Ethanol leaf extract of Hoslundia opposita in in vivo antioxidant and hepatoprotective activity using an animal model.

Introduction: The liver is a valuable organ responsible for detoxifying harmful substances from the body. It plays an essential role; hence the need to ensure its protection from damages. The management of liver diseases with orthodox medicine has been found to have side effects; consequently, there have been several calls on the use of alternative medicine for the effective management of liver diseases. Aim: This study aimed to evaluate the toxicity and antioxidant potentials of H. opposita. Materials and methods: The leaves of H. oppisota harvested from a forest were processed and extracted with ethanol. The extract concentrations of 100-400 mg/ml were used to evaluate acute toxicity, biochemical analysis, in vivo antioxidants, and histopathology using an animal model. Results: The acute toxicity test of H. opposita ethanol leaf extract studied for 21 days suggested safety at a concentration of 400 mg/kgbw. Weight gain in the negative control was 16.91 g, while weight loss in the positive control mice was (13.96 g). 400 mg/kg was found as the LD50 of the plant extract. A decrease in uric acid, cholesterol, urea, creatinine, and bilirubin contents was observed in the single extract-treated mice and the paracetamol-induced but co-administered with extracts, while increased values were observed for protein and albumin contents. The positive control values of ALT, AST, and ALP were 66.74 ± 3.51 IU/L, 68.52 ± 3.63 IU/L, and 342 ± 3.04 IU/L, respectively, in the negative control, values were 48.16 ± 3.68 IU/L, 37.46 ± 1.52, and 89.34 ± 2.66 IU/L. There was a reduction in lipid peroxidation in the extract-treated and satellite groups. At the same time, increased values were observed for catalase and glutathione biochemical activities. The effects of a high dose of paracetamol were alleviated by the ethanol leaf extract over time. Conclusion: The irregularities in the in vivo biochemical, in vivo antioxidant values, and the hepatic damages caused by paracetamol toxicity were regulated on extract treatments, suggesting its use traditionally for the treatment of liver diseases.

Natural Phenylethanoid Supplementation Alleviates Metabolic Syndrome in Female Mice Induced by High-Fructose Diet.

Tyrosol (T), hydroxytyrosol (H), and salidroside (S) are typical phenylethanoids and also powerful dietary antioxidants. This study aimed at evaluating the influence of three natural phenylethanoids, which are dietary phenylethanoids of natural origins, on reversing gut dysbiosis and attenuating nonalcoholic fatty liver features of the liver induced by metabolic syndrome (MetS) mice. C57BL/6J female mice induced with high-fructose diet were established and administrated with salidroside, tyrosol, and hydroxytyrosol for 12 weeks, respectively. Biochemical analysis showed that S, T, and H significantly improved glucose metabolism and lipid metabolism, including reduced levels of total cholesterol insulin (INS), uric acid, low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (ALT). Histopathological observation of the liver confirmed the protective effects of S, T, and H against hepatic steatosis, which were demonstrated by the results of metabolomic analysis, such as the improvement in glycolysis, purine metabolism, bile acid, fatty acid metabolism, and choline metabolism. Additionally, 16S rRNA gene sequence data revealed that S, T, and H could enhance the diversity of gut microbiota. These findings suggested that S, T, and H probably suppress lipid accumulation and have hepatoprotective effects and improve intestinal microflora disorders to attenuate metabolic syndromes.

