Alcoholic Liver Injury Research Articles

Antioxidative Therapy of Alcoholic Liver Injury by an Amorphous Two‐Dimensional Cobalt Hydroxide Nanocatalyst

The intake of excessive ethanol will activate an alternative ethanol metabolic pathway in the liver, resulting in the overproduction of reactive oxygen species (ROS), which further leads to alcoholic liver injury (ALI). Although several molecular antioxidants have been utilized in clinics for treating ALI, their efficacies are still less satisfactory. In this work, a nanocatalytic antioxidation therapeutic strategy is proposed for ALI treatment by constructing amorphous Co(OH)2 nanosheets with catalytic antioxidative property. The bis(μ‐hydroxo)CoIICoII dinuclear active sites of Co(OH)2 nanosheets are capable of coordinating with hydrogen peroxide (H2O2) with significantly reduced thermodynamic barrier to form a dihydroxyl adduct bis(μ‐hydroxo)CoIII(OH)CoIII(OH) favorable for catalytic H2O2 disproportionation, while amorphous and ultrathin structure further facilitates the reaction, resulting in a high catalytic efficiency (Km = 59.31 mM). Thanks to the inherent hepatic passive targeting ability of nanomaterials, the antioxidative nanosheets can accumulate in liver region efficiently after intravenous administration (35.5% ID/g accumulation efficiency), enabling efficient catalytic antioxidation in the liver to mitigate hepatic oxidative stress, protect hepatocytes from apoptosis/ferroptosis. This study provides a new methodology of nanocatalytic antioxidation for treating ALI and other hepatic diseases related to oxidative stress.

Antioxidative Therapy of Alcoholic Liver Injury by an Amorphous Two-Dimensional Cobalt Hydroxide Nanocatalyst.

The intake of excessive ethanol will activate an alternative ethanol metabolic pathway in the liver, resulting in the overproduction of reactive oxygen species (ROS), which further leads to alcoholic liver injury (ALI). Although several molecular antioxidants have been utilized in clinics for treating ALI, their efficacies are still less satisfactory. In this work, a nanocatalytic antioxidation therapeutic strategy is proposed for ALI treatment by constructing amorphous Co(OH)2 nanosheets with catalytic antioxidative property. The bis(μ-hydroxo)CoIICoII dinuclear active sites of Co(OH)2 nanosheets are capable of coordinating with hydrogen peroxide (H2O2) with significantly reduced thermodynamic barrier to form a dihydroxyl adduct bis(μ-hydroxo)CoIII(OH)CoIII(OH) favorable for catalytic H2O2 disproportionation, while amorphous and ultrathin structure further facilitates the reaction, resulting in a high catalytic efficiency (Km = 59.31 mM). Thanks to the inherent hepatic passive targeting ability of nanomaterials, the antioxidative nanosheets can accumulate in liver region efficiently after intravenous administration (35.5% ID/g accumulation efficiency), enabling efficient catalytic antioxidation in the liver to mitigate hepatic oxidative stress, protect hepatocytes from apoptosis/ferroptosis. This study provides a new methodology of nanocatalytic antioxidation for treating ALI and other hepatic diseases related to oxidative stress.

Lactobacillus plantarum LP104 improved intestinal and brain inflammation by modulating TLR4 pathway and gut flora in alcohol liver injury mice

In this study, Lactobacillus plantarum LP104 (LP104) originating from kimchi was treated to C57BL/6N mice fed a chronic-plus-single-binge ethanol diet for ten days, aiming to evaluate the effects of the probiotics on intestinal and brain inflammation in the alcohol-induced liver injury model. Dietary supplementation with LP104 significantly reduced the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in alcoholic hepatic injury mice. The 16S rDNA sequencing results inferred that LP104 modulated the intestinal microbiota by depleting inflammation-related bacterial genera Proteobacteria and enriching Lactobacillus and Roseburia. Furthermore, LP104 intervention attenuated alcohol-induced gut inflammation by the TLR4 signaling pathway, which regulated the expressions of intestinal tight junction proteins such as ZO-1, Claudin-1 and Occludin. Subsequently, LP104 intake exerted neuroprotection by restoring neurotrophic factor levels and the blood-brain barrier (BBB) function to decrease lipopolysaccharide (LPS) levels in the serum. The western blotting results suggested LP104 ameliorated alcohol-induced brain inflammation by inhibiting the LPS/TLR4 signaling pathway in mice. Spearman's correlation analysis demonstrated that differential intestinal bacterial taxa were connected with the expressions of inflammation-related proteins in both gut and brain of alcohol liver injury mice.

