Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously Hypertensive Rats

Abstract

Background/Aims: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), totally abbreviated as SABP. Although SM is often used to treat various cardiovascular diseases in traditional Chinese medicine, the efficacy and function of optimal compatibility ratio of SM's active ingredients (SABP) in the prevention and treatment of cardiovascular diseases remain uncertain. This study investigated antihypertensive effect and underlying mechanisms of SABP vs. SM lyophilized powder (SMLP) in spontaneously hypertensive rats (SHR) and to establish the ratio of the optimal compatibility of DSS, Sal-A, Sal-B and PAL in improving cardiovascular functions. Methods: The SHRs were treated with either SABP or SMLP and their systolic blood pressures (SBP) were monitored. The isolated thoracic aorta of SHRs was segregated for immunohistochemistry, Hematoxylin-Eosin stain and mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1, α-SMA and Smad7. Moreover, the adventitial fibroblasts (AFs) were isolated and cultured from SD rats' aorta and the reactive oxygen species (ROS) production was determined after SABP or SMLP treatment. Results: SABP, but not SMLP, significantly reduced SBP, which were accompanied by the inhibited morphological changes in the thoracic aorta and the reduced mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1 and α-SMA, but the increased Smad 7 expression in SHRs. Moreover, SABP also resulted in a decreased ROS production in AFs of SD rats. Conclusions: These results indicate that SABP, but not SMLP, treatment potently inhibits hypertension through improvements of vascular remodeling and oxidative stress. The present study provides new evidence that the efficacy and function from optimal compatibility ratio of SM active ingredients is much better than its lyophilized powder, which represents a strategy to develop SM's new beneficial effect in improving cardiovascular functions.

Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

“…In previous studies we have shown that prophylactic administration of SAA slowed the progression of pulmonary vascular remodeling, and may be associated with the Smad signaling pathway 32 . More recent evidence also reveals that SAA alleviates hypertension through inhibiting oxidative stress and TGF-β signal transduction pathway 34 .…”

Comparative Analysis of the Major Chemical Constituents in Salvia miltiorrhiza Roots, Stems, Leaves and Flowers during Different Growth Periods by UPLC-TQ-MS/MS and HPLC-ELSD Methods

“…Salvia miltiorrhiza (SM), a kind of perennial herb that derived from Salvia genus of the Labiatae family, the dry roots and rhizomes are officially listed in the Chinese Pharmacopoeia [ 1 , 2 ], and it is highly valued and one of the most widely used traditional Chinese medicines (TCM) by virtue of its function to “promote blood circulation and remove blood stasis” that was firstly recorded in Shennong's Classic of Materia Medica (200–300 AD, Han Dynasty). The remarkable effects of S. miltiorrhiza on treatment of complicated cardiovascular diseases and cerebrovascular diseases have been reported during the past decades [ 3 , 4 , 5 ]. Additionally, numerous studies have demonstrated that S. miltiorrhiza possesses a wide range of pharmacological effects, including anti-oxidative, myocardial infarction, anti-fibrotic [ 6 ], anti-inflammatory [ 7 ], anti-hypertension [ 8 ] and anti-neoplastic [ 9 ] effects.…”

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

“…It is often used for the treatment of cardio-cerebral-vascular disease caused by blood stasis [30,44,45]. Existing studies have shown that DSS, SAA, SAB, and HSYA have the ability to scavenge free oxygen radicals, inhibit apoptosis, and prevent inflammation [5][6][7][8][9][10][11][12][13][14][15][16][17][18][25][26][27][28], thereby protecting against cerebral ischemic injury. Over the past few years, the Dan-Hong injection and its ingredients have been widely studied in clinical and basic research [30,[46][47][48].…”

“…The compatibility of these three active ingredients with hydroxysafflor yellow A (HSYA) in C. tinctorius (Honghua in Chinese) has a better therapeutic effect on cerebral ischemia [2][3][4]. SAA can scavenge free oxygen radicals [5,6] and has a protective effect on cell damage caused by oxidative stress [7,8]. SAB not only has strong antioxidant effects [9][10][11][12][13], but it can also inhibit apoptosis [14][15][16][17][18].…”