Alleviate Liver Damage Research Articles

Lycopene alleviates aflatoxin B1 induced liver damage through inhibiting cytochrome 450 isozymes and improving detoxification and antioxidant systems in broiler chickens

The effects of lycopene on liver damage in Aflatoxin B1 (AFB1)-challenged broilers were investigated. A total of 240 Arbour Acres Broilers in five groups were fed basal diet (control), basal diet with 100 μg/kg AFB1 (AFB1), AFB1 diet with 100, 200, and 400 mg/kg lycopene (AL1, AL2, and AL3), respectively. Broilers in AFB1 group had higher hepatic activities of cytochrome P450 1A1 (CYP1A1) and cytochrome P450 2A6 (CYP2A6) than the control group (P < .05). The hepatic concentrations of AFB1-8,9-epoxide-DNA adduct (AFBO-DNA), reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), protein carbonyl (PC) and 8-hydroxydeoxyguanosine (8-OHdG) were higher in AFB1 group than the control group (P < .05). In lycopene supplementation groups, the activities of CYP1A1 and CYP2A6, and the concentrations of AFBO-DNA, ROS, MDA, and 8-OHdG were lower than AFB1 group (P < .05). The 4-HNE and PC concentrations in AL2 and AL3 groups were lower than AFB1 group (P < .05). Compared to the control group, broilers in the AFB1 group had reduced glutathione (GSH) concentration and decreased activities of glutathione-S-transferase (GST), glutamine-cysteine ligase (GCL), total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GPx) (P < .05). Whereas the GSH concentration in AL2 group, the GST activity in AL1 and AL3 groups, the GCL and CAT activities in AL1 group, and GPx activity in AL1, AL2, and AL3 groups were higher than AFB1 group (P < .05). Therefore, lycopene alleviated AFB1-induced liver damage possibly through inhibiting cytochrome P450 isozymes and improving detoxification and antioxidant systems in broilers. HIGHLIGHTS Dietary lycopene alleviated liver damage induced by aflatoxin B1 in broilers. Lycopene inhibited crucial cytochrome 450 isozymes involved in aflatoxin B1 bioactivation. Lycopene increased detoxification and antioxidant ability in aflatoxin B1 exposed broilers.

Mulberry fruit polysaccharides alleviate diethylnitrosamine/phenobarbital-induced hepatocarcinogenesis in vivo: the roles of cell apoptosis and inflammation

ABSTRACT Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and chemoprevention represents a feasible treatment to reduce the mortality of this carcinoma. Mulberry fruit polysaccharides (MFP) possess immunoregulatory and anti-inflammatory effects, which have been reported to alleviate liver damage evoked by CCl4 or alcohol in previous reports. However, its chemopreventive effect against liver carcinogenesis is insufficient. The present study was aimed to investigate the possible role of MFP as a pro-apoptosis, and anti-inflammatory agent to possess its chemoprevention property. Hepatocarcinogenesis was induced by diethylnitrosamine/phenobarbital (DEN/PB) for 14 weeks. The DEN/PB-administered rats were co-treated with different doses of MFP (50 or 100 mg/kg body weight) by oral gavage for 14 weeks. Basic hepatic function indexes (AST, ALT, ALP, GGT, total bilirubin, and albumin), and hepatic tumor biomarkers (AFP, CEA, and CA19.9), together with histological assessment were performed. Besides, the hepatic apoptosis markers (Bcl-2, Bax, caspase3, and caspase9), inflammation markers (IL-1β, TNF-α, and NF-κB), and mutT homologue gene 1 (MTH1) were examined. Oral gavage of MFP inhibited the elevations of hepatic function indexes and hepatic tumor biomarkers and alleviated pathological changes in hepatic tissue. In addition, the hepatic apoptosis markers, inflammation markers, and the mRNA level of MTH1 were abnormal in DEN/PB group, which were reversed by MFP treatment. In conclusion, MFP is an effective agent that provides chemoprevention against DEN/PB-evoked hepatocarcinogenesis via inhibition of inflammation and induction of apoptosis.

