Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats

Abstract

Context: Different parts of the walnut [Juglans regia L. (Juglandaceae)] have been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain.

Objective: The present study investigated the protective effect of walnut leaf extract against carbon tetrachloride (CCl₄)-induced liver damage in rats.

Materials and methods: The rats were randomly divided into seven groups: control, CCl₄ (i.p., 0.5?mL/kg b.w., 50% CCl₄ in olive oil), walnut extract (at dose level of 0.2?g/kg b.w.) alone, walnut extract (at dose levels of 0.05, 0.1, 0.2 and 0.4?g/kg b.w.) with CCl₄, and treatment was carried out accordingly. On the 28th day, rats were sacrificed and blood was withdrawn by cardiac puncture. Liver damage was assessed by serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin), antioxidant enzymes (superoxide dismutase and catalase) and histopathological observation.

Results: Administration of walnut leaf extract (ranging from 0.2 to 0.4?g/kg b.w.) significantly lowered serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in CCl₄-treated rats. Walnut leaf extract increased antioxidant enzymes, including superoxide dismutase and catalase. Histopathological examination of livers showed that walnut leaves extract reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl₄-treated rats.

Discussion and conclusion: These results suggest that walnut extract has a protective effect over CCl₄-induced oxidative damage in rat liver. These results demonstrate that walnut extract acts as a good hepatoprotective and antioxidant agent in attenuating hepatocellular damage.     

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 activity of Chhit-Chan-Than extract powder against carbon tetrachloride-induced liver injury in rats

The capability of Chhit-Chan-Than extract powder (CCTEP, 10% aqueous Ocimum gratissimum L. extract) to protect against carbon tetrachloride (CCl₄)-induced oxidative stress and hepatotoxicity in vivo was investigated. Wistar rats were divided into five groups. Group A was a normal control group given only vehicle; Group B, the hepatotoxic group, was injected intraperitoneally twice a week with repeated 8% CCl₄/olive oil (0.1 mL/100 g of body weight); Groups C–E, extract-treated groups received CCl₄ and different doses of CCTEP (100 mg/kg and 200 mg/kg) or silymarin (200 mg/kg of body weight) daily by gavage for 8 weeks, respectively. The results showed that the CCl₄-induced histopathogical changes may be prevented by CCTEP through reducing the intercellular collogen stack, dropping blood serum alanine aminotransferase and aspartate aminotransferase levels, and restoring the catalase activity and glutathione content. The hepatoprotective properties were further confirmed by the marked improvement in histopathological examination and by quantitative steatosis-fibrosis scoring. The above results suggest that CCTEP is able to prevent the liver inflammation and fibrosis induced by repeated CCl₄ administration, and the hepatoprotective effects might be correlated partly with its antioxidant and free radical scavenging effects.     

Hepatoprotective and antioxidant activity of Leucas aspera against d-galactosamine induced liver damage in rats

Context: Whole plant of Leucas aspera (LA) Willd. (Labiatae) is traditionally used in Siddha medicine for hepatic ailments.

Objective: LA was investigated for its hepatoprotective, antioxidant, and protective effect on microsomal drug metabolizing enzymes (MDMEs).

Materials and methods: LA aqueous extract (200 and 400 mg/kg, p.o.) was evaluated for its hepatoprotective and antioxidant activity in d-galactosamine (d-GalN)-induced hepatotoxicity in rats. Biochemical and histopathological studies were performed to assess hepatoprotective activity. Hexobarbitone-induced sleeping time model was used to study the protective effect of LA on MDMEs.

Results: d-GalN administration induced hepatotoxicity in rats which was manifested by increased levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglycerides, total bilirubin and oxidative stress. Pretreatment with LA extract significantly protected the liver in d-GalN administered rats. LA extract significantly elevated antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and decreased lipid peroxidation levels in liver. The total phenolic and flavonoid content in LA aqueous extract was found to be 28.33 ± 0.19 gallic acid equivalents mg/g of extract and 3.96 ± 0.57 rutin equivalent mg/g of extract, respectively. LA extract (200 and 400 mg/Kg) treatment with CCl₄ decreased the hexobarbitone-induced sleeping time in mice by 56.67 and 71.30%, respectively, which indicated the protective effect of LA on hepatic MDMEs. Histological studies showed that LA at 400 mg/kg attenuated the hepatocellular necrosis in d-GalN intoxicated rats.

Conclusion: Our results contribute towards validation of the traditional use of LA in hepatic disorders.     

GC-MS analysis and hepatoprotective activity of the n-hexane extract of Acrocarpus fraxinifolius leaves against paracetamol-induced hepatotoxicity in male albino rats

Context: In Egypt, the burden of liver diseases is exceptionally high.

