New insights into salvianolic acid A action: Regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways ameliorates HFD-induced NAFLD in rats

Abstract

Salvianolic acid A (SalA), one of the most efficacious polyphenol compounds extracted from Radix Salvia miltiorrhiza (Danshen), has been shown to possess many potential pharmacological activities. This study aimed to investigate whether SalA has hepatoprotective effects against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and to further explore the mechanism underlying this process. SalA treatment significantly attenuated HFD-induced obesity and liver injury, and markedly decreased lipid accumulation in HFD-fed rat livers. Moreover, SalA treatment ameliorated HFD-induced hepatic inflammation and oxidative stress by decreasing hepatotoxic levels of cytokines, suppressing the overproduction of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) and preventing the decreased expression of superoxide dismutase (SOD). Importantly, SalA reversed the HFD- or palmitic acid (PA)-induced activation of the NLRP3 inflammasome, the nuclear translocation of ChREBP and the up-regulation of FAS, and these effects were accompanied by TXNIP down-regulation. However, TXNIP siRNA treatment partially abrogated the above-mentioned effects of SalA in PA-treated HepG2 cells. Together, our results demonstrated, for the first time, that SalA protects against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation, and these protective effects may partially due to regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways.

LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

“…In this study, we identified that TXNIP was a direct target of miR‐335‐3p at its 3′‐UTR mRNA by bioinformatics, which was confirmed by luciferase reporter assays, and miR‐335‐3p overexpression suppressed NPC apoptosis and TXNIP expression at mRNA and protein levels, while silencing miR‐335‐3p led to an opposite effect. TXNIP, an endogenous inhibitor of thioredoxin, mediates NLRP3 inflammasome activation in various inflammatory diseases including, but not limited to diabetic retinopathy , rheumatoid arthritis (RA) , nonalcoholic fatty liver disease (NAFLD) . In this study, we confirmed that TXNIP expression at mRNA and protein levels was increased in IDD patients as compared to patients with spinal cord injury.…”

Melatonin alleviates cadmium‐induced liver injury by inhibiting the TXNIP‐NLRP3 inflammasome

“…Moreover, NLRP3 deficiency had no effects on Cd‐induced TXNIP overexpression (data not shown), indicating that TXNIP overexpression occurs upstream of NLRP3 inflammasome activation after Cd exposure. In fact, TXNIP could directly activate the NLRP3 inflammasome under oxidative stress . Therefore, we speculate that targeting the TXNIP‐NLRP3 inflammasome pathway may be an effective therapeutic approach to attenuate Cd‐induced liver injury.…”

Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation

“…Previous studies have indicated that HFD contributed to excessive production of reactive ROS [13] and, therefore, we investigated the effects of LDL on ROS levels of SW480, LoVo and RKO, using DCFH-DA fluorescence analysis. The results showed that all types of CRC cells treated with LDL exhibited significantly higher ROS levels compared with controls (Fig.…”

“…Studies have also suggested that HFD may contribute to inflammation and oxidative stress by causing excessive production of reactive oxygen species (ROS) [13]; moreover, both LDL and VLDL were shown to activate the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway [14]. ROS are a group of molecules and free radicals generated within cells through oxygen metabolism.…”