Salvia miltiorrhiza Bunge

2.12. Salvia miltiorrhiza Bunge The dried roots from Salvia miltiorrhiza Bunge (Danshen in Chinese) have been used for the treatment of cardiovascular and cerebrovascular pathologies in China and Japan. The main phytochemicals isolated from S. miltiorrhiza roots are hydrophilic phenolic acids and lipophilic diterpene quinones (Liang et al., 2017). The administration of a water-soluble extract of S. miltiorrhiza roots to rats resulted in a decrease of mean arterial BP, which was also observed in the tissues pretreated with phenylephrine (Leung et al., 2010). These data are in agreement with those by Zhang (Zhang et al., 2016), who observed that i.p. administration of a S. milthiorriza water roots extract and of a mixture of four constituents of the extract caused hypotension in spontaneously hypertensive rats. This was the result of several activities such as the decrease in plasma levels of angiontensin II, endothelin-1, malondialdehyde, transforming growth factor-β1, superoxide dismutase, the mRNA expression levels of collagen type I, α- smooth muscle actin, nicotinamide adenine dinucleotide phosphate oxidases (NOX), the suppression of angiotensin II-mediated effects including ROS-generation, morphological changes in the thoracic aorta tunica media and adventitia thickness. The hypotensive effect of a water extract from S. milthiorriza was confirmed in 2 K1C rats, where it mainly occurred by angiotensin converting enzyme inhibition (Kang et al., 2002). In conclusion, the hypotensive action of S. milthiorriza is mainly due to ACE inhibition properties and thus to the decrease in plasma levels of angiotensin II and endothelin-1, to the suppression of ROS generation and vascular remodelling. Fig. 12 shows the main danshen constituents characterized for antihypertensive and cardiovascular effects. Salvianolic acid A is one of the above cited four components (Zhang et al., 2016) and it has been singly studied, in spontaneously hypertensive rats, for its ability to inhibit endothelial dysfunctions (Teng et al., 2016) and, in particular, to prevent cardiac remodelling through matrix metalloproteinase-9 (MMP-9) inhibition (Jiang et al., 2013; Zhang et al., 2014). For salvianolic acid B, another of the above four components (Zhang et al., 2016), ACE inhibition (Kang et al., 2003) and endothelial function restoring associated with angiotensin receptor AT 1 inhibition have been proposed (Ling et al., 2017). Salvianolic acid A and B exert also antiatherosclerotic effects (Ba et al., 2014; Chen et al., 2011; Joe et al., 2012; Lin et al., 2007; Liu and Liu, 2002), while salvianolic acid B has been proved to inhibit platelets-mediated inflammation in vascular endothelial cells (Xu et al., 2015) and its magnesium salt, tanshinoate B, to decrease blood pressure also after treatment with phenylephrine (Leung et al., 2010) and to protect endothelium from hyperglycemiainduced dysfunction (Kim et al., 2010). Salvianic acid (danshensu), the third constituent (Zhang et al., 2016), seems to exert effects on several pharmacological targets in hypertension (Tang et al., 2011) and, in particular, it prevents pulmonary hypertension in rats inhibiting the proliferation of pulmonary artery smooth muscle (Zhang et al., 2018). For protocatechuic aldehyde, the last constituent of the four (Zhang et al., 2016), different mechanisms of action have been proposed in preventing atherosclerosis pathogenesis (Moon et al., 2012; Tong et al., 2016; Xing et al., 2012; Zhou et al., 2005). The complex mechanisms underlying the antiatherosclerosis activity and protecting effects against cardiac hypertrophy of tanshinone IIA have been recently investigated evidencing the involvement of different signalling pathways (Wang et al., 2017; Zhao et al., 2016; Zhu et al., 2017; Pang et al., 2014; Feng et al., 2017; Wu et al., 2017). Therapeutic potential in ameliorating atherosclerosis through vasodilatatory, anti-coagulant, anti-thrombotic, anti-inflammatory, anti-oxidant, and immunomodulatory activities (Fang et al., 2018) strongly supports the option of using tanshinones from S. milthiorriza, in particular tanshinone IIA and cryptotanshinone, as a strategy to counteract atherosclerosis-related cardiovascular and metabolic diseases. Interestingly, since hypertension is a common complication of type 2 diabetes mellitus, dihydrotanshinone I has been proposed as a substance with both anti-hypertensive activity, due to mineralocorticoid receptor antagonism, and antihyperglycemic effects (Liu et al., 2010). Diabetes-induced vascular dysfunction are attenuated by rosmarinic acid, which acts as a vasoactive substance and a cardioprotector through its antioxidant property (Karthik et al., 2011; Sotnikova et al., 2013; Javidanpour et al., 2017).Published as part of Micucci, M., Bolchi, C., Budriesi, R., Cevenini, M., Maroni, L., Capozza, S., Chiarini, A., Pallavicini, M. & Angeletti, A., 2020, Antihypertensive phytocomplexes of proven efficacy and well-established use: Mode of action and individual characterization of the active constituents, pp. 1-19 in Phytochemistry (112222) (112222) 170 on pages 10-11, DOI: 10.1016/j.phytochem.2019.112222, http://zenodo.org/record/829299