Objective: To investigate the components of the n-hexane extract of Acrocarpus fraxinifolius Arn. (Leguminosae) and its hepatoprotective activity against paracetamol (APAP)-induced hepatotoxicity in rats.

Material and methods: TRACE GC ultra gas chromatogaphic spectrometry was used for extract analysis. Thirty albino rats were divided into six groups (five rats in each). Group 1 was the healthy control; Groups 2 and 3 were healthy treated groups (250 and 500?mg/kg b.w. of the extract, respectively) for seven days. Group 4 was hepatotoxicity control (APAP intoxicated group). Groups 5 and 6 received APAP?+?extract 250 and APAP?+?extract 500, respectively.

Results: Chromatographic analysis revealed the presence of 36 components. Major compounds were α-tocopherol (18.23%), labda-8 (20)-13-dien-15-oic acid (13.15%), lupeol (11.93%), phytol (10.95%) and squalene (7.19%). In the acute oral toxicity study, the mortality rates and behavioural signs of toxicity were zero in all groups (doses from 0 to 5?g/kg b.w. of A. fraxinifolius). LD₅₀ was found to be greater than 5?g/kg of the extract. Only the high dose (500?mg/kg b.w.) of extract significantly alleviated the liver relative weight (4.01?±?0.06) and biomarkers, as serum aspartate aminotransferase (62.87?±?1.41), alanine aminotransferase (46.74?±?1.45), alkaline phosphatase (65.96?±?0.74), lipid profiles (180.39?±?3.51), bilirubin profiles (2.30?±?0.06) and hepatic lipid peroxidation (114.20?±?2.06), and increased body weight (11.58?±?0.20), serum protein profile (11.09?±?0.46) and hepatic total antioxidant capacity (23.78?±?0.66) in APAP-induced hepatotoxicity in rats.

Conclusion: Our study proves the antihepatotoxic/antioxidant efficacies of A. fraxinifolius hexane extract.     

Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats

Abstract

Context: Purslane (Portulaca oleracea L., Portulacaceae) has been traditionally used in folk medicine to afford protection against liver injury, although its actual efficacy remains uncertain.

Objective: To evaluate purslane as a hepatoprotective agent, we investigated the protective effect of its ethanol extract against carbon tetrachloride (CCl₄)-induced hepatic toxicity in rats.

Materials and methods: A total of 108 male Wistar rats were randomly divided into 12 groups. The first group was maintained as normal control, whereas CCl₄ (0.5?ml/kg bw, 50% CCl₄ in olive oil, i.p.), purslane extract (0.005, 0.01, 0.05, 0.1, and 0.15?g/kg bw, intragastrically), and purslane extract (five doses as above) along with CCl₄ were administered to the Groups II, III–VII, and VIII–XII, respectively. The rats were sacrificed on the 30th day, and blood was withdrawn by cardiac puncture. Liver damage was assessed by measuring hepatic marker enzymes (ALT, AST, ALP, GGT, and SOD) and histopathological observation.

Results: Treatment with CCl₄ resulted in increased serum activities of marker enzymes with a concomitant decrease in SOD. Histological alterations were also observed in the liver tissue upon CCl₄ treatment. Administration of purslane extract (0.01, 0.05, 0.1, and 0.15?g/kg b.w.) significantly showed a marked tendency towards normalization of all measured biochemical parameters in CCl₄-treated rats. Histopathological changes also paralleled the detected alteration in markers of liver function.

Discussion and conclusion: These results demonstrate that purslane exerts protective effects against CCl₄-induced damage in rat liver and supports a potential therapeutic use of purslane as an alternative for patients with liver diseases.     

The novel role of β-aescin in attenuating CCl4-induced hepatotoxicity in rats

Context: β-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties.

Objective: The present study investigated the hepatoprotective effect and underlying mechanisms of β-aescin in CCl₄-induced liver damage.

Materials and methods: Thirty-five Wistar rats were divided into six groups: normal control, CCl₄ control, silymarin (50?mg/kg, p.o) and β-aescin (0.9, 1.8 and 3.6?mg/kg, i.p.) treatment for 14 d. CCl₄ (1?mL/kg, i.p. for 3 d) was administered to produce hepatic damage. Ponderal changes and liver marker enzymes were estimated. Hepatic oxidative and nitrosative stress was estimated by levels of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and nitrite/nitrate. Serum TGF-β1 and TNF-α were estimated by ELISA technique. Hepatic collagen and histopathological studies were carried out.