Myricetin and myricetrin alleviate liver and colon damage in a chronic colitis mice model: Effects on tight junction and intestinal microbiota

This study investigated the protective effects of myricetin (MYR) and myricetrin (MYRR) in dextran sodium sulfate (DSS) induced liver and colon damage in mice. The results showed that MYR and MYRR alleviate liver damage of colitis mice via tumor necrosis factor-α (TNF-α)/nuclear factor kappa-B (NF-κB) pathway. After dexamethasone acetate (DXMS) and MYR treatment, the expressions of myosin light chain kinase (MLCK) were increased in mice colon. The expression of occludin was increased after MYR treatment, while MYRR significantly increased tight junction protein 1 (ZO1) expression compared to colitis mice. MYR significantly reduced the abundance of intestinal Proteobacteria and Cyanobacteria to alleviate colitis. At the species level, treatment with MYR and MYRR reduced the abundance of Helicobacter-sp-MIT and Lachnospiraceae bacterium, and increased the abundance of Lactobacillus gasseri. The protective role of MYR and MYRR in DSS induced colitis mice may attribute to their intestinal microbiota and tight junction proteins modulation activities.

Selenium alleviates mercury chloride-induced liver injury by regulating mitochondrial dynamics to inhibit the crosstalk between energy metabolism disorder and NF-κB/NLRP3 inflammasome-mediated inflammation

Mercury (Hg) is a persistent heavy metal contaminant with definite hepatotoxicity. Selenium (Se) has been shown to alleviate liver damage induced by heavy metals. Therefore, the present study aimed to explore the mechanism of the antagonistic effect of Se on mercury chloride (HgCl2)-induced hepatotoxicity in chickens. Firstly, we confirmed that Se alleviated HgCl2-induced liver injury through histopathological observation and liver function analyzation. The results also showed that Se prevented HgCl2-induced liver lipid accumulation and dyslipidemia by regulating the gene expression related to lipid as well as glucose metabolism. Moreover, Se blocked the nuclear factor kappa B (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, which was the key to alleviate the inflammation caused by HgCl2. Mechanically, Se inhibited immoderate mitochondrial division, fusion, and biogenesis caused by HgCl2, and also improved mitochondrial respiration, which were essential for preventing energy metabolism disorder and inflammation. In conclusion, our results suggested that Se inhibited energy metabolism disorder and inflammation by regulating mitochondrial dynamics, thereby alleviating HgCl2-induced liver injury in chickens. These results are expected to provide potential intervention and therapeutic targets for diseases caused by inorganic mercury poisoning.

Protective Effect of Naringenin on Cadmium-induced Toxicity in Rat Liver

Background: Cadmium (Cd) is a widespread environmental toxic heavy metal. Naringin (Nar) is reported to have a protective effect on Cd-induced liver injury. This study aimed to explore the hepatic injury induced by Cd and the protective effects of Nar on Cd-induced oxidative stress and apoptosis in rat liver. Methods: In accordance with groups, male SD rats were injected intraperitoneally with Cd and orally with Nar every day. The treatment period was 3 weeks. Body weight, the morphological changes in liver, the activity of antioxidant indices and expression of the apoptotic genes caspase-3 and -9 were assessed. Result: Results showed that the body weight of Cd-exposed rats decreased, the superoxide dismutase and catalase activities in liver decreased, the glutathione content decreased and the malondialdehyde content increased. Further, Cd-induced hepatic structural damage and cell apoptosis were observed. However, Nar could alleviate liver damage caused by Cd. Therefore, Cd caused oxidative damage and cell apoptosis in rat liver, while Nar had preventive and ameliorative effects on these injuries.