Alleviation of alcoholic liver injury through composite postbiotics regulation of intestinal flora and promotion of bile acid metabolism

Alcoholic liver disease (ALD) arises from chronic alcohol consumption, leading to liver damage and gut microbiota disruption. Current clinical treatments, including pharmacological interventions, are often inadequate for early-stage ALD, highlighting the urgent need for novel therapeutic approaches. In this study, we explored the therapeutic potential of composite postbiotics, combined with ursodeoxycholic acid (UDCA) as a farnesoid X receptor (FXR) agonist, to alleviate ALD by modulating gut microbiota and bile acid metabolism. Using a murine model of ALD, composite postbiotics were found to restore intestinal barrier integrity, promote bile acid metabolism, and reduce liver inflammation. The treatment increased beneficial gut microbes such as Firmicutes and Bacteroidetes, while reducing pathogenic Proteobacteria, which enhanced bile acid metabolism and activated the FXR pathway. This activation led to a reduction in pro-inflammatory cytokines, restoration of lipid metabolism, and overall alleviation of liver injury. The addition of UDCA further enhanced the activation of the FXR pathway, providing additional protection against liver damage. Our findings suggest that composite postbiotics, particularly when combined with FXR agonists like UDCA, represent a promising therapeutic strategy for ALD by targeting the gut-liver axis and optimizing bile acid metabolism. Future research should investigate the clinical application of these treatments to offer a non-invasive and effective approach for early ALD intervention.

Protective Effect and Mechanism of L-Theanine on Acute Alcoholic Liver Injury in Mice.

Acute alcoholic liver injury (AALI), a global health concern, is exacerbated by excessive episodic drinking. L-theanine (LTA), a compound found in tea leaves, mitigates the AALI-induced liver oxidative stress and inflammation. However, its relationship with alcohol metabolism and its liver-protective mechanism remains unexplored. This study investigates the protective mechanisms of LTA against AALI in mice. The results demonstrate that LTA mitigates liver tissue damage and reduces the serum levels of aspartate aminotransferase and alanine aminotransferase, and liver levels of triglycerides, malondialdehyde, reactive oxygen species (ROS), tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, LTA enhances the activity of ethanol-metabolizing enzymes and decreases ethanol and acetaldehyde serum levels. Mechanistically, LTA accelerates alcohol metabolism by upregulating the hepatic expression of ADH6, ALDH1B1, ALDH2, CAT, and ACSS1 mRNA and protein in AALI mice, LTA downregulates the expression of CYP2E1 mRNA and protein and promoting antioxidative activities thus reducing the accumulation of ROS. This attenuated inflammation by inhibiting the phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα) and downregulating the hepatic expression of NF-κB p65, TNF-α, IL-1β, IL-6 mRNA, and protein. LTA is a beneficial dietary supplement that protects against AALI by modulating alcohol metabolism and the TNF-α/NF-κB pathway.

High Fischer ratio oligopeptides from Antarctic krill: Ameliorating function and mechanism to alcoholic liver injury through regulating AMPK/Nrf2/IκBα pathways

In this study, we devoted attention to the hepatoprotective functions of high Fischer ratio oligopeptides (HFOPs) from Antarctic krill (HFOPs-AK) on alcoholic liver injury of mice. The results indicated that HFOPs-AK significantly improved the pathological state of mice liver and kidney, reduced alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, regulated lipid metabolism, and alleviated the burden on the liver. In addition, HFOPs-AK depicted anti-inflammatory and antioxidant effects by reducing tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) contents and increasing superoxide dismutase (SOD) and catalase (CAT) activities to reduce malondialdehyde (MDA) level. The hepatoprotective mechanism of HFOPs-AK was further revealed by quantitative reverse transcription PCR (RT-qPCR) analysis, and the results proved that HFOPs-AK had the ability to stimulate the adenosine 5‘-monophosphate-activated protein kinase (AMPK)/nuclearrespiratoty factor 2 (Nrf2)/inhibitor of NF-κB (IκBα) signaling pathways, thereby regulating the expression levels of downstream factors. The activation of these signaling pathways is essential for the regulation of lipid metabolism as well as anti-inflammatory and antioxidant functions. This finding offers a novel approach for the development of innovative hepatoprotective agents utilizing HFOPs-AK.

