Acute Alcoholic Liver Injury Research Articles

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.

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.

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.

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.

A Butyrate-Yielding Dietary Supplement Prevents Acute Alcoholic Liver Injury by Modulating Nrf2-Mediated Hepatic Oxidative Stress and Gut Microbiota.

Alcoholic liver disease (ALD) is a globally prevalent form of liver disease for which there is no effective treatment. Recent studies have found that a significant decrease in butyrate was closely associated with ALD development. Given the low compliance and delivery efficiency associated with oral-route butyrate administration, a highly effective butyrate-yielding dietary supplement, butyrylated high-amylose maize starch (HAMSB), is a good alternative approach. Here, we synthesized HAMSB, evaluated the effect of HAMSB on acute ALD in mice, compared its effect with that of oral administration of butyrate, and further studied the potential mechanism of action. The results showed HAMSB alleviated acute ALD in mice, as evidenced by the inhibition of hepatic-function impairment and the improvement in liver steatosis and lipid metabolism; in these respects, HAMSB supplementation was superior to oral sodium butyrate administration. These improvements can be attributed to the reduction of oxidative stress though the regulation of Nrf2-mediated antioxidant signaling in the liver and the improvement in the composition and function of microbiota in the intestine. In conclusion, HAMSB is a safe and effective dietary supplement for preventing acute ALD that could be useful as a disease-modifying functional food or candidate medicine.

Protective effect of Acanthus ilicifolius extracts against acute alcoholic liver injury via suppressing TLR4/NF-κB signal pathway and modulating intestinal microbiota in mice

Excessive alcohol consumption is leading to increased rates of liver injury and disease. A new research strategy focuses on manipulating gut microbiota to lessen alcohol-induced harm. This study examined the hepatoprotective effects of extracts from Acanthus ilicifolius (EAI) on acute alcoholic liver injury by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal microbiota in mice. The results showed that EAI dose-dependently reduced alcohol-induced elevations of AST, ALT, and ALP levels. EAI showed significant inhibitory effects on the expressions of TLR4, NF-κB, and pNF-κB proteins. Furthermore, EAI caused a notable reduction in hepatic levels of IL-1β, IL-6, and TNF-α. Supplementation with EAI could ameliorate alcohol-induced dysbiosis of intestinal bacteria. The levels of ALT, AST, and ALP levels were negatively correlated with Ligilactobacillus, Lactobacillus, and Alistipes, but positively correlated with Helicobacter and Bacteroides. Overall, EAI alleviated alcoholic liver injury in mice by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal bacteria.

Enhanced In Vitro Recapitulation of In Vivo Liver Regeneration by Co-Culturing Hepatocyte Organoids with Adipose-Derived Mesenchymal Stem Cells, Alleviating Steatosis and Apoptosis in Acute Alcoholic Liver Injury.

Hepatocyte organoids (HOs) have superior hepatic functions to cholangiocyte-derived organoids but suffer from shorter lifespans. To counteract this, we co-cultured pig HOs with adipose-derived mesenchymal stem cells (A-MSCs) and performed transcriptome analysis. The results revealed that A-MSCs enhanced the collagen synthesis pathways, which are crucial for maintaining the three-dimensional structure and extracellular matrix synthesis of the organoids. A-MSCs also increased the expression of liver progenitor cell markers (KRT7, SPP1, LGR5+, and TERT). To explore HOs as a liver disease model, we exposed them to alcohol to create an alcoholic liver injury (ALI) model. The co-culture of HOs with A-MSCs inhibited the apoptosis of hepatocytes and reduced lipid accumulation of HOs. Furthermore, varying ethanol concentrations (0-400 mM) and single-versus-daily exposure to HOs showed that daily exposure significantly increased the level of PLIN2, a lipid storage marker, while decreasing CYP2E1 and increasing CYP1A2 levels, suggesting that CYP1A2 may play a critical role in alcohol detoxification during short-term exposure. Moreover, daily alcohol exposure led to excessive lipid accumulation and nuclear fragmentation in HOs cultured alone. These findings indicate that HOs mimic in vivo liver regeneration, establishing them as a valuable model for studying liver diseases, such as ALI.