Structural simplification and bioisostere principle lead to Bis-benzodioxole-fibrate derivatives as potential hypolipidemic and hepatoprotective agents

The bis-benzodioxole-fibrate hybrids were designed by structural simplification and bioisostere principle. Lipids lowering activity was preliminarily screened by Triton WR 1339 induced hyperlipidemia mice model, in which T3 showed the best hypolipidemia, decreasing plasma triglyceride (TG) and total cholesterol (TC), which were better than sesamin and fenofibrate (FF). T3 was also found to significantly reduce TG, TC and low density lipoprotein cholesterin (LDL-C) both in plasma and liver tissue of high fat diet (HFD) induced hyperlipidemic mice. In addition, T3 showed hepatoprotective activity, which the noteworthy amelioration in liver aminotransferases (AST and ALT) was evaluated and the histopathological observation exhibited that T3 inhibited lipids accumulation in the hepatic and alleviated liver damage. The expression of PPAR-α receptor involved lipids metabolism in liver tissue significantly increased after T3 supplementation. Other potent activity, such as antioxidation and anti-inflammation, was also observed. The molecular docking study revealed that T3 has good affinity activity toward to the active site of PPAR-α receptor. Based on these findings, T3 may serve as an effective hypolipidemic agent with hepatoprotection.

Nebivolol alleviates liver damage caused by methotrexate via AKT1/Hif1α/eNOS signaling

Despite the wide clinical indications, methotrexate (MTX) use is limited because of serious side effects including liver toxicity. MTX was shown to cause tissue damage by mainly oxidative stress and also inflammation and apoptosis. Thus, Nebivolol (NEB) which has antioxidant and antiapoptotic properties were thought to be effective against MTX-induced injury. This study aimed to evaluate the effects of NEB on MTX-induced liver toxicity via AKT/Hypoxia-Inducible Factor 1 Alpha (HIF1α)/Endothelial Nitric Oxide Synthase (eNOS) signaling pathways. Rats were divided into three groups as control, MTX, and NEB. A single dose of MTX (20 mg/kg intraperitoneally) was given to the rats on the first day of the experiment and NEB (10 mg/kg, daily by oral gavage) was given to the treatment group for a week. At the end of the experiment, bloods were taken for aspartate transaminase (AST), alanine aminotransferase (ALT), and total bilirubin (T-BIL) analyses. Liver tissues were harvested for biochemical (total oxidant status (TOS) and total antioxidant status (TAS), genetic (PCR analyses for AKT1, eNOS, and HIF1a), and histological (Hemotoxylin-Eosin, Masson Trichome, Periodic Acid Schiff-Asien Blue, reticulin for histological, and CD3 for immunohistochemical staining) analyses. MTX increased the levels of TOS values, AST, ALT, T-BIL levels and decreased the expressions of AKT/HIF1α/eNOS. NEB treatment reversed all these changes markedly via decreasing inflammation by nitric oxid (NO) production. In conclusion, NEB treatment significantly preserves the liver by decreasing oxidant levels and inflammatory parameters through HIF1α/eNOS signaling. Due to the antioxidant properties of NEB, it can be used in other liver injury models sharing the same pathway.

Raloxifene Protects Cisplatin-Induced Renal Injury in Mice via Inhibiting Oxidative Stress.

PurposeCisplatin is one of the most widely used antineoplastic drugs but has limited therapeutic effects due to nephrotoxicity. The aim of this study was to determine the possible renoprotective effect of the antioxidant raloxifene on cisplatin-induced nephrotoxicity in mice.Materials and MethodsCisplatin-induced acute renal injury was established in female C57 mice that were treated with saline (normal control) or raloxifene over a 7-day period. The body weight of the mice was recorded. Histopathological examinations of the kidney tissues were performed using H&E, PAS staining and TEM. The histomorphology of liver and other organs was observed by H&E staining. The serum levels of creatinine, blood urea nitrogen (BUN), alanine transaminase (ALT) and glutamic oxalacetic transaminase (AST) were analyzed by specific kits. Superoxide dismutase (SOD) and glutathione (GSH) activity, and the content of malondialdehyde (MDA) in the kidney, liver homogenates and HK-2 cells were measured by WST-8 and thiobarbituric acid colorimetric methods. Moreover, the mitochondrial structures of HK-2 cells were performed using TEM. The viability and proliferation of HK-2 cells were examined by CCK-8 and EdU incorporation assays. The mitochondrial membrane potential was measured by JC-1 fluorescence.ResultsRaloxifene significantly reduced the levels of serum creatinine, urea, ALT and AST in the cisplatin-treated mice, and alleviated cisplatin-induced renal and hepatic tissue injury. Furthermore, raloxifene also increased the activity of GSH and SOD in the renal tissues and HK-2 cells, and reduced MDA levels, thereby limiting oxidative stress in the kidney.ConclusionRaloxifene protected against cisplatin-induced nephrotoxicity by activating the antioxidant system, along with alleviating liver damage. It should be considered as a potential adjuvant in cisplatin-based chemotherapeutic protocols.

