Xiao-Yu Hu

Entecavir vs lamivudine therapy for naïve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure.

AIM To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure (ACLF). METHODS This was a single center, prospective cohort study. Eligible, consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100 mg/d. All patients were given standard comprehensive internal medicine. The primary endpoint was survival rate at day 60, and secondary endpoints were reduction in hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) levels, and improvement in Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores at day 60 and survival rate at week 52. RESULTS One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B: 65 were included in the entecavir group and 54 in the lamivudine group (full analysis set). No significant differences were found in patient baseline clinical parameters. At day 60, entecavir did not improve the probability of survival (P = 0.066), despite resulting in faster virological suppression (P < 0.001), higher rates of virological response (P < 0.05) and greater reductions in the CTP and MELD scores (all P < 0.05) than lamivudine. Intriguingly, at week 52, the probability of survival was higher in the entecavir group than in the lamivudine group [42/65 (64.6%) vs 26/54 (48.1%), respectively; P = 0.038]. The pretreatment MELD score (B, 1.357; 95%Cl: 2.138-7.062; P = 0.000) and virological response at day 30 (B, 1.556; 95%Cl: 1.811-12.411; P =0.002), were found to be good predictors for 52-wk survival. CONCLUSION Entecavir significantly reduced HBV DNA levels, decreased the CTP and MELD scores, and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.

The Effects of High-Dose Qinggan Huoxue Recipe on Acute Liver Failure Induced by D-Galactosamine in Rats

Qinggan Huoxue Recipe is a traditional Chinese medicine, which has been usually used to improve liver function in hepatitis. In order to investigate the effects of high-dose Qinggan Huoxue Recipe on acute liver failure and explore the potential mechanism, we had built acute liver failure models in rats by intraperitoneal injection of D-galactosamine (D-GalN). High-dose Qinggan Huoxue Recipe was delivered by gavage. After treatment, the blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), cholinesterase (CHE), and prothrombin time (PT) were determined. The pathological score of liver tissue was recorded. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and Caspase-3 were performed. The survival curve was also depicted. Our results demonstrated that high-dose Qinggan Huoxue Recipe could significantly improve liver function and increase survival rates in rats with acute liver failure. These effects were supposed to be mediated by suppressing inflammatory reaction and apoptosis.

Effects of aqueous extracts from Panax ginseng and Hippophae rhamnoides on acute alcohol intoxication: An experimental study using mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE Acute alcohol intoxication (AAI) is a frequent emergency, but therapeutic drugs with superior efficacy and safety are lacking. Panax ginseng (PG) and Hippophae rhamnoides (HR) respectively has a wide application as a complementary therapeutic agent in China for the treatment of AAI and liver injury induced by alcohol. We investigated the effects of aqueous extracts from PG and HR (AEPH) on AAI mice and identified its underlying mechanisms. MATERIALS AND METHODS Models of AAI were induced by intragastric administration of ethanol (8g/kg). Seventy-two Specific pathogen-free (SPF) male Kunming mice were randomly divided into six groups: normal group, positive control group, AEPH of low dosage (100mg/kg) group, AEPH of medium dose (200mg/kg) group, AEPH of high dosage (400mg/kg) group and model group. The mice were treated with metadoxine (MTD, 500mg/kg) and AEPH. Thirty minutes later, the normal group was given normal saline, while the other groups were given ethanol (i.g., 8g/kg). The impact of AEPH was observed. In the same way, another seventy-two Kunming mice were randomly divided into six groups equally. The blood ethanol concentration at 0.5, 1, 1.5, 2, 3 and 6h after ethanol intake was determined by way of gas chromatography. The activity of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal ethanol oxidase (EO) in liver, and the concentration of β-endorphin (β-EP), leucine-enkephalin (LENK) in the brain were determined by enzyme-linked-immunosorbent serologic assay (ELISA). RESULTS AEPH markedly prolonged alcohol tolerance time and shortened sober-up time after acute ethanol administration. AEPH decreased blood ethanol levels in six tests after ethanol intake. The 7-day survival rate of AEPH group was obviously superior to model group. AEPH increased the activities of ADH, ALDH, and decreased EO activity in liver. The crucial find was that AEPH markedly decreased β-EP and LENK concentration in the brain. CONCLUSIONS AEPH can markedly increase the levels of ADH, ALDH, decrease EO activity in liver and decrease the concentration of β-EP and LENK in the brain to against acute alcohol intoxication in mice.

The effects of modified sini decoction on liver injury and regeneration in acute liver failure induced by D-galactosamine in rats.