Differences in the Ability of Lactic Acid Bacteria To Prevent Acute Alcohol-Induced Liver Injury via the Gut Microbiota-Bile Acid-Liver Axis.

Probiotics can regulate gut microbiota and protect against acute alcohol-induced liver injury through the gut-liver axis. However, efficacy is strain-dependent, and their mechanism remains unclear. This study investigated the effect of lactic acid bacteria (LAB), including Lacticaseibacillus paracasei E10 (E10), Lactiplantibacillus plantarum M (M), Lacticaseibacillus rhamnosus LGG (LGG), Lacticaseibacillus paracasei JN-1 (JN-1), and Lacticaseibacillus paracasei JN-8 (JN-8), on the prevention of acute alcoholic liver injury in mice. We found that LAB pretreatment reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) and reduced hepatic total cholesterol (TC) and triglyceride (TG). JN-8 pretreatment exhibited superior efficacy in improving hepatic antioxidation. LGG and JN-8 pretreatment significantly attenuated hepatic and colonic inflammation by decreasing the expression of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) and increasing the expression of interleukin 10 (IL-10). JN-1 and JN-8 pretreatments have better preventive effects than other LAB pretreatment on intestinal barrier dysfunction. In addition, the LAB pretreatment improved gut microbial dysbiosis and bile acid (BA) metabolic abnormality. All of the strains were confirmed to have bile salt deconjugation capacities in vitro, where M and JN-8 displayed higher activities. This study provides new insights into the prevention and mechanism of LAB strains in preventing acute alcoholic liver injury.

MLKL deficiency alleviates acute alcoholic liver injury via inhibition of NLRP3 inflammasome

Mixed lineage kinase domain-like protein (MLKL) is identified as the terminal executor of necroptosis. However, its role in acute alcoholic liver injury remains unclear. This study elucidates that MLKL can contribute to acute alcoholic liver injury independently of necroptosis. Although the expression of MLKL was upregulated, no significant increase in its phosphorylation or membrane translocation was observed in the liver tissues of mice treated with ethanol. This finding confirms that alcohol intake does not induce necroptosis in mouse liver tissue. Additionally, the deletion of Mlkl resulted in the downregulation of NLRP3 expression, which subsequently inhibited the activation of the NLRP3 inflammasome and the ensuing inflammatory response, thereby effectively mitigating liver injury induced by acute alcohol consumption. The knockout of Nlrp3 did not affect the expression of MLKL, further confirming that MLKL acts upstream of NLRP3. Mechanistically, inhibiting the nuclear translocation of MLKL reduced the nuclear entry of p65, the principal transcriptional regulator of NLRP3, thereby limiting the transcription of Nlrp3 mRNA and subsequent NLRP3 expression. Overall, this study unveils a novel mechanism of MLKL regulates the activation of NLRP3 inflammasomes in a necroptosis independent way in acute alcoholic liver injury

Microencapsulation improves the effects of octacosanol to ameliorate alcoholic liver injury

AbstractOctacosanol is a plant natural product with the potential to ameliorate alcoholic liver injury. However, its poor solubility limits its application in the food industry. This study first verified that octacosanol has a favorable effect on acute and subchronic alcoholic liver injury in mice by protecting the gastric mucosa and ameliorating disease levels. Additionally, octacosanol microcapsules were prepared under the optimal drying conditions of the feed flow rate of 400 mL/h and drying temperature of 180°C to improve the ameliorative effects of octacosanol, with moisture content, water activity, dispersibility, and solubility of 1.53%, 0.16%, 89.84%, and 95.30%, respectively. The microcapsules had a spherical structure, and the droplet sizes after redissolution ranged from 0.061 to 4.63 µm. Instrumental measurements and simulated digestion experiments have shown that microencapsulation enhanced the solubility and thermal stability of octacosanol, with 90.88% of the octacosanol being continuously released. As expected, microencapsulation significantly enhanced the effect of octacosanol in ameliorating alcoholic liver injury by determining the disease index in the mice model. This study demonstrated the beneficial effects of octacosanol on alcoholic liver injury and explored a viable method to improve its solubility and bioaccessibility, thereby enhancing its therapeutic efficacy for the treatment of alcoholic liver injury.

