Salvianolic acid A (Sal A or SAA) is a hydrophilic polyphenolic derivative isolated from Salvia miltiorrhiza Bunge as an anti-cancer and cardio-protective herbal medicine. The IC50 values were determined as 5.7 µM in the HEK293/ETAR cell line and 3.14 µM in HeLa cells, respectively[3]. in vitro, SAA enhances the activation of the Akt/GSK-3β/Nrf2 signaling pathway in H2O2-Induced HK-2 Cells. in vivo, administration of SAA significantly increased the activities of T-SOD, GPx, and CAT[4]. It also can inhibit platelet activation via the inhibition of PI3K, and attenuates arterial thrombus formation in vivo, suggesting that it may be developed as a therapeutic agent for the prevention of thrombotic disorders[5]. Salvianolic acid A is also a matrix metalloproteinase-9 inhibitor, can prevents cardiac remodeling in spontaneously hypertensive rats, and inhibits PDGF-BB-activated HSC proliferation, partially through apoptosis induction while exerting no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations[6].
Salvianolic acid A/丹酚酸A 细胞实验
Cell Line
Concentration
Treated Time
Description
References
C3H10T1/2 adipocytes
80 µM
0, 2, 4, 8 hours
To examine the time-course effects of Sal A on UCP-1 expression, results showed that UCP-1 expression significantly increased at 2 h, peaked at 4 h, and returned to basal levels at 8 h
Front Pharmacol. 2021 May 28;12:614406
HEK293/ET AR cells
5.7 µM (IC50)
10 min
Evaluate the antagonistic effect of Sal A on ET AR, results showed Sal A is a selective ET AR antagonist
Int J Mol Sci. 2016 Aug 2;17(8):1244
HepG2 cells
25, 50, 100 µM
12 hours
To evaluate the protective effects of Salvianolic acid A against palmitic acid-induced hepatocyte cytotoxicity. Results showed that Salvianolic acid A pretreatment significantly ameliorated palmitic acid-induced cell death.
Front Pharmacol. 2020 Nov 30;11:560905
H9c2 cardiomyocytes
5, 10, 20, 40 µM
12 hours
To evaluate the protective effects of Salvianolic acid A against palmitic acid-induced cardiomyocyte injury. Results showed that Salvianolic acid A significantly reversed PA-induced cell death, improved mitochondrial membrane potential and intracellular reactive oxygen species levels.
Front Pharmacol. 2021 Mar 8;12:627123
HeLa cells
3.14 µM (IC50)
15 min
Evaluate the inhibitory effect of Sal A on endogenous ET AR, results showed Sal A partially inhibited ET AR activation
Int J Mol Sci. 2016 Aug 2;17(8):1244
HiPS-CMs cells
10 µM
24 hours
Evaluate the cytotoxicity of Sal A on hiPS-CMs cells, results showed Sal A had no significant cytotoxicity
Int J Mol Sci. 2016 Aug 2;17(8):1244
RAW264.7 cells
15 and 30 µM
24 hours
To evaluate the effect of SAA on M2-like TAM polarization, results showed SAA increased the expression levels of CD86, IL-1β, and iNOS, and decreased the expression levels of Arg-1 and CD206.
Molecules. 2024 Mar 26;29(7):1469
ARPE-19 cells
20 µM
24 hours
To evaluate the cytotoxicity of RGD-PEI/SAA complexes, results showed that low concentrations of SAA (≤20 µM) had no obvious cytotoxic effect, and SAA in nanoparticle form was less toxic than free SAA.
J Nanobiotechnology. 2021 Jul 2;19(1):196
Human primary chondrocytes
10, 20, 40, 80 µg/mL
24 hours
To evaluate the effect of Salvianolic acid A on cell viability. Results showed no significant cytotoxicity at concentrations ≤80 µg/mL, and SAA significantly suppressed IL-1β-induced inflammatory factors (MMP1, MMP13, ADAMTS-5) expression while promoting collagen II and aggrecan synthesis.
