Protective role of Siberian onions against toxin-induced liver dysfunction: an insight into health-promoting effects.

Siberian onions (SOs) are delicious wild vegetables. Their taste is most unique, not only like scallions but also like leeks or garlic. They also have a traditional medicinal value for anti-inflammation, anti-oxidation, and anti-pyretic analgesia, particularly facilitating hepatoprotective effects. The current study investigates the potential mechanism of SOs against toxin-induced liver dysfunction. BALB/c mice were administrated with SO or silymarin by oral gavage for one week, followed by injecting carbon tetrachloride (CCl4) to induce hepatic fibrosis. The effect of SO against hepatic fibrosis was evaluated by examining the liver tissue for serum transaminase, oxidative stress, extracellular matrix, histological alterations, cytokine levels, and apoptosis. In vitro, HSC-T6 cells were cultured with the supernatant from Raw 264.7 cells stimulated with lipopolysaccharides, followed by SO extracts or Niclosamide (Signal Transducer and Activator of Transcription 3 (STAT3) inhibitor) at indicated time periods and doses. SO decreased serum transaminase levels and oxidative stress, and regulated the balance of ECM in CCl4-induced mice, including α-SMA, collagen-I and TIMP-1. SO reduced the release of inflammatory factors and regulated apoptosis-associated proteins, which is related to the inhibition of STAT3 phosphorylation. Moreover, SO reduced the positive expressions of α-SMA and NLRP3 by inhibiting STAT3 phosphorylation in activated HSCs. SO could show health-promoting effects for liver dysfunction by alleviating hepatic fibrogenesis, apoptosis and inflammation in the development of hepatic fibrosis potential depending on the STAT3 signaling pathway.

Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation.

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 µM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

Allium victorialis L. Extracts Promote Activity of FXR to Ameliorate Alcoholic Liver Disease: Targeting Liver Lipid Deposition and Inflammation.

Allium victorialis L. (AVL) is a traditional medicinal plant recorded in the Compendium of Materia Medica (the Ming Dynasty). In general, it is used for hemostasis, analgesia, anti-inflammation, antioxidation, and to especially facilitate hepatoprotective effect. In recent years, it has received more and more attention due to its special nutritional and medicinal value. The present study investigates the effect and potential mechanism of AVL against alcoholic liver disease (ALD). C57BL/6 mice were fed Lieber-DeCarli liquid diet containing 5% ethanol plus a single ethanol gavage (5 g/kg), and followed up with the administration of AVL or silymarin. AML12 cells were stimulated with ethanol and incubated with AVL. AVL significantly reduced serum transaminase and triglycerides in the liver and attenuated histopathological changes caused by ethanol. AVL significantly inhibited SREBP1 and its target genes, regulated lipin 1/2, increased PPARα and its target genes, and decreased PPARγ expression caused by ethanol. In addition, AVL significantly enhanced FXR, LXRs, Sirt1, and AMPK expressions compared with the EtOH group. AVL also inhibited inflammatory factors, NLRP3, and F4/80 and MPO, macrophage and neutrophil markers. In vitro, AVL significantly reduced lipid droplets, lipid metabolism enzymes, and inflammatory factors depending on FXR activation. AVL could ameliorate alcoholic steatohepatitis, lipid deposition and inflammation in ALD by targeting FXR activation.