Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats

Abstract

Context: Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties.

Objective: This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl₄-induced liver damage.

Materials and methods: The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200?mg/kg, p.o.) for 7?d prior to the induction of liver damage by CCl₄. Animals were then sacrificed 24?h after CCl₄ administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses.

Results: CCl₄-induced hepatotoxicity was confirmed by an increase (p?<?0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl₄-induced hepatotoxicity was also manifested by an increase (p?<?0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200?mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01?±?13.21), serum ALT (82.15?±?5.01), serum ALP (504.75?±?19.72), hepatic LPO (3.38?±?0.33), and increased levels of hepatic glutathione (0.34?±?0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl₄-intoxicated rats.

Discussion and conclusion: The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl₄-induced liver toxicity; hence, it can be used as a hepatoprotective agent.     

Hepatoprotective and antioxidant effect of ellagitannins and galloyl esters isolated from Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in HepG2 cells

Context In a previous study, the total extract of Melaleuca styphelioides Sm. (Myrtaceae) showed a significant hepatoprotective effect in a CCl₄-induced toxicity model in mice. However, the active components responsible for the activity of the extract were not identified.

Objective To determine the in vitro hepatoprotective activity of the isolated pure compounds from M. styphelioides leaves using the CCl₄-challenged HepG2 cell model.

Materials and methods The hepatoprotective activity of the compounds (at concentrations of 100, 50 and 25?μm), the total extract and silymarin (Sil) (100, 50 and 25?μg/ml) was determined by measuring the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) after pretreatment with the tested samples for one hour. Glutathione (GSH) and superoxide dismutase activity (SOD) were estimated to determine the mechanisms of the hepatoprotective activity.

Results Some compounds showed marked hepatoprotection, including tellimagrandin I, which produced 42, 36 and 31% decrease in ALT and 47, 43 and 37% decrease in AST, at the tested concentrations, respectively, pedunculagin (32, 32 and 30% decrease for ALT and 48, 48 and 45% for AST), tellimagrandin II (38, 32 and 26% decrease for ALT and 45, 40 and 34% for AST) and pentagalloyl glucose (30, 28 and 26% decrease for ALT and 45, 38 and 36% for AST). Tellimagrandin I and II showed the highest increase in GSH (113, 105 and 81% and 110, 103 and 79%, respectively), which was comparable to Sil. Pedunculagin produced the highest increase in SOD (497, 350 and 258%).

Conclusion This study highlights promising natural hepatoprotective candidates derived from M. styphelioides.     

Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats

Context: Several biological effects of Paullinia cupana (guarana) have been demonstrated, but little information is available on its effects on the liver. Objective: The current study was designed to evaluate the hepatoprotective and genoprotective effects of powder seeds from guarana on CCl₄-induced liver injury in rats. Materials and methods: Male Wistar rats were pretreated with guarana powder (100, 300 and 600?mg/kg) or silymarin 100?mg/kg daily for 14 days before treatment with a single dose of CCl₄ (50% CCl₄, 1?mL/kg, intraperitoneally). Results: The treatment with CCl₄ significantly increased the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, CCl₄ increased the DNA damage index in hepatocytes. Guarana in all concentrations was effective in decreasing the ALT and AST activities when compared with the CCl₄-treated group. The treatment with guarana decreased DNA damage index when compared with the CCl₄-treated group. In addition, the DNA damage index showed a significant positive correlation with AST and ALT. Discussion and conclusion: These results indicate that the guarana has hepatoprotective activity and prevents the DNA strand breakage in the CCl₄-induced liver damage in rats.     

Hepatoprotective and antioxidant activity of Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in mice

Context: Liver disease is a serious problem. Polyphenolic compounds have marked antioxidant effect and can prevent the liver damage caused by free radicals. In vitro studies have revealed the strong antioxidant activity of an ellagitannin-rich plant, namely, Melaleuca styphelioides Sm. (Myrtaceae).

Objective: In view of the limited therapeutic options available for the treatment of liver diseases, the hepatoprotective potential of the methanol extract of M. styphelioides leaves (MSE) was investigated against CCl₄-induced liver injury in mice.

Materials and methods: MSE was administered (500 and 1000?mg/kg/d p.o.) along with CCl₄ for 6 weeks. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. Glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. The bioactive components of MSE were identified by NMR, UV and HRESI-MS/MS data.

