Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls University of Heidelberg, Heidelberg, Germany.
Sanofi, Neuilly-Sur-Seine, France.
Pharmacol Rep. 2024 Jun;76(3):572-584. doi: 10.1007/s43440-024-00595-4. Epub 2024 Apr 26.
Essential phospholipids (EPL) are hepatoprotective.
The effects on interleukin (IL)-6 and -8 secretion and on certain lipid-metabolizing enzymes of non-cytotoxic concentrations of EPL (0.1 and 0.25 mg/ml), polyenylphosphatidylcholine (PPC), and phosphatidylinositol (PtdIns) (both at 0.1 and 1 mg/ml), compared with untreated controls, were assessed in human hepatocyte cell lines (HepG2, HepaRG, and steatotic HepaRG).
Lipopolysaccharide (LPS)-induced IL-6 secretion was significantly decreased in HepaRG cells by most phospholipids, and significantly increased in steatotic HepaRG cells with at least one concentration of EPL and PtdIns. LPS-induced IL-8 secretion was significantly increased in HepaRG and steatotic HepaRG cells with all phospholipids. All phospholipids significantly decreased amounts of fatty acid synthase in steatotic HepaRG cells and the amounts of acyl-CoA oxidase in HepaRG cells. Amounts of lecithin cholesterol acyltransferase were significantly decreased in HepG2 and HepaRG cells by most phospholipids, and significantly increased with 0.1 mg/ml PPC (HepaRG cells) and 1 mg/ml PtdIns (steatotic HepaRG cells). Glucose-6-phosphate dehydrogenase activity was unaffected by any phospholipid in any cell line.
EPL, PPC, and PtdIns impacted the secretion of pro-inflammatory cytokines and affected amounts of several key lipid-metabolizing enzymes in human hepatocyte cell lines. Such changes may help liver function improvement, and provide further insights into the EPL's mechanism of action.
必需磷脂(EPL)具有保肝作用。
评估了非细胞毒性浓度的 EPL(0.1 和 0.25mg/ml)、多烯磷脂酰胆碱(PPC)和磷脂酰肌醇(PtdIns)(均为 0.1 和 1mg/ml)与未处理对照相比,对人肝细胞系(HepG2、HepaRG 和脂肪变性 HepaRG)中白细胞介素(IL)-6 和 -8 分泌和某些脂质代谢酶的影响。
脂多糖(LPS)诱导的 HepaRG 细胞中 IL-6 分泌被大多数磷脂显著降低,而在至少一种 EPL 和 PtdIns 浓度的脂肪变性 HepaRG 细胞中显著增加。LPS 诱导的 HepaRG 和脂肪变性 HepaRG 细胞中 IL-8 分泌均显著增加。所有磷脂均显著降低脂肪变性 HepaRG 细胞中脂肪酸合酶的含量,并降低 HepaRG 细胞中酰基辅酶 A 氧化酶的含量。大多数磷脂显著降低 HepG2 和 HepaRG 细胞中卵磷脂胆固醇酰基转移酶的含量,而 0.1mg/ml PPC(HepaRG 细胞)和 1mg/ml PtdIns(脂肪变性 HepaRG 细胞)则显著增加。任何磷脂对任何细胞系中的葡萄糖-6-磷酸脱氢酶活性均无影响。
EPL、PPC 和 PtdIns 影响人肝细胞系中促炎细胞因子的分泌,并影响几种关键脂质代谢酶的含量。这些变化可能有助于改善肝功能,并进一步深入了解 EPL 的作用机制。