Hepatoprotective effects of sea buckthorn (Hippophae rhamnoides L.) against carbon tetrachloride induced liver injury in rats

BACKGROUND: Liver injuries induced by carbon tetrachloride are the best‐characterized system of xenobiotic‐induced hepatotoxicity and commonly used model for the screening of hepatoprotective activities of drugs. The present study evaluates the hepatoprotective activity of sea buckthorn (Hippophae rhamnoides L.), family Elaeagnaceae, on carbon tetrachloride (CCl₄)‐induced liver injury in male albino rats. The study was performed on Sprague–Dawley male albino rats weighing about 180–200 g. The animals were pretreated with three different doses of leaf extract (50, 100 and 200 mg kg^?1 body weight) for 5 days. Hepatotoxicity was induced by single oral administration of 1.5 mL CCl₄ kg^?1 body weight on the fifth day. The animals were then sacrificed and assessed for various biochemical parameters. RESULTS: Administration of CCl₄ significantly enhanced glutamate oxaloacetate transferase (GOT), glutamate pyruvate transferase (GPT), alkaline phosphatase (ALP) and bilirubin, and decreased total protein levels in the serum. Treatment with CCl₄ also significantly decreased reduced glutathione (GSH), and decreased glutathione peroxidase and superoxide dismutase activity. CCl₄ treatment also caused a significant increase in hepatic lipid peroxidation as assessed by malondialdehyde (MDA) levels in the tissue. Pretreatment of leaf extract at a concentration of 100 and 200 mg kg^?1 body weight significantly (P < 0.05) protected the animals from CCl₄‐induced liver injury. The extract significantly restricted the CCl₄‐induced increase of GOT, GPT, ALP and bilirubin and better maintained protein levels in the serum. Further, it also enhanced GSH and decreased MDA levels. CONCLUSION: The results show that sea buckthorn leaf extract has significant hepatoprotective effects which might be due to its antioxidant activity and can be developed as a nutraceutical or food supplement against liver diseases. Copyright © 2008 Society of Chemical Industry     

Hepatoprotective effect of fermented rice bran against carbon tetrachloride-induced toxicity in mice

The protective effect of fermented rice bran (GF) against carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice was investigated. Hepatic fibrosis was induced via long-term oral administration of CCl₄. GF was added to feed. Mice sera were analyzed 8 weeks after administration. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, both markers of hepatic injury, were reduced in the GF group. Total cholesterol (TC) and triglycerides (TG) levels were also reduced. The glutathione (GSH) level, an antioxidant in liver tissue, increased. Collagen is major component of the extracellular matrix (ECM). Persistent liver damage causes excess remodeling of liver tissue and ECM deposition, causing liver fibrosis. Liver injury was reduced and the amount of collagen, which is synthesized during recovery from liver injury, was significantly reduced in GF fed mice. Thus, the liver was protected against toxic chemicals by GF in mice with CCl₄-induced hepatic fibrosis with an increased antioxidative reaction.     

Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis

BACKGROUND: Liver fibrosis is chronic liver damage usually caused by alcohol, viruses or other toxins and is characterised by an excessive accumulation of extracellular matrix proteins such as collagen. The aim of this study was to establish an animal model of chronic liver damage and investigate molecular mechanisms of silymarin hepatoprotective effects. RESULTS: Thioacetamide (TAA; 100 mg kg^?1 intraperitoneal (i.p.) injection three times weekly) effectively induced chronic liver fibrosis in male ICR mice. Then 24 ICR mice were randomly divided into four groups: (1) saline (i.p.) + water (gavage); (2) saline (i.p.) + 150 mg kg^?1 silymarin (gavage); (3) 100 mg kg^?1 TAA (i.p.) + water (gavage); (4) 100 mg kg^?1 TAA (i.p.) + 150 mg kg^?1 silymarin (gavage). Eight weeks of TAA treatment resulted in lower body weight, serum cholesterol and triglycerides as well as increased liver size, ALT, AST and LDH values (P < 0.05). These TAA‐induced effects were attenuated by silymarin (P < 0.05); therefore silymarin also ameliorated TAA‐induced liver lesions. Effects of silymarin on TAA‐induced chronic liver damage may be attributed to down‐regulation of hepatic MMP‐2, MMP‐13, TIMP‐1, TIMP‐2, AP‐1, KLF6, TGF‐β1, α‐SMA and COL‐α1. CONCLUSION: A mouse model of chronic liver fibrosis was successfully established by injecting 100 mg kg^?1 TAA three times weekly in male ICR mice. Meanwhile, silymarin showed hepatoprotection against TAA‐induced damage. Copyright © 2011 Society of Chemical Industry     