Results: MSE treatment (500 and 1000?mg/kg/d) markedly inhibited the CCl₄-induced increase in the levels of AST (31 and 38%), ALT (29 and 32%), ALP (13 and 19%), and MDA (22 and 37%) at the tested doses, respectively. MSE treatment markedly increased the levels of GSH (29 and 57%) and antioxidant enzymes compared with the CCl₄-treated group. MSE was more effective than silymarin in restoring the liver architecture and reducing the fatty changes, central vein congestion, Kupffer cell hyperplasia, inflammatory infiltration, and necrosis induced by CCl₄. The LD₅₀ of MSE was more than 5000?mg/kg.

Conclusion: MSE confers potent antioxidant and hepatoprotective effects against CCl₄-induced toxicity.     

Hepatoprotective effect of Stachys pilifera ethanol extract in carbon tetrachloride-induce hepatotoxicity in rats

Context: Stachys pilifera Benth (Lamiaceae) has long been used to treat infectious diseases, respiratory and rheumatoid disorders in Iranian folk medicine. Antitumor and antioxidant activity of the plant have been reported.

Objective: The study was designed to assess the hepatoprotective activity of ethanol extract of Stachys pilifera in carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats.

Materials and methods: The rats were randomly divided into six equal groups (n?=?7). Group I was treated with normal saline; Group II received CCl₄ (1?mL/kg. i.p., twice a week) for 60 consecutive days; Groups III, IV and V were given CCl₄ plus Stachys pilifera (100, 200 and 400?mg/kg/d,p.o.); Group VI received the extract (400?mg/kg/d, p.o.). Histopathological analysis and measurement of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), total protein (TP) and albumin (ALB) were performed.

Results: CCl₄ caused a significant increase in the serum levels of AST, ALT, ALP and MDA as well as decreased ALB, and TP serum levels (p?4-elevated levels of ALT, AST, ALP and MDA (p?4 group (p4.

Discussion: The results revealed that the Stachys pilifera extract could provide considerable protection against CCl₄ hepatotoxicity in rats that may be related to its antioxidant properties.     

Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice

Abstract

Context: The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China.

Objective: The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl₄-induced acute liver damage in mice.

Materials and methods: Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken.

Results: Compared with the model group, administration of 400?mg/kg BELE for 7?d in mice significantly decreased the serum ALT (56.25?U/L), AST (297.67?U/L), ALP (188.20?U/L), and TBIL (17.90?mol/L), along with the elevation of TP (64.67?g/L). In addition, BELE (100, 200, and 400?mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67?U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33?nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl₄-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation.

Discussion and conclusion: The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl₄, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.     

Chemical composition and protective effect of Juniperus sabina L. essential oil against CCl4 induced hepatotoxicity

The hepatoprotective activity of the total extract of Juniperus sabina L. against CCl₄ induced toxicity in experimental animals was previously reported and indicated promising results. Essential oil of J. Sabina was prepared by hydrodistillation method. Components of the oil were identified by comparison of GC-MS and retention indexes with reported data. The hepatoprotective effect of the essential oil against CCl₄ induced toxicity was studied using male Wistar rats and silymarin at 10 mg/kg p.o as standard drug. The protective effect was evaluated via serum biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltranspeptidase (GGT), and total bilirubin as well as tissue parameters including non-protein sulfhydryl groups (NP-SH), malonaldehyde (MDA) and total protein (TP). Histopathological study was applied on the liver tissues using Mayer’s hematoxylin stain, Periodic Acid Schiff – Hematoxylin (PAS-H) and Masson trichrome technique on light microscope. Electron microscope images were also obtained for more detailed study.     

Antioxidant and hepatoprotective effects of Solanum xanthocarpum leaf extracts against CCl4-induced liver injury in rats

Context: Solanum xanthocarpum Schard. and Wendl. (Solanaceae) has been used in traditional Indian medicines for its antioxidant, anti-inflammatory, and antiasthmatic properties.

Objective: The present study demonstrates the antioxidant and hepatoprotective effects of S. xanthocarpum. On the basis of in vitro antioxidant properties, the active fraction from column chromatography of the methanol extract of S. xanthocarpum leaves (SXAF) was chosen as the potent fraction and used for hepatoprotective studies in rats.