Enteromorpha prolifera Polysaccharide Alleviates Acute Alcoholic Liver Injury in C57 BL/6 Mice through the Gut-Liver Axis and NF-κB Pathway.

Enteromorpha prolifera polysaccharide (EP2) protection against acute alcoholic liver injury (AALI) in mice was investigated. By integration of physiological indicators, gut microbiota, and short-chain fatty acids (SCFAs), the mechanism of EP2 in alleviating AALI was disclosed. The results showed that EP2 significantly ameliorated alcohol-induced abnormal transaminase activities, liver and intestinal systemic inflammation, and intestinal environmental disorders. EP2 significantly reduces liver and serum LPS contents by 1.69-fold and 1.54-fold. Furthermore, inhibition of the NF-κB signaling pathway by EP2 reduced the production of proinflammatory cytokines such as TNF-α (1.83-fold), IL-6 (11.09-fold), and IL-1β (1.99-fold). EP2 restored SCFAs to normal levels by upregulating the abundance of beneficial bacteria (Colidextribacter, Ruminococcus, unclassified_Lachnospiraceae, and Akkermansia). The alleviation of AALI by EP2 occurs through protection of the intestinal mucosal barrier and reduction of LPS permeating in serum. The decrease in LPS inactivates the NF-κB signaling pathway and prevents inflammation. In short, EP2 regulates the gut-liver axis and inflammation, alleviating effects in AALI mice.

Therapeutic effects of fecal microbial transplantation on alcoholic liver injury in rat models

ObjectiveDisruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques. MethodsThree liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats. ResultsFMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways. ConclusionFMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.

Protective mechanisms of Hovenia dulcis Thunb extracts on acute alcoholism and liver injury

As a traditional Chinese medicine for anti-alcoholism, Hovenia dulcis Thunb (HDT) is widely used in the treatment of alcoholism and alcohol-related liver diseases. However, the scientific evidence of its mechanism has not been clearly established. In this study, a mouse model of acute alcoholism was established to explore the protective mechanisms of three kinds of HDT extracts on acute alcoholism and liver injury from the perspectives of behavioral indicators, serum and liver biochemical indicators, alcohol metabolic enzyme activity, intestinal flora, and liver metabolomics. The results showed that the extracts of HDT shortened the time of sobering up, significantly increased the activity of alcohol metabolic enzymes and antioxidant capacity, promoted ethanol metabolism, and had a certain preventive effect on alcoholic liver injury while preventing adverse reactions caused by alcohol. Notably, HDT water extract (HDTs) demonstrated superior anti-alcohol and liver protective properties compared to polysaccharide and polyphenol extracts of HDTs. It may be through the regulation of intestinal flora imbalance, specifically Muribaculaceae and Dubosiella to modulate biosynthetic pathways of phenylalanine, tyrosine, and tryptophan, ultimately mitigating oxidative stress caused by ethanol consumption. This suggests that HDTs may have potential in preventing acute alcoholism and liver injury.

Clinical formulation Zhigan Oral Liquid intervenes in alcoholic liver injury by regulating the intestinal flora and PI3K\\AKT\\NF-κB pathway

Introduction: Zhigan Oral Liquid (ZOL) was developed from the empirical formulation of Professor Zhao Wenxia, a nationally renowned practitioner of Chinese medicine, and it has been used in Chinese medicine for many years for the effective treatment of alcoholic liver damage (ALD). However, the interventional mechanism of action of the dosage indications for different stages of ALD pathogenesis is not clear. Methods: The main chemical components of ZOL were qualitatively analyzed by ultra-high performance liquid chromatography (UHPLC-Q-Orbitrap HRMS) in tandem with quadrupole electrostatic field orbital well high resolution mass spectrometry and quantitatively analyzed by high-performance liquid chromatography (HPLC). Network pharmacological analysis was performed to predict the targets and pathways of the potential pharmacodynamic components. The pharmacodynamic effects and potential target mechanisms were verified in a murine model of ALD. To observe the effect of ZOL on the intestinal flora, 16s rDNA sequencing was performed on ALD mice. Results: ZOL can achieve alcohol detoxification by increasing the activity of ALDH and other detoxification enzymes and can intervene in the process of alcoholic liver injury and liver fibrosis by regulating the alcohol-induced bacterial dysbiosis, increasing the level of antioxidants, and inhibiting the activation of the PI3K\\AKT\\NF-κB signaling pathway. Kakkalide, Luteolin, Puerarin, tectoridin, and dihydromyricetin are related to the flavonoids that may be the main pharmacodynamic components that exert their medicinal effects. Conclusions: The findings have significant implications for the development of Empirical treatments for alcoholic liver injury. Furthermore, the study contributes to promoting development and utilization of new dosage forms of hospital preparations by emphasizing the composition identification and animal experimental efficacy of ZOL. Overall, this study provides valuable insights into establishing an alcohol-induced liver injury model, and demonstrates the potential of ZOL as a common treatment for alcoholic liver injury a rich source.

