title: Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously Hypertensive Rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Sheng Jun
authors.initials: SJ
authors.lastname: An
authors.forename: Jun Qiu
authors.initials: JQ
authors.lastname: Fu
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.forename: Tie Mei
authors.initials: TM
authors.lastname: Shao
authors.forename: Manli
authors.initials: M
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Zhan
authors.initials: Z
authors.lastname: Jiao
authors.forename: Xi Qing
authors.initials: XQ
authors.lastname: Chai
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D013599:Systole / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics; D066253:Vascular Remodeling / Q000187:drug effects*; D014867:Water / Q000737:chemistry*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D019332:Endothelin-1; D010936:Plant Extracts; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D014867:Water; D000804:Angiotensin II; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat