Gynostemma Pentaphyllum ameliorates CCl4-induced liver injury via PDK1/Bcl-2 pathway with comprehensive analysis of network pharmacology and transcriptomics.

BACKGROUND: Gynostemma pentaphyllum (Thunb.) Makino, commonly known as "southern ginseng", contains high amounts of ginsenoside derivatives and exhibits similar biological activities with Panax ginseng (C. A. MEY) (ginseng), which is usually used as a low-cost alternative to ginseng. G. pentaphyllum has therapeutic effects on liver diseases. However, the mechanisms underlying its hepatoprotective action have not been fully elucidated. METHODS: The protective effects of the ethanolic extract of G. pentaphyllum (GPE) were evaluated using an experimental carbon tetrachloride (CCl4)-induced liver disease model. Potential targets of GPE were predicted using the "Drug-Disease" bioinformatic analysis. Furthermore, comprehensive network pharmacology and transcriptomic approaches were employed to investigate the underlying mechanisms of GPE in the treatment of liver disease. RESULTS: The pathological examinations showed that GPE significantly alleviated hepatocyte necrosis and liver injury. GPE significantly downregulated Bax and cleaved-PARP expression and upregulated Bcl-2 expression during CCl4-induced hepatocyte apoptosis. We compared the effects of four typical compounds in GPE -a ginsenoside (Rb3) shared by both GPE and ginseng and three unique gypenosides in GPE. Notably, Gypenoside A (GPA), a unique saponin in GPE, markedly reduced hepatocyte apoptosis. In contrast, ginsenoside Rb3 had a weaker effect. Network pharmacology and transcriptomic analyses suggested that this anti-apoptotic effect was achieved by upregulating the PI3K/Akt signaling pathway mediated by PDK1. CONCLUSIONS: These results suggested that G. pentaphyllum had a promising hepatoprotective effect, with its mechanism primarily involving the upregulation of the PDK1/Bcl-2 signaling pathway by GPA, thereby preventing cell apoptosis.

Enhanced treatment of acute organophosphorus pesticide poisoning using activated charcoal-embedded sodium alginate-polyvinyl alcohol hydrogel.

BACKGROUND: The adsorption of activated charcoal is currently a major clinical treatment for acute organophosphorus pesticide poisoning (AOPP). However, the adsorption duration and efficiency of this method is unstable. OBJECTIVE: In this study, a hydrogel embedding activated charcoal was prepared and its alleviating effects on AOPP were investigated. METHODS: A composite hydrogel using sodium alginate and polyvinyl alcohol (SA-PVA) hydrogel was prepared in this study. The structural properties of the SA-PVA hydrogel were characterized via multiple analysis including FTIR, TGA, XRD, SEM, tensile strength and expansion rate. Based on these, activated charcoal (AC) was embedded within the SA-PVA hydrogel (SA-PVA-AC) and it was used for the treatment of AOPP. RESULTS: Structural characterization indicated SA-PVA hydrogel possesses excellent mechanical properties and biocompatibility. The in vivo study demonstrated that SA-PVA-AC significantly alleviated the inflammation and oxidative damage in the liver, as evidenced by reduced levels of IL-6, TNF-α, and, IL-1ß, SOD, and MDA. Furthermore, SA-PVA-AC treatment effectively re-regulated the activities of serum AST and ALT, exhibiting an improved effect on liver function. CONCLUSION: The findings suggest that activated charcoal embedded within SA-PVA hydrogel has significant potential as a therapeutic agent in treating AOPP, and offering a novel approach to managing pesticide-induced toxicity.

Melosira nummuloides Ethanol Extract Ameliorates Alcohol-Induced Liver Injury by Affecting Metabolic Pathways.

Melosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice. However, MNE administration increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK/AMPK) and PPARα, which was accompanied by a decrease in SREBP-1; this indicates that MNE can inhibit adipogenesis and improve fatty acid oxidation. Moreover, MNE administration upregulated the expression of antioxidant enzymes, including SOD, NAD(P)H quinone dehydrogenase 1, and GPX, and ameliorated alcohol-induced inflammation by repressing the Akt/NFκB/COX-2 pathway. Metabolomic analysis revealed that MNE treatment modulated many lipid metabolites in alcohol-treated HepG2 cells. Our study findings provide evidence for the efficacy and mechanisms of MNE in ameliorating alcohol-induced liver injury.

[Research progress on chemical constituents from Kadsura genus and its pharmacological activities and clinical application].

The 29 plant species in the Kadsura genus of the Schisandraceae family are mainly distributed in eastern and southeas-tern Asia. Ten species of plants in this genus are distributed in China, some of which are folk medicinal plants with activating blood circulation, relieving pain, dispelling wind, and dehumidifying effects. Their main constituents are lignans and triterpenes. The current pharmacology and clinical studies have shown that their extracts and constituents have anti-rheumatoid arthritis, liver protection, antioxidation, anti-inflammatory, and other biological activities. The rheumatologic and liver diseases can also be treated with the plants in the clinic. The new chemical constituents reported in the last decade(2012 to date) from the plants of Kadsura genus in China, as well as their pharmacological effects and clinical applications in recent years were reviewed, so as to provide a theoretical basis for further research on the genus.

High Fischer Ratio Oligopeptides of Gluten Alleviate Alcohol-Induced Liver Damage by Regulating Lipid Metabolism and Oxidative Stress in Rats.

High Fischer ratio oligopeptides (HFOs) exhibit diverse biological activities, including anti-inflammatory and antioxidant properties. HFOs from gluten origin were prepared through fermentation and enzymatic hydrolysis and then characterized using free amino acid analysis and scanning electron microscopy (SEM). Following intervention, the levels of serum total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic malondialdehyde (MDA) in the rats significantly decreased (p < 0.05). Simultaneously, there was an increasing trend in superoxide dismutase (SOD) levels, and glutathione (GSH) levels were significantly elevated (p < 0.05). The mRNA expression levels of alcohol metabolism-related genes (ADH4, ALDH2, and CYP2E1) exhibited a significant increase (p < 0.05). Histological examination revealed a reduction in liver damage. The findings indicate that high Fischer ratio oligopeptides, prepared through enzymatic and fermentation methods, significantly improve lipid levels, ameliorate lipid metabolism disorders, and mitigate oxidative stress, and exhibit a discernible alleviating effect on alcoholic liver injury in rats.

Development of a functional cake with probiotics and micro-encapsulated essential oils: Evaluation of nutritional properties, liver protection, and immune boosting.

This study used probiotics and micro-encapsulated clove and cinnamon oils to develop a functional cream-stuffed cake based on sweet potatoes flour and rice flour instead of wheat flour. The cake was evaluated for its physical, chemical, and sensory properties and its antioxidant capacity. The protective effect of the cake against liver injury and immunosuppression induced by thioacetamide injection in male rats was also evaluated. The study found that eugenol and cinnamaldehyde were the majority of volatile compounds in the essential oils used in the cake, with values of 78.73 % and 81.57 %, respectively, as determined by GC-MS analysis. The viable counts of added probiotics in the cake ranged from 13.15 to 11.21 log CFU/g and were still above the threshold for health benefits. The cake had an increased dietary fiber and protein content while containing a low-fat percentage compared to a commercial cake sample. The innovative cake also contained higher levels of water-soluble and fat-soluble vitamins and minerals such as iron, calcium, potassium, and zinc. The antioxidant capacity of the cake was evaluated, and it was found to contain 1827.23 mg GAE/100 g of total phenols and 97.13 mg QE/100 g of flavonoids. The cake was also found to have antioxidant activity and was effective in protecting the liver from oxidative stress and inflammation and reducing immunodeficiency associated with liver damage.

Hepatoprotective effects of Niudali (Callerya speciosa) root aqueous extracts against tetrachloromethane-induced acute liver injury and inflammation.