Inhibitory effect of yellow myrobalan (Terminalia chebula) extract on fibrosis induced by carbon tetrachloride in rat liver

Ethyl acetate layer of methanol extract (TCE) of yellow myrobalan (Terminalia chebula) contains 2.4% of chebulic acid, a standard compound in TCE, which have a strong anti-oxidative effect and was reported in our previous study. Thirty-one male SD rats were randomly divided into 5 groups (normal control, CCl₄ control, TCE control, CCl₄+high dose TCE, and low dose TCE). Liver fibrosis was induced by i.p. injection of CCl₄ and TCE were orally administrated. TCE decreased the up-regulated malondealdehyde value and increased the down-regulated ratio of GSH/GSSG content and activities of GRd, GPx, and GST compared to the CCl₄ control group. Decreased dysfunction and inflammatory reaction in liver was confirmed by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, relative liver weight and infiltration of neutrophils. Also, TCE inhibited phenotype change of hepatic stellate cells (HSC) by reducing α-smooth muscle actin (α-SMA) gene expression and protein production. Inhibition of collagen 1A1 gene expression and protein production were also confirmed. From these results, TCE may be a useful material for preventing liver fibrosis.     

Effect of long‐term dietary administration of oregano and rosemary on the antioxidant status of rat serum,liver, kidney and heart after carbon tetrachloride‐induced oxidative stress

BACKGROUND: This study was performed on female Wistar rats allocated to eight groups of six animals each. Groups 1 and 2 were fed the basal diet, groups 3 and 4 were fed the basal diet supplemented with ground oregano at 20 g kg^?1 level, groups 5 and 6 were fed the basal diet supplemented with ground rosemary at 20 g kg^?1 level, while groups 7 and 8 were fed the basal diet supplemented with both oregano and rosemary, each at 20 g kg^?1 level. Following 6 weeks feeding, groups 2, 4, 6 and 8 were injected with CCl₄ at 1 mL kg^?1 body weight, and 6 h thereafter all animals were sacrificed. RESULTS: Administration of CCl₄ to the control rats enhanced (P < 0.05) aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) activities, decreased cholesterol and triglycerides content in serum, increased (P < 0.05) lipid peroxidation and decreased (P < 0.05) the ABTS radical cation, the hydroxyl anion radical, the superoxide anion radical, and the hydrogen peroxide scavenging activities in all tested tissues, as compared to the control. Feeding oregano, rosemary or both before CCl₄ treatment resulted in decline (P < 0.05) of the increase in AST, ALT and ALP activities, increase (P < 0.05) of cholesterol and triglycerides in serum, decrease (P < 0.05) of lipid peroxidation, and increase (P < 0.05) of the ABTS radical cation, hydroxyl anion radical, superoxide anion radical and hydrogen peroxide scavenging activity. CONCLUSION: The results of this study suggest that long‐term dietary administration of oregano and rosemary has the potential to quench free radicals and alleviate CCl₄‐induced oxidative stress in rats. Copyright © 2009 Society of Chemical Industry     

The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis,Theaceae)

The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis, Theaceae) were investigated with a study of carbon tetrachloride (CCl₄)-induced oxidative stress and hepatic fibrosis in male ICR mice. Oral administration of green tea extract at doses of 125, 625 and 1250 mg/kg for 8 weeks significantly reduced (p < 0.05) the levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyls in the liver by at least 28% compared with that was induced by CCl₄ (1 mL/kg) in mice. Moreover, green tea extract administration significantly increased (p < 0.05) the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver. Our study found that oral administration of green tea extract prevented CCl₄-induced hepatic fibrosis, as evidenced by a decreased hydroxyproline level in the liver and a reduced incidence of hepatic fibrosis by histological observations. These results indicate that green tea exhibits potent protective effects against CCl₄-induced oxidative stress and hepatic fibrosis in mice by inhibiting oxidative damage and increasing antioxidant enzyme activities.     

