CCl4-induced Hepatotoxicity In Rats Research Articles

Phytochemical Screening and Hepatoprotective Potential of Aqueous Fruit Pulp Extract of Adansonia digitata against CCL4 Induced Liver Damage in Rats

Aim: The current study was carried out to evaluate the hepatoprotective effects of aqueous extract of Adansonia digitata fruit pulp on carbon tetrachloride (CCl4) induced liver damage in rats.
 Place and Duration of Study: Department of Biochemistry, Faculty of Basic Medical Sciences, College of Health Science, between November 2017 and January 2018.
 Methodology: A. digitata fruit pulp was extracted by maceration using water; and a concentration of 100 mg/ml was used. Two doses of the aqueous extract (200 mg/kg and 300 mg/kg) and Livoline (25 mg/kg) were used to investigate their hepatoprotective effects on CCl4-induced hepatotoxicity in rats.
 Results: The two doses of the plant extract showed dose-dependent hepatoprotective effect on CCl4-induced hepatotoxicity, as evident by the significant reduction (P<0.05) in serum levels of AST, ALT, ALP and bilirubin along with the improved histopathological liver sections compared to CCl4-treated animals.
 Conclusion: Due to its hepatoprotective potentials, A. digitata extract may be used to develop standard treatment drugs against some liver disorders when it is further evaluated through extensive researches.

In-depth hepatoprotective mechanistic study of Phyllanthus niruri: In vitro and in vivo studies and its chemical characterization.

Phyllanthus niruri L. is a widespread tropical plant which is used in Ayurvedic system for liver and kidney ailments. The present study aims at specifying the most active hepatoprotective extract of P. niruri and applying a bio-guided protocol to identify the active compounds responsible for this effect. P. niruri aerial parts were extracted separately with water, 50%, 70% and 80% ethanol. The cytoprotective activity of the extracts was evaluated against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cells. Bioassay-guided fractionation of the aqueous extract (AE) was accomplished for the isolation of the active compounds. Antioxidant activity was assessed using DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and ferric reducing antioxidant power (FRAP). The in vivo hepatoprotective activity of AE was evaluated in CCl4-induced hepatotoxicity in rats at different doses after determination of its LD50. Pretreatment of clone-9 and Hepg2 with different concentrations of AE (1, 0.1, 0.01 mg/ml) had significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) against CCl4 injures, and restored the activity of the natural antioxidants; glutathione (GSH) and superoxide dismutase (SOD) towards normalization. Fractionation of AE gave four fractions (I-IV). Fractions I, II, and IV showed a significant in vitro hepatoprotective activity. Purification of I, II and IV yielded seven compounds; corilagin C1, isocorilagin C2, brevifolin C3, quercetin C4, kaempferol rhamnoside C5, gallic acid C6, and brevifolin carboxylic acid C7. Compounds C1, C2, C5, and C7 showed the highest (p< 0.001) hepatoprotective potency, while C3, C4, and C6 exhibited a moderate (p< 0.001) activity. The AE exhibited strong antioxidant DPPH (IC50 11.6 ± 2 μg/ml) and FRAP (79.352 ± 2.88 mM Ferrous equivalents) activity. In vivo administration of AE in rats (25, 50, 100 and 200 mg/kg) caused normalization of AST, ALT, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total cholesterol (TC), triglycyrides (TG), total bilirubin (TB), glucose, total proteins (TP), urea and creatinine levels which were elevated by CCl4. AE also decreased TNF-α, NF-KB, IL-6, IL-8, IL10 and COX-2 expression, and significantly antagonizes the effect of CCl4 on the antioxidant enzymes SOD, catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GSP). The histopathological study also supported the hepatoprotective effect of AE. P. niruri isolates exhibited a potent hepatoprotective activity against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cell lines through reduction of lipid peroxidation and maintaining glutathione in its reduced form. This is attributable to their phenolic nature and hence antioxidative potential.

Bioactivities and Phytochemical Studies of Acrocarpus fraxinifolius Bark Wight Arn

Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to carry out the biological activity screening on the total ethanol and successive extracts of Acrocarpus fraxinofolius (A. fraxinofolius) bark, for the first time. The biological activity studied embraced, management of diabetes in alloxan induced diabetic rats, cytotoxic activity against four human tumor cell lines and hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the petroleum ether extract (PEE) showed the most bioactive extract where, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin. It also showed a significant anti-proliferative activity against MCF-7 (IC50=2.35µg), Hela (IC50=3.85µg) and HEPG-2 (IC50=9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity of the PEE was evidenced by a significant decrease in the liver function enzymes, i.e. AST, ALT and ALP by 29.18%, 28.26%, and 34.11%, respectively, using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. Based on the above outcomes, further phytochemical investigation including GC/MS analysis of its fractions, GLC analysis of its sterol fraction, column chromatography and TLC fractionation of PEE to separate its bioactive compounds were conducted.

Antioxidant and hepatopreventive effects of Cassia angustifolia extract against carbon tetrachloride-induced hepatotoxicity in rats

The present study aimed to investigate the preventive effects of methanol fraction from Cassia angustifolia leaf extract (MECA), associated with its phytochemical content, on CCl4-induced hepatic toxicity in adult rats. In the controls, CCl4 induced an increase of serum biochemical parameters and triggered oxidative stress in the liver. MECA caused significant reductions in CCl4-elevated levels of hepatic markers, total cholesterol, triglycerides, and low-density lipoprotein and increased the level of high-density lipoprotein compared to the CCl4 group. Moreover, pretreatment with the MECA produced significant reductions in lipid peroxidation (thiobarbituric acid reactive substances) and protein carbonyl level in liver tissues as compared with the untreated group. The formation of pathological hepatic lesions was strongly prevented by MECA. Overall, this study suggests that administration of MECA has a high potential to quench free radicals and alleviate CCl4-induced hepatotoxicity in rats.

Effect of Grape Seed Oil on Chronic Carbon Tetrachloride-Induced Hepatic Injury and Determination of Hepatic Apoptosis in Rats

Aims: The present study was designed to evaluate the hepatoprotective activity of grape seed oil (GSO) on liver lesions induced by carbon tetrachloride (CCl4) in rats. The effects on hepatic injury were investigated by measuring serum levels of ALT, triglyceride, total protein, total cholesterol and liver levels of MDA. Furthermore, caspase -3, -8 and -9 activities in cellular apoptosis were determined.&#x0D; Place and Duration of Study: Faculty of Veterinary Medicine, Department of Pathology, Erciyes University, Kayseri, between November 2017 and September 2018.&#x0D; Methodology: In this study 40 male Wistar albino rats were divided into four groups including 10 animals in each. Control group administered with 0.9% NaCl. The second group was administered with 4 mL/kg GSO for twelve weeks. Third group were given CCl4 (0.2 mL/kg) twice for 8-weeks. Fourth group was administered with 4 mL/kg GSO, for 12 weeks and also given CCl4 (0.2 mL/kg) twice for 8 weeks, starting from the 5th week.&#x0D; Results: Histopathological examination of CCl4 group showed intense macro and micro vesicular steatosis in hepatocytes, necrosis, and lymphocytes rich mononuclear cell infiltration in portal area and mild portal fibrosis in the parenchyma. The grape seed oil applications have partially normalized the altered histological changes and the activity of caspase -3, -8 and -9. Administration of GSO led to a decline in the activities of ALT and MDA levels while this treatment elevated serum triglycerides levels which are not significantly important.&#x0D; Conclusion: The results indicate that the antioxidant properties of GSO have not ameliorative effect in either the histopathological lesions or biochemical parameters against CCl4-induced hepatotoxicity in rats. Also, it has been concluded that duration‐dependent further research results are needed to determine the effects of grape seed oil in high doses which can give the best results without side effects.