Drug Des Devel Ther. 2020 May 8;14:1771-1778
HUVECs
25 µM
24 hours
To investigate the effect of Salvianolic acid A on high glucose-induced pyroptosis in endothelial cells. Results showed that SAA inhibited PKM2 Y105 phosphorylation, reduced nuclear translocation of PKM2, thereby suppressing NLRP3 inflammasome activation and endothelial cell pyroptosis.
Front Pharmacol. 2022 Nov 8;13:1009229
Mouse chondrocytes
6.25, 12.5, 25 µM
24 hours
To evaluate the inhibitory effect of SAA on IL-1β-induced inflammatory response and cartilage matrix degradation. Results showed that SAA significantly inhibited the production of inflammatory mediators (NO, PGE2, TNF-α, IL-6, iNOS, COX-2) induced by IL-1β and reduced the degradation of cartilage matrix.
Front Pharmacol. 2020 Jun 3;11:682
HL60 cells
25 µM
24 hours
Combination treatment of Sal A and ATO significantly enhanced ATO-induced cytotoxicity
Front Pharmacol. 2018 May 9;9:487
K562 cells
25 µM
24 hours
Combination treatment of Sal A and ATO significantly enhanced ATO-induced cytotoxicity
Front Pharmacol. 2018 May 9;9:487
HepaRG cells
25 µM
24 hours
Combination treatment of Sal A and ATO significantly enhanced ATO-induced cytotoxicity
Front Pharmacol. 2018 May 9;9:487
SGC7901 cells
25 µM
24 hours
Combination treatment of Sal A and ATO significantly enhanced ATO-induced cytotoxicity
Front Pharmacol. 2018 May 9;9:487
LX2 cells
25 µM
24 hours
To investigate the effect of SalA on PDGF-BB-induced fibrosis and ER stress in LX2 cells, results showed that SalA inhibited ER stress and fibrosis by up-regulating SIRT1
Front Pharmacol. 2018 Nov 5;9:1277
HK-2 cells
3, 10, 30 µM
24 hours
To evaluate the inhibitory effect of SAA on LPS-induced inflammatory response in HK-2 cells. Results showed that SAA significantly reduced the secretion of TNF-α and IL-1β and inhibited the activation of NF-κB and p38 MAPK signaling pathways.
Acta Pharmacol Sin. 2018 Dec;39(12):1855-1864
H9c2 cells
12.5 µM
24 hours
Significantly reduced oxidative stress, ferroptosis and CD36 expression, while increasing p-AMPK
Burns Trauma. 2024 Apr 9;12:tkad055
AML12 cells
10 µM
24 hours
To evaluate the protective effect of Salvianolic acid A on APAP-induced hepatotoxicity, results showed that Salvianolic acid A significantly increased cell viability and alleviated oxidative stress and inflammation.
Antioxidants (Basel). 2023 Apr 3;12(4):870
Primary rat cortical neurons
50 µM
24 hours
To evaluate the inhibitory effect of Salvianolic acid A on hemin-induced ferroptosis in primary cortical neurons. Results showed that Salvianolic acid A significantly improved cell viability, reduced intracellular ROS production, decreased MDA and Fe2+ levels, and increased the expression of GSH, XCT, and GPX4.
Sci Rep. 2024 May 30;14(1):12427
Human umbilical vein endothelial cells (HUVECs)
0.25 µM and 0.5 µM
24 hours
SalA promoted cell viability and proliferation rate, decreased LDH and ROS levels, increased SOD activity, significantly attenuated endothelial senescence, inhibited cell apoptosis, and reversed the increase in LC3 II/I ratio and NLRP3 accumulation.
Sci Rep. 2024 May 24;14(1):11931
Human glioma cell line U87
0, 5, 10, 15, 20, 25, 50, 100 µM
24, 48 hours
To evaluate the effects of Sal A on the viability, proliferation, migration, invasion, and apoptosis of glioma cells. Results showed that Sal A treatment reduced the viability of U87 cells in a dose-dependent manner, inhibited proliferation, migration, and invasion, and promoted apoptosis.