Extracts of oyster mushroom (Pleurotus ostreatus) grown on wheat ameliorate hepatotoxicity induced by carbon tetrachloride in rats

Pleurotus ostreatus (PO), which is also called the oyster mushroom, is the secondly most popular cultivated mushroom in the world and has been shown to display antioxidant activity. In this study, the hepatic protective effects of extracts of PO cultured in wheat (POW) on carbon tetrachloride (CCl₄)-induced liver injury in rats were evaluated by analyzing blood markers of liver injury. Sprague-Dawley rats were pretreated with POW extracts (0, 0.5, and 1.0 g/kg) orally for 14 days prior to the administration of CCl₄ for 3 days. Marked evaluation of alanine and aspartate aminotransferases, lactate dehydrogenase, alkaline phosphatase, and γ-glutamyltransferase were observed in the plasma from control rats after CCl₄ treatment. This increased liver injury markers were significantly reduced in a dose-dependent manner by pretreatment with the POW extract, suggesting that POW prevented acute liver damage in CCl₄-intoxicated rats by suppressing cellular leakage and loss of the functional integrity of cell membranes in the liver. POW extracts could also improve lipid profiles damaged caused by CCl₄ in liver through a reducing plasma triglyceride and total cholesterol and a recovering plasma HDL-cholesterol. These results suggest that the extracts of POW ameliorate hepatotoxicity induced by CCl₄ in the rat model.     

O-dihydroxyphenoloxidase action on natural polyhydric phenolics and enzymic browning of edible yams

Ten cultivars of five edible yam species were examined for o-dihydroxyphenoloxidase (o-DPOase) activity against yam extracts containing phenolic compounds, and for their propensity to brown when cut slices are exposed to air. (+)-Catechin levels in Dioscorea cayenensis (260 mg kg^?1) and D. bulbifera (240 mg kg^?1) were similar to those in D. dumetorum (270 mg kg^?1), but the latter contained less o-DPOase and showed less tendency to browning. D. alata contained more (+)-catechin than other yams, and one cultivar with a higher (+)-catechin content (660 mg kg^?1) showed more browning than another cultivar containing 430 mg kg^?1 (+)-catechin. Five cultivars of D. rotundata showed less tendency to brown, and had lower (+)-catechin content (90–190 mg kg^?1) than the other yams examined, but showed marked variation in o-DPOase activity. o-DPOase activity, assayed by recording the rate of oxygen consumption, varied between 75 units (1 unit=μmol O₂ consumed min^?1 100 g^?1 fresh yam tissue) in D. dumetorum and 2380 units in one D. rotundata cultivar when a crude extract of phenolic compounds diluted to contain 10 mM (+)-catechin was used as substrate and from 60 to 3480 units for these same two enzyme extracts when assayed using crude extracts of phenolic compounds (also adjusted to contain 10 mM (+)-catechin) prepared from the same yam as the enzyme extract. However, in general, the o-DPOase activities recorded using the D. alata extract showed little correlation with the activity when the phenolic extract was prepared from the same yam as the enzyme extract. Incubation of crude extracts containing phenolics with crude extracts of o-DPOase at 20°C for 24 h resulted in a decrease in the quantity of (+)-catechin estimated by h.p.l.c. Cyanidin released by hydrolysis with HCl under mild conditions was also measured. The level in D. alata was sufficiently high to account for ‘pinking’ when this species is boiled. It is concluded that the o-DPOase-catalysed oxidation of (+)-catechin is largely responsible for the browning of yams. The possible influence of other factors, including the reducing agent ascorbic acid in moderating the rate and extent of browning observed, is discussed.     