S4610 Unorthodox Alcoholic Liver Injury

S4610 Unorthodox Alcoholic Liver Injury

Lactobacillus helveticus attenuates alcoholic liver injury via regulation of gut microecology in mice.

Previous reports have demonstrated that alcohol consumption significantly reduces the abundance of Lactobacillus in the gut. In this study, we selected five species of the genus Lactobacillus, commonly found in fermented foods, and acknowledged them as safe, edible, and effective in preventing or treating certain diseases, to evaluate their effects on alcoholic liver disease (ALD). By comparing the liver damage indices in each group, we found that the type strain of Lactobacillus helveticus (LH, ATCC 15009) had the most marked alleviating effect on ALD-induced liver injury. Furthermore, experiments combining microbiomics and metabolomics were conducted to explore the mechanisms underlying the hepatoprotective effects of LH. Finally, we discovered that LH mitigated ethanol-induced liver steatosis and inflammation in ALD mice by altering the structure and function of the gut microbiome, increasing intestinal levels of short-chain fatty acids (SCFAs), and enhancing gut barrier integrity. These findings suggest a potential strategy for the clinical management of patients with ALD.

Protective effects of phenylethanol glycosides from Cistanche tubulosa against ALD through modulating gut microbiota homeostasis

Ethnopharmacological relevanceCistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of “homology of liver and kidney,” C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury. Aim of the studyWe aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the “gut–liver axis,” thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota. Materials and methodsAn ALD mouse model was established using the Lieber–DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed. ResultsCPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700 mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism. ConclusionsThe results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.

Ameliorative Effects of Camel Milk and Fermented Camel Milk on Acute Alcoholic Liver Injury

Probiotics, which are prevalent in camel milk (CM) and naturally fermented camel milk (FCM), can regulate the intestinal ecological structure to alleviate alcoholic liver disease (ALD) through the “gut–liver” axis. The protective effects and mechanisms of CM and FCM interventions on alcohol-induced acute liver injury were investigated by combining the behavior observed in rats following alcohol exposure. The results revealed that CM and FCM effectively controlled the increased levels of alcohol-induced ALT, AST, TG, MDA, and proinflammatory cytokines. Alcohol-induced oxidative depletion of hepatic CAT, GPX, GSH, and ALDH was reversed, diminishing lipid accumulation, ameliorating severe pathological damage, increasing antioxidant capabilities, and postponing oxidative stress. Additionally, the abundance of the phylum Bacteroidota (which reduces the F/B ratio); the family Prevotellaceae; the genera Clostridia_vadinBB60_group, parabacteroides, Alloprevotella, and Prevotellaceae_UC_G001; the gastrointestinal barrier; and the microbiological environment was increased. The steroid hormone biosynthesis pathway was altered to reduce alcohol-induced predominant steroid metabolites such as 17-hydroxyprogesterone, cortisol, and dehydroepiandrosterone, preventing alcoholic liver impairment. Taken together, CM could be a therapeutic dietary supplement for preventing alcoholic liver injury by ameliorating the intestinal ecology and hepatic metabolism.

Ge-Zhi-Jie-Jiu decoction alleviates alcoholic liver disease through multiple signaling pathways