Niudali (Callerya speciosa) is commonly grown in southeastern regions of China and consumed as a food ingredient. Although Niudali root extracts showed various biological activities, the hepatoprotective effects of Niudali root phytochemicals are not fully studied. Herein, we prepared two Niudali root aqueous extracts, namely, c and Niudali polysaccharides-enriched extract (NPE), and identified an alkaloid, (hypaphorine) in NEW. The hepatoprotective effects of NWE, NPE, and hypaphorine were evaluated in an acute liver injury model induced by carbon tetrachloride (CCl4) in mice. Pathohistological examination and blood chemistry assays showed that treatment of NWE, NPE, and hypaphorine alleviated CCl4-induced liver damage by lowering the liver injury score (by 75.51%, 80.01%, and 41.22%) and serum aspartate and alanine transaminases level (by 63.24%, 85.22%, and 49.74% and by 78.73%, 80.08%, and 81.70%), respectively. NWE, NPE, and hypaphorine also reduced CCl4-induced hepatic oxidative stresses in the liver tissue by decreasing the levels of malondialdehyde (by 40.00%, 51.25%, and 28.75%) and reactive oxygen species (by 30.22%, 36.14%, and 33.54%) while increasing the levels of antioxidant enzymes including superoxide dismutase (by 21.36%, 21.64%, and 8.90%), catalase (by 22.13%, 33.33%, and 5.39%), and glutathione (by 84.87%, 90.65%, and 80.53%), respectively. Mechanistic assays showed that NWE, NPE, and hypaphorine alleviated liver damage by mediating inflammatory biomarkers (e.g., pro-inflammatory cytokines) via the signaling pathways of mitogen-activated protein kinases and nuclear factor-κB. Findings from our study extend the understanding of Niudali's hepatoprotective effects, which is useful for its development as a dietary intervention for liver inflammation.

Preparation and evaluation of Angelica sinensis polysaccharide-modified chitosan sponge for acute liver injury protection.

In this study, a porous sponge material was formed by physically mixing chitosan (CS) and Angelica sinensis polysaccharide (ASP). After removing the water by freeze-drying, the CS/ASP sponge was obtained. The prepared sponges exhibited excellent swelling properties, thermal stability and biocompatibility as well as improvements over the insufficient mechanical properties of pure chitosan sponges. Notably, the ASP released from the CS/ASP sponge could be effectively absorbed by the liver, which endowed the CS/ASP sponge with effective liver-protective effects against CCl4-induced acute liver injury; these protective effects surpassed those of both blank CS and CS/Dextran sponges. The underlying protective mechanism may involve the activation of the Nrf2-mediated antioxidant signaling pathway and the inhibition of hepatocyte apoptosis. Understanding CS/ASP sponges may provide new insights and inspire new methods for the clinical application of ASP. At the same time, we hope to suggest future directions for the development of polysaccharide preparations.

Auricularia auricular Adsorbs Aflatoxin B1 and Ameliorates Aflatoxin B1-Induced Liver Damage in Sprague Dawley Rats.

Aflatoxin B1 (AFB1), as a class I carcinogen, poses a substantial health risk to individuals. Contamination of food sources, particularly grains and nuts, with Aspergillus flavus (A. flavus) contributes to the prevalence of AFB1. The impact of global warming has spurred research into the development of AFB1 prevention technologies. While edible fungi have shown potential in detoxifying AFB1, there is a scarcity of literature on the application of Auricularia auricular (A. auricular) in this context. This study aimed to investigate the ability and underlying mechanism of A. auricular mycelia to adsorb aflatoxin B1, as well as evaluate its protective effects on the AFB1-induced liver damage in SD rats. Additionally, the effects of temperature, time, pH, and reaction ratio on the adsorption rate were examined. Combining thermodynamic and kinetic data, the adsorption process was characterized as a complex mechanism primarily driven by chemical adsorption. In SD rats, the A. auricular mycelia exhibited alleviation of AFB1-induced liver damage. The protective effects on the liver attributed to A. auricular mycelia may involve a reduction in AFB1 adsorption in the intestine, mitigation of oxidative stress, and augmentation of second-phase detoxification enzyme activity. The adsorption method for AFB1 not only ensures safety and non-toxicity, but also represents a dietary regulation strategy for achieving effective defense against AFB1.

