Alcoholic liver disease (ALD) is a significant health burden with limited therapeutic options. This study aimed to elucidate the protective mechanisms of nobiletin (NOB) against alcohol-induced liver injury in mice, focusing on the gut-liver axis. After a 7-day high-dose NOB intervention, treated mice showed a significant increase in body weight (P < 0.05) and marked improvements in key serum parameters, including 25% reduced aspartate aminotransferase (AST), 45% decreased low-density lipoprotein cholesterol (LDL-C), 25% suppressed interleukin-6 (IL-6) and 10% reduced tumor necrosis factor-α (TNF-α) relative to the alcohol-induced model group. Untargeted metabolomics analysis revealed that NOB remodeled glycerophospholipid metabolism, specifically upregulating phosphatidylcholine (PC) and phosphatidylethanolamine (PE) while suppressing lysophospholipids (LysoPC/LysoPE). Concurrently, NOB enhanced intestinal barrier integrity via upregulation of the tight junction protein ZO-1 and Occludin, Furthermore, it modulated gut microbiota composition by enriching beneficial probiotics such as Lactobacillus. In liver tissue, NOB activated the Nrf2 antioxidant pathway, increasing enzymes (SOD, CAT, GSH) and reducing malondialdehyde (MDA), while simultaneously inhibiting the NF-κB pathway and its downstream pro-inflammatory cytokines (TNF-α, IL-1β). Spearman correlation analysis further linked specific microbial shifts (Lactobacillus murinus) with the observed serum metabolic changes (PC, PE). Collectively, these findings demonstrate that NOB mitigates alcoholic liver injury through multi-pathway involvement of the “intestinal flora–glycerophospholipid metabolism–hepatic inflammation” axis, presenting a novel therapeutic candidate for ALD that warrants further clinical investigation.

Alcoholic liver injury (ALI) has emerged as a significant public health concern, necessitating the urgent identification of medicinal-food resources for its prevention and treatment. As a natural medicinal food resource, Chenpi (CHE) is rich in various flavonoid bioactive compounds and exhibits potential antioxidant, anti-inflammatory, and hepatoprotective effects. However, the effect and mechanism of CHE in preventing and improving ALI are not yet known. This study sought to elucidate CHE’s hepatoprotective mechanisms in ALI from the biochemical markers, microbiome and transcriptome perspectives. Results showed that CHE ameliorated ALI by improving oxidative stress, inflammatory cytokines and liver function. 16S rRNA analysis revealed that CHE alleviated ALI pathological progression primarily by restoring gut microbiota composition. Transcriptomic analysis showed that CHE improved ALI mainly related to MAPK signaling pathway. Pearson correlation analysis revealed that Candidatus_Saccharimonas, Turicibacter, and Clostridium_sensu_stricto_1 play key roles in the process by which CHE ameliorates alcohol-induced inflammation and pathological angiogenesis. These findings revealed that CHE has the potential to be used as a functional food to prevent or improve ALI.

Impaired lactation often causes early cessation of exclusive breastfeeding, increasing health risks for infants and mothers. Hemerocallis citrina Baroni, as a food ingredient, is renowned for its potential to improve lactation. However, its active compounds and specific lactation-promoting mechanisms remain unclear. Herein, we employed an integrated multi-omics strategy combining network pharmacology, transcriptomics, proteomics, molecular docking and experimental validation to analyze the lactation-promoting mechanism of H. citrina. Our results showed that ethanol extract of H. citrina (HEE) significantly upregulated serum lactation-related hormone levels and promoted mammary gland development, which resulted in improved lactation. In total, 159 phenolics were identified by UHPLC-Q-Exactive Orbitrap-MS. Based on the network pharmacology result, 67 intersecting target genes between HEE phenolics and lactation-related targets were identified. The constructed HEE phenolics-target-pathway network indicated that HEE might act on key targets (TNF, AKT1, EGFR, HIF1A and CASP3) through active phenolics including caffeic acid, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chromen-4-one, gnaphaliin, chrysoeriol, and diosmetin. Further combined analysis using network pharmacology and multi-omics (transcriptomics and proteomics) suggested that the regulation of AKT1, CASP3, and the PI3K-AKT signaling pathway could be important mechanisms by which HEE improves impaired lactation. Molecular docking and MD simulation validated that the key active phenolics in HEE bind well and stably with core targets. Cellular experiments further showed that HEE significantly promoted mammary epithelial cell proliferation and enhanced milk components synthesis via the PI3K-AKT signaling pathway, providing new insights into exploring the development and application of H. citrina to alleviate impaired lactation.

Gut microbiota plays a crucial role in the pathophysiology of depression. This study aimed to explore the antidepressant effect of mature whole Citrus aurantium fruit extract (FEMC) in the chronic unpredictable mild stress (CUMS) model. The behavioral tests were applied to assess antidepressant effect and 16S rRNA sequencing was used to analyze the changes of gut microbiota. The results showed that the major components of FEMC were naringin and neohesperidin and significantly increased the sucrose preference index of the mice. FEMC also could reduce the feeding latency in an open field test and the rest time in a novelty suppressed feeding test. In addition, FEMC could increase CUMS-induced reduction in the levels of BDNF, PSD95, and SYN in the hippocampus. Moreover, FEMC intervention slightly decreased the ratio of Firmicutes to Bacteroidota. Meanwhile, FEMC reduced the abundance of the Prevotellaceae_Ga6A1_group, [Ruminococcus]_torques_group, which have been reported to be closely related to inflammation. Bioinformatics analysis revealed that mitogen-activated protein kinase (MAPK) signaling pathway and lipopolysaccharide biosynthesis were involved in the anti-inflammatory effect of FEMC in the CUMS animal model. Finally, the ELISA results showed that FEMC could significantly reduce the expression of pro-inflammatory cytokines IL-6 and TNF-α in the serum of depressive mice. Our results suggest FEMC can ameliorate depressive behavior by inhibiting gut microbiota-mediated inflammation in mice.

The microbial potential of Penicillium has received critical attention. The present research aimed to elucidate the efficacy of crude enzyme secreted from Penicillium oxalicum WX-209 in degrading citrus segments and evaluate the safety of the process. Results showed that citrus segment membranes gradually dissolved after treatment with the crude enzyme solution, indicating good degradation capability. No significant differences in body weight, food ingestion rate, hematology, blood biochemistry, and weight changes of different organs were found between the enzyme intake and control groups. Serial experiments showed that the crude enzyme had high biological safety. Moreover, the whole genome of P. oxalicum WX-209 was sequenced by PacBio and Illumina platforms. Twenty-five scaffolds were assembled to generate 36 Mbp size of genome sequence comprising 11369 predicted genes modeled with a GC content of 48.33%. A total of 592 genes were annotated to encode enzymes related to carbohydrates, and some degradation enzyme genes were identified in strain P. oxalicum WX-209.