Bioengineered. 2022 May;13(5):11646-11655
Human Vascular Smooth Muscle Cells (HVSMC)
10 µM
4 hours
To identify protein targets of SAA, transgelin and actin were identified as direct targets of SAA via LC-MS/MS
EBioMedicine. 2018 Nov;37:246-258
H9c2 cardiomyocytes
10 µM
4 hours
Sal A pretreatment alleviated ATO-induced mitochondrial structural and functional damage
Front Pharmacol. 2018 May 9;9:487
C3H10T1/2 adipocytes
20, 40, 80 µM
4 hours
To investigate the effects of Sal A on UCP-1 expression, results showed that Sal A upregulated UCP-1 mRNA and protein levels in a dose-dependent manner
Front Pharmacol. 2021 May 28;12:614406
HEK293 cells
2.81 μg/mL
4 hours and 24 hours
Evaluate the antagonistic effect of Sal A on DOX-induced renal cytotoxicity, results showed Sal A significantly reduced DOX-induced damage to HEK293 cells
J Nanobiotechnology. 2022 Sep 24;20(1):425
HUVEC cells
10 µM
48 hours
Evaluate the cytotoxicity of Sal A on HUVEC cells, results showed Sal A had no significant cytotoxicity
Int J Mol Sci. 2016 Aug 2;17(8):1244
MCF-7/PTX cells
12 µM
48 hours
To evaluate the reversal effect of Salvianolic acid A on paclitaxel resistance and its inhibitory effect on cell migration and invasion abilities. Results showed that SAA significantly enhanced the sensitivity of MCF-7/PTX cells to paclitaxel and inhibited cell migration and invasion abilities.
Cancer Biol Ther. 2015;16(9):1407-14
Human brain microvascular endothelial cells (HBMECs)
10 µM
6 hours
To evaluate the protective effect of SAA on OGD-induced cell viability reduction and degradation of tight junction proteins. Results showed that SAA pretreatment significantly inhibited OGD-induced cell viability reduction and degradation of tight junction proteins (ZO-1, occludin, claudin-5).
Acta Pharmacol Sin. 2021 Mar;42(3):370-381
A549 cells
6.461 µM (IC50)
72 hours
Evaluate the inhibitory effect of Sal A on A549 cell proliferation, results showed Sal A significantly inhibited cell proliferation
Int J Mol Sci. 2016 Aug 2;17(8):1244
DU145 cells
9.512 µM (IC50)
72 hours
Evaluate the inhibitory effect of Sal A on DU145 cell proliferation, results showed Sal A significantly inhibited cell proliferation
Int J Mol Sci. 2016 Aug 2;17(8):1244
HUVECs
20 µM
8 hours
To evaluate the anti-angiogenesis effect of RGD-PEI/SAA complexes, results showed that the RGD-PEI/SAA treatment group exhibited the strongest anti-angiogenesis effect among all groups.
J Nanobiotechnology. 2021 Jul 2;19(1):196
Salvianolic acid A/丹酚酸A 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
MCT-induced pulmonary hypertension model by a single subcutaneous injection of MCT (60 mg/kg)
Oral
0.3, 1, 3 mg/kg/day
Once daily for 4 weeks
SAA significantly attenuated pulmonary arterial remodeling in MCT-induced PAH rats, likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.
Acta Pharmacol Sin. 2016 Jun;37(6):772-82
Zucker diabetic fatty rats
Type 2 diabetes mellitus with atherosclerosis induced by high-fat diet and Vitamin D3 injections
Tail vein injection
1 mg/kg
Once daily for 6 weeks
To evaluate the therapeutic effects of Salvianolic acid A on type 2 diabetes mellitus with atherosclerosis. Results showed that SAA significantly reduced HbA1c levels, improved lipid disorders, reduced foam cells and cholesterol crystals in aortic tissues, and inhibited NLRP3 inflammasome activation and NF-κB signaling pathway.
Molecules. 2020 Feb 28;25(5):1089
C57/BL6 mice
Myocardial ischemia model
Oral
10 mg/kg
Once daily for one week
To evaluate the protective effects of SAA and SAA-30 on myocardial ischemia, results showed that SAA-30 was more effective than SAA in improving myocardial ischemia symptoms
EBioMedicine. 2018 Nov;37:246-258
SD rats
Autologous thrombus stroke model
Oral
10 mg/kg
Twice daily for 5 days
To evaluate the preventive effect of SAA on cerebrovascular endothelial injury caused by ischemic stroke. Results showed that SAA pretreatment significantly improved neurological deficits, intracerebral hemorrhage, BBB disruption, and vascular endothelial dysfunction.