灵芝孢子油对四氯化碳联合高脂饮食诱导大鼠肝纤维化的作用研究

探究灵芝孢子油(GSO)对四氯化碳(CCl₄)联合高脂饮食诱导的大鼠肝纤维化的改善作用及机制。将雄性SPF级SD大鼠分为空白对照组、模型对照组、阳性药物组和灵芝孢子油低、中、高剂量组(人体推荐量的5、15、30倍)。采用CCl₄联合高脂饲料诱导6周建立大鼠肝纤维化模型,造模过程中灌胃GSO干预8周。通过检测血清生理生化指标和大鼠肝脏组织形态、氧化应激水平、纤维化相关蛋白,评价GSO对肝纤维化的保护作用。研究结果表明,中、高剂量GSO能够显著提升肝纤维化大鼠的存活率,使得大鼠存活率恢复至空白对照组水平。病理染色结果表明,GSO处理的大鼠肝组织纤维化得到不同程度的改善,GSO中、高剂量处理显著降低大鼠肝脏胶原面积占比及面密度。GSO高剂量干预可显著降低大鼠血浆肝功能相关指标(谷丙转氨酶、谷草转氨酶、总胆红素、碱性磷酸酶)水平,减少血浆中肝纤维化指标(透明质酸、层黏蛋白、Ⅳ型胶原、羟脯氨酸)水平。同时,高剂量GSO干预还显著降低肝组织中丙二醛含量,提高还原型谷胱甘肽含量与超氧化物歧化酶活性,显著升高基质金属蛋白酶-9的表达。研究结果证实,中、高剂量...     

Amaranthus viridis Linn., a common spinach, modulates C-reactive protein, protein profile, ceruloplasmin and glycoprotein in experimental induced myocardial infarcted rats

BACKGROUND: Glycoprotein is one of the components of the cardiac extracellular matrix and plays an important role in cardiac remodelling during various cardiac diseases, including myocardial infarction (MI). This study was aimed at evaluating the preventive role of Amaranthus viridis Linn. on C‐reactive protein (CRP), total protein, albumin, globulin, ceruloplasmin and glycoproteins in the serum and heart of experimental induced myocardial infarcted (MI) rats. RESULTS: MI was induced in male Wistar rats by subcutaneous injection of 20 mg kg^?1 isoproterenol (ISO) kg^?1 body weight (BW) twice at an interval of 24 h. ISO‐induced MI rats showed a significant increase in the levels of serum CRP and ceruloplasmin and a significant decrease in the levels of serum total protein, albumin and globulin. Glycoprotein levels in the serum and heart were increased in ISO‐induced MI rats. Oral administration of 300 mg A. viridis kg^?1 BW day^?1 for a period of 45 days altered the metabolic derangement in ISO‐induced MI rats. CONCLUSION: This study exemplifies the protective effect of A. viridis on ISO‐induced cardiotoxicity in male Wistar rats. The data further reinforce the cardioprotective effect of A. viridis by altering CRP and glycoprotein levels. Copyright © 2012 Society of Chemical Industry     

Protective effect of Pracparatum mungo extract on carbon tetrachloride-induced hepatotoxicity in rats

Pracparatum mungo is a traditional and functional food in Traditional Chinese Medicine, especially for treating a variety of liver disorders. In this study, we first report the in vivo hepatoprotective effect of P. mungo extract (PME) on carbon tetrachloride (CCl₄)-induced acute hepatotoxicity in rats. Pre-treatment with PME for 56 days significantly reduced the impact of CCl₄ toxicity on the serum markers of liver damage, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The results were confirmed histopathologically. In addition, an increased lipid hydroperoxide (LPO), a decreased glutathione (GSH) concentration and a decreased superoxide dismutase (SOD) were observed in the hepatic tissues. On the contrary, treatment of PME prior to the administration of CCl₄ resulted in markedly decreased lipid peroxidation, increased the levels of GSH and SOD in rats. The results indicated that PME has a protective effect against acute hepatotoxicity induced by the administration of CCl₄ in rats, and that the hepatoprotective effects of PME may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.     

