Salvianolic acid B protects against acute and chronic liver injury by inhibiting Smad2C/L phosphorylation

Abstract

Salvianolic acid B (Sal B) has strong antioxidant and anti-fibrosis effects, which are related to the transforming growth factor β/Smad signaling pathway. However, how Sal B affects this antioxidant pathway and the phosphorylation (p-) of Smad2 at both the COOH-terminal (pSmad2C) and linker region (pSmad2L) are unknown. The aims of the present study were to investigate the underlying mechanisms of Sal B on acute and chronic liver injury induced by CCl 4 and H 2 O 2 , and its effects on p-Smad2C/L. In in vivo experiments, acute and chronic liver injury models were induced by CCl 4 , and the oxidative damage cell model was established in vitro with H 2 O 2. Liver histopathology was assessed using hematoxylin and eosin and Van Gieson's staining. Moreover, serum biochemical indicators were analyzed using specific assay kits. Furthermore, the present study evaluated the oxidant/antioxidant status in acute and chronic liver injury models by oxidative stress parameters such as malondialdehyde, glutathione and superoxide dismutase. In addition, western blot analysis was performed to analyze the protein expression levels of pSmad2C, pSmad2L, nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). It was found that Sal B improved liver histology, decreased the levels of aminotransferase and attenuated oxidative stress in acute and chronic liver injury models. Additionally, the protein expression levels of pSmad2C and pSmad2L were decreased, but Nrf2 and HO-1 expression levels were increased both in vivo and in vitro. Collectively, the present results suggested that Sal B may protect against acute and chronic liver injury via inhibition of Smad2C/L phosphorylation, and the Nrf2/HO-1 signaling pathway may play an important role in this process.

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

“…roots and rhizomes in both the Chinese Pharmacopoeia and United States Pharmacopoeia. This phytochemical has revealed multiple bioactivities including (1) a protective effect on the brain from ischemia/reperfusion-induced injury by inhibiting reactive oxygen species (ROS)-mediated inflammation [ 205 ]; (2) a protective effect on the liver from acute and chronic injury by the inhibition of Smad2C/L phosphorylation [ 206 ]; (3) an anti-inflammatory effect on atherosclerosis through the mitogen-activated protein kinase/nuclear factor-κB (MAPKs/NF-κB) signaling pathways in vivo and in vitro [ 207 ]; (4) an anti-tumor effect against human breast cancer adenocarcinoma cells [ 208 ]; and (5) anti-diabetic effects [ 209 ].…”

Tanshinone IIA regulates CCl4 induced liver fibrosis in C57BL/6J mice via the PI3K/Akt and Nrf2/HO‐1 signaling pathways

“…On the one hand, the activation of Nrf2 could effectively inhibit the occurrence of LF, but on the other hand, sustained activation of Nrf2 may promote liver injury and further induce LF and the occurrence of liver cancer. [48,49] Fauconneau et al reported that under oxidative stress conditions, HO-1, as a downstream target of Nrf2, its expression level was increased. [50] However, Tan IIA may effectively inhibit LF by reducing the expression level of HO-1, [51] which was consistent with our results.…”

Salvianolic Acid B: A Review of Pharmacological Effects, Safety, Combination Therapy, New Dosage Forms, and Novel Drug Delivery Routes

“…Treatment with salvianolic acid B inhibits the phosphorylation of Smad2 both at the C-terminus and link region via the TGF-β/Smad signaling pathway, improves the histological characteristics of the liver, decreases the levels of aspartate aminotransaminase (AST) and alanine aminotransferase (ALT), and attenuates oxidative stress (increased SOD levels and decreased GSH levels) to protect against acute and chronic liver injury. In addition, upregulation of the Nrf2/HO-1 signaling pathway by salvianolic acid B plays a key role in suppressing CCl 4 -induced acute liver injury [ 154 , 155 ]. In mouse models of senecionine-induced acute liver injury, salvianolic acid B can regulate oxidative stress (increased SOD levels and decreased GSH levels) and inhibit liver fibrosis-related factors, including MMP-9, TGF-β1, and phosphorylated STAT3, by modulating the coagulation system (decreased expression of plasminogen activator inhibitor 1 (PAI-1)).…”