Materials and methods: The antioxidant activity was evaluated by 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reducing power assays. Rats were pre-treated with 100 and 200?mg/kg b.w. of SXAF for 14?d with a single dose of CCl₄ in the last day. Hepatoprotective properties were determined by serum biochemical enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), antioxidant enzymes (SOD, CAT, GSH, and GST), and histopathology studies.

Results: SXAF exhibited significant antioxidant activity in scavenging free radicals with IC₅₀ values of 11.72?µg (DPPH) and 17.99?µg (ABTS). Rats pre-treated with SXAF demonstrated significantly reduced levels of serum LDH (1.7-fold), ALP (1.6-fold), and AST (1.8-fold). Similarly, multiple dose SXAF administration at 200?mg/kg b.w. demonstrated significantly enhanced levels of SOD (1.78?±?0.13), CAT (34.63?±?1.98), GST (231.64?±?14.28), and GSH (8.23?±?0.48) in liver homogenates. Histopathological examination showed lowered liver damage in SXAF-treated groups.

Discussion and conclusion: These results demonstrate that SXAF possesses potent antioxidant properties as well as hepatoprotective effects against CCl₄-induced hepatotoxicity.     

Hepatoprotective effects of Ficus racemosa stem bark against carbon tetrachloride-induced hepatic damage in albino rats

In the present study, the hepatoprotective effects of petroleum ether (FRPE) and methanol (FRME) extract of Ficus racemosa Linn. (Moraceae) stem bark were studied using the model of hepatotoxicity induced by carbon tetrachloride (CCl₄) in rats. CCl₄ administration induced a significant decrease in serum total protein, albumin, urea and a significant increase (P?≤?0.01) in total bilirubin associated with a marked elevation in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as compared to control rats. Further, CCl₄ intoxication caused significant increase in the TBARS and decrease in glutathione (GSH) levels in serum, liver and kidney. Pretreatment with FRPE and FRME restored total protein and albumin to near normal levels. Both the extracts resulted in significant decreases in the activities of AST, ALT and ALP, compared to CCl₄-treated rats. However, a greater degree of reduction was observed in FRME pretreated group (FRPE 43%, 38%, and 33%; FRME 55%, 73%, and 38%). Total bilirubin content decreased from 2.1?mg/dL in CCl₄-treated rats to 0.8 and 0.3?mg/dL in FRPE and FRME pretreated rats, respectively. The extracts improved the antioxidant status considerably as reflected by low TBARS and high GSH values. FRME exhibited higher hepatoprotective activity than a standard liver tonic (Liv52), while the protective effect of FRPE was similar to that of Liv52. The protective effect of F. racemosa was confirmed by histopathological profiles of the liver. The results indicate that F. racemosa possesses potent hepatoprotective effects against CCl₄-induced hepatic damage in rats.     

Ameliorative effects of 7-methylcoumarin and 7-methoxycoumarin against CCl4-induced hepatotoxicity in rats

The available conventional remedies for the treatment of drug-induced liver diseases are highly inadequate and possess serious adverse effects; therefore, the development of new, effective drugs is considered necessary. This article explores the hepatoprotective and antioxidant potential of 7-methylcoumarin (MC) and 7-methoxycoumarin (MOC) in CCl₄-induced hepatotoxicity in rats. MC and MOC individually, at doses of 50 and 100 mg/kg body weight, were administered orally once-daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin (TB), total protein (TP), and albumin (TA). Serum antioxidant enzyme [e.g., superoxide dismutase (SOD) and catalase (CAT)] levels were determined. Also, thiobarbituric-acid–related substances (TBARS) levels, along with histopathological studies of liver tissue, were scrutinized. Pretreatment with MC and MOC significantly decreased ALT, AST, and TB in the serum of CCl₄-induced liver damaged rats in a dose-dependent manner. TA and TP levels in the serum were also restored significantly in all presupplemented MC and MOC groups. In addition, oxidative stress induced by CCl₄ was prevented significantly; thereby, increasing SOD and CAT levels and decreasing TBARS levels in liver homogenates. Histopathological studies revealed the ameliorative natures of both the compounds. This study demonstrates the strong hepatoprotective activity of MC and MOC, which could be attributed to their potent antioxidant effects.     

