Soybean polyenylphosphatidylcholine (PPC) is beneficial in liver and extrahepatic tissue injury: An update in experimental research.

Polyenylphosphatidylcholine (PPC) is a purified polyunsaturated phosphatidylcholine extract of soybeans. This article updates PPC's beneficial effects on various forms of liver cell injury and other tissues in experimental research. PPC downregulates hepatocyte CYP2E1 expression and associated hepatotoxicity, as well as attenuates oxidative stress, apoptosis, lipoprotein oxidation and steatosis in alcoholic and nonalcoholic liver injury. PPC inhibits pro-inflammatory cytokine production, while stimulating anti-inflammatory cytokine secretion in ethanol or lipopolysaccharide-stimulated Kupffer cells/macrophages. It promotes M2-type macrophage polarization and metabolic reprogramming of glucose and lipid metabolism. PPC mitigates steatosis in NAFLD through inhibiting polarization of pro-inflammatory M1-type Kupffer cells, alleviating metabolic inflammation, remodeling hepatic lipid metabolism, correcting imbalances between lipogenesis and lipolysis and enhancing lipoprotein secretion from hepatocytes. PPC is antifibrotic by preventing progression of alcoholic hepatic fibrosis in baboons and also prevents CCl4-induced fibrosis in rats. PPC supplementation replenishes the phosphatidylcholine content of damaged cell membranes, resulting in increased membrane fluidity and functioning. Phosphatidylcholine repletion prevents increased membrane curvature of the endoplasmic reticulum and Golgi and decreases sterol regulatory element binding protein-1-mediated lipogenesis, reducing steatosis. PPC remodels gut microbiota and affects hepatic lipid metabolism via the gut-hepatic-axis and also alleviates brain inflammatory responses and cognitive impairment via the gut-brain-axis. Additionally, PPC protects extrahepatic tissues from injury caused by various toxic compounds by reducing oxidative stress, inflammation, and membrane damage. It also stimulates liver regeneration, enhances sensitivity of cancer cells to radiotherapy/chemotherapy, and inhibits experimental hepatocarcinogenesis. PPC's beneficial effects justify it as a supportive treatment of liver disease.

Schisandrin B targets cannabinoid 2 receptor in Kupffer cell to ameliorate CCl4-induced liver fibrosis by suppressing NF-κB and p38 MAPK pathway.

BACKGROUND: Lignans, the major bioactive components of Schisandra chinensis, displays an anti-liver fibrosis effect. However, which one is the most effective lignan and what is its molecular mechanisms are still unclear. PURPOSE: This research aimed to screen the most effective components of lignans, identify and verify its pharmacological target, and investigate its molecular mechanism against liver fibrosis. METHODS: First, the most effective lignans were screened by a comprehensive RAW264.7/CMC system and LPS-induced RAW264.7. Second, the potential targets were predicted by a liver fibrosis domain-specific chemo-genomics knowledgebase and further verified by competition binding assay. Third, the effect of anti-liver fibrosis was evaluated by employing RAW264.7, co-cultured hepatic stellate cells (HSC) and CCl4-induced liver fibrosis CB2-/- mice. The qPCR, ELISAs, western blot analyses, and immunofluorescence were used to evaluate the expression of main inflammatory factors and key proteins in NF-κB and p38 MAPK pathway. RESULTS: Schisandrin B was identified as the most effective component for attenuating liver fibrosis, and CB2 was proven to be a potential target for anti-liver fibrosis. The in vitro and in vivo assays indicated that schisandrin B ameliorated CCl4-induced liver fibrosis through suppressing NF-κB and p38 MAPK pathway in Kupffer cells by targeting CB2 receptor CONCLUSION: Schisandrin B targets CB2 receptor to inhibit Kupffer cell polarization by downregulating the NF-κB and p38 MAPK signaling pathways for ameliorating liver fibrosis.

Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviate Traumatic Hemorrhagic Shock Induced Hepatic Injury via IL-10/PTPN22-Mediated M2 Kupffer Cell Polarization.

Traumatic hemorrhagic shock (THS) is a major cause of mortality and morbidity worldwide in severely injured patients. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and tissue repair potential mainly through a paracrine pathway mediated by MSC-derived extracellular vesicles (MSC-EVs). Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine that plays a crucial role during the inflammatory response, with a broad range of effects on innate and adaptive immunity, preventing damage to the host and maintaining normal tissue homeostasis. However, the function and mechanism of IL-10 in MSC-mediated protective effect in THS remain obscure. Here, we show that MSCs significantly attenuate hepatic injury and inflammation from THS in mice. Notably, these beneficial effects of MSCs disappeared when IL-10 was knocked out in EVs or when recombinant IL-10 was administered to mice. Mechanistically, MSC-EVs function to carry and deliver IL-10 as cargo. WT MSC-EVs restored the function of IL-10 KO MSCs during THS injury. We further demonstrated that EVs containing IL-10 mainly accumulated in the liver during THS, where they were captured by Kupffer cells and induced the expression of PTPN22. These effects subsequently shifted Kupffer cells to an anti-inflammatory phenotype and mitigated liver inflammation and injury. Therefore, our study indicates that MSC-EVs containing IL-10 alleviate THS-induced hepatic injury and may serve as a cell-free therapeutic approach for THS.