Effect of Flax Seed Oil on Acute Carbon Tetrachloride-induced Hepatic Injury and Determination of Hepatic Apoptosis in Rats

Aims: The present study was designed to evaluate the hepatoprotective activity of flaxseed oil (FSO) on liver lesions induced by carbon tetrachloride (CCl4) in rats by measurement of caspase 3, 8 and 9 activities in cellular apoptosis, ALT activities, triglyceride, total protein, total cholesterol and liver MDA levels.&#x0D; Place and Duration of Study: Faculty of Veterinary Medicine, Department of Pathology, Erciyes University, Kayseri, between June 2017 and July 2018.&#x0D; Methodology: In this study 32 male Wistar albino rats were divided into four groups of 8 animals in each. The first group was identified as the control and received an intraperitoneal 0.9% NaCl and the second group was given per os at dose of 4 ml/kg FSO for 4 weeks. The third group received an intraperitoneal dose of 1.0 ml/kg CCl4 twice in the first week. The fourth group received an intraperitoneal dose of 1.0 ml/kg CCl4 twice in the first week and simultaneously 4 ml/kg FSO by gavage for 4 weeks.&#x0D; Results: Histopathological examination of CCl4 group showed intense macro and micro vesicular steatosis in hepatocytes, necrosis, lymphocytes rich mononuclear cell infiltration in portal area and parenchyma. The flaxseed oil application did not ameliorate the histological changes induced by CCl4, however reduced the activity of caspase 3, 8 and 9 by a limited number. CCl4 administration produced significantly elevated levels of serum ALT activity, total cholesterol, triglyceride and liver MDA levels, and these increases were not normalized with FSO treatment. In addition, decreased serum total protein levels in CCl4 treated group were ameliorated by FSO application.&#x0D; Conclusion: The results indicate that the antioxidant properties of FSO do not have an ameliorative effect in either the histopathological lesions or biochemical parameters against CCl4-induced hepatotoxicity in rats. In addition, it was concluded that duration‐dependent further research results are needed to determine the effects of flaxseed oil in high doses that can give the best results without side effects.

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats.

It has been proposed carbon tetrachloride (CCl4 ) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl4 -induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl4 (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl4 significantly inhibited alterations in the serum levels of AST, ALP (** P < 0.01), and ALT (*** P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl4 -induced hepatotoxicity in rats.

Does Curcuma longa root powder have an effect against CCl4-induced hepatotoxicity in rats: a protective and curative approach.

This study was conducted to investigate potentially protective and curative effects of Curcuma longa root (turmeric) powder on CCl4-induced hepatotoxicity in rats. Turmeric was administered before (preventive effect) or after (curative effect) treatment with CCl4. Total phenolic and flavonoid levels were 26.35mg GAE/g and 12.35mg CE/g, respectively. Using HPLC analysis, turmeric powder was rich in curcumin (62.97%), demethoxycurcumin (20.86%) and bisdemethoxycurcumin (16.17%). Curcuma longa powder showed important in vitro antioxidant activities. Results showed that the activities of aspartate aminotransaminase and alanine aminotransaminase, and the levels of bilirubin and serum lipids were increased in CCl4-treated animals. However, total protein and albumin levels and antioxidant enzyme activities were decreased. Turmeric administration, before or after CCl4 treatment, significantly decreased the activities of marker enzymes and lipid levels in serum. Moreover, total protein and albumin contents were restored to nearly normal levels after turmeric administration accompanied with increase of antioxidant enzymes activities.

Dual protective effect of ginger and rosemary extracts against CCl4-induced hepatotoxicity in rats.

The present study aimed to investigate the protective effect of aqueous extracts of ginger (GE) and rosemary (RE), both individually and in combination, on carbon tetrachloride (CCl4)-induced liver injury in adult male rats. CCl4 induced significant increase in liver enzymes, bilirubin, triglycerides, and total cholesterol while total protein, albumin, and globulin were significantly decreased. Also, the activity of cytochrome P450 (CYP) and oxidative stress markers were found to be elevated with a concomitant decrease in the activity of antioxidant enzymes in hepatic tissue. Supplementation with extracts of ginger or rosemary effectively relieved most of the CCl4-induced alterations when administered singly. The joint therapy of the two extracts was more effective. The histological investigation strongly confirmed the highly protective effect of the two plant extracts in the hepatocytes. These findings suggest that rosemary and ginger extracts are effective in improving both the function and structure of the hepatocytes through their potent antioxidant effect and point out to the possibility of using a combination of both as an adjunct therapy in liver diseases.

