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Abstract Background and aims Epidemiological evidence suggests that the phenotype of glutathione S-transferase mu 1 (GSTM1), a hepatic high-expressed phase II detoxification enzyme, is closely associated with the incidence of alcohol-related liver disease (ALD). However, whether and how hepatic GSTM1 determines the development of ALD is largely unclear. This study was designed to elucidate the role and potential mechanism(s) of hepatic GSTM1 in the pathological process of ALD. Methods GSTM1 was detected in the liver of various ALD mice models and cultured hepatocytes. Liver-specific GSTM1 or/and micro (miR)-743a-3p deficiency mice were generated by adenoassociated virus-8 delivered shRNA, respectively. The potential signal pathways involving in alcohol-regulated GSTM1 and GSTM1-associated ALD were explored via both genetic manipulation and pharmacological approaches. Results GSTM1 was significantly upregulated in both chronic alcohol-induced mice liver and ethanol-exposed murine primary hepatocytes. Alcohol-reduced miR-743a-3p directly contributed to the upregulation of GSTM1, since liver specific silencing miR-743a-3p enhanced GSTM1 and miR-743a-3p loss protected alcohol-induced liver dysfunctions, which was significantly blocked by GSTM1 knockdown. GSTM1 loss robustly aggravated alcohol-induced hepatic steatosis, oxidative stress, inflammation, and early fibrotic-like changes, which was associated with the activation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), and p38. GSTM1 antagonized ASK1 phosphorylation and its downstream JNK/p38 signaling pathway upon chronic alcohol consumption via binding with ASK1. ASK1 blockage significantly rescued hepatic GSTM1 loss-enhanced disorders in alcohol-fed mice liver. Conclusions Chronic alcohol consumption-induced upregulation of GSTM1 in the liver provides a feedback protection against hepatic steatosis and liver injury by counteracting ASK1 activation. Down-regulation of miR-743a-3p improves alcohol intake-induced hepatic steatosis and liver injury via direct targeting on GSTM1. The miR-743a-3p–GSTM1 axis functions as an innate protective pathway to defend the early stage of ALD. Graphical Abstract

This study aimed to evaluate the protective role and potential mechanisms of Xie Zhuo Tiao Zhi decoction (XZTZ) on alcohol-associated liver disease (ALD). XZTZ significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration. Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by XZTZ, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by XZTZ. In conclusion, XZTZ demonstrates potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease.

Objectives: To screen lactic acid bacteria (LAB) produced angiotensin-converting enzyme (ACE) inhibitory peptides and to evaluate their probiotic properties. Methods: Lactic acid bacteria were inoculated into skimmed milk, the proteolysis degree and ACE inhibition rate of fermented milk were determined by colorimetric assays. Two LAB (ZJUIDS09 and ZJUIDS11) that resulted in the highest proteolysis degree and ACE inhibition rate were selected, and their probiotic properties were evaluated, including acid resistance, bile salt resistance, antibiotic resistance, and antibacterial activity. The fermented milk produced by the two strains was treated with simulated gastrointestinal digestive juices, and their ACE inhibition rates were determined. Finally, the two strains were used as starter cultures in the fermentation of Holstein skim milk, Holstein whey, buffalo skim milk and buffalo whey, and the ACE inhibition rates of the fermented milk were determined. Results: The degrees of proteolysis of fermented milk produced by strain ZJUIDS09 and ZJUIDS11 were 5.79%±0.14% and 5.75%±0.10%, respectively. Their ACE inhibition rates were 87.39%±2.44% and 90.41%±0.99%, respectively. And their IC50 were 0.31 and 0.25 mg/mL, respectively. Their ACE inhibition rates after digestion with simulated gastrointestinal juices were decreased to 70.13%±0.15% and 76.39%±2.91%, respectively. Strains ZJUIDS09 and ZJUIDS11 were resistant to acid and bile salt, exhibited antibacterial activity and antibiotic sensitivity, and were identified as Lactobacillus reuteri and Lactobacillus helveticus by 16S rDNA. Comparing Holstein skim milk, Holstein whey, Buffalo skim milk and Buffalo whey after strain fermentation, Holstein skim milk was the most suitable substrates for strains ZJUIDS09 and ZJUIDS11 to produce ACE-inhibitory peptides. Conclusion: Lactobacillus reuteri ZJUIDS09 and Lactobacillus helveticus ZJUIDS11 screened in this study had a strong ability to produce ACE inhibitory peptides and had the potential to develop fermented dairy products with blood pressure-lowering effect.