Efficacy of Rhamnus utilis Decne. Aqueous extract in mice with acute alcoholic liver injury and metabolomic study

Rhamnus utilis Decne. (Family Rhamnaceae Juss.) leaf is commonly prepared as a anti-inflammatory herbal medicine and used for tea production. To investigate the mechanism of Rhamnus utilis Decne. aqueous extract (RDAE) against acute alcoholic liver disease (ALD) in mice. The ALD mouse (Male ICR) model was induced via intragastric administration of 52 % alcohol. Mice in each group were treated by gavage once daily with the RDAE (1.12, 2.25, 4.500 g/kg). The expression of proteins involved in the MAPKs/NF-κB/COX-2-iNOS pathway was measured by western blotting. Non-targeted metabolomics was used to determine metabolic profiles and critical pathways, while targeted metabolomics validated key amino acid metabolites. After administration of RDAE, the body mass of mice was significantly increased. The liver index was significantly decreased. Meanwhile, the serum levels of AST, ALT, TG, TC, MDA, TNF-α, IL-1β and IL-6 were significantly decreased (P < 0.05, P < 0.01), but GSH level was inversely increased (P < 0.05). Metabolomic analysis revealed nine major pathways involved in the therapeutic effect of RDAE, including fructose and mannose metabolism. The levels of 7 amino acids including leucine, proline and alanine/sarcosine were significantly upregulated. Additionally, protein levels of p–NF–κB (p65)/NF-κB (p65), p-ERK1/2/ERK1/2, p-JNK/JNK, p-p38/p38, COX-2 and iNOS were significantly decreased (P < 0.01, P < 0.05). RDAE is used to treat acute ALD by improving lipid metabolism, inhibiting the expression of pro-inflammatory cytokines and regulating MAPKs/NF-κB/COX-2-iNOS signalling pathway. These findings provide valuable insights for acute ALD therapy based on traditional Chinese medicine (TCM).

Structural characterization of Aspalatus linearis polysaccharide and its improving effect on acute alcoholic liver injury.

Polysaccharides from natural sources can regulate the composition of intestinal flora through the "gut-liver axis" pathway, potentially ameliorating alcoholic liver injury. Aspalathus linearis, also known as rooibos, is one such natural product that has shown promise in this regard. This study looked at the structural properties of A. linearis polysaccharide (ALP) and how well it would work to treat acute alcoholic liver impairment. This study looks at the composition of monosaccharides, functional groups, and molecular weight (Mw) of a newly discovered water-soluble polysaccharide, named ALP. The polysaccharide is composed of pyranose rings, amide groups, and sulfate groups linked by β-glycosidic linkage. It has a relative Mw of 4.30×103kDa and is composed of glucose, rhamnose, and some other monosaccharides. The study found that treating mice with the model of acute alcoholic liver disease with ALP could alleviate pathological symptoms, inhibit the release of inflammatory cytokines, and suppress indicators of oxidative stress. Experiments have shown that different doses of ALP can activate the P4502E1/Keap1-Nrf2-HO-1 signaling pathway. The regulation of inflammatory factors and downstream antioxidant enzymes occurs as a result. Based on these data, it is likely that ALP protects the liver via the "gut-liver axis" pathway by reducing oxidative stress-related damage, inflammation, and alcohol-related alterations to the gut microbiome. The results indicate that ALP mitigates injury caused by oxidative stress, inflammatory responses, and changes in the gut microbiota induced by alcohol through the "gut-liver axis" pathway, which provides protection to the liver. This provides preliminary evidence for the development of related drugs. PRACTICAL APPLICATION: Researchers extracted a polysaccharide from fresh leaves of Auricularia auricula. The polysaccharide was purified and determined to have a predominantly homogeneous molecular weight. An acute alcoholic liver damage mouse model was established, and it was concluded that the polysaccharide could ameliorate liver injury in mice through the "gut-liver axis" pathway. This novel polysaccharide can be used as an additive to develop functional foods with beneficial effects, which can positively impact the daily maintenance of consumers.

