Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro

Zhang, Qiao; Wang, Shifeng; Yu, Yangyang; Sun, Shengnan; Zhang, Yuxin; Zhang, Yanling; Yang, Wei; Li, Shiyou; Qiao, Yanjiang

doi:10.3390/ijms17081244

Cited by 14 publications

(10 citation statements)

References 44 publications

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“…Sal-A also inhibits AGE (advanced glycation end products)-induced endothelial cell injury [109] . A more recent study has shown that Sal-A is a safe ET1 type A receptor (ET A R) antagonist in HEK293 cells overexpressing ET A R (IC 50 =5.7 µmol/L) [113] , suggesting that Sal-A could have therapeutic effects in hypertension-associated vascular remodeling. Sal-A does not affect basal endothelial cell proliferation and NO production, but it reduces Ang II-induced proliferation of human endothelial cells by inhibiting ROS generation as well as blocking the phosphorylation of Src and Akt [114] .…”

Section: Effects Of Sal-a On Endothelial Dysfunction and Vascular Remmentioning

confidence: 99%

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics

2018

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Salvia miltiorrhiza Burge (Danshen) is an eminent medicinal herb that possesses broad cardiovascular and cerebrovascular protective actions and has been used in Asian countries for many centuries. Accumulating evidence suggests that Danshen and its components prevent vascular diseases, in particular, atherosclerosis and cardiac diseases, including myocardial infarction, myocardial ischemia/reperfusion injury, arrhythmia, cardiac hypertrophy and cardiac fibrosis. The published literature indicates that lipophilic constituents (tanshinone I, tanshinone IIa, tanshinone IIb, cryptotanshinone, dihydrotanshinone, etc) as well as hydrophilic constituents (danshensu, salvianolic acid A and B, protocatechuic aldehyde, etc) contribute to the cardiovascular protective actions of Danshen, suggesting a potential synergism among these constituents. Herein, we provide a systematic up-to-date review on the cardiovascular actions and therapeutic potential of major pharmacologically active constituents of Danshen. These bioactive compounds will serve as excellent drug candidates in small-molecule cardiovascular drug discovery. This article also provides a scientific rationale for understanding the traditional use of Danshen in cardiovascular therapeutics.

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Section: Effects Of Sal-a On Endothelial Dysfunction and Vascular Remmentioning

confidence: 99%

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics

2018

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“…Salvianolic acid A (SAA) is one of the most bioactive components extracted from Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese herbal medicine with anti‐inflammation, antiplatelet, antihypertension, antithrombosis, antioxidation, and antirenal disease activities, as well as cardioprotective effects on myocardial infarction . Moreover, in recent years, SAA has been shown to possess other antitumor properties, including suppressive effects on tumor proliferation through targeting endothelin A receptor in DU145 cells and on the lung cancer multidrug resistance gene MDR1 through regulating microRNA expression . SAA could induce apoptosis and reduce c‐met expression by targeting the AKT/mTOR signaling pathway in lung adenocarcinoma cells .…”

Section: Introductionmentioning

confidence: 99%

Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP‐2 and the c‐Raf/MEK/ERK pathway

Fang

Chen

et al. 2018

Environmental Toxicology

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The metastasis of oral squamous cell carcinoma (OSCC) is one of the most important causes of cancer-related deaths. Thus, various therapeutic strategies have been developed to prevent the metastasis of OSCC. Salvianolic acid A (SAA), a traditional Chinese medicine, has antithrombosis, antiplatelet, anti-inflammation, and antitumor activities. Here, we provide molecular evidence indicating that SAA exerts its antimetastatic effects by markedly inhibiting the invasion and migration of oral squamous SCC-9 and SCC-25 cells. SCC-9 and SCC-25 cells were treated with various concentrations of SAA to further investigate the precise involvement of SAA in cancer metastasis. The results of zymography, and Western blotting indicated that SAA treatment may decrease matrix metallopoteinase-2 (MMP-2) expression. SAA also inhibited p-c-Raf, p-MEK1/2, and p-ERK1/2 protein expression. In addition, treating SCC-9 cells with U0126, a MEK-specific inhibitor, decreased MMP-2 expression and concomitantly inhibited cell migration. Our findings suggested that SAA inhibits the invasion and migration of OSCC by inhibiting the c-Raf/MEK/ERK pathways that control MMP-2 expression. Our findings provide new insights into the molecular mechanisms that underlie the antimetastatic effect of SAA and are thus valuable for the development of treatment strategies for metastatic OSCC.

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“…Earlier studies in other cells such as HEK293/ETAR cell line, human mesenchymal stem cells and neuronal cells revealed that the inhibitory effect of SAA, SAB, and SAC had a minor effect on cells viability. [28][29][30] In this study, at concentrations greater than 200 μM, only SAA showed ACE2 h cytotoxicity and decreases cell viability. Moreover, the concentrations we chose in our experiment were below the toxic dose.…”

Section: Discussionmentioning

confidence: 54%

Three salvianolic acids inhibit 2019‐nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2

Wang

Zhang

et al. 2021

Journal of Medical Virology

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Since December 2019, the new coronavirus (also known as severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, 2019-nCoV])-induced disease, COVID-19, has spread rapidly worldwide. Studies have reported that the traditional Chinese medicine Salvia miltiorrhiza possesses remarkable antiviral properties; however, the anti-coronaviral activity of its main components, salvianolic acid A (SAA), salvianolic acid B (SAB), and salvianolic acid C (SAC) is still debated. In this study, we used Cell Counting Kit-8 staining and flow cytometry to evaluate the toxicity of SAA, SAB, and SAC on ACE2 (angiotensin-converting enzyme 2) high-expressing HEK293T cells (ACE2 h cells). We found that SAA, SAB, and SAC had a minor effect on the viability of ACE2 h cells at concentrations below 100 μM. We further evaluated the binding capacity of SAA, SAB, and SAC to ACE2 and the spike protein of 2019-nCoV using molecular docking and surface plasmon resonance. They could bind to the receptorbinding domain (RBD) of the 2019-nCoV with a binding constant (K D ) of (3.82 ± 0.43) e−6 M, (5.15 ± 0.64)e−7 M, and (2.19 ± 0.14)e-6 M; and bind to ACE2 with K D (4.08 ± 0.61)e−7 M, (2.95 ± 0.78)e−7 M, and (7.32 ± 0.42)e−7 M, respectively. As a result, SAA, SAB, and SAC were determined to inhibit the entry of 2019-nCoV Spike pseudovirus with an EC 50 of 11.31, 6.22, and 10.14 μM on ACE2 h cells, respectively. In conclusion, our study revealed that three Salvianolic acids can inhibit the entry of 2019-nCoV spike pseudovirus into ACE2 h cells by binding to the RBD of the 2019-nCoV spike protein and ACE2 protein.

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Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro

Cited by 14 publications

References 44 publications

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics

Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP‐2 and the c‐Raf/MEK/ERK pathway

Three salvianolic acids inhibit 2019‐nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2

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