Phenolic Compounds and Hepatoprotective Activity of Centaurea aegyptiaca L. on Carbon Tetrachloride-induced Hepatotoxicity in Rats

Objectives: This study aimed to isolate phenolic compounds from the 70% aqueous methanol extract of the aerial parts (leaves, flowers and stems) of Centaurea aegyptiaca , evaluate in-vivo hepatoprotective activity and determine total phenolic and total flavonoid contents. Methods: 70% aqueous methanol extract of the aerial parts subjected to different chromatographic separation techniques. The identities of the isolated compounds were established on the basis of their spectral data and comparing with previously reported data. The crude extract was evaluated for in-vivo hepatoprotective activity on CCl4-induced hepatotoxicity in rats. Total phenolic and total flavonoid contents of the aqueous methanol extract were determined using Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Results: The aqueous methanol extract of the aerial parts of Centaurea aegyptiacaafforded seven compounds. A phenolic acid ester; protochatechuic acid methyl ester (1) along with six known flavonoids; apigenin-6-C-β-D-glucopyranoside (isovitexin) (2), apigenin-8-C-β-D-glucopyranoside (vitexin) (3), quercetin-3-O-b-D-glucopyranoside (isoquercetin) (4), apigenin (5), 3-O-methylquercetin (6) and quercetin (7). Administration of the extract at doses of 100 and 200 mg/kg b.wt showed a hepatoprotective activity similar to that of the standard drug; silymarin at a dose of 25 mg/kg b.wt. Comparative histopathological study of liver exhibited moderate changes in liver histoarchitecture when compared to the CCl4 group. The methanolic extract showed high concentration of phenolic and flavonoid contents. Conclusion: The aqueous methanol extract of the aerial parts of C. aegyptiaca afforded seven phenolic compounds for the first time from this species, with promising in-vivo hepatoprotective activity.

Effect of Roots of Origanum majorana in Methanolic and Ethyl Acetate Extracts on CCl4-Induced Hepatotoxicity in Rat

To evaluate the hepatoprotective activity of different solvent extracts of Origanum majorana. The root materials were shade dried and were extracted in a soxhlet apparatus successively with ethyl acetate and methanol. The solvent was removed by the process of distillation and the crude extract was dried under vacuum. The extracts were subjected to hepatoprotective activities, the extract producing significant activity was column chromatographed. The extract was preliminarily screened using thin layer chromatography (TLC) and nuclear magnetic resonance (NMR) to know the types of compounds present in the extracts. TLC was developed in n hexane: ethyl acetate solvent systems of different polarities and then plates were visualized under Iodine vapour exposure, UV short wave 254 nm and long wave 366 nm. Plates were sprayed with a solution of visualizing reagent 10% H2SO4 in methanol followed by heating in an oven at 110°C for up to five minutes. The methanolic extracts of Origanum majorana at different doses, Silymarin and Drug vehicle were administered p.o in sodium carboxy methyl cellulose suspension. The serum was used for the estimation of various biochemical parameters like SGOT, SGPT, ALKP, TBL, CHL, TPTN and ALB. The results clearly depicted that CCl4 intoxication in normal rats elevated the serum levels of SGOT, SGPT, ALKP, TBL and CHL, where as decreased the levels of TPTN, ALB significantly when compared to control indicating acute hepatocellular damage and biliary obstruction leading to necrosis.

Antioxidant and hepatoprotective effects of Artemisia dracunculus against CCl4-induced hepatotoxicity in rats.