Ameliorating effects of white mulberry on iron-overload-induced oxidative stress and liver fibrosis in Swiss albino mice

Excess iron causes oxidative damage of biomolecules, leading to tissue injury primarily liver failure. In this study, we explored the remediating effects of Morus alba L. (MAME) on iron-overload-induced oxidative stress and liver injury in mice. The In vitro study revealed the antioxidant and free radical scavenging properties of MAME. Intraperitoneal injection of iron-dextran was administered in Swiss albino mice to induce iron-overload condition and the mice were further treated with MAME. MAME treatment significantly decreased liver iron, serum ferritin level, oxidative stress, and restored serum parameters and liver antioxidants. Moreover, biochemical and histopathological analyses confirmed the alleviated liver damage and fibrosis upon MAME treatment. The protective effect of MAME against iron-overload-induced apoptosis was confirmed by upregulation of protein levels of Bax, Caspase-3, and PARP. The treatment also affected the expression of MAPKs (ERK, JNK, and p38). GC-MS analysis revealed the presence of various bioactive phytochemicals in MAME that may be responsible for ameliorating effects of excess iron. Thus MAME can be envisaged as an effective iron chelator in the treatment of iron-overload-induced liver injury and fibrosis.

Human umbilical cord-derived mesenchymal stem cell-exosomal miR-627-5p ameliorates non-alcoholic fatty liver disease by repressing FTO expression.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-based therapy is currently considered to be an effective treatment for NAFLD. The present study aimed to determine whether hUC-MSCs-exosomes have a hepatoprotective effect on NAFLD. We constructed NAFLD rat model by high-fat high-fructose feeding. Liver cells (L-O2) were treated with palmitic acid (PA) to mimic NAFLD model. NAFLD rats and PA-treated L-O2 cells were treated with hUC-MSCs-exosomes, and then we determined the influence of exosomes on liver damage and glucose and lipid metabolism in vivo and in vitro. We found that hUC-MSCs-exosomes exhibited an up-regulation of miR-627-5p. Exosomal miR-627-5p promoted cell viability and repressed apoptosis of PA-treated L-O2 cells. Exosomal miR-627-5p also enhanced the expression of G6Pc, PEPCK, FAS and SREBP-1c and suppressed PPARα expression in PA-treated L-O2 cells. Moreover, miR-627-5p interacted with fat mass and obesity-associated gene (FTO) and inhibited FTO expression in L-O2 cells. MiR-627-5p-enriched exosomes improved glucose and lipid metabolism in L-O2 cells by targeting FTO. In vivo, exosomal miR-627-5p ameliorated insulin tolerance, liver damage, glucose and lipid metabolism and reduced lipid deposition in NAFLD rats. Exosomal miR-627-5p also reduced body weight, liver weight, and liver index (body weight/liver weight) in NAFLD rats. In conclusion, these data demonstrate that HUC-MSCs-derived exosomal miR-627-5p improves glucose and lipid metabolism and alleviateliver damage by repressing FTO expression, thereby ameliorating NAFLD progression. Thus, hUC-MSCs-exosomes may be a potential treatment for NAFLD.