Results: β-Aescin (3.6?mg/kg) markedly decreased CCl₄-induced increased levels of ALT, AST, ALP (71.77 versus 206.7, 71.39 versus 171.82, 121.20 versus 259?IU/L, respectively), total bilirubin (0.41 versus 1.35?mg/dL), TBARS (2.0 versus 8.83?nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15?μg/mL) and increased CCl₄-induced decreased GSH levels (0.095 versus 0.048?μmol/mg protein). β-Aescin (3.6?mg/kg) induced focal regenerative changes in liver and markedly decreased TBARS (2.0 versus 8.83?nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15?μg/mL), TGF-β1 (92.28 versus 152.1?pg/mL), collagen content (110.75 versus 301.74?μmol/100?mg tissue) and TNF-α (92.82 versus 170.56?pg/mL) when compared with CCl₄ control.

Discussion and conclusion: The findings suggest that β-aescin has a protective effect on CCl₄-induced liver injury, exhibited via its anti-inflammatory, antioxidative, antinitrosative and antifibrotic properties inducing repair regeneration of liver. Hence, it can be used as a promising hepatoprotective agent.     

Zea mays,Stigma maydis prevents and extenuates acetaminophen-perturbed oxidative onslaughts in rat hepatocytes

Context: Zea mays L. (Poaceae) Stigma maydis is an underutilized product of corn cultivation finding therapeutic applications in oxidative stress-related disorders.

Objectives: This study investigated its aqueous extract against acetaminophen (APAP)-perturbed oxidative insults in rat hepatocytes.

Materials and methods: Hepatotoxic rats were orally pre- and post-treated with the extract (at 200 and 400?mg/kg body weight) and vitamin C (200?mg/kg body weight), respectively, for 14 days. Liver function, antioxidative and histological analyses were thereafter evaluated.

Results: The APAP-induced marked (p?<?0.05) increases in the activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and the concentrations of bilirubin, oxidized glutathione, protein carbonyls, malondialdehyde, conjugated dienes, lipid hydroperoxides and fragmented DNA were dose-dependently extenuated in the extract-treated animals. The extract also significantly (p?<?0.05) improved the reduced activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase as well as total protein, albumin and glutathione concentrations in the hepatotoxic rats. These improvements may be attributed to the bioactive constituents as revealed by the gas chromatography–mass spectrometric chromatogram of the extract. The observed effects compared favourably with vitamin C and are informative of hepatoprotective and antioxidative attributes of the extract and were further supported by the histological analysis.

Conclusion: The data from the present findings suggest that Stigma maydis aqueous extract is capable of preventing and ameliorating APAP-mediated oxidative hepatic damage via enhancement of antioxidant defence systems.     

Antioxidant activity and protective effect of Turnera ulmifolia Linn. var. elegans against carbon tetrachloride-induced oxidative damage in rats

The present study aimed to determine whether the leaves of Turnera ulmifolia Linn. var. elegans extract exert significant antioxidant activity. The antioxidant activity of its hydroethanolic extract (HEETU) was evaluated by assessing (a) its radical scavenging ability in vitro, and (b) its in vivo effect on lipid peroxidation and antioxidant enzyme activities. The in vitro antioxidant assay (DPPH) clearly supported HEETU free radical scavenging potential. Moreover, glutathione content and antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase and catalase) were significantly enhanced in CCl₄-treated rats due to oral HEETU-treatment (500 mg/kg b.w.) over 7 and 21 days. In addition, an improvement was observed in lipid peroxidation and serum biochemical parameters (aspartate aminotransferase and alanine aminotransferase), indicating a protective effect against CCl₄-induced liver injuries, confirmed by histopathological studies. The HEETU effect was comparable to the standard drug Legalon® (50 mg/kg b.w.) under the same experimental condition. Quantitative analysis of the HPLC extract revealed the presence of flavonoids, wich mediate the effects of antioxidant and oxidative stress. In conclusion, extract components exhibit antioxidant and hepatoprotective activities in vitro and in vivo.     

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.     

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 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.     

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.     

Hepatoprotective role of Abelmoschus esculentus (Linn.) Moench., on carbon tetrachloride-induced liver injury

Abstract

Context: Chronic liver disease has become a global health problem. The research for prominent herbal agents for the management of liver diseases is widely increased.

Objective: The root of Abelmoschus esculentus (Linn.) Moench., (Malvaceae) has been used as a remedy for liver disorders. The aim of the present study was to evaluate the antioxidant and hepatoprotective effects of the ethanol extract of A. esculentus root.

Materials and method: The antioxidant effect was assessed using DPPH and hydroxy radical scavenging assays. The hepatoprotective effect of the extract was evaluated using CCl₄ intoxicated HepG₂ cell line and Wistar rats by estimating the levels of hepatic and antioxidant markers.

