Preclinical investigation and clinical trials of Red ginseng as an immunomodulator: a narrative review from 2015 to 2025

Background Red ginseng (Ginseng Radix et Rhizome Rubra, RG) is the steamed and dried root of Panax ginseng C.A. Meyer. It has been used for centuries in Asia for Qi tonifying, which has been reported to align with immune regulation in humans. Accordingly, the immune regulatory effects of RG were extensively studied in various health conditions. However, few publications are available retrieving the clinical and preclinical advancements of RG on immunity. Purpose This review endeavors to summarize the clinical and preclinical studies conducted to investigate the immunomodulatory effects of RG from 2015 to 2025. The limitations of previous studies and potential future directions are discussed. Methods All relevant clinical and pharmacological studies aimed at elucidating the immune regulatory effects of RG and published from 2015 to 2025 were included. The studies were retrieved from Web of Science, Scopus, PubMed, Springer and Google Scholar. Results In vitro, in vivo and clinical studies have consistently shown that RG modulates immunity across various species and exhibits bidirectional immunoregulatory effects depending on health status (i.e ., good health, sub-health and disease). Major bioactive groups rare ginsenosides, polysaccharides and Arginyl-Fructose endow RG with a regulatory effect on innate immune system (e.g., macrophages, dendritic cells, neutrophils and mucosa cells) and adaptive immune system (e.g., T and B cells). Multiple signaling pathways are involved in the regulatory effects of RG on immune cells, including TLR4/NF-κB, RORγ, glucocorticoid receptors and gut microbiota. It is noteworthy that with the development of separation, purification and detection techniques, an increasing number of researchers are devoting efforts toward uncovering the fine structure of RG polysaccharides, which will help to elucidate the correlation between structure and the immune regulatory effects of RG polysaccharides. Conclusion Preclinical and clinical studies demonstrated that RG regulates immunity to relieve diseases and enhance body performance, providing scientific evidence for its traditional use as Qi-tonifying agent. Further efforts are needed to elucidate the relationship between the structure and biological activities of RG ingredients, as well as the holistic immune regulatory effects of RG.