Astaxanthin Alleviates Nonalcoholic Fatty Liver Disease by Regulating the Intestinal Flora and Targeting the AMPK/Nrf2 Signal Axis

Abstract

Nonalcoholic fatty liver disease (NAFLD) is among the most prevalent chronic liver diseases around the globe. The accumulation of lipids in the liver and oxidative stress are important pathological mechanisms of NAFLD. Astaxanthin (AT) is a carotenoid extracted from shrimps and crabs with beneficial biological activities, including anti-oxidative and anti-inflammatory activities. 16S microflora sequencing, H&E staining, and the western blot technique were employed to investigate the impacts of AT on a high-fat diet (HFD)-induced NAFLD. Significant mitigation in lipid metabolism-related disorders and decreased oxidative stress in HFD-induced mice were observed due to AT, and significant changes in the gut flora of the model mice were also observed. The in vitro study showed that AT considerably lowered the protein expression level of fatty acid synthetase (FAS), sterol regulatory element-binding protein-1c (SREBP-1c), and acetyl-COA carboxylase (ACC) and increased the protein expression of nuclear factor-E2 associated factor 2 (Nrf2) and AMP-activated protein kinase (AMPK) in oleic acid (OA) and palmitic acid (PA)-induced HepG2 cells. Additionally, mechanistic studies revealed that compound C (AMPK inhibitor, CC) inhibited the regulatory effect of AT on the SREBP-1c and Nrf2 signaling pathways. In conclusion, AT can inhibit the SREBP-1c, FAS, and ACC signaling pathways, activate the AMPK and Nrf2 signaling pathways, and improve the structure of intestinal flora.

Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

“…37 The role of Nrf2 in liver steatosis, inflammation, fibrosis, as well as related therapeutic strategies has been recently summarized by Bukke et al 38 Besides, the studies that the natural plants components alleviate NAFLD via AMPK/Nrf2 pathway have been reported extensively. 36,39,40 In this study, the downregulation in the relative protein level of p-AMPK/AMPK, Nrf2, and HO-1 in HFD-feeding rats was restored by the treatment of PMS, suggesting that PMS activated the AMPK/Nrf2 pathway in HFD-induced NAFLD rats. Zeng et al 28 have reported that PMS promotes the activation of Nrf2/HO-1 pathway in hypoxia/reoxygenation-induced injury.…”

“…Nrf2 plays an important role in neutralizing oxidative stress and conserving redox homeostasis in the cell through the generation of cytoprotective and antioxidant enzymes, such as HO‐1 and NQO1 37 . The role of Nrf2 in liver steatosis, inflammation, fibrosis, as well as related therapeutic strategies has been recently summarized by Bukke et al 38 Besides, the studies that the natural plants components alleviate NAFLD via AMPK/Nrf2 pathway have been reported extensively 36,39,40 . In this study, the downregulation in the relative protein level of p‐AMPK/AMPK, Nrf2, and HO‐1 in HFD‐feeding rats was restored by the treatment of PMS, suggesting that PMS activated the AMPK/Nrf2 pathway in HFD‐induced NAFLD rats.…”

Astaxanthin Protects against Alcoholic Liver Injury via Regulating Mitochondrial Redox Balance and Calcium Homeostasis

“…In particular, the calcium signaling pathway also showed a high enrichment score in GSEA analysis, suggesting ameliorative mitochondrial calcium balance by AX. A previous study showed that the Nrf2-ARE pathway, the most classical signaling pathway for AX activation, is mainly responsible for regulating intracellular antioxidants and maintaining redox balance in mitochondria. − Nonetheless, it remains unclear whether AX contributes to maintaining cellular redox balance by activating the Nrf2-ARE pathway, thereby altering calcium signaling molecular events and thus improving the normal function of mitochondria in ALD.…”

Bioprotective Role of Phytocompounds Against the Pathogenesis of Non-alcoholic Fatty Liver Disease to Non-alcoholic Steatohepatitis: Unravelling Underlying Molecular Mechanisms

“…In vitro OA and PAtreated L02 and HepG2 cells; in vivo HFD-fed mice Downregulated SREBP-1c, ACC, FAS, CD36, CPT1α, FOXA, PGC1α, TNF-α, and IL-1β; upregulated AMPK and Nrf2 [281][282][283] 76 This article is protected by copyright. All rights reserved.…”