CCl4-induced Hepatotoxicity In Rats Research Articles

HEPATOPROTECTIVE ACTIVITY OF FRUIT AND LEAF EXTRACTS OF FICUS CARICA AND FICUS BENGHALENSIS IN EXPERIMENTAL RATS

Ficus plants have traditionally been used as potential remedies for treating various diseases. Hepatotoxicity is one of the severe threats to human health which must be adequately cured. The study was planned to investigate the hepato-protective potential of methanolic extracts of fruit and leaves of Ficus carica and Ficus benghalensis against carbon tetrachloride (CCl4)-induced hepatotoxicity in an experimental rat model. The study was planned using a randomized control design (RCD). The study included 6 groups of animals (n= 5 per group) having average body weight (230±20 g), out of which 5 groups were treated with CCl4 (15 µL kg-1 body weight), and the remaining one was left as healthy control. Four of the five CCl4-treated groups were administered individually with fruit and leaf extracts (25 mg kg-1 body weight) of F. carica and F. benghalensis, while the fifth was left as CCl4-treated control. The total serum bilirubin (TSB), total serum protein (TSP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels of the control group during the treatment period ranged from 0.54±0.16 to 0.59±0.15 mgdL-1, 8.56±0.73 to 8.66±0.75 gdL-1, 46.00±21.41 to 49.41±22.68 UL-1, 41.6±13.99 to 44.41±13.16 UL-1, and 139.80±28.72 to 145.62±28.82 UL-1, respectively. CCl4 administration significantly (p<0.05) increased the TSB, ALT, AST, and ALP levels in the range of 1.48±0.30-2.30±0.19 mgdL-1, 147.6±34.22 to 233.81±14.94 UL-1, 118.8±15.88 to 167.8±16.4143 UL-1, and 213.8±21.46 to 260±26.664 UL-1, respectively. The elevated TSB, ALT, AST, and ALP levels were significantly (p<0.05) decreased after F. carica and F. benghalens extract treatment to 1.06±0.15-1.70±0.21 mgdL-1, 115.00±28.19-190.21±25.68 UL-1, 89.8±16.29-111.8±23.81 UL-1, and 195.38±42.29-218.4±35.02 UL-1 respectively. Moreover, TSP level was significantly decreased after CCl4 administration and improved after extract treatment. It was concluded that methanolic extract from the leaf and fruit of both F. benghalensis and F. carica protects against CCl4-induced hepatotoxicity in rats. Keywords: Hepatoprotective potential, Ficus carica, Ficus benghalensis, Hepatic damage, Experimental rat model

An analysis of Heptoprotective effects of plant extract on albino rats by Deep Learning analysis using ResNet and VGG16 algorithms

The hepatoprotective and anti-inflammatory effects of Terminalia catappa L. and Pergularia daemia hydroalcoholic extracts in albino rats with CCl4-induced liver damage (HAETC and HAEPD, respectively). The extracts significantly reduced the harm induced by CCl4 when given orally at a dosage of 200mg/kg. They also showed strong hepatoprotective and antioxidant properties. Wistar albino rats in good health were divided into seven groups, each with six animals. Group I acted as the control and received no treatment, whereas Group II was given 30% CCl4 (1ml/kg, intraperitoneally) to cause hepatotoxicity. After administering Silymarin (25 mg/kg, orally) as per protocol, Group III underwent CCl4 therapy. The CCl4-induced rats showed significant reductions in antioxidant enzymes like SOD, catalase, glutathione peroxidase (GPX), and glutathione-S-transferase (GST), as well as increases in serum marker enzymes like SGOT, SGPT, alkaline phosphatase (ALK), ACP, LDH, and lipid peroxidation (LPO) activity. However, rats given HAEPD and HAETC showed significant improvements, returning these parameters to levels that are almost normal (P 0.001).The hepatoprotective and antioxidant benefits of Terminalia catappa L. (HAETC) and Pergularia daemia (HAEPD) against CCl4-induced hepatotoxicity in rats were further validated by histopathological analysis of liver tissues. It encourages the use of pre-trained CNN architectures, such as VGG16 and ResNet (Residual Network), in the proposed method, which uses convolutional neural networks (CNNs) for histopathological image analysis to assess the hepatoprotective properties of Pergularia daemia and Terminalia catappa L. leaf extracts against CCl4-induced hepatotoxicity. These well-known CNN models may be modified for precise and effective histopathological image interpretation, assisting in the evaluation of the impact of plant extracts on liver health.

Phenolic Compounds From Ephedra Alata veill Growing in Libya and The Ameliorative Effect Towards CCl4-Induced Hepatotoxicity in Rats

Phenolic Compounds From Ephedra Alata veill Growing in Libya and The Ameliorative Effect Towards CCl4-Induced Hepatotoxicity in Rats

Blueberry and cranberry extracts mitigate CCL4-induced liver damage, suppressing liver fibrosis, inflammation and oxidative stress

The current study aims to evaluate potential hepatoprotective effect of lingonberry, cranberry and blueberry polyphenols on carbon tetrachloride (CCL-4)-induced acute and subacute liver injury in rats. A total of 55 male Wistar rats, divided into six experimental and control groups. With the exception of the negative control group, all groups received an intraperitoneal injection of CCl-4, twice a week for 14 days. An extract of lingonberry, cranberry, blueberry polyphenols and the positive control, silymarin were administered daily via intragastric route, for 14 consecutive days. The untreated control group showed characteristic of classical oxidative stress-mediated liver damage with vacuolization of the hepatocyte cytoplasm, infiltration by immune cells and proliferation of collagen fibers, decrease in body weight and increase in liver weight; increased levels of AST and ALT in serum, an increased lipid peroxidation in the liver. However, the use of cranberry and blueberry polyphenols significantly suppressed liver damage, exerting an effect comparable to the hepatoprotective effect of the positive control. The extracts prevented and reduced inflammatory liver damage by reducing IL-6, TNF-α and IFN-γ levels. In conclusion, blueberry and cranberry extracts have a protective effect against acute and subacute CCl4-induced hepatotoxicity in rats.

