Sodium tanshinone IIA sulfonate ameliorates hepatic steatosis by inhibiting lipogenesis and inflammation

Xiao-Xiao Li,Xin-Yi Lu,Shi-Jie Zhang,Amy P Chiu,Lilian H Lo,David A Largaespada,Qu-Bo Chen,Vincent W Keng

doi:10.1016/j.biopha.2018.12.019

Abstract

Non-alcoholic fatty liver disease (NAFLD) is becoming an epidemic disease in adults and children worldwide. Importantly, there are currently no approved treatments available for NAFLD. This study aims to investigate the potential applications of sodium tanshinone IIA sulfonate (STS) on improving the NAFLD condition using both in vitro and in vivo approaches. The results showed that STS markedly inhibited lipid accumulation in oleic acid (OA) and palmitic acid (PA) treated HepG2 and primary immortalized human hepatic (PIH) cells. STS suppressed lipogenesis by inhibiting expression of sterol regulatory element binding transcription factor 1 (SREBF1), fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD). In addition, STS reduced inflammation in cells treated with OA-PA, shown by decreased transcriptional levels of tumor necrosis factor (TNF), transforming growth factor beta 1 (TGFB1) and interleukin 1 beta (IL1B). Consistently, protective effects on hepatic steatosis in db/db mice were observed after STS administration, demonstrated by decreased lipid accumulation in mouse hepatocytes. This protective effect might be associated with STS induced activation of sirtuin 1 (SIRT1)/protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1) pathways. Our findings suggest a potential therapeutic role for STS in the treatment of NAFLD.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is becoming a prevalent chronic liver diseases in adults and children worldwide
There was a study showing sodium tanshinone IIA sulfonate (STS) ameliorated myocardial inflammation and lipid accumulation in Beagle dogs [11]. These studies led to the hypothesis that STS might show protective effects on NAFLD development and progression, where lipid accumulation and inflammation are the main pathological factors [6]
We have demonstrated that STS treatment elicited a protective effect against lipid accumulation both in vitro and in vivo

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is becoming a prevalent chronic liver diseases in adults and children worldwide. NAFLD is closely related with insulin resistance and a variety of metabolic diseases, including type 2 diabetes, obesity and atherosclerotic cardiovascular disease [2]. NAFLD induces a spectrum of liver damages including simple steatosis and steatosis with liver inflammation, commonly referred to as non-alcoholic steatohepatitis (NASH). Weight loss is highly recommended as a prevention for NAFLD and NASH, in order to reverse the accumulation of triglycerides (TG) in hepatocytes. Suppression of hepatic inflammation can prevent NAFLD progression [6]. Some studies have suggested that pioglitazone, a type 2 diabetes medicine, could improve NASH, but further exploration are still required to evaluate its toxicity for long-term use [7]

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