Lactic acid bacteria alleviate liver damage caused by perfluorooctanoic acid exposure via antioxidant capacity, biosorption capacity and gut microbiota regulation

Perfluorooctanoic acid (PFOA) is an environmental pollutant that has multiple toxic effects. Although some medicines and functional food ingredients are currently being used to alleviate the biological toxicity effects caused by PFOA, these candidates all show potential side effects and cannot prevent the accumulation of PFOA in the body, making them unable to be used as a daily dietary supplement to relieve the toxic effects of PFOA. However, new research has shown that lactic acid bacteria (LAB) can alleviate toxicity caused by exposure to foreign substances. In this study, multiple strains of LAB with different adsorption capacities or antioxidant capacities were used to analyse their mitigation effects of on liver damage caused by PFOA exposure. The results showed that the adsorption capacity and antioxidant capacity of LAB could alleviate the liver toxicity of PFOA to a certain extent. Moreover, treatment with some strains of LAB was able to recover the gut microbiota dysbiosis caused by PFOA exposure, such as by increasing the relative abundances of Patescibacteria, Proteobacteria, Akkermansia and Alistipes or decreasing the abundances of Bacteroides and Blautia. In addition, a strain with neither outstanding antioxidant capacity nor adsorption capacity also reversed the decline in short-chain fatty acid levels caused by PFOA exposure. The ability of these strains to relieve gut microbiota dysbiosis partly explains the inconsistency between the capacity for antioxidant or PFOA adsorption and the ability of the strains to alleviate PFOA toxicity. The results indicate that the PFOA adsorption capacity and antioxidant capacity of LAB may be involved in the alleviation of PFOA liver toxicity. In addition, LAB could also alleviate liver damage caused by PFOA by adjusting the gut microbiota and short-chain fatty acid content. Therefore, some strains of LAB can be used as a potentially safe dietary supplement to relieve PFOA-induced liver damage.

PPARγ Plays an Important Role in Acute Hepatic Ischemia-Reperfusion Injury via AMPK/mTOR Pathway.

Background Hepatic ischemia-reperfusion (IR) injury is one of the severe complications associated with liver surgery and leads to liver dysfunction. PPARγ is always linked with various physiologic pathways, and it can alleviate liver damage in IR injury. Aim In this study, we explored the potential mechanism of PPARγ in the pathogenesis of hepatic IR injury by mice model. Methods After treated with si-PPARγ or rosiglitazone, mice were subjected to hepatic ischemia-reperfusion. Liver tissue and blood samples were collected to evaluate liver injury and detected relative mRNA and protein expressions. Results The expression of PPARγ was increased after reperfusion. And the alleviation of PPARγ aggravated the liver damage in IR; at the same time, upregulation of the expression of PPARγ released the liver damage. And these effects of PPARγ in IR were related to the AMPK/mTOR/autophagy signaling pathway. Conclusion PPARγ plays an important role in hepatic IR injury at least partly via the AMPK/mTOR/autophagy pathway.

The role of ADAM17 during liver damage.

A disintegrin and metalloprotease (ADAM) 17 is a membrane bound protease, involved in the cleavage and thus regulation of various membrane proteins, which are critical during liver injury. Among ADAM17 substrates are tumor necrosis factor α (TNFα), tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), the epidermal growth factor receptor (EGFR) ligands amphiregulin (AR) and heparin-binding-EGF-like growth factor (HB-EGF), the interleukin-6 receptor (IL-6R) and the receptor for a hepatocyte growth factor (HGF), c-Met. TNFα and its binding receptors can promote liver injury by inducing apoptosis and necroptosis in liver cells. Consistently, hepatocyte specific deletion of ADAM17 resulted in increased liver cell damage following CD95 stimulation. IL-6 trans-signaling is critical for liver regeneration and can alleviate liver damage. EGFR ligands can prevent liver damage and deletion of amphiregulin and HB-EGF can result in increased hepatocyte death and reduced proliferation. All of which indicates that ADAM17 has a central role in liver injury and recovery from it. Furthermore, inactive rhomboid proteins (iRhom) are involved in the trafficking and maturation of ADAM17 and have been linked to liver damage. Taken together, ADAM17 can contribute in a complex way to liver damage and injury.