Results: The extract of A. esculentus showed IC₅₀ values of 270.99 and 532.86?µg/mL for DPPH and hydroxy radical scavenging assays, respectively. The incubation of HepG2 cells with CCl₄ drastically decreased the cell viability and increased the leakage of transaminases. Pre-treatment with the extract significantly restored the cell death by 31.25 and 39.04% at 200 and 400?µg/mL concentrations, respectively. The reduction of ALT leakage by the treatment was 18.62, 38.59 and 52.15% compared to the CCl₄ treated cells at 100, 200 and 400?µg/mL, respectively. In in-vivo experiments also the treatment reduced the levels of transaminases, ALP, MDA, total bilirubin and hepatic TNFα levels as well as increased the antioxidant levels in a dose dependent manner. Histological observations of liver sections showed reduction in steatosis, necrosis and inflammation.

Conclusion: The results substantiated the hepatoprotective activity of A. esculentus through its antioxidant capacity.     

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.     

Phytochemical,antioxidant and protective effect of cactus cladodes extract against lithium-induced liver injury in rats

Context: Opuntia ficus-indica (L.) Mill. (Castaceae) (cactus) is used in Tunisian medicine for the treatment of various diseases.

Objective: This study determines phytochemical composition of cactus cladode extract (CCE). It also investigates antioxidant activity and hepatoprotective potential of CCE against lithium carbonate (Li₂CO₃)-induced liver injury in rats.

Materials and methods: Twenty-four Wistar male rats were divided into four groups of six each: a control group given distilled water (0.5?mL/100?g b.w.; i.p.), a group injected with Li₂CO₃ (25?mg/kg b.w.; i.p.; corresponding to 30% of the LD₅₀) twice daily for 30 days, a group receiving only CCE at 100?mg/kg of b.w. for 60 days and then injected with distilled water during the last 30 days of CCE treatment, and a group receiving CCE and then injected with Li₂CO₃ during the last 30 days of CCE treatment. The bioactive components containing the CCE were identified using chemical assays.

Results: Treatment with Li₂CO₃ caused a significant change of some haematological parameters including red blood cells (RBC), white blood cells (WBC), haemoglobin content (Hb), haematocrit (Ht) and mean corpuscular volume (VCM) compared to the control group. Moreover, significant increases in the levels of glucose, cholesterol, triglycerides and of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities were observed in the blood of Li₂CO₃-treated rats. Furthermore, exposure to Li₂CO₃ significantly increased the LPO level and decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the hepatic tissues.

Conclusion: CCE possesses a significant hepatoprotective effect.     

Efficacy of Rosmarinus officinalis leaves extract against cyclophosphamide-induced hepatotoxicity

Context Cyclophosphamide (CTX) is used to treat different cancer types, although it causes severe hepatotoxicity due to its oxidative stress effect. Rosmarinus officinalis, L. (Lamiaceae) has a therapeutic potential against hepatotoxicity due to its antioxidant activity.

Objective The objective of this study is to investigate the phytochemical analysis of the methanol extract of Rosmarinus officianalis leaves (MEROL) and its efficacy against CTX-induced hepatotoxicity.

Materials and methods The phytochemical analyses were assessed spectrophotometericaly. To assess the MEROL efficacy, 72 Swiss albino mice were divided into six groups. Group 1 was control, groups 2 and 3 included mice which were injected intraperitoneally (i.p.) with 100 or 200?mg/kg of MEROL at days 1, 4, 7, 10, 13 and 16; group 4 was injected (i.p.) with CTX (200?mg/kg) at day 17, groups 5 and 6 were injected (i.p.) with MEROL as groups 3 and 4 followed by 200?mg/kg CTX at day 17, respectively. At day 22, six mice from each group were sacrificed and the others were sacrificed at day 37.

Results MEROL has a high content of total phenolics, saponins, total antioxidant capacity and DPPH radical scavenging activity. The median lethal dose (LD₅₀) value of MEROL was 4.125?g/kg b.w. The inhibitory concentration 50 (IC₅₀) value for DPPH radical scavenging was 55?μg/mL. Pretreatment with 100?mg/kg MEROL for 16 d ameliorated CTX-induced hepatotoxicity represented in lowering the levels of the aspartate aminotransferase (AST) and lipid profile and minimizing the histological damage.

Conclusions Pretreatment with 100?mg/kg b.w. MEROL mitigated CTX-induced hepatotoxicity due to its antioxidant activity.     