Acta Pharmacol Sin. 2021 Mar;42(3):370-381
Sprague-Dawley rats
Intracerebral hemorrhage model
Intraperitoneal injection
10 mg/kg
Once daily for 5 days
To evaluate the therapeutic effect of Salvianolic acid A on the intracerebral hemorrhage model in rats. Results showed that Salvianolic acid A significantly improved neurological deficits, reduced brain edema and hematoma volume, decreased iron deposition and neuronal degeneration, and inhibited ferroptosis by activating the Akt/GSK-3β/Nrf2 signaling pathway.
Sci Rep. 2024 May 30;14(1):12427
Sprague-Dawley rats
Electrocoagulation-induced autologous thrombus stroke model
Intragastric administration
10 mg/kg
Once daily for 14 days
SAA administration significantly decreased infarction volume and vascular embolism, and ameliorated pathological injury in the hippocampus and striatum as well as the neurological deficits as compared with the model rats. Furthermore, SAA significantly promoted neural stem/progenitor cells (NSPCs) proliferation, migration and differentiation into neurons, enhanced axonal regeneration and diminished neuronal apoptosis around the ipsilateral subventricular zone (SVZ), resulting in restored neural density and reconstructed neural circuits in the ischemic striatum.
Acta Pharmacol Sin. 2022 Sep;43(9):2212-2225
ApoE−/− mice
Diabetic atherosclerosis model
Oral gavage
10 mg/kg and 20 mg/kg
Once daily for four weeks
To investigate the effect of Salvianolic acid A on diabetic atherosclerosis. Results showed that SAA significantly reduced atherosclerotic plaque formation, inhibited pathological changes in the aorta, and ameliorated diabetic atherosclerosis by suppressing NLRP3 inflammasome activation and endothelial cell pyroptosis.
Front Pharmacol. 2022 Nov 8;13:1009229
Sprague-Dawley rats
Bile duct ligation (BDL)-induced liver fibrosis model
Intragastric administration
10 mg/kg/day and 20 mg/kg/day
Once daily for 3 weeks
To investigate the effect of SalA on BDL-induced liver injury and fibrosis, results showed that SalA attenuated ER stress and liver fibrosis by up-regulating the SIRT1/HSF1 pathway
Front Pharmacol. 2018 Nov 5;9:1277
Mice
Diabetic myocardial ischemia-reperfusion injury model
Intravenous injection
10 mg/kg/h
Continuous infusion
The combined application of low-dose propofol and salvianolic acid A conferred synergistic protective effects against myocardial ischemia-reperfusion injury in diabetes, superior to the use of high-dose propofol alone.
Burns Trauma. 2024 Apr 9;12:tkad055
SD rats
Gentamicin-induced AKI model and 5/6 nephrectomy-induced CKD model
Intragastric administration
10, 20, 40 mg/kg/d
7 consecutive days (AKI model) or four weeks (CKD model)
Salvianolic acid A improved gentamicin-induced AKI and 5/6 Nx-induced CKD, which may be achieved by inhibiting the release of inflammatory factors and alleviating oxidative stress injury, as well as regulating the MAPKs and TGF-β1/smads signaling pathways.
Molecules. 2023 Apr 21;28(8):3630
C57BL/6 mice
APAP-induced hepatotoxicity model
Oral
15 mg/kg/day and 30 mg/kg/day
Once daily for 3 days
To evaluate the protective effect of Salvianolic acid A on APAP-induced hepatotoxicity, results showed that Salvianolic acid A significantly reduced serum ALT and AST levels and alleviated liver tissue damage.