Protective Effect of Water Extract of Citri Grandis Exocarpium on Alcohol-induced Acute Liver Injury / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of the water extract of Citri Grandis exocarpium （WEC） on mice with alcohol-induced acute liver injury and provide data support for the development of this medicinal for anti-alcoholism and liver protection. MethodThe main components of WEC were determined by high performance liquid chromatography （HPLC）. Sixty Balb/c mice were randomized into 6 groups： control group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， model group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， low-， medium-， and high-dose WEC groups （0.5， 1.0， 2.0 g·kg-1）， and Haiwang Jinzun tablet positive control group （2.0 g·kg-1）. The administration lasted 14 days. One day before the end of the administration， mice were fasted for 12 h with free access to water. The mice， except the control group， were given 56° Chinese liquor （13 mL·kg-1）. After 2 h， blood was taken from eyeballs and the liver was dissected and weighed. Automatic biochemical analyzer was employed to detect the expression of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and alcohol dehydrogenase （ADH）. The pathological changes of liver tissues were observed based on hematoxylin-eosin （HE） staining， and apoptosis of hepatocytes based on TUNEL/DAB staining. The expression of proteins related to apoptosis was detected by Western blot. ResultAccording to the HPLC fingerprint， the main components of WEC were rhoifolin and naringin. Compared with the control group， the model group showed increase in liver/body weight ratio （P<0.01） and the expression of ALT and AST （P<0.05， P<0.01）， decrease in the expression of ADH （P<0.05）， blurred structure of hepatic lobules， pathological changes of liver tissue， loose cytoplasm with edema， severe steatosis， rise of the TUNEL-positive rate （P<0.01）， reduction in expression of Bcl-2 （P<0.01）， and increase in Bax and Caspase-3 （P<0.01）. Compared with the model group， medium-dose WEC lowered liver/body weight ratio （P<0.05）. All doses of WEC depressed the activity of ALT and AST （P<0.05， P<0.01）， up-regulated the expression of ADH （P<0.05）， significantly improved the pathological features of alcohol-induced cytoplasmic porosity， edema， and steatosis， down-regulated the TUNEL-positive rate （P<0.05， P<0.01）， enhanced the expression of Bcl-2 （P<0.05）， and decreased Bax and Caspase-3 （P<0.01）. ConclusionWEC regulates the expression of ALT， AST， and ADH and improves hepatic steatosis and hepatocyte apoptosis to fight against acute liver injury.

Protective Effect of Water Extract of Citri Grandis Exocarpium on Alcohol-induced Acute Liver Injury / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of the water extract of Citri Grandis exocarpium （WEC） on mice with alcohol-induced acute liver injury and provide data support for the development of this medicinal for anti-alcoholism and liver protection. MethodThe main components of WEC were determined by high performance liquid chromatography （HPLC）. Sixty Balb/c mice were randomized into 6 groups： control group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， model group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， low-， medium-， and high-dose WEC groups （0.5， 1.0， 2.0 g·kg-1）， and Haiwang Jinzun tablet positive control group （2.0 g·kg-1）. The administration lasted 14 days. One day before the end of the administration， mice were fasted for 12 h with free access to water. The mice， except the control group， were given 56° Chinese liquor （13 mL·kg-1）. After 2 h， blood was taken from eyeballs and the liver was dissected and weighed. Automatic biochemical analyzer was employed to detect the expression of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and alcohol dehydrogenase （ADH）. The pathological changes of liver tissues were observed based on hematoxylin-eosin （HE） staining， and apoptosis of hepatocytes based on TUNEL/DAB staining. The expression of proteins related to apoptosis was detected by Western blot. ResultAccording to the HPLC fingerprint， the main components of WEC were rhoifolin and naringin. Compared with the control group， the model group showed increase in liver/body weight ratio （P<0.01） and the expression of ALT and AST （P<0.05， P<0.01）， decrease in the expression of ADH （P<0.05）， blurred structure of hepatic lobules， pathological changes of liver tissue， loose cytoplasm with edema， severe steatosis， rise of the TUNEL-positive rate （P<0.01）， reduction in expression of Bcl-2 （P<0.01）， and increase in Bax and Caspase-3 （P<0.01）. Compared with the model group， medium-dose WEC lowered liver/body weight ratio （P<0.05）. All doses of WEC depressed the activity of ALT and AST （P<0.05， P<0.01）， up-regulated the expression of ADH （P<0.05）， significantly improved the pathological features of alcohol-induced cytoplasmic porosity， edema， and steatosis， down-regulated the TUNEL-positive rate （P<0.05， P<0.01）， enhanced the expression of Bcl-2 （P<0.05）， and decreased Bax and Caspase-3 （P<0.01）. ConclusionWEC regulates the expression of ALT， AST， and ADH and improves hepatic steatosis and hepatocyte apoptosis to fight against acute liver injury.

Structural characteristics and improved in vitro hepatoprotective activities of Maillard reaction products of decapeptide IVTNWDDMEK and ribose.