Hepatoprotection using sweet orange peel and its bioactive compound,hesperidin, for CCl4-induced liver injury in vivo

The hepatoprotective effect of water extracts of sweet orange (Citrus sinensis) peel (WESP) and its biological compound, hesperidin (HD), on oxidative stress in vivo, were investigated. HD was the major compounds among the ten compounds identified using HPLC-DAD and HPLC-MS/MS analysis. Oral administration of WESP to rats at 10 and 100 mg/kg bw for 28 consecutive days before a single dose of CCl₄ (2 ml/kg bw) demonstrates a significant protective effect by lowering the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and by improving the histological architecture of the rat liver. WESP attenuated oxidative stress by increasing the content of hepatic glutathione (GSH), and by a dramatic increase in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). WESP induced a significant CYP2E1 activity, which suggests that WESP may be a substrate of CYP2E1. WESP at a dose of 1.0 mg/kg bw and HD at 0.1 mg/kg bw did not sustain the protective effect against oxidative stress, in vivo. This study demonstrated that citrus peel protects rat liver from CCl₄-induced injury by attenuating hepatic oxidative stress, which suggests that WESP can be used as a therapeutic antihepatotoxic agent for the treatment of hepatic injury.     

Protective effects of dehydroglyasperin c against carbon tetrachloride-induced liver damage in mice

Dehydroglyasperin C (DGC) isolated from licorice has been shown to exhibit antioxidant activity as well as induce phase 2 detoxifying enzymes in mouse hepatoma cells. This study investigated whether or not DGC exerts hepatoprotective effects through modulation of phase 1 and 2 detoxifying enzymes. ICR mice were divided into five groups with 10 mice per group: (1) negative control, (2) positive control injected with carbon tetrachloride (CCl₄, 0.6 mL/kg BW) alone, (3) ICR mice injected with DGC (5 mg/kg BW) alone, (4) ICR mice injected with DGC followed by CCl₄, and (5) ICR mice injected with DGC and CCl₄ simultaneously. Mice were adapted for 1 week, followed by injection with DGC on day 7, CCl₄ on day 8, and sacrifice on day 9 of the experiment. Treatment with DGC induced NQO1 activity in kidney only, but not in the other tissues of mice. Compared to mice injected with CCl₄ alone, mice simultaneously injected with both DGC and CCl₄ showed reduced lipid droplet formation in liver tissue, as assessed by histological examination. Further, DGC demonstrated a slight protective effect against centrilobular injury caused by CCl₄ injection, perhaps through suppression of CYP2E1 expression. In conclusion, DGC possesses hepatoprotective effects against CCl₄-induced injury.     

Hepatoprotective effect of 2,3-dehydrosilybin on carbon tetrachloride-induced liver injury in rats

The aim of this study was to investigate the protective effect of 2,3-dehydrosilybin (DHS) against carbon tetrachloride (CCl₄)-induced liver injury in rats. Administration of DHS significantly attenuated the levels of serum aspartate aminotransferase, alanine aminotransferase, and liver lipid peroxidation in CCl₄-treated rats. Moreover, we showed that DHS prevented DNA damage and decreased the protein levels of γ-H2AX, which is a specific DNA damage marker, in CCl₄-treated rat livers. DHS also markedly increased the activity of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in CCl₄-treated rat livers. Furthermore, we found that DHS significantly inhibited the production of serum nitric oxide as well as the levels of serum IL-6, IFN-γ, and TNF-α in CCl₄-treated rats. Additionally, DHS significantly suppressed iNOS expression on the protein levels in CCl₄-treated rat livers. Collectively, the present study suggests that DHS protects the liver from CCl₄-induced hepatic damage via antioxidant and anti-inflammatory mechanisms.     

