Folic acid ameliorates alcohol-induced liver injury via gut–liver axis homeostasis

Abstract

The gut–liver axis (GLA) plays an important role in the development of alcohol-induced liver injury. Alcohol consumption is typically associated with folic acid deficiency. However, no clear evidence has confirmed the effect of folic acid supplementation on alcohol-induced liver injury via GLA homeostasis. In this study, male C57BL/6J mice were given 56% (v/v) ethanol and 5.0 mg/kg folic acid daily by gavage for 10 weeks to investigate potential protective mechanisms of folic acid in alcohol-induced liver injury via GLA homeostasis. Histopathological and biochemical analyses showed that folic acid improved lipid deposition and inflammation in the liver caused by alcohol consumption and decreased the level of ALT, AST, TG, and LPS in serum. Folic acid inhibited the expression of the TLR4 signaling pathway and its downstream inflammatory mediators in the liver and upregulated the expression of ZO-1, claudin 1, and occludin in the intestine. But compared with the CON group, folic acid did not completely eliminate alcohol-induced intestine and liver injury. Furthermore, folic acid regulated alcohol-induced alterations in gut microbiota. In alcohol-exposed mice, the relative abundance of Bacteroidota was significantly increased, and the relative abundance of unclassified_Lachnospiraceae was significantly decreased. Folic acid supplementation significantly increased the relative abundance of Verrucomicrobia, Lachnospiraceae_NK4A136_group and Akkermansia, and decreased the relative abundance of Proteobacteria. The results of Spearman’s correlation analysis showed that serum parameters and hepatic inflammatory cytokines were significantly correlated with several bacteria, mainly including Bacteroidota, Firmicutes, and unclassified_Lachnospiraceae. In conclusion, folic acid could ameliorate alcohol-induced liver injury in mice via GLA homeostasis to some extent, providing a new idea and method for prevention of alcohol-induced liver injury.

Astragaloside IV ameliorate acute alcohol-induced liver injury in mice via modulating gut microbiota and regulating NLRP3/caspase-1 signaling pathway

“…AS-IV treatment was more effective in modulating the abundance of the following five genera: Butyricicoccus , Turicibacter , Akkermansia , Anaerotruncus , and Mucispirillum . These results of gut microbiota are not completely consistent with previous studies [ 35 , 36 ], which may be attributed to the strain of experimental animals, the duration of alcohol intake, and drug intervention [ 37 ].…”

Folic Acid Rescues Dopaminergic Neurons in MPTP-Induced Mice by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment

“…Intracellular ROS initiates the assembly of the NLRP3:ASC:pro-caspase-1 complex, leading to microglial activation. Effective ROS modulation, however, may inhibit activation, thereby reducing neuroinflammation. , FA is a free radical scavenger with a crucial role in this modulation by exerting antioxidant activity essential for nucleotide synthesis, redox state maintenance, and methylation reactions. ,, Additionally, the influence of FA on the homocysteine (Hcy) levels is notable. Elevated Hcy, a cytotoxic sulfur-containing amino acid, exacerbates oxidative stress , and is linked to increased dopaminergic neuron depletion in MPTP models .…”

“…56,57 FA is a free radical scavenger with a crucial role in this modulation by exerting antioxidant activity essential for nucleotide synthesis, redox state maintenance, and methylation reactions. 14,28,29 Additionally, the influence of FA on the homocysteine (Hcy) levels is notable. Elevated Hcy, a cytotoxic sulfur-containing amino acid, exacerbates oxidative stress 34,58 and is linked to increased dopaminergic neuron depletion in MPTP models.…”

“…FA (5 mg/kg of body weight) and Madopar (48 mg/kg of body weight) were administered orally 6 days a week for 8 weeks, while the control and MPTP model groups received equal volumes of saline (Figure A). The dose selection was determined based on the findings of previous studies. ,− Mouse body weight was monitored every 3 days to adjust the dosing volumes. Behavioral assessments were performed following treatment completion.…”

Astaxanthin Protects against Alcoholic Liver Injury via Regulating Mitochondrial Redox Balance and Calcium Homeostasis

“…Western blotting was carried out as described in previous studies, , with slight modifications. Briefly, the liver tissues from different groups were homogenized on ice and centrifuged at low temperature, followed by collecting the supernatant and determining the protein concentrations by BCA assay (Meilunbio Biotechnology, China).…”