Erythritol Improves Nonalcoholic Fatty Liver Disease by Activating Nrf2 Antioxidant Capacity

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a kind of serious fat disorder that has become a critical problem to human society. Therefore, finding drugs that are safe and effective has become more and more important. Erythritol (Ery) is a polyol sweetener with a variety of biological functions. However, whether Ery has a relieving effect on NAFLD has not been reported yet. Therefore, we induced HepG2 cells with oleic acid and palmitic acid as our in vitro model. Moreover, we choose wild-type mice with tyloxapol and high-fat diet and nuclear factor E2-related factor 2 (Nrf2) knockout mice with high-fat diet as our in vivo model. We found that Ery could reverse the lipid accumulation, oxidative stress, and endoplasmic reticulum stress caused by the NAFLD model. The mechanism studies showed that Ery promoted the translocation of Nrf2 from cytoplasm to nucleus, and the molecular simulation docking results of Ery and Nrf2 showed that there was a hydrogen bond between them. Moreover, Ery could promote the production of HO-1 and NQO1 antioxidant proteins and inhibit the expression of endoplasmic reticulum stress proteins GPR78, p-PERK, and CHOP. On the contrast, when Nrf2 was knocked out in mice, Ery lost its protective effect on NAFLD. In conclusion, we found that the potential mechanism of Ery’s protective effect is that it plays an antioxidant role by activating the Nrf2 signaling pathway, thereby inhibiting endoplasmic reticulum stress and lipid accumulation in NAFLD.

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

“…Humid conditions were optimized with a CO 2 concentration of 5% to culture HepG2 cells in DMEM with 10% FBS at 37 °C. The cells were subjected to pre-treatment with AT (200 μM) for 1 h and then treated with a certain amount of palmitic acid (PA; 660 μM; Sigma, Missouri) and oleic acid (OA; 330 μM; Sigma, Missouri) for 24 h. PA and OA were dissolved in alcohol prior to their application …”

“…The cells were subjected to pre-treatment with AT (200 μM) for 1 h and then treated with a certain amount of palmitic acid (PA; 660 μM; Sigma, Missouri) and oleic acid (OA; 330 μM; Sigma, Missouri) for 24 h. PA and OA were dissolved in alcohol prior to their application. 19 Cell Counting Kit-8 (CCK8) Assay. The viability of HepG2 cells was detected by employing CCK8 (Saint-Bio, Shanghai, China).…”

Triptolide Induces Liver Injury by Regulating Macrophage Recruitment and Polarization via the Nrf2 Signaling Pathway

“…The Nrf2 signaling pathway has been reported to play an antioxidant role in nonalcoholic steatohepatitis [ 24 ], liver fibrosis [ 25 ], and liver ischemia/reperfusion [ 26 ], which may offer a novel potential strategy for the prevention and treatment of liver diseases [ 27 ]. Sulforaphane (SFN), an agonist of Nrf2 that has been demonstrated to promote the nuclear translocation of Nrf2 and suppress oxidative stress [ 28 ], was chosen to verify the protective role of the Nrf2 pathway in TP-induced cytotoxicity.…”

1,3-Dichloro-2-propanol-Induced Renal Tubular Cell Necroptosis through the ROS/RIPK3/MLKL Pathway

“…32,33 Nuclear factor erythroid 2-related factor 2 (Nrf2), a nuclear transcription factor, transferred into the nucleus and regulated the expressions of many antioxidant-related proteins such as heme oxygenase 1 (HO-1), glutamyl cysteine ligase, peroxiredoxin, superoxide dismutase, and NAD(P)H quinone dehydrogenase 1 (NQO1). 34,35 The expressions of antioxidant proteins could decrease excessive ROS and alleviate cell death induced by ROS. In addition to the effects of antioxidant proteins on ROS, mitophagy participated in the regulation of ROS levels.…”

“…These studies demonstrated that excessive ROS participated in the regulation of necroptosis. Organelles of ROS generation in cells include mitochondria, endoplasmic reticulum, and peroxisomes. , Nuclear factor erythroid 2-related factor 2 (Nrf2), a nuclear transcription factor, transferred into the nucleus and regulated the expressions of many antioxidant-related proteins such as heme oxygenase 1 (HO-1), glutamyl cysteine ligase, peroxiredoxin, superoxide dismutase, and NAD­( P )H quinone dehydrogenase 1 (NQO1). , The expressions of antioxidant proteins could decrease excessive ROS and alleviate cell death induced by ROS. In addition to the effects of antioxidant proteins on ROS, mitophagy participated in the regulation of ROS levels. , Damaged mitochondria could be encapsulated and degraded by autophagy, known as mitophagy.…”