Fatty acid metabolization and insulin regulation prevent liver injury from lipid accumulation in Himalayan marmots.

Fat storage and weight gain are dominant traits for hibernating mammals. However, excessive fat accumulation may cause liver damage. Here, we explore the lipid accumulation and metabolic processes of the Himalayan marmot (Marmota himalayana), a hibernating rodent species. We find that the unsaturated fatty acid (UFA) content in food was consistent with a large increase in the body mass of Himalayan marmots. Metagenomic analysis shows that Firmicutes Bacterium CAG:110 plays a synergistic role by synthesizing UFAs, which is demonstrated by fecal transplantation experiments, indicating that the gut microbiome promotes fat storage in Himalayan marmots for hibernation. Microscopic examination results indicate that the risk of fatty liver appears at maximum weight; however, liver function is not affected. Upregulations of UFA catabolism and insulin-like growth factor binding protein genes provide an entry point for avoiding liver injury.

Protective Effect of Ganoderma lucidum Spore Powder on Acute Liver Injury in Mice and its Regulation of Gut Microbiota.

BACKGROUND: Ganoderma lucidum spore powder (GLSP) has abundant pharmacological activities. However, the difference in the hepatoprotective function of sporoderm-broken and sporoderm-unbroken Ganoderma spore powder has not been studied. This study is the first to investigate the effects of both sporoderm-damaged and sporoderm-intact GLSP on the improvement of acute alcoholic liver injury in mice and gut microbiota of mice. METHODS: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and interleukin 1ß (IL-1ß), interleukin 18 (IL-18), and tumor necrosis factor-α (TNF-α) levels in liver tissues from mice in each group were detected by enzyme-linked immunosorbent assay (ELISA) kits, and histological analysis of liver tissue sections was performed to evaluate the liver-protecting effects of both sporoderm-broken and sporoderm-unbroken GLSP. Additionally, 16S rDNA sequencing of feces from the bowels of mice was performed to compare the regulatory effects of both sporoderm-broken and sporoderm-unbroken GLSP on the gut microbiota of mice. RESULTS: Compared with those in the 50% ethanol model group (MG), sporoderm-broken GLSP significantly reduced serum AST and ALT levels (p < 0.0001) and the release of the inflammatory factors, including IL-1ß, IL-18, and TNF-α (p < 0.0001), and effectively improved the pathological state of liver cells; sporoderm-unbroken GLSP significantly reduced the ALT content (p = 0.0002) and the release of the inflammatory factors, including IL-1ß (p < 0.0001), IL-18 (p = 0.0018), and TNF-α (p = 0.0005), and reduced the serum AST content, but the reduction was not significant; compared with the gut microbiota of the MG, sporoderm-broken GLSP reduced the levels of Verrucomicrobia and Escherichia_Shigella, increased the relative abundance of beneficial bacteria such as Bacteroidetes, and decreased the abundance levels of harmful bacteria, such as Proteobacteria and Candidatus_Saccharibacteria; sporoderm-unbroken GLSP could reduce the abundance levels of harmful bacteria, such as Verrucomicrobia and Candidatus_Saccharibacteria; and GLSP treatment alleviates the downregulation of the levels of translation, ribosome structure and biogenesis, and lipid transport and metabolism in liver-injured mice; Conclusions: GLSP can alleviate the imbalance of gut microbiota and improve liver injury, and the effect of sporoderm-broken GLSP is better.

A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum.

