Medicinal Plant Research 2025, Vol.15, No.3, 129-141 http://hortherbpublisher.com/index.php/mpr 135 5.3 Molecular target validation Western blotting and immunofluorescence techniques, are widely used to validate the molecular targets of ginsenosides in cell and animal models. These experiments confirmed the inhibitory effect on key inflammatory signaling proteins (e.g., NF-κB p65, STAT3, p38 MAPK), as well as the down-regulation of inflammatory mediators at the protein level (Gao et al., 2020a; Kang et al., 2023; Nam et al., 2024). Immunofluorescence experiments further demonstrated the nuclear translocation of transcription factors, like NF-κB decreased, mechanologically supporting the basis of ginsenoside action (Lee et al., 2022; Nam et al., 2024; Pan et al., 2024). Studies on gene knockout and overexpression, have provided direct evidence for the involvement of specific molecular targets in the anti-inflammatory effects of ginsenosides. For instance, studies using TLR4, STAT3 or MerTK deletion models have shown that, the anti-inflammatory effect of ginsenosides depends on these pathways (Yang et al., 2018; Gao et al., 2020; To et al., 2022). The overexpression of TLR4 or STAT3, can partially reverse the inhibitory effect of ginsenosides on inflammatory signals, further confirming their direct molecular targets (Xu et al., 2022). 6 Clinical Applications and Anti-inflammatory Potential 6.1 Clinical trials and progress The therapeutic potential of ginsenosides in a variety of chronic inflammatory diseases has been explored, including colitis, rheumatoid arthritis, chronic sinusitis and inflammatory lung disease. Preclinical studies and limited clinical trials have shown that ginsenosides such as Rg1, Rg3, Rb1, Rh2 and compound K can alleviate disease severity, tissue inflammation and clinical symptoms in models of colitis, arthritis and lung injury (Gao et al., 2020a; Kim et al., 2021; Zhang et al., 2021; Wang et al., 2022). For instance, Rg1 performs exceptionally well in alleviating colitis, and its mechanism is related to regulating macrophage polarization and restoring the intestinal metabolite profile (Qu et al., 2025). Rg3 has been proven to have therapeutic effects in reducing pulmonary inflammation, neuroinflammation and organ damage, and this effect has been supported in both animal experiments and early clinical trials (Wang et al., 2022). Regarding the safety of ginsenosides, most studies have shown that they have very few adverse reactions at therapeutic doses (Gao et al., 2020b; He et al., 2020; Jang et al., 2023). In animal experiments and early human trials, ginsenosides did not show obvious toxicity or organ damage. The efficacy of some preparations could even be comparable to that of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, but with fewer side effects (Lee et al., 2018; 2019; He et al., 2020). But, large-scale, well-designed clinical trials are still limited, and their long-term safety and efficacy require further studies to be fully validated in different patient populations (Kim et al., 2017; Jang et al., 2023). 6.2 Comparison with conventional anti-inflammatory drugs Ginsenosides exert their effects through multi-target mechanisms, including inhibiting NF-κB, MAPK and JAK/STAT pathways, and regulating immune cell function and cytokine expression (Im, 2020; Yi, 2021; To et al., 2022; Wang et al., 2022). Unlike traditional NSAIDs and glucocorticoids, these drugs take effect through a single pathway and often cause immunosuppression or metabolic side effects. Ginsenosides can not only inhibit excessive inflammation, but promote the resolution of inflammation by promoting the polarization of M2-type macrophages, and exerting antioxidant effects (Yang et al., 2018; Lee et al., 2022; Jang et al., 2023). Some studies suggest that, ginsenosides can be used in combination with conventional drugs to improve efficacy, and reduce the required dose, thereby potentially reducing the risk of adverse reactions (He et al., 2020; Arafa et al., 2021). One key advantage of ginsenosides over traditional anti-inflammatory drugs is their lower risk of adverse reactions. For instance, Rg1 can act as a selective glucocorticoid receptor agonist, exerting anti-inflammatory effects without damaging tissue regeneration, while impaired tissue repair is a common side effect of glucocorticoids (He et al., 2020). Black ginseng exhibited anti-inflammatory efficacy comparable to that of NSAIDs due to the change in saponin profile, but with better safety (Lee et al., 2019).
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