Digestive properties and effects of Chimonanthus nitens Oliv polysaccharides on antioxidant effects in vitro and in immunocompromised mice

The study was aimed to investigate the simulated digestion behavior of the bioactive polysaccharides from Chimonanthus nitens Oliv (COP1), antioxidant activity in vitro, and prevention against cyclophosphamide (CP) induced oxidative damage in mice. The results showed that COP1 were 18.843 kDa, and consisted of arabinose (56.6 mol%), galactose (24.9 mol%), xylose (11.1 mol%), and glucose (7.4 mol%). Gastrointestinal digestion significantly improved the radical (DPPH, OH, and ABTS+) scavenging activities of COP1. Meanwhile, administration of COP1 (150, 300, and 600 mg/kg, continuous 16 days) prevented hepatotoxicity in CP-induced mice (reducing liver index and transaminase levels, alleviating liver damage). COP1 also attenuated oxidative stress as evident from as shown by reduced levels of MDA and enhanced activity of antioxidant enzymes (CAT, SOD, and GSH-Px). In addition, COP1 regulated the Nrf2/Keap1 signaling pathway in CP-treated mice, decreasing the upstream factor Keap1 and increasing the upstream factor Nrf2, which in turn enhanced the expression of downstream factors (NQO1, HO-1, GSH-Px, SOD1, and CAT). COP1 also protected the body from CP-induced oxidative damage by down-regulating Bax and caspase3 in the apoptosis pathway and up-regulating Bcl-2 mRNA levels. Overall, COP1 might be harnessed as an effective natural antioxidant for medical and food industries.

Protective effect of baicalein on high fat-induced hepatocytes oxidative damage

Objective: To investigate the effect of baicalein in improving non-alcoholic fatty liver disease caused by high fat-induced oxidative damage in mice. Methods: Male C57BL/6J mice weighing 18-20 g were randomly divided into 4 groups: normal control group (C, 10% fat for energy), high-fat group (H, 60% fat for energy), high-fat + scutellaria baicalein group (H+B, baicalein: 400 mg·kg(-1)·bw(-1)), and baicalein control group (B, baicalein: 400 mg·kg(-1)·bw(-1)). After 12 weeks, mice were sacrificed, and the tissue samples were collected. Liver pathological changes were observed by hematoxylin and eosin staining. Mitochondrial morphology was examined by ultramicropathology. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and mitochondrial membrane potential (MMP) changing levels in the liver were determined by kit. Sestrin2 and protein carbonylation (PCOS) levels were detected by Western blotting. Small interfering RNA (siRNA) was used to knock-down the Sestrin2 protein expression in HepG2 cells. Intramyocellular lipid changes in HepG2 cells was detected by fluorescent dye BODIPY493/503. One way ANOVA was used LSD pairwise comparison method was used to test the statistical difference. Results: Compared with the normal control group, high-fat fed caused significant fatty degeneration, decreased GSH and SOD levels (P ​​< 0.05), increased MDA and protein carbonylation levels, and increased Sestrin2 expression (P < 0.05) in mice. Mitochondrial shape changes, swelling, lack of cristae, and MMP was down-regulated by 33.3% (t = 13.456, P ​​< 0.001). Baicalein intervention had effectively inhibited hepatic steatosis and oxidative damage caused by high-fat fed, and further up-regulated Sestrin2 expression, MMP (t = 10.104, P ​​< 0.001), and significantly alleviated liver damage in mice. Sestrin2 expression knock-down had further increased the intracellular lipid deposition and PCOs expression (P ​​< 0.05), and reduced baicalein ability to antagonize lipid deposition and antioxidant capacity in Hep2 cells. Conclusion: Baicalein alleviate non-alcoholic fatty liver by regulating Sestrin2 expression and high-fat fed-induced liver oxidative damage.

Bilobalide Enhances AMPK Activity to Improve Liver Injury and Metabolic Disorders in STZ-Induced Diabetes in Immature Rats via Regulating HMGB1/TLR4/NF-κB Signaling Pathway.