Platycodon grandiflorum (PG) is a traditional Chinese medicine with a long history, but its active compounds have not been reported. In this study, novel carbon dots (CDs), PG-based CDs (PGC-CDs), were discovered and prepared from PG via calcinations and characterized by transmission electron microscopy; high-resolution transmission electron microscopy; X-ray diffraction, fluorescence, ultraviolet-visible, and Fourier-transform infrared spectrometers; X-ray photoelectron spectroscopy; and high-performance liquid chromatography. In addition, the safety and antioxidant activity of PGC-CDs was evaluated by RAW264.7 cells and LO2 cells. The therapeutic effects of PGC-CDs on hyperbilirubinemia and liver protection were evaluated in a bilirubin-induced hyperbilirubinemia mice model. The experiment confirmed that the diameter range of PGC-CDs was from 1.2 to 3.6 nm. PGC-CDs had no toxicity to RAW264.7 cells and LO2 cells at a concentration of 3.91 to 1000 µg/mL and could reduce the oxidative damage of cells caused by H2O2. PGC-CDs could inhibit the increase levels of bilirubin and inflammation factors and increase the levels of antioxidants and survival rate, demonstrating that PGC-CDs possessed anti-inflammatory and anti-oxidation activity. PGC-CDs may reduce the content of bilirubin, so as to reduce a series of pathological lesions caused by bilirubin, which has potential in treating hyperbilirubinemia and preventing liver damage induced by hyperbilirubinemia.

Determination of lead in Gentiana rigescens and evaluation of the effect of lead exposure on the liver protection of the natural medicine.

In this work, ultrasound-assisted rapidly synergistic cloud point extraction (UARS-CPE) and inductively coupled plasma optical emission spectrometry (ICP-OES) were combined to determine trace Pb in Gentiana rigescens Franch. ex Hemsl. (G. rigescens) samples. Under the optimal conditions, the enhancement factor (EF), limit of detection (LOD), limit of quantitation (LOQ) and precision were 33, 0.11 µg L-1, 0.37 µg L-1 and 1.3%, respectively. This method was applied to the analysis of G. rigescens samples, and the outcomes were in good agreement with the results determined by inductively coupled plasma mass spectrometry (ICP-MS). A mice model of immune liver injury induced by concanavalin A (ConA) was established, and the liver protection of G. rigescens and gentiopicroside (GPS) on it and the effects of various dosages of Pb exposure on its liver protection were studied. Pb at a dosage of 5 mg kg-1 had little effect on the liver protection of G. rigescens and GPS, while 25, 125 mg kg-1 dosages of Pb could significantly attenuate the liver protection of both. In addition, it aggravated the necrosis of hepatocytes and inflammatory cell infiltration, and these effects were dose-dependent.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

[Current status and treatment strategies for liver injury before targeted immunotherapy for liver cancer].

The occurrence rate of primary liver cancer in malignant tumors ranks sixth in the world, and the mortality rate ranks third, with a poor prognosis and a five-year survival rate of less than 5%. Most patients with liver cancer in China are found to be in the intermediate and advanced stages, and a targeted immunotherapy combination has become the main treatment option. However, many patients have underlying liver lesions, and their liver function cannot meet the requirements of targeted immunotherapy, which directly affects the treatment of liver cancer patients. Therefore, it is very important to optimize the patient's liver function in a timely manner so as to obtain the opportunity for anti-tumor therapy. This article reviews the current status and response strategies before liver injury related to targeted immune therapy in patients with primary liver cancer.

Dietary bile acid supplementation alters plasma biochemical and hormone indicators, intestinal digestive capacity, and microbiota of piglets with normal birth weight and intrauterine growth retardation.