The present study was conducted to investigate the antioxidant and hepatoprotective activity of the hydro-alcoholic extract of aerial parts of Artemisiadracunculus (HAAD) against CCl4-induced hepatotoxicity in rats. The antioxidant activity was evaluated by reducing power, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 20-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Rats were pre-treated with either 50, 100, and 200 mg/kg of HAAD or silymarin (100 mg/kg; served as the positive control group) for 15 days and they received a single dose of CCl4 on the last day. Hepatoprotective effects were investigated by assessment of serum biochemical enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein (TP), total bilirubin (TB), malondialdehyde (MDA), and antioxidant enzymes (SOD, CAT, GST and GSH), along with histopathological studies. Total phenolic content was 197.22±3.73 mg gallic acid equivalent/g HAAD dry weight. HAAD indicated powerful activity in FRAP, DPPH and ABTS tests. Acute toxicity study showed that the extract had an LD50 of >5000 mg/kg. Oral treatment with HAAD exhibited a significant decrease in the levels of AST, ALT, ALP and TB and an increase in the level of TP. The extract significantly diminished MDA levels. The activities of the antioxidant enzymes were significantly augmented in rats pretreated with HAAD 200 mg/kg. Histopathological examination demonstrated lower liver damage in HAAD-treated groups as compared to CCl4 groups. Our findings indicated hepatoprotective effects of the hydro-alcoholic extract of A. dracunculus on CCl4-induced hepatic damage in rats and suggested that these effects may be produced by reducing oxidative stress.

Prophylactic and Curative Effects of Thymoquinone against CCL4-Induced Hepatotoxicity in Rats

Prophylactic and Curative Effects of Thymoquinone against CCL4-Induced Hepatotoxicity in Rats

Hepatoprotective Effect of Eriobotrya japonica Leaf Extract and Its Various Fractions against Carbon Tetra Chloride Induced Hepatotoxicity in Rats.

Eriobotrya japonica is traditionally used as an antipyretic, digestive, and diuretic agent. Its flowers possess free radical–scavenging, antioxidative, and hepatoprotective effects. We investigated the hepatoprotective potential of E. japonica leaf extract and its various fractions against hepatotoxicity in rats. Liver injury was stimulated by the oral administration of carbon tetrachloride (CCl4; 2.5 mL/kg b.wt.). Male albino rats (n = 55) were distributed arbitrarily into 11 groups: Group I, normal control group; Group II, CCl4 (positive control group); Group III, CCl4 + silymarin; Groups IV and V, CCl4 + two doses of 250 and 500 mg/kg of the 80% methanolic extract of E. japonica leaves, respectively; Groups VI and VII, CCl4 + 250 mg/kg and 500 mg/kg of the ethyl acetate fraction, respectively; Groups VIII and IX, CCl4 + 250 and 500 mg/kg of the butanol fraction, respectively; and Groups X and XI, CCl4 + 250 and 500 mg/kg of the aqueous fraction of E. Japonica leaves, respectively. CCl4-treated rats that were given 250 or 500 mg/kg of the methanol extract of E. Japonica leaves, or its ethyl acetate, butanol, or aqueous fractions, had significantly lower levels of biochemical parameters such as alanine aminotransferase, aspartate transaminase, alkaline phosphate, total protein, gamma-glutamyl transferase, and bilirubin levels than those of the CCl4 positive group. However, the extract and fractions did not significantly affect lipid profiles. Thus, we conclude that Eriobotrya leaf extract and its fractions have a hepatoprotective effect against CCl4-induced hepatotoxicity in rats.

White butterfly (Clerodendrum volubile) leaf extract protects against carbon tetrachloride-induced hepatotoxicity in rats