Here, a novel decapeptide IVTNWDDMEK with Maillard reactivity derived from scallop Chlamys farreri mantle was identified. The structural characteristics and in vitro hepatoprotective effects of IVTNWDDMEK conjugated with ribose were further investigated. The changes in decapeptide structures were determined by ultraviolet-visible (UV-vis), Fourier transform infrared (FTIR), and atomic force microscopy (AFM), and the modification sites induced by Maillard reaction of IVTNWDDMEK and ribose were monitored by high performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). Maillard reaction products (MRPs) of IVTNWDDMEK-ribose demonstrate hepatoprotective benefits through the suppression of DNA damage and apoptosis induced by oxidative stress in human HepG2 cells in addition to enhancing the antioxidant activities. Moreover, after treatment with decapeptide-ribose MRPs, the activities of cellular antioxidative enzymes, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx) were remarkably increased, while the content of malondialdehyde (MDA) was decreased compared with H2 O2 - treated group, thereby enhancing the intracellular antioxidant defenses. These findings demonstrate the potential utilization of decapeptide IVTNWDDMEK-ribose MRPs as food antioxidants to suppress oxidative damage. PRACTICAL APPLICATION: In recent years, several food-derived bioactive peptides and their derivatives are regarded as good dietary antioxidants for reducing oxidative stress and improving liver function. Here, a novel Maillard reactive decapeptide IVTNWDDMEK, identified from scallop mantle hydrolysates by peptidomics in the previous study was synthesized. Then, the correlation between intercellular antioxidant activities and chemical structure changes of IVTNWDDMEK-ribose Maillard reaction conjugates was further studied. The preferable hepatoprotective activities of decapeptide IVTNWDDMEK-ribose MRPs indicated that these MRPs could be potentially utilized as food antioxidants or additives in the production of nutritional foods.

Phenolic Compounds from Carissa spinarum Are Characterized by Their Antioxidant, Anti-Inflammatory and Hepatoprotective Activities.

Carissa spinarum has been traditionally used for the treatment of various diseases due to its different pharmacological activities. However, the active compounds responsible for its potentially specific activities have rarely been explored. To this end, the ethyl acetate (EA) fraction was screened out and selected for further phytochemical isolation because of its promising activities in preliminary 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and COX-2 inhibition assays. As a result, 10 compounds (1-10), including a new one (5), were isolated, with eight of these being identified as phenolic compounds, as expected. Compound 9 possessed an IC50 value of 16.5 ± 1.2 µM, which was lower than that of positive control (vitamin C, 25.5 ± 0.3 µM) in the DPPH assay, and compounds 2, 6, 7 and 9 showed better total antioxidant capacity than vitamin C in the FRAP assay. Meanwhile, compounds 1-6 and 9 also had IC50 values of less than 1.0 µM, which was even better than the positive control indomethacin in the COX-2 inhibition assay. In this context, compounds 2 and 9 were further evaluated to exhibit clear hepatoprotective activities by improving the L02 cell viability and reducing ROS production using a H2O2-induced L02 cell injury model. This study provides initial evidence revealing the most potent phenolic compounds from the root bark of C. spinarum responsible for its antioxidant, anti-inflammatory and hepatoprotective activities.

Effect of Cynara scolymus and its derivatives on broilers: an updated review.

Medicinal plants and their derivatives are human-friendly, nutritional supplements, and their use in the poultry industry is increasing today. Cynara scolymus is a very high-quality antioxidant medicine plant that has recently attracted the attention of poultry and nutrition researchers to supplement their rations and reduce feed costs. In the present study, the effect of powder and extract of C. scolymus on broilers has reviewed. This review shows that the impact of C. scolymus on production performance, carcass characteristics, liver enzymes activity, and meat characteristics of broiler chickens are not significant. However, the negative impact of this compound on these properties has not reported. Moreover, cholesterol levels reduced by the dietary C. scolymus supplementation. The impact of C. scolymus powder and extract on chickens' broiler immunity was not significant in the cited literature, but dietary C. scolymus powder increases Newcastle antibody titers and lowers blood pressure. Dietary C. scolymus under heat stress increased anti-sheep red blood cell titers. No substantial studies have conducted on the effect of C. scolymus on broilers. Therefore, it is not possible to determine a single dosage for the use of C. scolymus powder or extract in broiler diets to the improvement of the broiler characteristics. More researches are needed to determining the appropriate dosage to achieve maximum performance.

Effects of surface-deacetylated chitin nanofibers on non-alcoholic steatohepatitis model rats and their gut microbiota.

