3.4 Tanshinone IIA, Salvianolic acid B, Tanshinol
Tanshinone, extracted from the traditional Chinese medicine Salvia miltiorrhiza Bunge, is a fat-soluble phenanthrene quinone compound with bacteriostatic effect (D. Wang et al., 2017). Among tanshinone, tanshinone IIA has been clinically proved to have a more significant effect on cardiovascular diseases, especially its anti-inflammatory effect on macrophages. Tanshinone IIA reduces the production of inflammatory factors and adipogenesis in macrophages by up-regulating miR-130b and down-regulating WNT5A, thereby relieving the development of atherosclerosis (L. Yuan et al., 2020). Previous studies have demonstrated that miR-712 is involved in atherosclerosis-related pathological processes, such as VSMCs calcification and endothelial cell inflammation (Son et al., 2013). Tanshinone IIA can inhibit VSMCs inflammation and proliferation by inhibiting miR-712-5p (Y. Qin et al., 2020). Krüppel-like factor 4 (KLF4), an evolutionarily conserved zinc-finger-containing transcription factor, is thought to induce M2 and inhibit M1 macrophage polarization (Liao et al., 2011). A study found that the miR-375/KLF4 pathway plays a dominant role in macrophage polarization and autophagy, and tanshinone IIA could activate KLF4 by inhibiting miR-375, leadind to enhanced autophagy as well as M2 polarization of macrophages (W. Chen et al., 2019). Tropomyosin 1 (TPM1), as a target gene for miR-21-5p (Baker, 2011), is involved in the formation, stabilization, and regulation of cytoskeletal actin fibers (Gunning, Hardeman, Lappalainen, & Mulvihill, 2015). It was found that tanshinone IIA could down-regulate miR-21-5p and then target TPM1, which helps to inhibit the proliferation and migration of VSMCs (Jia et al., 2019).
Salvianolic acid B, a water-soluble compound extracted from Salvia miltiorrhiza Bunge, has been used to treat cardiovascular diseases for hundreds of years. MiR-146a is involved in the regulation of cell proliferation, migration, differentiation, and apoptosis (H. S. Cheng et al., 2013). A study has found that salvianolic acid B can inhibit angiotensin II-induced VSMCs proliferation and improve carotid artery ligation-induced neointimal hyperplasia by downregulating miR-146a (Zhao et al., 2019).
Tanshinol is also an active ingredient isolated from Salvia miltiorrhiza Bunge which has the effect of protecting vascular endothelium and reducing atherosclerosis (W. Song, Pu, & He, 2014). MiR-26a has been proved to have anti-apoptotic effect on endothelial cells (Y. Zhang et al., 2015). A study found that tanshinol inhibits apoptosis of endothelial cells and reduces atherosclerotic lesions via decreasing lncRNA TUG1 and increasing miR-26a in endothelial cells (C. Chen et al., 2016).