Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites—C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)—involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) has the potential to alleviate alcoholic liver injury may play essential roles in treating for alcohol-exposed liver disease, however, the hepatoprotective effects and mechanisms remain unclear. In this study, the hepatoprotective effects of HDPs and its potential mechanisms were investigated in alcohol-exposed mice by liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. By applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria while significant increases in Firmicutes at the phylum level, and increased Lactobacillus abundance while decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid metabolism and glycerophospholipid metabolism and identified two important metabolites C00157 and C04230 involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs has a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Both epidemiological and laboratory evidence indicate a significant relationship between formaldehyde (FA) exposure and allergic asthma. However, the mechanisms underlying the relationship remain unclear. Research has demonstrated that endoplasmic reticulum (ER) stress is closely associated with the onset of allergic asthma. Nonetheless, it has yet to be established whether FA exposure exacerbates allergic asthma by activating ER stress. To systematically investigate the exacerbation of allergic asthma-like symptoms due to FA exposure (0.5 mg/m3) in Balb/c mice, we assessed lung function and histopathology, serum immunoglobulin levels, neuropeptide substance P (SP) and calcitonin gene-related peptide (CGRP) levels, Th2 (IL-4, IL-5, IL-13) and Th17 (IL-22, IL-17A) cytokine levels and biomarkers of the ER stress pathway (IRE1α, PERK, and ATF-6). Additionally, we employed the ER stress antagonist phenylbutyric acid (4-PBA) to confirm the mediating role of ER stress in FA-aggravated allergic asthma. Our findings suggest that prolonged exposure to FA increases levels of ER stress markers, SP, CGRP, Th2 and Th17 cytokines, and immunoglobulin, leading to increased airway mucus hyperplasia and airway remodeling. Furthermore, we demonstrated that blocking ER stress with 4-PBA effectively alleviated associated allergic asthma-like symptoms. In conclusion, we provide evidence that the ER stress signaling pathway plays a significant role in the exacerbation of allergic asthma due to FA exposure.