Nonalcoholic steatohepatitis (NASH), a more advanced form of nonalcoholic fatty liver disease (NAFLD), is associated with increased cardiovascular and liver-related mortality. Stroke-prone spontaneously hypertensive rats (SHRSP5/Dmcr) that are fed a high-fat and high-cholesterol diet develop hepatic lesions that are similar to those observed in human NASH pathology. We investigated the hepatic protective and antioxidant effects of surface-deacetylated chitin nanofibers (SDACNFs) that were administered to SHRSP5/Dmcr rats for 8 weeks. The administration of SDACNFs (80 mg/kg/day) resulted in a significant decrease in hepatic injury, oxidative stress, compared with the non-treatment. The SDACNFs also caused a reduction in the population of harmful members of the Morganella and Prevotella genus, and increased the abundance of the Blautia genus, a useful bacterium in gut microbiota. We therefore conclude that SDACNF exerts anti-hepatic and antioxidative effects not only by adsorbing lipid substances but also by reforming the community of intestinal microflora in the intestinal tract.

Comparative effect of desflurane and sevoflurane on liver function tests of patients with impaired hepatic function undergoing cholecystectomy: A randomized clinical study.

BACKGROUND AND AIM: Desflurane and sevoflurane are the most common volatile anesthetics used during laparoscopic and hepatic surgery. The objective of the study was to evaluate the effect of desflurane and sevoflurane in patients with elevated preoperative liver functions undergoing laparoscopic cholecystectomy. METHODS: The study was a randomized study and included 162 patients classified randomly into two groups: Desflurane group: The patients received desflurane (end-tidal concentration 4%-6%) as an inhalational agent during the whole procedure. Sevoflurane group: The patients received sevoflurane (end-tidal concentration 2%-4%) as an inhalational agent during the whole procedure. The investigations included serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total bilirubin. The values were serially collected at the following timepoints; T0:at the preoperative period, T1:directly after surgery, T2:1st postoperative day, T3:2nd postoperative day, T4:3rd postoperative day, T5:5th postoperative day, T6:7th postoperative day, and T7:10th postoperative day. The statistics were described in terms of mean ± standard deviation, frequencies, and percentages. RESULTS: The preoperative liver enzymes and total bilirubin were higher than the normal range in patients of the two groups. Postoperatively, there was a decrease in the AST and ALT with desflurane more than sevoflurane from T1 to T6(P < 0.05). The ALP, GGT, and bilirubin decreased in patients of the two groups, but the comparison was insignificant (P > 0.05). CONCLUSION: The desflurane is a safe inhalational volatile for maintenance of anesthesia in patients with impaired liver function undergoing laparoscopic cholecystectomy. It was associated with a decrease in the liver enzymes more than the sevoflurane.

Paeoniflorin, a Natural Product With Multiple Targets in Liver Diseases-A Mini Review.

Paeoniflorin is derived from Paeonia suffruticosa Andr., Paeonia lactiflora Pall., or Paeonia veitchii Lynch and has been used in traditional medical applications for more than 2,000 years. Paeoniflorin is a monoterpenoid glycoside with various effects on liver diseases. Recent studies have revealed that paeoniflorin demonstrates a wide range of activities, including hepatic protection, cholestasis alleviation, liver fibrosis attenuation, nonalcoholic fatty liver disease prevention, and hepatocellular carcinoma inhibition involved in multiple pathways. Moreover, anti-inflammation, antioxidation, and immune regulation with the regulation of TLR4-NF-κB, ROCK/NF-κB, HO-1, mitochondria-dependent as well as HMGB1-TLR4 signaling pathways are correlated with hepatic protection in liver injury and nonalcoholic fatty liver disease. Antioxidative mechanisms, anti-inflammation, and hepatic transporter regulation involved in NOX4, PI3K/Akt/Nrf2, NF-κB, NTCP, BSEP, as well as MRP2 signals are mainly relevant to the anticholestatic effect of paeoniflorin. The inhibition of hepatic stellate cell activation and alleviation of extracellular matrix deposition via vast signals such as mTOR/HIF-1α, TGF-ß1/Smads, and JAK2/STAT6 are primarily involved in the antifibrotic effect of paeoniflorin. The regulation of macrophages also contributes to the alleviation effect on liver fibrosis. In addition, the reduction of invasion, metastasis, and adhesion and the induction of apoptosis-related targets, including Bax, Bcl-2, and caspase-3, are related to its effect on hepatocellular carcinoma. The literature indicates that paeoniflorin might have potent efficacy in complex liver diseases and demonstrates the profound medicinal value of paeoniflorin.

Tanshinol A Ameliorates Triton-1339W-Induced Hyperlipidemia and Liver Injury in C57BL/6J Mice by Regulating mRNA Expression of Lipemic-Oxidative Injury Genes.