Antioxidants (Basel). 2023 Apr 3;12(4):870
BALB/c nude mice
4T1 breast cancer model
Tail vein injection
2 mg/kg DOX and 20 mg/kg Sal A
Once every two days, total of 6 administrations
Evaluate the anti-tumor effect and nephrotoxicity of E-[c(RGDfK)2]/FA-NLC-Sal A/DOX, results showed the best anti-tumor effect (tumor volume inhibition rate 90.72%, tumor weight inhibition rate 83.94%) and low nephrotoxicity (serum creatinine concentration 52.58 μmoL/L)
J Nanobiotechnology. 2022 Sep 24;20(1):425
Sprague-Dawley rats
5/6 nephrectomized rat model
Intraperitoneal injection
2.5, 5, 10 mg/kg/day
Once daily for 28 days
To evaluate the protective effect of SAA on kidney injury in 5/6 nephrectomized rats. Results showed that SAA dose-dependently reduced the levels of urine protein, blood urea nitrogen, serum creatinine, plasma total cholesterol, and plasma triglycerides, and improved renal pathological lesions and fibrosis. Additionally, SAA inhibited the activation of NF-κB and p38 MAPK signaling pathways and reduced the secretion of inflammatory cytokines.
Acta Pharmacol Sin. 2018 Dec;39(12):1855-1864
C57BL/6J mice
Laser-induced choroidal neovascularization model
Intravitreal injection
20 µM
Single injection, observed for 7 days
To evaluate the anti-angiogenesis effect of RGD-PEI/SAA complexes in a laser-induced CNV mouse model, results showed that the RGD-PEI/SAA treatment group reduced the CNV area by 55.78% compared to the PBS group.
J Nanobiotechnology. 2021 Jul 2;19(1):196
C57BL/6J mice
High-fat and high-carbohydrate diet-induced fatty liver model
Intraperitoneal injection
20 and 40 mg/kg
Every other day for 10 weeks
To evaluate the protective effects of Salvianolic acid A against high-fat and high-carbohydrate diet-induced fatty liver. Results showed that Salvianolic acid A attenuated body weight gain, liver injury, and hepatic steatosis.
Front Pharmacol. 2020 Nov 30;11:560905
Male C57BL/6 mice
High-fat diet-induced obesity model
Intraperitoneal injection
20 and 40 mg/kg
Administered every other day for 13 weeks
To investigate the protective anti-obesity mechanisms of Sal A, results showed that Sal A significantly attenuated weight gain and lipid accumulation, and induced browning of white adipose tissue
Front Pharmacol. 2021 May 28;12:614406
BALB/c mice
ATO-induced cardiotoxicity model
Intraperitoneal injection
3 mg/kg
Once daily for 2 weeks
Sal A pretreatment alleviated ATO-induced cardiac mitochondrial damage
Front Pharmacol. 2018 May 9;9:487
C57BL/6J mice
High-fat diet-induced obese mouse model
Intraperitoneal injection
40 mg/kg
Every other day for 12 weeks
To evaluate the protective effects of Salvianolic acid A against high-fat diet-induced myocardial injury. Results showed that Salvianolic acid A significantly improved myocardium morphological changes and myocardial damage, and reduced plasma AST and CK-MB levels.
Front Pharmacol. 2021 Mar 8;12:627123
Sprague-Dawley rats
CCl4-induced liver fibrosis model
Intraperitoneal injection
5 mg/kg and 15 mg/kg
Once daily for 6 weeks
To evaluate the therapeutic effect of salvianolic acid A on CCl4-induced liver fibrosis. The results showed that salvianolic acid A significantly reduced the degree of liver fibrosis, improved liver function indicators, reduced collagen deposition, and inhibited hepatic stellate cell activation and hepatocyte apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway and regulating the Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways.
Drug Des Devel Ther. 2019 May 31;13:1889-1900
BALB/c mice
Pristane-induced systemic lupus erythematosus model
Oral gavage
5 mg/kg/d
Once daily for 5 months
To evaluate the protective effect of salvianolic acid A on renal injury in pristane-induced systemic lupus erythematosus mice. The results showed that salvianolic acid A significantly reduced the levels of anti-Sm autoantibodies, alleviated renal histopathological changes, and significantly inhibited the phosphorylation of IKK, IκB and NFκB in renal tissues.
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