Piglets with intrauterine growth retardation (IUGR) have poor small intestinal morphology and function, resulting in impaired digestion and absorption of nutrients and lower growth performance. Bile acids (BA) are important in regulating digestive enzyme activity, digestion and absorption of lipids, intestinal development, and protecting the liver. The present study aimed to investigate the effects of dietary BA supplementation on plasma biochemical and hormone indicators, intestinal morphology and function, and microbial community in piglets with normal birth weight (NBW) and IUGR. Weaned piglets (24 IUGR and 24 NBW) were allocated to four groups (12 piglets per group) and fed the following diets: (i) NBW group, NBW piglets fed a basal diet; (ii) NBW + BA group, NBW piglets fed a basal diet with 400 mg/kg BA; (iii) IUGR group, IUGR piglets fed a basal diet; and (iv) IUGR + BA group, IUGR piglets fed a basal diet with 400 mg/kg BA. The feeding trial lasted 28 days. The results showed that IUGR decreased the weight of the jejunum, whereas dietary BA supplementation decreased the jejunum weight and increased the length, weight, and index of ileum in NBW piglets (p < 0.05). In addition, IUGR increased (p < 0.05) the plasma choline esterase (CHE) and glucose levels of weaned piglets regardless of BA supplementation. Dietary BA supplementation increased the plasma albumin, triglyceride, and total protein concentrations while decreased plasma aspartate transaminase (AST), alanine aminotransferase (ALT), CHE, lactate dehydrogenase, and NH3 levels regardless of IUGR (p < 0.05). The IUGR increased trypsin level in the ileum, whereas dietary BA supplementation decreased jejunal trypsin and lipase and ileal lipase levels of weaned piglets regardless of IUGR (p < 0.05). Spearman's correlation analysis revealed the potential link between the intestinal microbial community and intestinal health-related indices of weaned piglets. These findings suggest that IUGR could decrease small intestinal morphology and function, whereas dietary BA supplementation could promote the ileum development of NBW piglets, protect the liver by reducing plasma ALT and AST levels, and increase the proportion of potentially beneficial bacteria in the small intestine of NBW and IUGR piglets, contributing to intestinal development and health of weaned piglets.

Long-Term Dietary Lycium ruthenicum Murr. Anthocyanins Intake Alleviated Oxidative Stress-Mediated Aging-Related Liver Injury and Abnormal Amino Acid Metabolism.

In recent years, the relationship between Lycium ruthenicum Murr. anthocyanins (LRA) and health has attracted increasing attention. The purpose of this study is to investigate the anti-aging effect and mechanism of LRA through a D-galactose (DG)-induced aging rat model. Our results showed that the long-term intake of LRA, for 8 weeks, improved motor function, reduced serum aging markers, promoted the endogenous antioxidant system, and suppressed the serum inflammatory cytokines in aging rats. Besides, the LRA treatment alleviated DG-induced liver injuries by relieving the inflammation and inhibiting Fas/FasL-mediated cell death. More importantly, the abnormal serum metabolome profiles of the aging rats were restored by the LRA, relating to 38 metabolites and 44 pathways. Specifically, the LRA significantly affected the amino acid and protein-related metabolic pathways by regulating the levels of L-threonine, L-aspartic acid, glycine, L-histidine, D-homocysteine, L-homocitrulline, L-homoserine, guanidineacetic acid, and kynurenine. These results have important implications for the development of LRA as an anti-aging and liver-protective ingredient.

Jia-ga-song-tang protection against alcoholic liver and intestinal damage.

Gut-liver axis and cellular homeostasis play key roles in alcohol liver disease (ALD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis. We investigated whether the beneficial effects and underlying mechanisms of Jia-ga-song Tang (JGST) against ALD were associated with gut-liver axis and cellular homeostasis. A predictive network depicting the relationship between Jia-Ga-Song-Tang (JGST) and alcoholic liver disease (ALD) was designed by Network pharmacology. Next, 5% v/v Lieber-DeCarli alcohol liquid diet was used to establish the ALD. JGST protected the liver damage, repaired the intestines to alleviate the Two-hit on the liver, and balanced the cellular homeostasis. It was manifested in repairing the liver and intestinal pathological structure, reducing serum ALT, AST, and liver TG, TC, MDA, CAT, and increasing liver GSH, and intestine GSH-Px. JGST mainly inhibited the liver mRNA levels of HO-1, NQO1, GCLC, FASN, and PPARα and activated the intestinal mRNA levels of HO-1 and NQO1, while inhibiting the liver protein levels of HO-1, NQO1. Furthermore, LPS and LBP in the plasma and the expression of inflammatory factors such as IL-1ß, TNF-α, IL-6, TGFß1, CD14, and Myd88 were reduced after treatment to prove that JGST protects the liver from Two-hit. Ethanol was used to intervene in HepG2 and IEC-6 to establish an ALD cell model and treated by Germacrone, ML385, and TBHQ. repaired the intestinal barrier, and inhibited Nrf2 in IEC-6, but protect the HepG2 by activating Nrf2 to balance cellular homeostasis. Our results reinforce that JGST provides an effective protective method for alcoholic liver disease (ALD) by regulating Gut-liver axis and cellular homeostasis.

