Medicinal Plant Research 2025, Vol.15, No.5, 233-243 http://hortherbpublisher.com/index.php/mpr 238 In vitro experiments have shown that, the extract of S. miltiorrhiza can inhibit the expression of pro-inflammatory cytokines, like TNF-α, IL-1β, and apoptotic markers (Bax, caspase-3, etc.), while increasing the level of anti-apoptotic proteins (such as Bcl-2). These results were verified by western blot, ELISA and qPCR analyses, supporting the anti-inflammatory and anti-apoptotic properties of S. miltiorrhiza extract in cardiomyocyte models (Ren et al., 2019; Jung et al., 2020). In antioxidant experiments at the cellular level, S. miltiorrhiza extract can reduce intracellular ROS and malondialdehyde (MDA) levels, while enhancing the activities of superoxide dismutase (SOD) and catalase (CAT). These results further confirm that, S. miltiorrhiza extract has a strong free radical scavenging and antioxidant capacity in protecting cardiomyocytes from oxidative damage (Jiang et al., 2019; Mu et al., 2024). 6.2 Animal model studies In myocardial ischemia/reperfusion (I/R) injury models of rats and mice, administration of S. miltiorrhiza extract can improve cardiac function, reduce infarction area, and restore hemodynamic parameters to normal. Whether it was the water extract, ethanol extract, or isolated monomer components, like tanshinoone IIA and salvianolic acid B, they all showed cardioprotective effects in these models (Zhou et al., 2012; Ren et al., 2019; Jung et al., 2020). Animal studies also established dose-dependent relationships, that is, the cardioprotective effects of tanshinone IIA and salvianolic acid B increased with dose, manifested as improved cardiac function, increased antioxidant enzyme activity and reduced tissue damage, and no significant toxicity was observed at the therapeutic level (Ren et al., 2019; Jung et al., 2020). Long-term animal experiments on administration have shown that, S. miltiorrhiza extract can continuously improve cardiac prognosis and demonstrates good safety. No obvious adverse reactions or organ toxicity were found at the therapeutic dose, providing support for its long-term application in cardiovascular diseases. 6.3 Mechanistic validation experiments Institutional studies confirmed through Western blotting and qPCR that, S. miltiorrhiza extract can activate the PI3K/Akt and Nrf2/HO-1 pathways, and regulate the MAPK signaling pathway. These molecular changes are closely related to enhanced antioxidation, reduced inflammation and improved cell survival, and have been verified in cell and animal models (Ren et al., 2019; Jung et al., 2020; Mu et al., 2024). Gene knockout and inhibitor experiments further verified the role of the related pathways. For instance, in the Nrf2−/− or TLR4−/− models, the protective effect of S. miltiorrhiza was weakened, confirming the specificity of these molecular targets in their cardioprotective effects (Jiang et al., 2019; Jung et al., 2020). Multi-omics studies, including metabolomics and network pharmacology, have identified key active ingredients and their molecular targets, providing evidence for understanding the systemic cardioprotective mechanism of S. miltiorrhiza (Ren et al., 2019; Jung et al., 2020; Mu et al., 2024). Metabolomics analysis reveals that, the aqueous extract of S. miltiorrhiza mainly exerts cardioprotective effects, by regulating metabolic pathways, such as histidine, alanine, aspartic acid and glutamic acid, glycerophospholipids, as well as glycine, serine and threonine (Figure 2). 7 Case Studies 7.1 Cardiovascular protective effect of Salvianolic acid B The water-soluble phenolic acid component - salvianolic acid B in S. miltiorrhiza has powerful anti-inflammatory and antioxidant effects. It can inhibit the expression of pro-inflammatory cytokines, like TNF-α, IL-6, reduce the generation of ROS, and protect cells from lipid peroxidation damage, effectively alleviating myocardial injury in cell and animal models (Huang et al., 2016; Li et al., 2023; Shan et al., 2024). Salvianolic acid B also can maintain endothelial integrity, and promote vasodilation, improving coronary blood flow and microcirculation. Studies show that, it can enhance angiogenesis and reduce endothelial dysfunction, improve myocardial perfusion and reduce ischemic injury (Lin et al., 2021; Li et al., 2023; Zhang et al., 2023).
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