Hepatoprotective activities of two Ethiopian medicinal plants

The present study evaluated the in vivo hepatoprotective activity of two medicinal plants, namely, Justicia schimperiana (Hochst. ex Nees) (Acanthaceae) and Verbascum sinaiticum Benth. (Scrophulariaceae) used in Ethiopian traditional medical practices for the treatment of liver diseases. The levels of hepatic marker enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were used to assess their hepatoprotective activity against carbon tetrachloride (CCl₄)-induced hepatotoxicity in Swiss albino mice. The results revealed that pretreating mice with the hydro-alcoholic extracts of both plants significantly suppressed the plasma AST ((P?<?0.01) J. schimperiana; (P?<?0.05) V. Sinaiticum) and ALT ((P?<?0.05) J. schimperiana) activity when compared with the CCl₄ intoxicated control. Among the Soxhlet extracts of each of the plants, the methanol extract of J. schimperiana showed significant hepatoprotective activity. Further fractionation of this extract using solid phase extraction and testing them for bioactivity indicated that the fractions did not significantly reverse liver toxicity caused by CCl₄. However, the percentage hepatoprotection of the distilled water fraction was comparable with that of the standard drug silymarin at the same dose (50?mg/kg) as evidenced by biochemical parameters. Histopathological studies also supported these results. In vitro DPPH assay conducted on the water fraction of J. schimperiana and the Soxhlet methanol fraction of V. sinaiticum showed that they possess moderate radical scavenging activity (IC₅₀?=?51.2 and 41.7 μg/mL, respectively) which led to the conclusion that the hepatoprotective activity of the plants could be in part through their antioxidant action.     

Amelioration of hyperglycaemia and modulation of antioxidant status by Alcea rosea seeds in alloxan-induced diabetic rats

Context: Alcea rosea L. (Malvaceae) has various medicinal uses including anticancer, anti-inflammatory and analgesic properties. However, there is no report on its antidiabetic activity.

Objective: Alcea rosea seed extracts were evaluated for antihyperglycaemic and antioxidative potential in diabetic rats.

Materials and methods: Single intra-peritoneal injection of alloxan (130?mg/kg b.w.) was used for induction of diabetes in Albino Wistar rats. Antihyperglycaemic and antioxidant activities of methanol and aqueous extracts of Alcea rosea seed (100 and 300?mg/kg b.w.), administered orally on daily basis for 15 days, were assessed in vivo for fasting blood glucose level and antioxidant status of liver and pancreas. Metformin was used as a positive control.

Results: Aqueous and methanol extracts (300?mg/kg b.w.) decreased blood glucose level in diabetic rats by 24% and 46%, respectively. Administration of aqueous and methanol extracts at 300?mg/kg b.w. significantly (p?2O₂ decomposed/min/mg of protein), respectively. Similar results were observed for pancreas.

Discussion and conclusions: Antihyperglycaemic and antioxidative potentials of Alcea rosea seeds suggest its usefulness in management of diabetes and its complications. This is the first report on antidiabetic activity of this plant.     

Ligularia fischeri extract attenuates liver damage induced by chronic alcohol intake

Context Ligularia fischeri (Ledebour) Turcz. (Compositae) has been used as a leafy vegetable and in traditional medicine to treat hepatic disorder in East Asia.

Objective The present study explores the antioxidant activity of LF aqueous extract on EtOH-induced oxidative stress accompanied by hepatotoxicity both in vitro and in vivo.

Materials and methods In vitro study using the mouse liver NCTC-1469 cell line was conducted to estimate the cytotoxicity as well as the inhibitory effect of LF extract against alcohol-treated cell damage. In vivo study used an alcohol-fed Wister rat model orally administered EtOH (3.95?g/kg of body weight/d) with or without LF extract (100 or 200?mg/kg body weight) for 6 weeks. Serum and liver tissue were collected to evaluate hepatic injury and antioxidant-related enzyme activity.

Results The EC₅₀ value for the DPPH radical scavenging capacity of LF extract was 451.5?μg/mL, whereas the IC₅₀ value of LF extract in terms of EtOH-induced reactive oxygen species (ROS) generation was 98.3?μg/mL without cell cytotoxicity. LF extract (200?mg/kg body weight) significantly reduced the triglyceride content of serum (33%) as well as hepatic lipid peroxidation (36%), whereas SOD activity was elevated three-fold. LF extract suppressed expression of CYP2E1 and TNF-α, and attenuated alcohol-induced abnormal morphological changes.

Discussion and conclusion LF extract attenuated liver damage induced by alcoholic oxidative stress through inhibition of ROS generation, down-regulation of CYP2E1, and activation of hepatic antioxidative enzymes. Homeostasis of the antioxidative defence system in the liver by LF extract mitigated hepatic disorder following chronic alcohol intake.