Yerba-mate (Ilex paraguariensis) extract prevents ethanol-induced liver injury in rats

Ethanol metabolism-associated oxidative stress contributes to the pathogenesis of alcoholic liver disease. We examined the effect of a Mate tea extract on ethanol-induced liver injury in vitro and in vivo models. Isolated hepatocytes were incubated with ethanol. An extract of Yerba-Mate tea (EMT) was added to the cultures simultaneously with ethanol. EMT treatment suppressed the ethanol-induced increase in cell death by inhibiting cytochrome p450 2E1 (CYP2E1) activity, which is related to the production of reactive oxygen species. Furthermore, we examined the effects of EMT on serum transaminase activity, and the progression of liver fibrosis in rats treated with ethanol and CCl₄. Rats were fed a diet that included 0.005% or 0.02% EMT or no EMT. For a period of 3 weeks, the animals were provided drinking water containing 5% ethanol and were also treated with carbon tetrachloride (CCl₄) (0.1 ml/kg of body weight). EMT treatment suppressed plasma ALT and AST activities in the ethanol- and CCl₄-treated rats. EMT treatment also decreased CYP2E1 expression and increased ADH expression in the ethanol- and CCl₄-treated rats. EMT treatment fully protected the rats against ethanol- and CCl₄-induced liver injury. These results suggest that EMT may serve as a candidate for preventing ethanol-induced liver injury.     

Cyanidin-3-glucoside ameliorates CCl4-induced liver injury in mice

The protective effect of cyanidin-3-glucoside (C3G) against carbon tetrachloride (CCl₄)-induced liver injury in mice was investigated. Administration of C3G attenuated the levels of serum aspartate aminotransferase, alanine aminotransferase, and liver lipid peroxidation in CCl₄-treated mice. Histopathological examination of mouse livers showed that C3G reduced the incidence of liver lesions induced by CCl₄. Moreover, C3G prevented DNA damage and decreased the protein levels of γ-H2AX in CCl₄-treated mouse livers. C3G also increased the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, which were decreased due to CCl₄ administration in CCl₄-treated mouse livers. C3G inhibited the expression levels of IL-6 and iNOS in CCl₄-treated mice. C3G apparently protects the liver from CCl₄-induced hepatic damage through antioxidant and anti-inflammatory mechanisms.     

Curcumin Protects Against Intestinal Origin Endotoxemia in Rat Liver Cirrhosis by Targeting PCSK9

Intestinal origin endotoxemia always occurs in severe liver injury. The aim of the current study was to test antiendotoxemia effect of curcumin on tetrachloride (CCl₄)‐induced liver cirrhosis rats, and to elucidate the underlying molecular mechanism. Rat cirrhosis models were constructed with CCl₄ subcutaneous injections with curcumin (200 mg/kg/d) administered via gavages for 12 wk until the rats were sacrificed. We found that the administration of curcumin improved the physiological condition pertaining to activity index and temperature, and ameliorated the liver injury in CCl₄‐induced cirrhosis rats. Enzyme‐linked immunosorbent assay (ELISA) and real‐time quantitative polymerase chain reaction (qRT‐PCR) showed that curcumin could reduce c‐reaction protein levels and inflammatory cytokine (TNF‐α, IL‐1β, IL‐6, and CINC‐1/IL‐8) concentrations in peripheral serum and liver tissue. Furthermore, curcumin treatment decreased lipopolysaccharide (LPS) levels in peripheral vein, but not in portal vein. As low‐density lipoprotein receptor (LDLR) is the important receptor on the surface of hepatocyte during LPS detoxification process, we used qRT‐PCR, western blot, and immunohistochemistry (IHC), finding that curcumin significantly increased LDLR protein levels, but not gene levels in the liver tissues. We also tested proprotein convertase subtilisin/kexin type 9 (PCSK9), one negative regulator of LDLR, by qRT‐PCR, western blot, and IHC. The results showed that PCSK9 significantly decreased both gene and protein levels in the rat liver tissues of curcumin treatment. Thus, we concluded that curcumin could function to protect against intestinal origin endotoxemia by inhibiting PCSK9 to promote LDLR expression, thereby enhancing LPS detoxification as one pathogen lipid through LDLR in the liver.     

