Table. 1.
Bioactive alleviators for hepatic ER stress and UPR in mammalian cells
| Compound | Full Name/Source | Mechanisms of Action | Ref |
|---|---|---|---|
| 4-AAQB | 4-acetylantroquinonol B (natural ubiquinone derivative extracted from mycelia of Antrodia cinnamomea) | Ameliorates ER stress and inflammation in J774A.1 and RAW264.7 cellular model of NAFLD and C57BL/6J mice fed choline/methionine-deficient diet | (87) |
| Berberine | Natural compound found in several herbal plants | Reverses ER stress and ER stress-induced lipogenesis via ATF6α /SREBF1 axis in mice and hepatocyte cell lines, confers resistance to steatosis, and diminishes liver fibrosis, and lipid peroxides | (88) |
| Betaine | Nutrient | Reduces serum homocysteine levels, dampens severe ER stress and UPR in the liver in alcohol-fed mice | (89) |
| Bicyclol | Chemical compound | Ameliorates mouse fatty liver by attenuating ER stress-triggered apoptosis and downregulation of DDIT3, HSPA5, ERN1, and ATF6α | (90) |
| Curcumin | Natural compound derived from Curcuma Longa | Reduces liver ER stress and ER stress markers (BiP, PERK, IRE1, TRAF2, TNF, IL1B, MAPK14, MAP3K5, CEBPB) in diabetic rat liver, suppresses ER stress-mediated apoptosis and boosts liver histopathological and morphological changes and function | (91) |
| Empagliflozin | Medication for type 2 diabetes treatment | Reduces fasting glucose, total triglyceride and cholesterol levels, levels of inflammatory molecules and lipogenic enzymes, ER stress proteins (BiP, IRE1, XBP1, eIF2α, ATF6α, ATF4, CHOP, SQSTM1, HSP90B1), induces adaptive autophagy, and inhibits CASP8 cleavage and apoptosis to relieve NAFLD in HFD-fed mice | (92) |
| Fenofibrate | Medication to reduce blood TG and cholesterol | Ameliorates NAFLD in high-cholesterol diet-fed C57BL/6 mice via suppressing ER stress, inflammation, apoptosis, downregulating ERN1 and XBP1, and reducing MAPK8 phosphorylation | (93) |
| Ginsenoside Mc1 | Compound found in ginseng | Protects from ER stress-induced apoptosis, lipogenesis, and insulin resistance in palmitate-treated HepG2 cells and obese mice | (94) |
| Homocysteine | An amino acid | Mitigates ER stress and replenishes liver S-adenosylmethionine, resulting in alleviation of steatohepatitis in a mouse model of steatohepatitis and cultured hepatocytes. Reduces TNF production from liver macrophages in NASH | (95) |
| Kaempferol | Antioxidation and anti-inflammatory flavonoid | Reduces lethality, increases survival time and alleviates liver injury via inhibition of ER stress-induced apoptosis, downregulation of DDIT3, and upregulation of HSPA5 in mice with acute liver failure and in vitro model | (96) |
| Lactobacillus rhamnosus GG | Friendly bacteria in intestines | Downregulates ER stress and ROS and liver HSPA5 and DDIT3 expression, and normalizes autophagy in acute alcohol-triggered liver damage in C57BL/6 mice | (97) |
| Liraglutide | Analog of glucagon-like peptide-1 | Alleviates ER stress and attenuates chemerin expression in rat livers in HFD-induced insulin resistance | (98) |
| Matrine | Alkaloid obtained from Sophora flavescens | Reverses ER stress, repairs mitochondrial dysfunction, shrinks lipid accumulation and Ca2+ overload by inhibiting ATP2A2, and reduces lipid peroxides and inflammation in the liver of C57BL/6J mice under HFD | (99) |
| Melatonin | Pineal gland released hormone | Suppresses severe UPR activation and ER stress-induced apoptosis, and attenuates expression of DDIT3, HSPA5, HSP90B1, MAPK8, and CASP12 in a rabbit model of fulminant hepatitis ATP2A2 | (100) |
| Disrupts tunicamycin-caused ER stress via downregulation of MIR-23a in primary hepatocytes, alleviates liver steatosis and inflammation | (101) | ||
| Metformin | Medication for type 2 diabetes treatment | Inhibits palmitate-caused ER stress and liver insulin resistance, downregulates HSPA5, DDIT3, ATF6α, eIF2α, and XBP1 in HepG2 cells | (102) |
| Pioglitazone | Anti-diabetic medication | Suppresses ER stress and insulin resistance in diabetic mouse liver | (103) |
| Quercetin | Natural flavonoid | Resolves ER stress, oxidative stress and hepatotoxicity in rat livers exposed to lead. Reduces IRE1 and MAPK8 levels in rat livers | (104) |
| Rapamycin | Macrolide compound | Protects the liver from I/R injury via downregulation of ER stress proteins, inhibits maladaptive UPR in murine and in vitro models of I/R injury | (105) |
| Salvianolic acid B | Natural antioxidant | Suppresses ER stress and hyperactivation of ER stress molecules (CHOP, PERK, IRE1), Refines glucose tolerance, and improves insulin resistance in the liver of ob/ob mice | (106) |
| Schisandra chinensis methanol extract | Chinese herbal medicine | Suppresses ER stress, levels of lipogenic and inflammatory genes, and triglyceride accumulation, alleviates NAFLD in HepG2 cells and obese mice under tunicamycin or palmitate treatment | (107) |
| Silymarin | Chemical compound | Reverses pathologies associated with NAFLD such as ER stress, lipid profile, AST, ALT, HSAP5, and XBP1 levels | (108) |
| Taurine | Amino sulfonic acid | Suppresses ER stress, oxidative stress, CASP3 activation, and apoptosis in H4IIE cells and primary hepatocytes in diet-induced NAFLD models. Counters liver injury, inflammation, lipid accumulation, plasma TG levels | (109) |
| Vitamin C | Vitamin abundantly found in foods | Ameliorates perfluorooctane sulfonate-triggered murine liver steatosis via suppression of maladaptive UPR and ER stress as demonstrated by downregulation of ATF6α, eIF2α, HSPA5, and XBP1, and inhibition of hepatocellular inflammation | (110) |