Currently, there is increasing attention towards flavonoids and phenolic compounds of plant origin because of their association with decrease in the incidence of cardiovascular diseases and different types of cancer. The present study investigates the protective effect of Clerodendrum volubile (C. volubile) methanolic extracts against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Control rats (group I) received olive oil (1 mL/kg, i.p.), group II received CCl4 in olive oil (1 ml/kg, i.p.) to induce hepatotoxicity, groups III, IV and V were pretreated with leaf extract of C. volubile at 125 mg/kg, 250 mg/kg and 500 mg/kg body weight respectively for 14 days prior to CCl4 administration, group VI received vitamin E (100 mg/kg, p.o.) as standard antioxidant to compare with antioxidant effects of the extract. CCl4 hepatotoxicity, characterized by significant (P < 0.05) increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), hepatic degeneration, and inflammation was attenuated by C. volubile methanolic extracts. The serum lipid parameters which include high density lipoprotein (HDL) and low density lipoprotein (LDL) were significantly (P < 0.05) decreased, and increased respectively by CCl4. Methanolic extracts of C. volubile significantly prevented the decrease in the level of HDL and the increase in LDL in a dose-dependent manner (P < 0.05). Decrease in total protein induced by CCl4 was moderately increased following administration of methanolic extracts of C. volubile. Lipid peroxidation was significantly (P < 0.05) reduced while the reduced glutathione (GSH) level and the activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were significantly elevated by C. volubile extract in the CCl4-treated rats. Our findings indicate that C. volubile extract has a significant protective effect against CCl4-induced hepatotoxicity in rats which may be due to its antioxidant properties which is comparable to the reference antioxidant, vitamin E, used in this study.

Hepatoprotective Effect of &lt;i&gt;Croton macrostachyus&lt;/i&gt; Hochst. Ex Del Leaves Against CCl4-Induced Liver Damage

Croton macrostachyus Hochst is a medicinal plant widely used in Ethiopia for the treatment of dysentery, abdominal pain, hepatitis and jaundice. The aim of this study was to evaluate the hepatoprotective activity of aqueous extract of leaves of C. macrostachyus (AECM) in CCl4-induced hepatotoxicity in rats and mice. Seven groups of animals (n = 6) were used. Distilled water was given to group I; animals in group II were given distilled water along with CCl4 (1 mg/kg) every 72 h for 16 days, third group served as a positive control and received silymarin 100 mg/kg, and for the other groups 100, 200, 400 and 800 mg/kg AECM were given orally once daily for 16 days. Hepatotoxicity was induced by intra-peritoneal administration of 1 ml/kg of CCl4 every 72 h. At the 18th day blood samples were collected from the jugular vein. Serum concentrations of biochemical markers and histopathological analysis of the liver were conducted. Thiopentone-induced sleep time test was also conducted. The crude extract at all doses produced significant hepatoprotection by decreasing the level of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilurbin (IBIL). The extract at 100, 200 and 400 mg/kg also produced significant hepatoprotection by decreasing levels of alkaline phosphatase (ALP) as well as produced significant elevation of serum albumin (ALB) level. These results correlated well with the histopathological studies and thiopentone-induced sleeping time assessment. The study revealed that aqueous extract of the leaves of C. macrostachyus possesses hepatoprotective activity and could be used as a potential source of new hepatoprotective drugs.Keywords: Croton macrostachyus, hepatoprotective, carbon tetrachloride, biochemical markers, histopathological analysis