This study was aimed at examining the effect and underlying mechanisms of bilobalide (BB) on hepatic injury in streptozotocin- (STZ-) induced diabetes mellitus (DM) in immature rats. Immature rats (one day old) were randomly divided into five groups: group I, control nondiabetic rats; group II, STZ-induced, untreated diabetic rats; groups III/IV/V, STZ-induced and BB-treated diabetic rats, which were intraperitoneally injected with BB (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) after 3 days followed by STZ treatment. We observed that BB improved the histopathological changes and maintained normal glucose metabolism, blood lipid, and liver function indicators, such as fasting blood glucose, obesity index, HbA1c, HOMA-IR, fast serum insulin, adiponectin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), aspartate transaminase (AST), and alanine transaminase (ALT) in STZ-induced DM in immature rats by a biochemical analyzer or ELISA. Meanwhile, Western blot analysis showed that in STZ-induced DM immature rats, BB decreased the expression of apoptosis-related proteins Bax, cleaved caspase-3, and cleaved caspase-9 while enhancing the Bcl-2 expression; BB downregulated the expression of ACC related to fat anabolism, while upregulating the expression of CPT-1 related to fat catabolism. Strikingly, treatment with BB significantly increased the expression of AMPKα1 as well as inhibited HMGB1, TLR4, and p-P65 expression in hepatic tissues of immature DM rats. AMPK inhibitor (compound C, CC) cotreated with BB undermined the protective effect of BB on the liver injury. The results of the present study suggested BB may have a significant role in alleviating liver damage in the STZ-induced immature DM rats.

Therapeutic efficacy and safety of mesenchymal stem cells transplantation for patients with liver failure: a systematic review and meta-analysis

The aim was to pool the present clinical studies to assess the therapeutic efficacy and safety of mesenchymal stem cell transplantation (MSCT) compared with traditional supportive treatment (TST) for patients with liver failure. Publications were searched to identify relevant clinical trials in which LF patients accepted mesenchymal stem cell transplantation from the online databases of PUBMED, EMBASE, and Cochrane Library up to June 2020. Then, the short-term outcomes of 6 months, including models of end-stage liver disease (MELD) score, total bilirubin (TBIL), albumin (ALB), prothrombin activity (PTA), alanine aminotransferase (ALT), prothrombin time (PT) and cumulative survival rate were enrolled in a meta-analysis. In total, 446 patients, reported on 2 randomized controlled trials (RCTs) and 4 non-randomized trials, were included. Compared with TST, MSCT was associated with a faster decline of MELD score at 2-, 4-, 12- and 24-week, greater improvement of ALT levels at1-, 4-, 24-week, significant increase of ALB levels at 4-,12-week and remarkable raise of PTA levels at 12-, 24-week, while PT levels changed greatly at 4-week and TBIL levels observably decreased at 4-week. The cumulative survival rate of MSCT was shown significant difference at 12-week. There were no serious complications and HCC occurred after MSCT. This study suggests MSCT may be a more effective and safe strategy than TST to improve liver function parameters and alleviate liver damage in LF patients during the short-term duration of 6 months. However, more multi-center, large-scale RCTs are needed.

Less polar ginsenosides have better protective effects on mice infected by Listeria monocytogenes

Listeria monocytogenes widely exists in the natural environment and does great harm, which can cause worldwide public safety problem. Infection with L. monocytogenes can cause rapid death of Kupffer cell (KCs) in liver tissue and liver damage. American ginseng saponins is a natural compound in plants, which has great potential in inhibiting L. monocytogenes infection. Therefore, American ginseng stem-leaf saponins (AGS) and American ginseng heat-transformed saponins (HTS) were used as raw materials to study their bacteriostatic experiments in vivo and in vitro. In this experiment, female Kunming mice were randomly divided into five groups: control group, negative group, AGS group, HTS group (10 mg/kg/day in an equal volume via gastric administration) and penicillin group, each group containing six mice. Profiles AGS and HTS components were evaluated by high-performance liquid chromatography (HPLC) analysis. The bacteriostatic effect of AGS and HTS on L. monocytogenes was evaluated by inhibition zone test, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The bacteriostatic effect of AGS and HTS pretreatment on mice infected with L. monocytogenes were studies by animal experimental. The results showed that the content of polar saponins in AGS was 0.81 ± 0.003 mg/mg, less polar saponins was 0.08 ± 0.02 mg/mg, the content of polar saponins in HTS was 0.10 ± 0.01 mg/mg, less polar saponins was 0.76 ± 0.02 mg/mg. The in vitro bacteriostatic diameter of HTS (16.6 ± 0.8 mm) is large than that of AGS (10.2 ± 1.2 mm). AGS and HTS pretreatment could reduce the colony numbers in the livers of mice infected with Listeria monocytogenes. The levels of alanine aminotransferase (ALT), IL-1β, IL-6, TNF-α and IFN-γ in the livers of mice in the pretreatment group were significantly lower than those in the negative group. There were obvious leukoplakia, calcification and other liver damage on the liver surface in the negative control group, and obvious inflammatory cell infiltration in HE sections. AGS and HTS pretreatment can reduce liver injury caused by L. monocytogenes and protect the liver. Compared with AGS, HTS has higher content of less polar saponins and better bacteriostatic effect in vitro. The count of bacterial in liver tissue of HTS group was significantly lower, the survival rate was significantly higher than that of AGS group. Less polar saponins had better bacteriostatic effect. Collectively, less polar saponins pretreatment has a protective effect on mice infected with L. monocytogenes, to which alleviated liver damage, improved anti-inflammatory ability and immunity of the body, protected liver may contribute.