Ethnopharmacological relevanceAlcoholic liver disease (ALD) is a growing public health concern caused by excessive alcohol consumption, but effective treatments are limited. Ge-Zhi-Jie-Jiu decoction (JJY) is a modified traditional Chinese herbal remedy that aims to alleviate ALD. This formula contains various components such as Ge Hua, Ge Gen, Zhi Ju Zi, and other medicinal-food herbs. However, the specific pharmacotherapeutic compounds of JJY and its pharmacological mechanisms remain unclear. Aim of the studyThis study aimed to elucidate the molecular mechanism and pharmacodynamic basis of JJY in treating ALD. Materials and methodsUPLC-Q-Orbitrap HRMS, HPLC fingerprinting, and LC-MS techniques were used for the composition identification and quality control of JJY. The pharmacological components and molecular mechanisms of JJY in anti-ALD were then predicted using network pharmacology and molecular docking approaches. Ultimately, an acute alcoholic liver injury mouse model was developed, and the potential mechanisms were verified by hematoxylin-eosin (H&E), Oil Red O, and TUNEL staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking analysis. ResultsThe results showed that the main components of JJY are organic acids, flavonoids, and isoflavonoids, in which puerarin, daidzein, glycitein, ononin, quercetin, and tectorigenin can be used as the indicator components of JJY. In addition, JJY might ameliorate ALD through several pathways, including potentially promoting alcohol metabolism via alcohol-metabolizing enzymes, and possibly inhibiting oxidative stress, inflammation and apoptosis via the Nrf2/Keap1/HO-1 and MAPK signaling pathways. Furthermore, JJY may also alleviated hepatic lipid accumulation through the PPARα signaling pathway. ConclusionsJJY has significant anti-ALD efficacy with multiple mechanisms. This study offers a solid experimental foundation for JJY's development as a medicine with anti-ALD characteristics and elucidates its probable active components.

Involvement of BRD4 in Alcoholic Liver Injury: Autophagy Modulation via Regulation of the SIRT1/Beclin1 Axis

Alcoholic liver disease (ALD) caused by chronic alcohol abuse involves complex processes from steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma, posing a global health issue. Bromodomain protein 4 (BRD4) typically serves as a “reader” modulating the functions of transcription factors involved in various biological processes and disease progression. However, the specific mechanisms underlying alcoholic liver injury remain unclear. In this study, we detected aberrant BRD4 expression in the alcohol-induced ALD mouse model of chronic and binge ethanol feeding developed by the National Institute on Alcohol Abuse and Alcoholism, consistent with the in vitro results in Aml-12 mouse hepatocytes. Blocking and inhibiting BRD4 restored the impaired autophagic flux and lysosomal functions in alcohol-treated Aml-12 cells, whereas BRD4 overexpression reduced the expression levels of autophagy marker and lysosomal genes. Furthermore, mouse BRD4 knockdown, mediated by a short hairpin RNA carried by the adeno-associated virus serotype 8, significantly attenuated the alcohol-induced hepatocyte damage, including lipid deposition and inflammatory cell infiltration. Mechanistically, BRD4 overexpression in alcoholic liver injury inhibited the expression of sirtuin (SIRT)1 in Aml-12 cells. Chromatin immunoprecipitation and dual-luciferase reporter assays revealed that BRD4 functions as a transcription factor and suppressor, actively binding to the SIRT1 promoter region and inhibiting its transcription. SIRT1 activated autophagy, which was suppressed in alcoholic liver injury via Beclin1 deacetylation. In conclusion, our study revealed that BRD4 negatively regulated the SIRT1/Beclin1 axis and that its deficiency alleviated alcohol-induced liver injury in mice, thus providing a new strategy for ALD treatment.

Therapeutic Potential of Foodborne Indole Derived from Chinese Stinky Tofu in Reducing Intestinal Inflammation and Enhancing Barrier Function to Mitigate Alcoholic Liver Injury.

Indole, a compound in Chinese stinky tofu (ST), acts as a ligand for the aryl hydrocarbon receptor (AHR). Despite extensive research on prebiotic compounds, indole's specific role in ST remains unexplored. This study used an ethanol gavage method to create an ALD (alcoholic liver disease) mouse model and investigate dietary indole's effects on the intestinal barrier. Our findings indicate that after 6 weeks of being fed ST, the indole present (2 mg/day) robustly activated the intestinal AHR, upregulating its target gene, CYP1A1 (cytochrome P450 1A1 enzyme). This activation significantly reduced intestinal permeability, mitigated alcohol-induced oxidative stress and inflammation, and restored intestinal barrier function. Consequently, the study demonstrates that foodborne indole substantially reduces alcohol absorption and lowers the expression levels of liver inflammation-related factors, thereby slowing the progression of ALD. These results highlight indole's therapeutic potential for treating ALD and its role in developing functional foods.

Ursolic Acid Ameliorates Alcoholic Liver Injury through Attenuating Oxidative Stress-Mediated Ferroptosis and Modulating Gut Microbiota.