Effects of Mactra chinenesis Peptides on Alcohol-Induced Acute Liver Injury and Intestinal Flora in Mice.

Food-borne bioactive peptides have shown promise in preventing and mitigating alcohol-induced liver injury. This study was the first to assess the novel properties of Mactra chinenesis peptides (MCPs) in mitigating acute alcoholic liver injury in mice, and further elucidated the underlying mechanisms associated with this effect. The results showed that MCPs can improve lipid metabolism by modulating the AMPK signaling pathway, decreasing fatty acid synthase activity, and increasing carnitine palmitoyltransferase 1a activity. Meanwhile, MCPs ameliorate inflammation by inhibiting the NF-κB activation, leading to reduced levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Additionally, a 16S rDNA sequencing analysis revealed that MCPs can restore the balance of gut microbiota and increase the relative abundance of beneficial bacteria. These findings suggest that supplementation of MCPs could attenuate alcohol intake-induced acute liver injury, and, thus, may be utilized as a functional dietary supplement for the successful treatment and prevention of acute liver injury.

Inulin alleviates acute alcoholism in mice by enhancing ethanol metabolism and regulating the intestinal flora

AbstractInulin, a recognized prebiotic with diverse biological activities, has not yet been reported for its potential in treating alcoholism. Therefore, this study investigated the antialcoholic effects of short, long, and phosphorylated long‐chain inulin and the possible mechanisms. An acute alcoholic intoxication mice model was established, with the water extract of Hovenia dulcis Thunb serving as a positive control. The different inulins were used for intervention, and the drunkenness of the mice was observed by an animal behavior experiment. The serum liver function indexes (TP, ALB, GLB, ALT, and ALP), as well as the activity of ethanol metabolizing enzymes (ADH and ALDH) in the liver were measured, and the changes in intestinal flora were analyzed. The results showed that short‐chain inulin could alleviate acute alcoholism by activating ethanol metabolizing enzyme activity and improving intestinal flora, and it had a potential protective effect on acute alcoholic liver injury in mice.

Study on the pharmacokinetics, tissue distribution and excretion of Penthorum chinense Pursh in normal and acute alcoholic liver injury rats using validated UPLC-MS/MS method

Penthorum chinense Pursh (PCP), as a traditional medicine of Miao nationality in China, is often used for the treatment of various liver diseases. At present, information regarding the in vivo process of PCP is lacking. Herein, a sensitive and robust ultra-performance liquid chromatography tandem with mass spectrometry (UPLC-MS/MS) was developed and validated for the quantification of several components to study their pharmacokinetics, tissues distribution and excretion in normal and acute alcoholic liver injury (ALI) rats. Prepared samples were separated on a Thermo C18 column (4.6 mm × 50 mm, 2.4 μm) using water containing 0.1 % formic acid (A) and acetonitrile (B) as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) mode for each component. The validated UPLC-MS/MS assay gave good linearity, accuracy, precision, recovery rate, matrix effect and stability. This method was successfully applied to the pharmacokinetics, tissue distribution and excretion in normal and acute ALI rats. There were differences in pharmacokinetic process, tissue distribution and excretion characteristics, indicating that ALI had a significant influence on the in vivo process of PCP in rats. The research provided an experimental basis for the study of PCP quality control and further application in the clinic.

Polysaccharides from Eucommia ulmoides Oliv. Leaves Alleviate Acute Alcoholic Liver Injury by Modulating the Microbiota-Gut-Liver Axis in Mice.