Hepatoprotective activity of Feronia limonia root

Objectives The aim of this study was to evaluate the hepatoprotective potential of a methanolic extract and of marmesin isolated from the root bark of Feronia limonia. Methods Activity levels of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), cell viability and cell death were evaluated in HepG2 cells (human liver hepatoma cells) treated with CCl₄ in the presence or absence of F. limonia extract or marmesin. Plasma activity levels of AST, ALT, bilirubin, alkaline phosphatase, protein, hepatic antioxidants, lipid peroxidation and histopathological evaluations were carried out in rats treated with CCl₄ alone or co‐supplemented with F. limonia extract or marmesin in a dose‐dependent manner. Key findings In‐vitro co‐supplementation of F. limonia methanolic extract or marmesin significantly minimized alteration in levels of AST and ALT and improved cell viability. Oral administration of F. limonia methanolic extract or marmesin significantly prevented CCl₄‐induced elevation in the plasma markers of hepatic damage and hepatic lipid peroxidation and a decrease in hepatic antioxidants. In‐vivo hepatoprotective potential of F. limonia methanolic extract and marmesin was evident from the minimal alterations in the histoarchitecture of liver. Conclusions This has been the first scientific report on the hepatoprotective potential of F. limonia root bark methanolic extract and marmesin.     

Protective effect of Acacia confusa bark extract and its active compound gallic acid against carbon tetrachloride-induced chronic liver injury in rats

Acacia confusa Merr. (Leguminosae), a species native to Taiwan, is widely distributed on the hills and lowlands of Taiwan, and has been traditionally used as a medicine. The hepatoprotective effects of A. confusa bark extract (ACBE) and its active constituent gallic acid were evaluated against carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. CCl₄-induced hepatic pathological damage and significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) in plasma, and cytochrome P4502E1 (CYP2E1) protein expression in hepatic samples, and decreased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) in erythrocytes. Treatment with ACBE, gallic acid or silymarin could decrease significantly the AST, ALT, and MDA levels in plasma, and CYP2E1 expression in liver tissues, and increase the activities of SOD and GPX in erythrocyte when compared with CCl₄-treated group. Liver histopathology also showed that ACBE, gallic acid or silymarin could significantly reduce the incidence of liver lesions induced by CCl₄. These results suggested that the ACBE and gallic acid exhibit potent hepatoprotection against CCl₄-induced liver damages in rats, and the hepatoprotective effects of ACBE and gallic acid may be due to the modulation of antioxidant enzymes activities and inhibition of lipid peroxidation and CYP2E1 activation.     

Hepatoprotection of 1β-hydroxyeuscaphic acid – the major constituent from Rubus aleaefolius against CCl4-induced injury in hepatocytes cells

Abstract

Context: Rubus aleaefolius Poir. (Rosaceae) is used as a folk medicine to treat various types of hepatitis with significant effects in Fujian Province of China. The ethyl acetate fraction of R. aleaefolius root ethanol extract proved effective after our testing in vivo animal experiments.

Objective: The protective effects of a major constituent, 1β-hydroxyeuscaphic acid isolated from R. aleaefolius was first investigated against carbon tetrachloride (CCl₄)-induced injury in liver cells from hepatocytes cell line (BRL-3A).

Materials and methods: Treatment of BRL-3A with CCl₄ led to generation of free radicals detected after a 2?h incubation and produced cell injury demonstrated by increased leakage of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) in the media. Exposure to CCl₄ caused apoptosis to cells but did not induce lipid peroxidation. Following treatment with 1β-hydroxyeuscaphic acid at doses ranging from 1 to 100?µg/mL for 24?h, cellular morphology, cell growth function (MTT assay), ALT, AST, malondialdehyde (MDA) and superoxide dismutase (SOD) were assessed and evaluated under control and exposed conditions.

Results: The IC₅₀ of 1β-hydroxyeuscaphic acid was 15?μg/mL. Exposure of injured BRL-3A at 20?μg/mL changed abnormal size, cellular shrinkage, and enhanced regulation. ALT, AST, MDA enzyme levels were reduced and SOD activity was increased.

Discussion and conclusion: Treatment with 1β-hydroxyeuscaphic acid has significant hepatoprotective activity by lowering the leakage of intracellular enzymes, reducing the oxidation of proteins and decreasing the incidence of apoptosis. These results provide a basis for confirming the traditional uses of R. aleaefolius in treating hepatic diseases.     