This present study was designed to explore the protective role of Lactobacillus plantarum ZJUIDS14 against Non-alcoholic Fatty Liver Disease (NAFLD) in a high-fat-diet (HFD)-induced C57BL/6 mice model. The probiotic (109 CFU/every other day) was administered by oral gavage for 12 weeks. We found that L. plantarum ZJUIDS14 intervention significantly alleviated HFD related hepatic steatosis, liver damage, insulin resistance, and increased hepatic expression of peroxisome proliferator activated receptor α (PPAR-α) while stimulating the activation of AMP-activated protein kinase (AMPK). Furthermore, L. plantarum ZJUIDS14 improved mitochondrial function as reflected by an increase in dynamin related protein 1 (DRP1) and a decrease of proteins associated with oxidative phosphorylation (OXPHOS) after the treatment. Additionally, mice from the L. plantarum ZJUIDS14 group had a restored intestinal flora and homeostasis involving Coprostanoligenes group, Ruminococcaceae UCG-014, Allobaculum, Ruminiclostridium 1, and Roseburia. Meanwhile, these five genera exhibited a significant (negative or positive) association with ileum inflammation mRNA levels and SCFA contents, by Spearman’s correlation analysis. In general, our data demonstrated that L. plantarum ZJUIDS14 mitigates hepatic steatosis and liver damage induced by HFD. Specifically, they strengthened the integrity of the intestinal barrier, regulated gut microbiota, and improved mitochondrial function. Our data provide an experimental basis for L. plantarum ZJUIDS14 as a promising candidate to prevent NAFLD.

The encapsulation of krill oil high in docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and astaxanthin as a multifunctional dietary supplement for the purpose of enhancing its physical and chemical stability and to expand its application in aqueous-based food was attempted. Nanostructured lipid carriers (NLCs) containing high content of krill oil were successfully prepared using palm stearin as a solid lipid and lecithin as a surfactant. The results demonstrated that the developed NLC had spherical or ovoid structure with small size (96%). DSC (differential scanning calorimetry) result showed a less-ordered crystalline structure leading to high loading capacity. NLC was found to offer bioactives in krill oil significant protection against photooxidation upon exposure to UV light. Good physical and chemical stabilities were revealed by long-term storage at different temperatures. Feasibilities of pasteurization and lyophilization were also demonstrated, showing promise for application in functional drinks and milk powder fortification.

Chimonanthus nitens Oliv. (CN) is a species in the family Calycanthaceae. Its leaf is widely used to make traditional herbal tea in southern China and has a wide range of therapeutic effects. The profile of the ethanol extracts from CN leaves was identified by UPLC-QTOF-MS/MS. Forty seven compounds were determined including organic acids, phenolic acids and derivatives, flavonoids, coumarins, fatty acids and other compounds. The effect of the CN extracts on the inflammatory damage in zebrafish and in RAW 264.7 cells was investigated. The extracts demonstrated a strong ability to inhibit the recruitment of neutrophils in LPS-stimulated zebrafish, but macrophage migration was not significantly affected. Pro-inflammatory cytokines (i.e., TNF-α, IL-6 and IL-1β) were also determined by q-PCR. The extracts strongly reduced mRNA expression of TNF-α, IL-6 but not IL-1β in zebrafish model, while significantly inhibited the production of the factors in the RAW 264.7 cells. Therefore, our results suggest that the ethanol extracts of CN leaves may serve as a source of nutraceutical compounds with anti-inflammatory properties.