Tanshinol A, which is derived from a traditional Chinese herbal Radix Salviae Miltiorrhizae is indicative of a hypolipidemic candidate. Therefore, we aim to validate its hypolipidemic activity of tanshinol A and explore its mechanism in triton-1339W-induced hyperlipidemic mice model, which possess multiply pathogenesis for endogenous lipid metabolism disorder. Experimental hyperlipidemia mice are treated with or without tanshinol A (i.g. 40, 20, 10 mg/kg), and blood and liver tissue were collected for validating its hypolipidemic and hepatic protective effect, and hepatic mRNA expression profile, which was associated with lipid metabolism dysfunction and liver injury, was detected by RT-qPCR. As results show, triton-1339W-induced abnormal of serum TC, TAG, HDL-C, LDL-C, SOD, MDA, GOT, and GPT is remarkably attenuated by tanshinol A. In pathological experiment, triton-1339W-induced hepatocellular ballooning degeneration, irregular central vein congestion, and inflammation infiltration are alleviated by tanshinol A. Correspondingly, hepatic mRNA expression of Atf4, Fgf21, Vldlr, Nqo1, Pdk4, and Angptl4, which are genes regulating lipemic-oxidative injury, are significantly increased by tanshinol A by 2~6 fold. Abcg5, Cd36, and Apob, which are responsible for cholesterol metabolism, are mildly upregulated. Noticeably, triton-1339W-suppressed expressions of Ptgs2/Il10, which are genes responsible for acute inflammation resolution in liver injury, are remarkably increased by tanshinol A. Conclusively, tanshinol A exerted hypolipidemic effect and hepatoprotective effect through restoring triton-1339W-suppressed mRNA expression, which may be involved in Atf4/Fgf21/Vldlr and Ptgs2/Il-10 signaling pathways.

Hepatoprotective properties of Curcuma longa L. extract in bleomycin-induced chronic hepatotoxicity.

Curcuma longa L. (CLL) extract has previously been reported to alleviate liver damage. The current study examined the antioxidant activity of CLL by which the extract protects the liver against bleomycin (BLM)-induced hepatotoxicity in mice. The hypothesis was that CLL extract would protect the liver by reducing oxidative stress (induced superoxide dismutase (SOD) and catalase (CAT) activity), inhibiting lipid peroxidation, lowering biochemical parameters, and decreasing ROS production. Hepatic toxicity was induced by intraperitoneal injection of mice once daily with BLM (0.069 U/mL; 0.29 U/kg bw.) for a period of 4 weeks. The CLL was administered once a day for 4 weeks, 2 h prior at dose (40 mg/mL; 0.187 mg/kg/day). CLL extract significantly protected the liver, it decreased plasma bilirubin (BL) and gamma glutamyl transpeptidase (GGT), and it reduced lipid peroxidation levels. BLM intoxication produced oxidative stress, in which the antioxidant system functioned incorrectly and ROS production significantly increased. The CLL extract provided significant hepatic protection against BLM toxicity by improving SOD, CAT (p < 0.05), and MDA levels and decreasing ROS in the group receiving BLM (p < 0.05), leading to reduced membrane lipid peroxidation. Throughout this study, the CLL extract facilitated recovery from BLM-induced hepatic injury by suppressing oxidative stress. Therefore, the CLL extract has the potential to serve as an antioxidant compound to treat chronic hepatotoxicity.

Impaired TFEB-Mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-Induced Liver Injury and Steatosis in Mice.