Hepatoprotective effect of polyphenols rich methanolic extract of Amorphophallus commutatus var. wayanadensis against CCl4 induced hepatic injury in swiss albino mice

The present study is to evaluate the hepatoprotective and antioxidant activity of methanolic extract of Amorphophallus commutatus var. wayanadensis against carbon tetrachloride induced hepatotoxicity in mice models. Hepatic injury was induced by injecting 0.2% CCl₄ in olive oil intra peritoneally on 15th day of drug administration. Hepatoprotective activity was evaluated by estimating the levels of serum markers like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and histopathological studies. Antioxidant potential of the extract was estimated by measuring the levels of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), glutathione peroxidase (GPx) and total reduced glutathione in the liver samples. Histopathological and biochemical results elicited the methanolic extract of A. commutatus has significant hepatoprotective activity comparable to the standard silymarin. The extract also showed dose dependent increase of antioxidant enzymes in CCl₄ induced hepatotoxicity models. The methanolic extract of A. commutatus showed significant hepatoprotective and antioxidant activity which might be attributed due to the polyphenolic compounds present in the extract.     

Hepatoprotective effects and HSV-1 activity of the hydroethanolic extract of Cecropia glaziovii (embaúba-vermelha) against acyclovir-resistant strain

Context: Cecropia glaziovii Snethl. (Cecropiaceae), commonly known as “embaúba-vermelha”, is widely distributed throughout Latin America and has been reported in Brazilian folk medicine to treat cough, asthma, high blood pressure and inflammation.

Objective: Investigate the hepatoprotective properties of crude hydroethanolic extract of C. glaziovii as well as its in vitro antioxidant and antiviral (HSV-1 acyclovir resistant strain) activities.

Materials and methods: The hepatoprotective effect, the antioxidant properties and antiviral activity of crude hydroethanol extract (RCE40) from C. glaziovii leaves were evaluated by carbon-tetrachloride (CCl₄)-induced hepatotoxicity, by TBARS (thiobarbituric acid reactive species) and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assays, respectively.

Results: The RCE40 extract (20?mg/kg) inhibited lipid peroxidation on liver in post injury treatment and decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, in this protocol the RCE40 (20?mg/kg) enhanced the activity of hepatic enzymes (SOD/CAT) which are involved in combating reactive oxygen species (ROS), suggesting that it possesses the capacity to attenuate the CCl₄-induced liver damage. Moreover the RCE40 (20?mg/kg) inhibited TBARS formation induced by several different inductors of oxidative stress showing significant antioxidant activity, including physiologically relevant concentration, as low as 2 µg/mL. Concerning antiviral activity, the RCE40 was effective against herpes simplex virus type 1 replication (29R acyclovir resistant strain) with EC₅₀?=?40 µg/mL and selective index (SI)?=?50.

Discussion and conclusion: These results indicate that C. glaziovii could be a good source of antioxidant and anti-HSV-1 lead compounds.     

Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats

Abstract

Context: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve liver ischemia-reperfusion-induced injury in rats.

Objective: This study was designed to determine whether the recombinant BPTI (rBPTI) can prevent the chronic liver injury induced by CCl₄ in rats.

Materials and methods: Fifty male Wistar rats were divided into five groups. Rats were treated with 40% CCl₄ at a dose of 2?ml/kg body weight twice a week subcutaneously for 12 weeks. In the 8th week, they were administered intraperitoneally with rBPTI (80 MU/kg), BPTI (80 MU/kg) or hepatocyte growth-promoting factor (pHGF; 100?mg/kg) daily for the next 4 weeks.

Results: rBPTI significantly prevented the disruption of liver function of alanine aminotransferase (ALT; 172.7?±?18.16 versus 141.2?±?15.28, p?=?0.003), aspartate aminotransferase (AST; 225.10?±?36.54 versus 170.06?±?27.14, p?=?0.007) and hydroxyproline (Hyp; 1.14?±?0.27 versus 0.62?±?0.17, p?=?0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive substances (TBARS; 1.15?±?0.16 versus 0.87?±?0.15, p?=?0.003) and increased the activities of superoxide dismutase (SOD; 6.07?±?0.95 versus 7.75?±?1.12, p?=?0.007). rBPTI reduced the production of cytokines of IL-1β and TGF-β. The hepatocyte necrosis, fibrosis, fatty degeneration and inflammatory cell infiltration were ameliorated by rBPTI administration.

