Medicinal Plant Research 2025, Vol.15, No.5, 233-243 http://hortherbpublisher.com/index.php/mpr 234 angiogenesis, and signaling pathways, like PI3K/Akt, NF-κB, and TGF-β/Smad (Lin et al., 2021; Zhang et al., 2023; Cai et al., 2024; Mu et al., 2024). This study attempts to clarify the multi-target protective mechanism of Salvia miltiorrhiza extract in an experimental model of ischemic heart disease, with a focus on exploring its role in regulating oxidative stress, inflammation, apoptosis, metabolism and cardiac remodeling. By revealing the molecular and cytological effects of Salvia miltiorrhiza, we strive to provide new insights and scientific basis for the prevention and treatment of ischemic heart disease, and promote the integration of traditional medicine and modern pharmacology. 2 Bioactive Constituents of S. miltiorrhizaExtracts 2.1 Lipophilic components The main liposoluble components of S. miltiorrhiza are tanshinones, a class of compounds with a shell-taxane-type diterpene quinone structure, contains tanshinone I, tanshinone IIA, cryptotanshinone and dihydrotanshinone. These compounds mainly exist in the root, and are one of the core substances of the pharmacological activity of S. miltiorrhiza, especially playing an important role in cardiovascular protection (Li et al., 2018; Jiang et al., 2019; Ren et al., 2019; Ye et al., 2023). Among them, tanshinone IIA is the most abundant and has been studied the most deeply. It has been proven to play an important role in clinical and experimental cardiovascular treatment (Jiang et al., 2019; Ren et al., 2019). The biosynthesis of tanshinone involves a complex cytochrome P450 enzyme network, and its content is affected by genetic and environmental factors (Lu, 2021; Li et al., 2021; 2024). Tanshinoone has antioxidant activity, can eliminate reactive oxygen species (ROS), and enhance endogenous antioxidant defense in the body, reducing oxidative stress in ischemic tissues (Jiang et al., 2019; Ye et al., 2023). Tanshinone also has anti-apoptotic effects. It can protect cardiomyocytes from ischemia-induced cell death by regulating signaling pathways, such as PI3K/Akt and Nrf2, and inhibiting inflammatory mediators (Li et al., 2018; Ye et al., 2023). These effects help reduce myocardial damage and improve cardiac function in ischemic heart disease models. 2.2 Hydrophilic components The main water-soluble components of Salvia miltiorrhiza are phenolic acids, mainly including salvianolic acid B, salvianolic acid A, rosmarinic acid and salvia miltiorrhiza (Wei et al., 2023; Mu et al., 2024). Among them, salvianolic acid B is the most abundant, and has the strongest biological activity. Due to its antioxidant and anti-inflammatory effects, it has received more attention (Li et al., 2018; Ren et al., 2019). These phenolic acid components are soluble in water, and exist in the roots and aboveground parts of Salvia miltiorrhiza (Wu et al., 2016; Shi et al., 2018; Hou et al., 2020). Phenolic acid compounds in S. miltiorrhiza are potent free radical scavengers, and can protect vascular endothelial cells and myocardial cells from oxidative damage (Li et al., 2018; Wei et al., 2023; Mu et al., 2024). They can activate antioxidant pathways, like Nrf2/HO-1, inhibit lipid peroxidation, reduce inflammatory damage, and thereby alleviate ischemic injury (Li et al., 2018; Mu et al., 2024). Genetic engineering studies have shown that, by enhancing the biosynthesis of phenolic acids, antioxidant activity can be increased in engineered Salvia miltiorrhiza plants (Fu et al., 2020; Zhou et al., 2021). 2.3 Synergistic actions of constituents The liposoluble tanshinones and water-soluble phenolic acids in S. miltiorrhiza act on different, but complementary molecular targets. Tanshinoone mainly regulates oxidative stress, apoptosis and inflammatory response, while phenolic acids have outstanding advantages in free radical scavenging and vascular endothelial protection (Li et al., 2018; Wei et al., 2023; Ye et al., 2023). The combined application of the two, can jointly act on multiple signaling pathways, such as PI3K/Akt, Nrf2, MAPKs and TGF-β/Smad, enhancing the overall therapeutic effect (Ren et al., 2019; Wei et al., 2023; Mu et al., 2024).
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