BACKGROUND & AIMS: Defects in lysosome function and autophagy contribute to the pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes by evaluating the functions of transcription factor EB (TFEB), which regulates lysosomal biogenesis. METHODS: We performed studies with GFP-LC3 mice, mice with liver-specific deletion of TFEB, mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB and TFE3 double-knockout mice), and Tfebflox/flox albumin cre-negative mice (controls). TFEB was overexpressed from adenoviral vectors or knocked down with small interfering RNAs in mouse livers. Mice were placed on diets of regular ethanol feeding plus an acute binge to induce liver damage (ethanol diet); some mice also were given injections of torin-1, an inhibitor of the kinase activity of the mechanistic target of rapamycin (mTOR). Liver tissues were collected and analyzed by immunohistochemistry, immunoblots, and quantitative real-time polymerase chain reaction to monitor lysosome biogenesis. We analyzed levels of TFEB in liver tissues from patients with alcoholic hepatitis and from healthy donors (controls) by immunohistochemistry. RESULTS: Liver tissues from mice on the ethanol diet had lower levels of total and nuclear TFEB compared with control mice, and hepatocytes had decreased lysosome biogenesis and autophagy. Hepatocytes from mice on the ethanol diet had increased translocation of mTOR into lysosomes, resulting in increased mTOR activation. Administration of torin-1 increased liver levels of TFEB and decreased steatosis and liver injury induced by ethanol. Mice that overexpressed TFEB in the liver developed less severe ethanol-induced liver injury and had increased lysosomal biogenesis and mitochondrial bioenergetics compared with mice carrying a control vector. Mice with knockdown of TFEB and TFEB-TFE3 double-knockout mice developed more severe liver injury in response to the ethanol diet than control mice. Liver tissues from patients with alcohol-induced hepatitis had lower nuclear levels of TFEB than control tissues. CONCLUSIONS: We found that ethanol feeding plus an acute binge decreased hepatic expression of TFEB, which is required for lysosomal biogenesis and autophagy. Strategies to block mTOR activity or increase levels of TFEB might be developed to protect the liver from ethanol-induced damage.

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl4-induced liver injury.

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl4-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl4-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl4-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

Improved physicochemical properties and hepatic protection of Maillard reaction products derived from fish protein hydrolysates and ribose.

High amounts of waste products generated from fish-processing need to be disposed of despite their potential nutritional value. A variety of methods, such as enzymatic hydrolysis, have been developed for these byproducts. In the current study, we investigated the physicochemical, biological and antioxidative properties of fish protein hydrolysates (FPH) conjugated with ribose through the Maillard reaction. These glycated conjugates of FPH (GFPH) had more viscous rheological properties than FPH and exhibited higher heat, emulsification and foaming stability. They also protected liver HepG2 cells against t-BHP-induced oxidative stress with enhanced glutathione synthesis in vitro. Furthermore, it was shown that GFPH induced upregulation of phase II enzyme expression, such as that of HO-1 and γ-GCL, via nuclear translocation of Nrf2 and phosphorylation of ERK. Taken together, these results demonstrate the potential of GFPH for use as a functional food ingredient with improved rheological and antioxidative properties.

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl-induced liver injury / 中国天然药物

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

Role of Nrf2 in chronic liver disease.

Nuclear erythroid 2-related factor 2 (Nrf2) is a central regulator of antioxidative response elements-mediated gene expression. It has a significant role in adaptive responses to oxidative stress by interacting with the antioxidant response element, which induces the expression of a variety of downstream targets aimed at cytoprotection. Previous studies suggested oxidative stress and associated damage could represent a common link between different forms of diseases. Oxidative stress has been implicated in various liver diseases, including viral hepatitis, nonalcoholic fatty liver disease/steatohepatitis, alcoholic liver disease and drug-induced liver injury. Nrf2 activation is initiated by oxidative or electrophilic stress, and aids in the detoxification and elimination of potentially harmful exogenous chemicals and their metabolites. The expression of Nrf2 has been observed throughout human tissue, with high expression in detoxification organs, especially the liver. Thus, Nrf2 may serve as a major regulator of several cellular defense associated pathways by which hepatic cells combat oxidative stress. We review the relevant literature concerning the crucial role of Nrf2 and its signaling pathways against oxidative stress to protect hepatic cell from oxidative damage during development of common chronic liver diseases. We also review the use of Nrf2 as a therapeutic target to prevent and treat liver diseases.

Liver protective activity of a hydroethanolic extract of Arrabidaea chica (Humb. and Bonpl.) B. Verl. (pariri).

BACKGROUND: Folk medicine uses preparations of Arrabidaea chica (pariri) leaves to treat various liver pathologies. We evaluated the effects of the hydroethanolic extract of these leaves (CHEE) on an in vivo model of liver intoxication. MATERIALS AND METHODS: Different groups of rats were treated orally for 7 days with CHEE at doses of 300, 500 or 600 mg/kg or silymarin at 35 mg/kg. The control group received only 0.5 ml of distilled water. After 7 days of treatment, both the groups received CCl(4), and activities of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and bilirubin level were assessed. The ability of CHEE to suppress hepatic injury triggered by CCl(4) was evaluated based on suppression (%) of activities of GOT, GPT and bilirubin levels. RESULTS: The chromatograms of the CHEE obtained at 330 and 400 nm show features of two main classes of secondary metabolites: quinones and flavonoids. The administration of 300, 500 or 600 mg/kg of CHEE resulted in the reduction of GPT levels by 85.34%, 88.59% and 93.72%, respectively. The suppression of GOT levels was 56.86%, 65.27% and 68.95%, respectively, and that of plasma bilirubin was 83.81%, 83.12% and 84.14%, respectively. These results demonstrate the protective character of CHEE and its ability to maintain the functional integrity of hepatic cells. CONCLUSIONS: The results obtained are possibly due to the presence of quinones and flavonoids in A. chica CHEE, both detected using high performance liquid chromatography.