Conclusion: This study demonstrated that rBPTI exerted a hepatoprotective effect on chronic liver fibrosis induced by CCl₄, which suggests that rBPTI may have the potential application for chronic liver injury induced by drugs metabolism and toxic substances.     

Potential antioxidant properties and hepatoprotective effects of an aqueous extract formula derived from three Chinese medicinal herbs against CCl4-induced liver injury in rats

The hepatoprotective effects of an aqueous extract formula (AEF) derived from Artemisia capillaris, Lonicera japonica and Silybum marianum (ratio 1:1:1) were evaluated by its antioxidant properties and its attenuation of carbon tetrachloride (CCl₄)-induced liver damage in rats. The antioxidant analyses revealed that the AEF showed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide anion radical scavenging activities as well as ferric reducing antioxidant potential (FRAP) and Trolox equivalent antioxidant capacity (TEAC) compared with the individual herbs, suggesting a synergism in antioxidation between the three herbs. The animal experiments showed that the CCl₄ treatment increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, but decreased triglyceride (TG) and glutathione (GSH) levels as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities. However, AEF administration can successfully lower serum ALT and AST activities, restore the GSH level, ameliorate or restore GPx and CAT activities as well as improve SOD action depending on AEF dosage. Histological examination of liver showed that CCl₄ increased the extent of bile duct proliferation, necrosis, fibrosis and fatty vacuolation throughout the liver, but AEF can improve bile duct proliferation, vacuolation and fibrosis, and restore necrosis. The present study demonstrated the hepatoprotective potential of AEF as an alternative to the traditional silymarin.     

Hepatoprotective effect of the ethanol extract of Polygonum orientale on carbon tetrachloride-induced acute liver injury in mice

Polygonum orientale L. (Polygonaceae) fruits have various medicinal uses, but their hepatoprotective effects have not yet been studied. This study investigated the hepatoprotective activity of the ethanolic extract of P. orientale (POE) fruits against carbon tetrachloride (CCl₄)-induced acute liver injury (ALI). Mice were pretreated with POE (0.1, 0.5, and 1.0 g/kg) or silymarin (0.2 g/kg) for 5 consecutive days and administered a dose of 0.175% CCl₄ (ip) on the 5th day to induce ALI. Blood and liver samples were collected to measure antioxidative activity and cytokines. The bioactive components of POE were identified through high-performance liquid chromatography (HPLC). Acute toxicity testing indicated that the LD₅₀ of POE exceeded 10 g/kg in mice. Mice pretreated with POE (0.5, 1.0 g/kg) experienced a significant reduction in their serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels and reduction in the extent of liver lesions. POE reduced the malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels, and increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in liver. HPLC revealed peaks at 11.28, 19.55, and 39.40 min for protocatechuic acid, taxifolin, and quercetin, respectively. In summary, the hepatoprotective effect of POE against CCl₄-induced ALI was seemingly associated with its antioxidant and anti-proinflammatory activities.     

Protective effects of Dunaliella salina – A carotenoids-rich alga,against carbon tetrachloride-induced hepatotoxicity in mice

The protective effects of Dunaliella salina (D. salina) on liver damage were evaluated by carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice. Male ICR mice were orally treated with D. salina or silymairn daily with administration of CCl₄ twice a week for 8 weeks. CCl₄ induced liver damage and significantly (p < 0.05) increased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum and decreased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and GSH content in liver whereas increased hepatic malondialdehyde (MDA) content as compared with control group. Treatment with D. salina or silymarin could significantly (p < 0.05) decrease the ALT, AST, and ALP levels in serum and increase the activities of SOD, catalase, GSH-Px, glutathione reductase, and GSH content and decrease the MDA content in liver when compared with CCl₄-treated group. Liver histopathology also showed that D. salina reduced the incidence of liver lesions induced by CCl₄. The results suggest that D. salina exhibits potent hepatoprotective effects on CCl₄-induced liver damages in mice, and that the hepatoprotective effects of D. salina may be due to both the increase of antioxidant enzymes activities and inhibition of lipid peroxidation.