Salvianolic acid A is a polyphenolic compound with multi-target pharmacological activities. Salvianolic acid A inhibits the activity of the TGF-β1 signaling pathway by targeting TGF-β receptor I (TβRI) and downregulates the expression of MMP9 protein[1]. Salvianolic acid A is commonly used in cardiovascular diseases and organ fibrosis research. Derived from Salvia miltiorrhiza (Danshen), Salvianolic acid A suppresses mitochondrial lipid peroxidation, maintains ATPase activity, eliminates superoxide, and exhibits strong antioxidant and neuroprotective effects[2]. Additionally, Salvianolic acid A demonstrates broad pharmacological activities, including anti-inflammatory, anticancer, and antifibrotic properties[3, 4].
In vitro, in a hemorrhagic stroke model using hemin-incubated cortical neuronal cells, Salvianolic acid A (30-60μM) improved cell viability, enhanced the expression of Solute Carrier Family 7 Member 11 (XCT) and glutathione peroxidase 4 (GPX4), and reduced reactive oxygen species (ROS) production[5]. In hydrogen peroxide (H₂O₂)-induced human umbilical vein endothelial cell (HUVEC) injury models, Salvianolic acid A (0.25-16μM) treatment significantly increased cell viability and proliferation, reduced H₂O₂-induced cell death and oxidative stress, downregulated cell cycle-related proteins p53 and p21, and upregulated cyclin E1 levels[6].
In vivo, In chloroform-induced liver fibrosis rats treated with Salvianolic acid A (5, 15 mg/kg/day) via intraperitoneal injection for 6 weeks, Salvianolic acid A alleviated hepatic inflammation and fibrosis, reduced collagen deposition and pseudolobule formation, and decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA), laminin (LN), type IV collagen (CIV), and N-terminal propeptide of type III procollagen (PIIINP)[7]. In gentamicin-induced acute kidney injury rats treated with Salvianolic acid A (10, 20, 40mg/kg/day) via intraperitoneal injection for 7 days, Salvianolic acid A reduced renal index, serum levels of kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), as well as urinary protein levels[8].
References:
[1] QIN T, RASUL A, SARFRAZ A, et al. Salvianolic acid A & B: potential cytotoxic polyphenols in battle against cancer via targeting multiple signaling pathways [J]. Int J Biol Sci, 2019, 15(10): 2256-2264.
[2] QIU J M, QIN C F, WU S G, et al. A novel salvianolic acid A analog with resveratrol structure and its antioxidant activities in vitro and in vivo [J]. Drug Dev Res, 2021, 82(1): 108-114.
[3] ZENG X, CHEN X, QIN H, et al. Preventive effects of a natural anti-inflammatory agent Salvianolic acid A on acute kidney injury in mice [J]. Food Chem Toxicol, 2020, 135(110901.
[4] GONG D F, SUN S C, WANG R R, et al. Salvianolic acid A improve mitochondrial respiration and cardiac function via inhibiting apoptosis pathway through CRYAB in diabetic cardiomyopathy [J]. Biomed Pharmacother, 2023, 160(114382.
[5] SHI Y, YAN D, NAN C, et al. Salvianolic acid A inhibits ferroptosis and protects against intracerebral hemorrhage [J]. Sci Rep, 2024, 14(1): 12427.
[6] QIAO X, CAO S, CHEN S, et al. Salvianolic acid A alleviates H(2)O(2)-induced endothelial oxidative injury via miR-204-5p [J]. Sci Rep, 2024, 14(1): 11931.
[7] WANG R, SONG F, LI S, et al. Salvianolic acid A attenuates CCl(4)-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways [J]. Drug Des Devel Ther, 2019, 13:1889-1900.
[8] DIAO H Y, ZHU W, LIU J, et al. Salvianolic Acid A Improves Rat Kidney Injury by Regulating MAPKs and TGF-beta1/Smads Signaling Pathways [J]. Molecules, 2023, 28(8).
Salvianolic acid A是一种多靶点药理活性的多酚化合物，其通过靶向TGF-β受体I（TβRI）抑制TGF-β1信号通路的活性，还能下调MMP9蛋白的表达[1]。它通常被用于心血管疾病和器官纤维化的研究。Salvianolic acid A是一种源自丹参的多酚类化合物，能抑制线粒体脂质过氧化，维持线粒体脂质过氧化，维持ATP酶活性和消除超酶活性，具有很强的抗氧化活性和神经保护作用[2]。Salvianolic acid A还具备具抗炎、抗癌、抗纤维化等广泛的药理活性[3, 4]。
在体外，Salvianolic acid A（30-60μM）处理以血红素孵育皮质神经元细胞模拟的神经元中的出血性中风，改善了细胞活力，有效增强了Solute Carrier Family 7 Member 11（XCT）和谷胱甘肽过氧化物酶 4 （GPX4）的表达，减少了ROS的产生[5]。Salvianolic acid A（0.25-16μM）处理过氧化氢诱导的人脐静脉内皮细胞 （HUVEC）损伤模型，显著增强了细胞活力、增殖水平，降低了过氧化氢引起的细胞死亡和氧化应激水平，降低了细胞周期相关蛋白p53、p21的表达，但增加了周期蛋白E1水平[6]。
在体内，Salvianolic acid A（5、15mg/kg/day）通过腹腔注射治疗氯仿诱导的肝纤维化大鼠6周，Salvianolic acid A改善了肝纤维化大鼠的肝组织炎症和纤维化，减少胶原纤维的沉积和假小叶的形成。降低血清了中天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）的水平透明质酸（HA）、层粘连蛋白（LN）、Ⅳ型胶原（CIV）和Ⅲ型前胶原 N-末端肽（PIIINP）的水平[7]。Salvianolic acid A（10、20、40mg/kg/ day）通过腹腔注射治疗庆大霉素诱导的急性肾损伤大鼠7天，降低了大鼠的肾脏指数，降低血清中肾脏损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂蛋白（NGAL）的水平，同时降低肾损伤大鼠的尿蛋白[8]。