Atividade hepatoprotetora do extrato alcoólico da Camellia sinensis (L. ) Kuntze (chá-verde) em ratos Wistar tratados com dietilnitrosamina / Hepatic protection effect of the alcoholic extract from Camellia sinensis (L. ) Kuntze (green tea) in Wistar rats treated with diethylnitrosamine

O chá-verde (Camellia sinensis (L.) Kuntze) é utilizado por suas propriedades: antioxidante, quimioprotetora e antiinflamatória em varias situações patológicas, principalmente frente a compostos químicos cancerígenos. Para tanto se avaliou o efeito hepatoprotetor do extrato de chá verde (ECV) sobre a lipoperoxidação e necrose provocada pelo agente cancerígeno Dietilnitrosamina (DEN) no fígado de ratos machos Wistar. Os ratos foram expostos a dose única de 200 mg/kg de DEN via intra peritoneal e tratados por via oral de 120 mg/kg de ECV em diferentes momentos experimentais. Após 24 h em relação a exposição ao DEN, os animais foram sacrificados sendo avaliado: os níveis de AST/ALT no plasma, a lipoperoxidação por quantificação de TBARS e FOX no fígado e a ocorrência de necrose e hemorragia hepática através do estudo histopatológico. A ação quimioprotetora e a diminuição da lipoperoxidação foram verificadas pela diminuição das transaminases, TBARS, FOX e redução da necrose hepática. A avaliação confirmou a importância de se utiliza o chá verde como agente quimioprotetor, principalmente na forma preventiva.

Green tea (Camellia sinensis (L.) Kuntze) is used for its properties: antioxidant, chemoprotector and anti-inflammatory in several pathological situations, mainly those facing carcinogen chemical substances. This work has evaluated the hepatic protection effect of the green tea extract (GTE) on lipoperoxidation and necrosis, induced by the carcinogenic DEN in rats´ liver. Adult male Wistar rats were used and exposed to one only intra peritoneal dose of 200 mg/kg of DEN, and orally 120 mg/kg of ECV in different experimental moments. After 24 h of a DEN treatment, the animals were sacrificed and the following aspects were evaluated: the AST/ALT levels in plasma, lipoperoxidation of TBARS and FOX in the liver. Necrosis and Hepatic hemorrhage were observed through a histological examination. The chemoprotector action and the decrease in lipoperoxidation were detected after a decrease of AST/ALT, TBARS, FOX and hepatic necrosis. The evaluation of these results confirmed the importance of the use of the green tea as a chemoprotector agent, particularly as a preventive method.

INFLUENCE OF GARDENIA YELLOW ON CCl_4- HEPATOTOXICITY IN MICE / 营养学报

Objective: To study the protective function of Gardenia yellow (GY) against CCl 4 induced hepatotoxicity in mice.Methods: Healthy Kunming male mice, weighting (20?2) g, 10 per group were randomized into 5 groups:control group, CCl 4 injured group, low dose group(CCl 4 injured+0.1 ml GY solution), medium dose group(CCl 4 injured+ 0.2 ml GY solution) and high dose group(CCl 4 injured+0.4ml GY solution). GY solution was given i.g. 5 d prior to CCl 4 injury. Serum glutamate pyruvate transaminase(SGPT) and glutamic oxaloacetic transaminase(SGOT) and lactic dehydrogenase(LDH) activities were determined 18 h after CCl 4 injury. Hepatic malondialdehyde(MDA), glutathione(GSH) and liver index were also detected. Results: In GY treated groups, the increases of serum SGOT, SGPT, LDH activities and liver GSH were inhibited obviously. The elevations of MDA and liver index were prevented significantly. The lesions in liver lobule were ameliorated obviously. Conclusion: Gardenia yellow can protect against CCl 4 induced hepatotoxicity.