Ursolic acid (UA), a triterpenoid found in plants, has many health benefits for liver function. However, understanding how UA intervenes in alcohol-induced ferroptosis remains unclear because of the lack of research. This study explored the protective effects of UA on alcohol-induced liver injury and further elucidated its mechanism of action. Using a mouse model, acute liver injury was induced via high-dose alcohol gavage, and UA's protective effects were assessed by analyzing serum and liver indicators. The results indicated that UA has a significant protective effect against alcohol-induced liver injury in mice. UA significantly decreased serum ALT, AST, TC, and TG levels. Histopathological examination revealed that UA significantly ameliorated liver damage. UA increased ADH, ALDH, and CYP2E1 enzyme expression levels and alleviated alcohol-induced oxidative damage by regulating alcohol metabolism. Moreover, UA increased SOD and GSH-Px levels and lowered the MDA levels in the liver. Furthermore, UA regulated ACC expression by activating the LKB1/AMPK pathway, thereby inhibiting lipid synthesis and peroxidation. UA also upregulated the expression of GPX4 and SLC7A11 in the liver and exerted hepatoprotective effects by inhibiting alcohol-induced ferroptosis. Additionally, 16S rRNA amplicon sequencing showed that excessive alcohol consumption significantly affected the composition of the mouse gut microbiota, with UA intervention proving to be beneficial for improving gut microbiota imbalance. We also validated the protective effects of UA on alcohol-treated HepG2 cells at the cellular level. In summary, these results revealed that UA can alleviate alcoholic liver injury by inhibiting oxidative stress-mediated ferroptosis and regulating gut microbiota. These findings suggest that UA may serve as a functional component in the prevention of alcoholic liver disease.

Near-Infrared Fluorescent Probe Reveals Elevated Mitochondrial Viscosity during Acute Alcoholic Liver Injury.

Acute alcoholic liver injury (AALI) has become an important cause of liver disease worldwide, and there is an urgent need to develop noninvasive and sensitive methods to detect and evaluate AALI. We report herein three novel but readily available mitochondrial targeting fluorescence probes (ICR, ICJ, and ICQ) for AALI detection. These probes contain different electron-donating groups, among which ICQ exhibits NIR fluorescence (740 nm), a large Stokes shift (110 nm), and a sensitive response to viscosity (73-fold enhancement in fluorescence from water to glycerol), making it suitable for in vivo imaging. ICQ also exhibits an excellent ability to image mitochondrial viscosity changes in cells. More importantly, ICQ can target the liver selectively and image the viscosity changes in the liver noninvasively. Through establishing an AALI mouse model, ICQ was successfully applied to the in situ imaging changes in liver viscosity during the AALI process. The results showed a significant increase in liver viscosity in AALI mice, indicating that viscosity can serve as a marker for AALI, and ICQ is a promising noninvasive and sensitive tool for detecting and evaluating AALI.

Protective Effect of Corilagin on Alcoholic Liver Injury

Objectives The herbal product corilagin is renowned for its liver-protecting benefits and antioxidant properties. However, the protective role of corilagin in alcoholic liver injury remains unexplored. The objective of this study is to delve into the protective effects of corilagin on alcoholic liver injury, both in HepG2 cells and a mouse model. Methods To assess the antioxidant capacity of corilagin in vitro, DPPH and ABTS assays were conducted. HepG2 cells were pretreated with 800 mM ethanol for 24 hours, followed by corilagin treatment for another 24 hours, to evaluate its liver-protecting activity. For in vivo studies, ICR mice, with and without corilagin treatment, were given ethanol for 4 weeks to induce alcoholic liver injury. At the end of the study, serum and liver tissue samples were collected to analyze liver function, enzymatic antioxidants, reactive oxygen species (ROS) levels, alcohol dehydrogenase, and liver tissue histology. Results The findings reveal that corilagin exhibits remarkable free radical scavenging ability and alleviates alcohol-induced cell damage in vitro. In vivo, corilagin significantly reduced liver index and serum levels of aminotransferase aspartate, alanine transaminase, total cholesterol, and triglyceride in mice with alcoholic liver injury. Additionally, corilagin decreased ROS levels in liver tissue and increased the activities of antioxidant enzymes CAT, SOD, and GSH-Px. GSH content increased, while lipid peroxide MDA decreased in liver tissue. Conclusion Our data strongly suggests that corilagin possesses protective effects on alcoholic liver injury, both in vitro and in vivo, which is likely attributed to its exceptional antioxidant capacity. In summary, corilagin holds promise as a potential preventive or therapeutic agent for alcoholic liver injury.