Protective effect of HV-P411, an herbal mixture,on carbon tetrachloride-induced liver fibrosis

This study was performed to examine the anti-fibrotic activity of HV-P411, an herbal mixture of seeds of Vitis vinifera, Schisandra chinensis and Taraxacum officinale extract, against carbon tetrachloride (CCl₄)-induced liver fibrosis. Hepatic fibrosis was induced by intraperitoneal injection of CCl₄ (0.5 ml/kg, twice weekly) for 8 weeks. Rats were treated orally with HV-P411 at 50, 100, 200, and 400 mg/kg once a day. After chronic exposure to CCl₄, the levels of hydroxyproline were markedly increased; these were significantly reduced by HV-P411 at all dose levels. The level of serum aminotransferases and lipid peroxidation were increased after the CCl₄ treatment, while reduced glutathione was decreased. These changes were attenuated by HV-P411. In addition, HV-P411 attenuated CCl₄-induced raised serum concentration of transforming growth factor-β1, and the levels of matrix metalloprotease-2 and tissue inhibitor of metalloprotease-1 mRNAs. Our results suggest that HV-P411 may prevent liver fibrosis by modulating fibrogenesis and fibrolysis.     

Disodium Guanylate Alleviates Acute Hepatic Injury Induced by Carbon Tetrachloride Via Antioxidative Stress and Antiapoptosis In Vivo and In Vitro

Hepatic injury is one of the most common digestive system diseases worldwide in clinic. Guanylic acid or guanosine monophosphate (GMP) was an important component of nucleotides, which is mainly in the form of sodium salt (disodium guanylate, GMP‐Na₂). However, its effect on hepatic injury has not yet been investigated. This study is to investigate the protective effects of GMP‐Na₂ on acute hepatic injury induced by carbon tetrachloride (CCl₄), and to explore its mechanism. The hepatic injury models of mice and HL‐7702 cells were induced by CCl₄. The alanine transaminase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), malondialdehyde (MDA), total antioxidant capacity (T‐AOC) were determined by biochemical method. Hematoxylin–eosin staining were used to determine the morphological changes on liver tissue in mice. The mRNA and protein expressions of caspase‐3, Bax, and Bcl‐2 were detected by RT‐PCR and Western blot analysis. Our results show that GMP‐Na₂ treatment significantly decreased the activities of ALT and AST, and the levels of MDA as well as increased the levels of SOD, GSH‐Px, and T‐AOC. Importantly, GMP‐Na₂ effectively enhanced the antiapoptosis function by upregulating Bcl‐2 expression and downregulating caspase‐3 and Bax expressions in vivo and in vitro. Moreover, the histopathological changes of liver tissue were obviously improved after GMP‐Na₂ treatment. These findings suggest that GMP‐Na₂ has protective effects on hepatic injury, and its mechanisms may be associated with antioxidative stress and antiapoptosis.     

Hepatoprotective effect of the root extract of Decalepis hamiltonii against carbon tetrachloride-induced oxidative stress in rats

Decalepis hamiltonii, a climbing shrub, grows in the forests of peninsular India and is consumed for its health promoting properties. The hepatoprotective activity of the aqueous extract of the roots of D. hamiltonii with known antioxidant constituents was studied against carbon tetrachloride (CCl₄)-induced oxidative stress and liver injury in rats. Pretreatment of rats with aqueous extract of the roots of D. hamiltonii, single (50, 100 and 200 mg/kg b.w.) and multiple doses (50 and 100 mg/kg b.w. for 7 days) significantly prevented the CCl₄ (1 ml/kg b.w.) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, ALP, and LDH). Parallel to these changes, the root extract also prevented CCl₄-induced oxidative stress in the rat liver by inhibiting lipid peroxidation and protein carbonylation, and restoring the levels of antioxidant enzymes (SOD, CAT, GPx, GR, and GST) and glutathione. The biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the root extract in a dose dependent manner. Protective effect of the aqueous extract of the roots of D. hamiltonii against CCl₄-induced acute hepatotoxicity could be attributed to the antioxidant constituents.