Interactive Effects of Copper and Functional Substances in Wine on Alcoholic Hepatic Injury in Mice.

This study analyzed the interaction between copper and functional substances in wine under different drinking amounts on alcoholic liver injury in mice. When the daily drinking amount reached 500 mL/60 kg/day (14% abv) with just ethyl alcohol, the liver aspartate aminotransferase, alanine aminotransferase, and total triglyceride levels of mice were significantly increased to 130.71 U/L, 37.45 U/L, 2.55 U/L, the total antioxidant capacity, catalase, and glutathione level decreased significantly to 1.01 U/mL, 30.20 U/mgprot, and 2.10 U/mgprot, and the liver became gradually damaged. Wine could alleviate and reduce the damage caused by ethyl alcohol well. Low concentrations of copper (0.33, 0.66 mg/L) in wine hardly caused hepatic injury in mice and only significantly improved the aspartate aminotransferase values (109.21 U/L, 127.29 U/L) of serum. Combined with the staining evidence, in the case of medium and high intragastric doses (≥500 mL/60 kg/day), 0.99 mg/L copper (the maximum allowed by China's national standards) in wine began to damage the liver, indicating that under this concentration, the damage of copper to the liver had begun to exceed the protective effect of wine's functional substances on alcoholic hepatic injury. At all experimental doses, high concentrations (1.33 mg/L, 2.00 mg/L) of copper significantly aggravated alcoholic hepatic injury in mice, indicating that high concentrations of copper have a great toxicological risk. In the future, it is necessary to further strengthen the control of copper content in wine and the inspection of market wines in order to protect the health of consumers.

Chronic Uptake of A Probiotic Nutritional Supplement (AB001) Inhibits Absorption of Ethylalcohol in the Intestine Tract - Results from a Randomized Double-blind Crossover Study.

Background: Regular alcohol consumption, e.g. by social drinking, is a potential source of consecutive health problems in many countries worldwide. A probiotic nutritional supplement (AB001) has been developed to reduce alcohol absorption from the intestine tract and to mitigate potential health care risks. Methods: This randomized placebo-controlled double-blind crossover study was conducted with 24 healthy subjects (13 male, 11 female, age: 25.4 ± 7.7 years, BMI: 23.6 ± 2.5 kg/m²). The subjects were randomized to take 2 capsules/day of AB001 or placebo for 1 week prior to an alcohol exposure experiment. On the experimental day, they ingested a light breakfast and drank a moderate glass of spirit (0.3 g/kg body weight). Breath alcohol tests and blood draws for determination of blood alcohol levels were performed for up to 6 hours. After crossover, the experiment was repeated in the following week. Areas under the curves were calculated to determine alcohol absorption rates. Results: A significant reduction of blood alcohol levels by 70.3% (P < 0.005 vs. placebo) was seen with AB001, (breath test: -30.7%; P < 0.005 vs. placebo). No difference was seen in a cognitive function test performed 60 minutes after alcohol ingestion (22.4 ± 7.7 seconds vs. 22.7 ± 5.6 seconds, n.s.). There were no adverse events or serious adverse events reported in this study. Conclusions: One week of supplementation with AB001 resulted in a substantially reduced absorption of alcohol into the body. Regular uptake of AB001 may help to prevent liver and other organ damage, and may reduce the negative medical and economical impact of social drinking on the individual and the society.