Study on the effect of Mongolian medicine Qiwei Qinggan Powder on hepatic fibrosis through JAK2/STAT3 pathway.

This research aimed to evaluate the antihepatic fibrosis effect and explore the mechanism of Qiwei Qinggan Powder (QGS-7) in vivo and in vitro. Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. QGS-7 treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Meanwhile, the hydroxyproline of liver was significantly decreased. Histopathological results indicated that QGS-7 alleviated liver damage and reduced the formation of fibrosis septa. Moreover, QGS-7 significantly attenuated expressions of Alpha smooth muscle actin, Collagen I, Janus kinase 2 (JAK2), phosphorylation-JAK2, signal transducer and activator of transcription 3 (STAT3), phosphorylation-STAT3 in the rat hepatic fibrosis model. QGS-7 inhibited HSC proliferation and promoted it apoptosis. QGS-7 may affect hepatic fibrosis through JAK2/STAT3 signaling pathway so as to play an antihepatic fibrosis role.

Garlic flavonoids alleviate H2 O2 induced oxidative damage in L02 cells and induced apoptosis in HepG2 cells by Bcl-2/Caspase pathway.

Liver damage is a common liver disorder, which could induce liver cancer. Oral antioxidant is one of the effective treatments to prevent and alleviate liver damage. In this study, three flavonoids namely myricetin, isoquercitrin, and isorhamnetin were isolated and identified from Laba garlic. The isolated compounds were investigated on the protective effects against H2 O2 -induced oxidative damages in hepatic L02 cells and apoptosis inducing mechanism in hepatic cancer cells HepG2 by using MTT assay, flow cytometry and western blotting analysis. Myricetin, isoquercitrin, and isorhamnetin showed proliferation inhibition on HepG2 cells with IC50 value of 44.32± 0.213µM, 49.68± 0.192µM, and 54.32± 0.176µM, respectively. While they showed low toxicity on normal cell lines L02. They could significantly alleviate the oxidative damage towards L02 cells (P < 0.05),via inhibiting the morphological changes in mitochondria and upholding the integrity of mitochondrial structure and function. The fluorescence intensity of L02 cells pre-treated with myricetin, isoquercitrin, and isorhamnetin (100µM) was 89.23± 1.26%, 89.35± 1.43% and 88.97± 0.79%, respectively. Moreover, the flavonoids could induce apoptosis in HepG2 cells via Bcl-2/Caspase pathways, where it could up-regulate the expression of Bax and down-regulate the expression of Bcl-2, Bcl-xL, pro-Caspase-3, and pro-Caspase-9 proteins in a dose dependent manner. Overall, the results suggested that the flavonoids from Laba garlic might be a promising candidate for the treatment of various liver disorders. PRACTICAL APPLICATION: Flavonoids from Laba garlic showed selective toxicity towards HepG2 cells in comparison to L02 cells via regulating Bcl-2/caspase pathway. Additionally, the isolated flavonoids expressively barred the oxidative damage induced by H2 O2 in L02 cells. These results suggested that the flavonoids from laba garlic could be a promising agent towards the development of functional foods.