Medicinal Plant Research 2025, Vol.15, No.3, 129-141 http://hortherbpublisher.com/index.php/mpr 137 Figure 3 Functional mechanisms and targets of Rg3 on antioxidant and anti-inflammatory effects. Rg3 upregulates Nrf2 to enhance antioxidase activity. Rg3 inhibits the NF-κB pathway and downstream COX-2 to ameliorate inflammation and oxidative stress. Rg3 activates SIRT1 to inhibit the NF-κB pathway. Rg3 protects tissue from apoptosis through the PI3K/Akt pathway (Adopted from Wang et al., 2022) There are also differences among different saponin molecules. Rg3 has attracted attention due to its multi-target and multi-pathway characteristics and has performed outstandingly in lung, liver and neuroinflammatory models. Research on Rb1, Rg1 and Rh2 has been relatively in-depth, mainly focusing on inhibiting inflammatory mediators and regulating immune responses. Some secondary saponins and their derivatives (like compounds K, Rh4), exhibit stronger anti-inflammatory efficacy and even present new mechanisms of action. But, most of the current evidence comes from cell and animal experiments, and clinical research is still significantly insufficient. There is a lack of large-scale, strictly designed trials to verify its efficacy and safety in the population. Clinical transformation still faces many challenges, such as differences in ginsenoside content, individual differences among patients, and the gap in formulation standardization. Besides, its low oral utilization and rapid metabolism also increase the difficulty of dose optimization and application. Future research will need to rely on multi-omics approaches, like genomics, proteomics and metabolomics, to more systematically reveal the mechanism of action of ginsenosides and search for new therapeutic targets. In the field of medicinal chemistry, through molecular modification or enzymatic transformation, some derivatives with stronger activity and better stability have been obtained. With the continuous development and clinical verification of new compounds, it is expected that safe and effective ginsenoside anti-inflammatory drugs will be formed, providing new options for the treatment of various inflammatory diseases.
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