Medicinal Plant Research 2025, Vol.15, No.3, 129-141 http://hortherbpublisher.com/index.php/mpr 129 Research Perspective Open Access Pharmacological Mechanisms of Ginsenosides in Anti-inflammatory Activity Yudie Wang 1, Haomin Chen 2 1 Traditional Chinese Medicine Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China 2 Tropical Medicinal Plant Research Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572025, Hainan, China Corresponding author: haomin.chen@hitar.org Medicinal Plant Research, 2025, Vol.15, No.3 doi: 10.5376/mpr.2025.15.0014 Received: 15 Apr., 2025 Accepted: 30 May, 2025 Published: 20 Jun., 2025 Copyright © 2025 Wang and Chen, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Wang Y.D., and Chen H.M., 2025, Pharmacological mechanisms of ginsenosides in anti-inflammatory activity, Medicinal Plant Research, 15(3): 129-141(doi: 10.5376/mpr.2025.15.0014) Abstract This study explored the anti-inflammatory mechanism of ginsenosides, revealed their mode of action in regulating inflammatory responses through multiple signaling pathways. Studies have shown that, ginsenosides can effectively down-regulate the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6, as well as inflammatory mediators, such as iNOS and COX-2, by inhibiting the NF-κB, MAPK, JAK-STAT, and PI3K/Akt pathways, and simultaneously activating the Nrf2/HO-1 pathway. In terms of immune regulation, ginsenosides promote the polarization of macrophages and microglia towards M2 type, and maintain the Treg/Th17 balance, achieving a dual effect of inhibiting inflammation and promoting regression. Cell and animal experiments have confirmed that saponins, like Rb1, Rg1, Rg3, and Rh2, have all demonstrated excellent therapeutic effects in models of colitis, acute lung injury, and neuroinflammation. Preliminary studies on clinical and functional foods have also shown their potential in chronic inflammatory diseases. Future research should focus on dose optimization, formulation improvement and clinical transformation to promote its application in the treatment of inflammatory diseases. Keywords Ginsenosides; Anti-inflammatory mechanism; Signal pathway; Immune regulation; Clinical application 1 Introduction Ginsenosides, belonging to damane triterpene saponins, are characterized by a steroid-like tetracyclic skeleton and multiple glycosides linked at specific sites (Kim et al., 2017; Im, 2020). According to the position of the sugar residue, ginsenosides are mainly classified into the protoginsenodiol type (PPD), and the protoginsenotriol type (PPT). PPD (e.g., Rb1, Rb2, Rc, Rd, Rg3) contain sugar groups at the C-3 site, while PPT-type (like Rg1, Re, Rf, Rg2) contain sugar groups at the C-6 site (Kim et al., 2017; Im, 2020; Jang et al., 2023). This structural diversity determines the extensive biological activities, exhibited by different ginsenosides. Among the nearly 100 identified ginsenosides, Rg1, Rb1 and Rg3 are the most widely studied representative components, for their anti-inflammatory effects (Gao et al., 2020a; Im, 2020; Wang et al., 2022; Qu et al., 2025). Rg1 and Rb1 are abundant in Asian ginseng and American ginseng, while Rg3 is mainly enriched in processed (red ginseng) ginseng, and is renowned for its significant anti-inflammatory and antioxidant activities (Gao et al., 2020a; Wang et al., 2022; Qu et al., 2025). Other important ginsenosides with potential anti-inflammatory effects include Rc, Rd, Re, Rh1 and compound K (Yi, 2019; 2021; Jang et al., 2023). Inflammation is a complex multi-step immune response of the body to infection or injury, involving the activation of innate immune cells, and the release of pro-inflammatory mediators (Kim et al., 2017; Gao et al., 2020b; Jang et al., 2023). The key signaling pathways involved in the inflammatory cascade response include nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPKs), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) (Gao et al., 2020a; b; Yi, 2021; Wang et al., 2022; Qu et al., 2025). These pathways regulate the expression of cytokines (TNF-α, IL-1β, IL-6 etc.) and related enzymes (such as iNOS, COX-2), thereby driving the inflammatory response (Kim et al., 2017; Wang et al., 2022; Jang et al., 2023). Chronic and unresolved inflammation, is an important factor in the occurrence and development of various diseases, including metabolic diseases, cardiovascular diseases, neurodegenerative diseases and malignant tumors,
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