Hepatoprotective naphthalene diglucoside from Neanotis wightiana aerial parts

BackgroundNeanotis wightiana (Wall. ex Wight & Arn) W.H. Lewis has been used in traditional medicine in India for the treatment of liver disorders. In fact, this plant is frequently used by the local people of Tripura for the treatment of liver disorder problems. In previous study on this plant we have isolated a hepatoprotective saponin, neanoside A. PurposeEvaluation of in vivo hepatoprotective effects of isolated compounds from N. wightiana aerial parts on serum hepatic-biomarkers in CCl4- induced hepatotoxicity in rats to validate the traditional use of the plant. Study designThis study was designed to isolate more hepatoprotective compounds from N. wightiana aerial parts and evaluate their in vivo hepatoprotective activity in animal model. MethodsThe phytochemicals from the polar n-butanol fraction of methanolic extract of N. wightiana aerial parts were isolated by repeated column chromatography over Diaion HP-20 and silica gel. Among the isolated three compounds, two were known triterpenoids, ursolic acid and oleanolic acid. The new compound was named neanoside B and its structure was established as naphthalene diglucoside 1 on the basis of extensive spectroscopic (including 2D NMR) analysis. Furthermore, the hepatoprotective activity of 1 was evaluated on CCl4 -induced hepatic injured rats by oral administration at three doses (5, 10 mg and 20 mg/kg) for 7 d and the assay of serum hepatic injury marker enzymes, SGPT, SGOT, ALP and bilirubin contents and histopathological changes of injured liver tissue after 7 d The herbal hepatoprotective drug, silymarin (100 mg/kg) was as positive control. ResultsThe structure of the new compound, neanoside B (1) was elucidated as 1,4-dihydroxy-2-(methoxymethyl)naphthalen-3-yl-methyl-3-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside on the basis of extensive spectroscopic (including 2D-NMR) and chemical studies. The compound 1 exhibited significant in vivo hepatoprotective effect at the tested doses of 5, 10 and 20 mg/kg bw in CCl4-induced hepatotoxicity in rats. In a dose-dependent manner, 1 normalized the elevated levels of hepatic injury marker enzymes, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin and ameliorated the damage of liver tissue by reducing the necrosis and vacuoles. Possibly compound 1 ameliorated the hepatic damage in hepatotoxic rats by improving the antioxidant status. The higher dose (20 mg/kg) showed more hepatoprotective effect by reducing the elevated levels of SGPT, SGOT, ALP and bilirubin content to 388.5 ± 2.156, 160.7 ± 3.00, 198.6 ± 4.562 and 0.652 ± 0.036 IU/ml, respectively, compared to the levels in the control group (583.2 ± 6.922, 324.6 ± 4.711, 263.9 ± 4.939 and 1.533 ± 0.042 IU/ml, respectively) and the effect was comparable to that of the positive control silymarin (100 mg/kg bw) (389.4 ± 6.348, 167.9 ± 4.289, 203.3 ± 4.448 and 0.816 ± 0.030 IU/ml, respectively). ConclusionsThis study indicated that isolated neanoside B (1) from Neanotis wightiana could be a potential drug in liver disorders. Further study in pharmacokinetics and long-term toxicity of compound 1 is requested for its clinical setting as effective drug in liver disorders.

Study of the Protective Effects of Benfotiamine Against CCl4-Induced Hepatotoxicity in Rats

Liver is considered as the first target for the toxic effects of toxins and other xenobiotics, and this can be attributed to its role as a site which receive all absorbed xenobiotics from the gastrointestinal tract and its role as a major site for biotransformation of xenobiotics. The present study was designed to evaluate the possible hepatoprotective effect of benfotiamine against CCl4-induced hepatotoxicity in rats. The study was conducted on 48 male albino rats; the animals were allocated into 8 groups (6 rats in each group) and treated as follow: 4 groups treated with oral doses of either normal saline, benfotiamine (100 mg/kg), thiamine (100 mg/kg), N-acetylcystein (400 mg/kg) only without induction of hepatic damage. The other 4 groups were treated as indicated previously with induction of hepatic damage with CCl4; at the end of treatment period, rats were scarified, blood samples obtained and livers excised for the assessment of the oxidative stress parameters (MDA and GSH), cholesterol and triglycerides levels. Additionally, serum levels of total bilirubin, albumin, total protein and the activities of ALT, AST and ALP enzymes were evaluated before and after treatment with benfotiamine. Tissue sections were prepared for evaluation of histopathological changes. The results indicated that benfotiamine has the ability to protect hepatic tissue against the toxicity induced by CCl4, revealed through reduction of serum levels of TSB and liver enzymes, decrease in the hepatic tissue MDA levels and elevation of GSH there. Histological evaluation of tissue sections prepared for this purpose confirmed the previous finding. In conclusion, benfotiamine is capable to protect liver tissue against CCl4-induced toxicity in rats more than thiamine.&#x0D; Key words: Benfotiamine, CCl4, Hepatotoxicity

Hepatoprotective Activity of Hydroalcoholic Extract of Murraya Koeinigii Leaves against CCl4-Induced Hepatotoxicity in Rats

Hepatoprotective Activity of Hydroalcoholic Extract of Murraya Koeinigii Leaves against CCl4-Induced Hepatotoxicity in Rats

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.