ETHNOPHARMACOLOGICAL RELEVANCE Modified sini decoction (MSND) is a well-known traditional Chinese medical formula that has been used to treat cardiovascular and liver diseases for many years. We investigated the effects of MSND on acute liver failure and identified the possible mechanisms of these effects. MATERIAL AND METHODS Acute liver failure was induced by intraperitoneal injection of d-galactosamine (d-GalN) into specific pathogen-free male Wistar rats. Next, the rats were treated with Stronger Neo-Minophagen C and MSND via gavage. Biochemical parameters, histological changes in the liver, the survival of rats and the mRNA levels of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), high mobility group box 1 (HMGB1) caspase-3 and proliferating cell nuclear antigen (PCNA) were analyzed. RESULTS MSND prolonged the survival times of the acute liver failure rats. The biochemical parameters were improved, and necrosis in the liver tissues was reduced by both Stronger Neo-Minophagen C (SNMC) and MSND, but MSND induced greater effects. The mRNA expressions of HMGB1, TLR4, NF-κB, and Caspase-3 were remarkably decreased, and the expression of PCNA was remarkably increased by SNMC and MSND, and the effects of MSND were greater. CONCLUSIONS MSND protected the liver and increased the survival rate of acute liver failure rats. These effects were likely mediated by the inhibitions of the inflammatory reaction and apoptosis and the promotion of liver tissue regeneration.

Aqueous extract from Aconitum carmichaelii Debeaux reduces liver injury in rats via regulation of HMGB1/TLR4/NF-ΚB/caspase-3 and PCNA signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE Aconitum carmichaelii Debeaux is a well-known Chinese herb that has been used to treat liver diseases for many years in China. We investigated the effects of aqueous extract from Aconitum carmichaelii Debeaux (AEACD) on acute liver failure and identified the possible mechanisms of these effects. MATERIAL AND METHODS Specific pathogen-free (SPF) male Wistar rats were used to establish acute liver failure model by intraperitoneal injection of D-galactosamine (D-GalN) and treated with Stronger Neo-Minophagen C (SNMC) and AEACD by gavage. Then, the serum biochemical parameters, the pathological scores in the liver tissue, the mRNA expressions of toll- like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), high mobility group box 1 (HMGB1) and caspase-3, the proliferating cell nuclear antigen (PCNA) positive rates were analyzed. RESULTS The liver function was improved, the pathological scores were decreased, the expressions the TLR4, NF-κB, HMGB1, and caspase-3 were inhibited, and the PCNA positive rates were increased by both SNMC and AEACD, but AEACD induced greater effects. CONCLUSIONS AEACD protected liver function by inhibiting inflammatory reaction, apoptosis and promoting liver tissue regeneration in the acute liver failure rats induced by D-galactosamine.

Effect of ASF (a Compound of Traditional Chinese Medicine) on Behavioral Sensitization Induced by Ethanol and Conditioned Place Preference in Mice

ASF composed by semen and epimedium herbal is a traditional plant compound that is widely used in the treatment of insomnia. Studies have shown that saponins and flavonoids contained in semen can significantly decrease the content of excitatory neurotransmitter Glu in mice. And the total flavone of YinYangHuo can increase the release of GABA in the anterior periventricular system of rat and increase the affinity of GABA for the receptors GABAA. It can be inferred that their synergism may have effect on the neurotransmitter that causes behavioral sensitization and conditioned place preference in experimental animals and affects their drinking behaviors, which is the starting point of this research. The present study found that ASF can inhibit development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. We demonstrate the inhibition of ASF on behavioral sensitization partly due to its effect on the mesolimbic neurotransmitter system, including decreasing level of DA and Glu and increasing the content of GABA. It suggested that the ASF may have pharmacological effects in the treatment of alcohol addiction.

The Protective Effects of Buzui on Acute Alcoholism in Mice

This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism.

Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats

AIM To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats. METHODS Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed. RESULTS D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/β-actin (0.06 ± 0.03, 0.11 ± 0.04 vs 0.25 ± 0.04, P < 0.05); TLR4 mRNA/β-actin (0.07 ± 0.02, 0.22 ± 0.08 vs 0.41 ± 0.22, P < 0.05); NF-κB mRNA/β-actin (0.74 ± 0.41, 1.78 ± 0.64 vs 2.68 ± 1.35, P < 0.05); and caspase-3 mRNA/β-actin levels were all significantly reduced (1.61 ± 0.45, 2.57 ± 1.04 vs 3.41 ± 0.85, P < 0.05). The gene expression levels were significantly lower in the IPTT group than in the SNMC group (P < 0.05). Compared with the model group, the PCNA expression in liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 ± 4.91, 25.57 ± 2.94 vs 17.55 ± 2.40, P < 0.05). CONCLUSION IPTT attenuates inflammation in ALF via inhibition of HMGB1 production, which may contribute to limited liver regeneration.