The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

Abstract

Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α.

Blueberry, combined with probiotics, alleviates non-alcoholic fatty liver diseaseviaIL-22-mediated JAK1/STAT3/BAX signaling

“…In our previous study, we have reported that BP can reduce the damage to hepatocytes caused by the action of inflammatory cytokines, regulate lipid metabolism and reduce hepatocyte adipose degeneration in vivo. 23 In this study, we show that blueberries mixed with probiotics reduce the formation of lipid droplets, improve lipid indicators, and improve the pathology of fatty liver, both in vitro and in vivo, which further supports the alleviatory effect of BP on NAFLD.…”

Protection of hepatocyte mitochondrial function by blueberry juice and probiotics via SIRT1 regulation in non-alcoholic fatty liver disease

“…Our previous study revealed that the combination of blueberry juice and probiotics exhibits a better ameliorating effect on Non-Alcoholic Steatohepatitis (NASH) compared to only blueberry or probiotics. 10 Nevertheless, the molecular mechanisms underlying the effects of BP in NAFLD remain unclear. In the present study, we demonstrated that BP substantially restored the pathogenesis of HFD-induced NAFLD by improving mitochondrial function via activation of the SIRT1/PGC-1α pathway.…”

“…Our previous study showed that BP could effectively improve NAFLD by regulating a PPAR-α-mediated SREBP-1c/PNPLA-3 pathway. 10 Nevertheless, the mechanisms of how BP influences NAFLD are still poorly understood.…”

Anti‐Diabetic Effects of Gynura Bicolor Aqueous Extract in Mice

“…Partial liver tissue was cut and fixed in formalin buffered with 10% phosphate solution. Then, liver tissue was embedded in paraffin to form paraffin blocks (Ren, Zhu, Zhu, & Cheng, 2017). Each block was cut at 5-µm-thickness, and followed by staining with Oil Red O (ORO) dye.…”