The interplay among gut microbiota, intestines, and liver is crucial in preventing acute alcoholic liver injury. In this study, the hepatoprotective potential of polysaccharides from Eucommia ulmoides Oliv. leaves (EULP) on acute alcoholic liver injury in Kunming male mice was investigated. The structural features suggested that the EULP appeared as a heterogeneous mixture of polysaccharides with a molecular weight of 186132 Da. A 14-day pretreatment of EULP ameliorated acute alcoholic-induced hepatic inflam mation (TNF-α, IL-6, and IL-10), oxidative stress (GSH, SOD, and T-AOC), and liver damage (ALT and AST) via enhancing intestinal barrier (Occludin, Claudin 1, and ZO-1) and modulating microbiome, which subsequently inhibiting endotoxemia and balancing the homeostasis of the gut-liver axis. EULP restored the composition of intestinal flora with an increase in the relative abundance of Lactobacillaceae and a decrease in Lachnospiraceae and Verrucomicrobiaceae. Notably, prolonged EULP pretreatment (14 days) but no single gavage of EULP achieved excellent hepatoprotection. These findings endorsed the potential of EULP as a functional food for mitigating acute alcoholic-induce d liver damage, attributed to its anti-inflammatory, antioxidant, and prebiotic properties facilitated by the microbiota-gut-liver axis.

Prevent effects of soybean meal peptides in acute alcoholic liver injury based on gut microbiota and metabolome alteration

Prevent effects of soybean meal peptides in acute alcoholic liver injury based on gut microbiota and metabolome alteration

Sea Cucumber Polysaccharide from Stichopus japonicu and Its Photocatalytic Degradation Product Alleviate Acute Alcoholic Liver Injury in Mice.

To prevent alcoholic liver disease, the addition of bioactive substances to the alcoholic drink Baijiu has been considered a feasible option. In the present study, the hepatoprotective effects of a sea cucumber sulfated polysaccharide (SCSP) isolated from Stichopus japonicu were investigated. Moreover, in order to enhance its solubility in an alcohol solution, it was depolymerized using a photocatalytic reaction, and the photocatalytic degradation products (dSCSPs) with an average molecular weight of less than 2 kDa were studied and compared with SCSP. They were characterized by a series of chemical and spectroscopy methods and the oligosaccharide fragments in the dSCSP were further identified by HPLC-MSn analysis. Then, the in vivo experiment showed that the addition of SCSP or dSCSP to Baijiu could alleviate alcoholic liver injury in mice. Further analysis also revealed their protective effect in reducing oxidative stress damage and their regulation of the metabolism of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the liver. Of note, dSCSP was more effective at reducing the level of malondialdehyde in the liver. These findings indicate that the addition of sea cucumber polysaccharide or its low-molecular-weight derivative in Baijiu has the potential to alleviate alcoholic liver injury.

Hepatoprotective Effect of Annulohypoxylon stygium Melanin on Acute Alcoholic Liver Injury in Mice.

Annulohypoxylon stygium melanin (AsM) has various functional properties such as antioxidant and anti-radiation, but its biological activity in vivo has not been fully investigated. In this study, we researched the effects of AsM on the protection against acute liver injury in mice and its mechanism. The results showed that AsM had no significant effect on body weight in mice but reduced the liver index. It was able to significantly decrease the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the contents of triglyceride (TG) and total cholesterol (TC) in mice. Simultaneously, it raised the levels of superoxide dismutase (SOD), peroxidase (CAT), and glutathione peroxidase (GSH-Px), which obviously exceeded those of the EtOH group. AsM could significantly lower the levels of inflammatory factors, with inhibition rates of 68.30%, 29.0%, and 19.50% for IL-1β, IL-6, and TNF-α, respectively. H&E and Oil red O staining also showed that AsM ameliorated liver damage and lipid accumulation in mice. The protective mechanism of AsM may be associated to the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signaling pathway, which could activate the downstream antioxidant enzymes heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). These findings confirmed that AsM had an alleviating effect on alcoholic liver injury and provided new thoughts for the development of natural product.