and patient-reported outcomes in patients with HF. However, these findings should be considered preliminary, as they are derived predominantly from low- and very low-certainty evidence, with no data on hard clinical endpoints such as mortality or hospitalization. Given these substantial limitations, the available evidence does not support the routine clinical use of GBS in HF management. Individualized application may be considered only in the context of shared decision-making and acknowledgment of the underlying evidence uncertainty. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251003193.