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).