UHPLC-Q/Orbitrap/MS based chemical fingerprinting and hepatoprotective potential of a medicinal plant, Morinda angustifolia Roxb.

Morinda angustifolia Roxb. is used to treat jaundice in the indigenous system of medicine in Bangladesh. The objective of the present study was to assess the hepatoprotective potential and in silico-based identification of the active constituents of M. angustifolia bark extract. In vivo hepatoprotective activity was evaluated in CCl4-induced hepatotoxicity in rats. The secondary metabolite content of the extract was identified by ultra-performance liquid chromatography coupled with a quadrupole orbitrap mass spectrometer (UHPLC-Q/Orbitrap/MS). Furthermore, UHPLC-Q/Orbitrap/MS identified compounds of the extract were assessed for their effect on liver-protective enzymes, namely superoxide dismutase, catalase, and peroxidase, using an in-silico study. The extract revealed significant (p<0.05) in vivo hepatoprotective potential evident from the change in the levels of liver biomarker enzymes ALT, AST, and ALP. The flavonoids cosmosiin, wogonin, and baicalein are among the seven compounds identified by the LC-MS analysis of the extract. A molecular docking study of LC-MS identified compounds confirmed the therapeutic potential in free radical-induced hepatotoxicity, with good binding affinities (-6.0 to -10.4 Kcal/mol) and interaction patterns. Furthermore, in Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA), wogonin revealed the best stable complex in catalase, with a binding energy of 104.091 KJ/mol. In contrast, digoxigenin formed the supreme stable complex in peroxidase (35.277 KJ/mol) and superoxide dismutase (27.505 KJ/mol). Both experimental and computational studies supported the folkloric use of M. angustifolia in hepatic disorders. Besides, the in silico study indicates a possible role of baicalein, digoxigenin, and wogonin in amelioration of oxidative damage of the liver

Acute toxicity, hepato-curative activity of extracts of a combination of plants on CCL4-induced hepatotoxicity in rats and antiradical activity

Acute toxicity, hepato-curative activity of extracts of a combination of plants on CCL4-induced hepatotoxicity in rats and antiradical activity

Acute toxicity, hepato-curative activity of extracts of a combination of plants on CCL4-induced hepatotoxicity in rats and antiradical activity

Traditional healers combine four medicinal plants (Cochlospermum tinctorium, Terminalia macroptera, Leptadenia hastata and Commiphora Africana to treat hepatitis in Burkina Faso. The aimed was to evaluate the hepato-curative activity of lyophilized aqueous decoction (LAD) and hydroethanolic macerate (LHM) of plant extracts on CCl4-induced hepatitis in rats. We assessed the acute toxicity and scavenging activity of the 2, 2-Diphenyl-1-picrylhydrazyl (DPPH). Hepato-curative activity study included nine groups with five rats each. We used rats as followed: group 1 as neutral controls, group 2 as negative controls, and the other groups were experimental groups. Rats in groups 2-9 received a single dose (1 mL/kg) of CCl4 in intraperitoneal injection to induce hepatitis. We fed orally the rats for seven consecutive days with sylimarin in group 3, LAD and LHM respectively in groups 4-6 and groups 7-9 by 400, 200 and 100 mg/kg/day. This study revealed LAD and LHM had a LD50&gt; 2000 mg/kg and both showed radical-scavenging properties with IC50= 5.95 and 8.66 µg/mL respectively. All experimental rats regardless of the treatment group showed a significantly reduced plasma transaminases level as compared to negative controls. LAD and LHM at 400, 200 mg/kg significantly reduced alkaline phosphatase and gamma-glutamyl transferase. Histologically, treated rats showed normal to almost normal liver in a dose-dependent manner as compared to the controls. Conclusion: LAD and LHM decreased liver enzyme and allowed a dose-Dependent liver damage recovery after CCl4-induced hepatitis in rats.

GC-MS Analysis, Molecular Docking and Hepatoprotective Effect of Ethanolic Extract of Capparis zeylanica on CCl4-Induced Hepatotoxicity in Rats

Capparis zeylanica (Capparaceae) is a climbing shrub, commonly known as ‘Asadua’ in Oriya language. Folkloric it is used as anti-inflammatory, anti-rheumatic, hepatitis and liver tonics. The present work aimed to investigate the hepatoprotective activity of Capparis zeylanica root. The ethanolic extract was subjected to GC-MS analysis and quantification of rutin, quercetin and gallic acid by HPLC. In vitro antioxidant study was evaluated by DPPH, nitric oxide radical and hydrogen peroxide assay. Hepatoprotective activity was performed by CCl4 (1.25 ml/kg, I.P) induced Wistar albino rats at dose of 200 and 300 mg/kg using silymarin (100 mg/kg) as standard. The liver tissue homogenate was examined for lipid peroxidation, SOD, CAT and GSH assay. Serum was taken for biochemical analysis and liver for histopathological study. In silico molecular docking study was performed by the indentified compounds. Gallic acid was quantified as highest in HPLC analysis. Fifty compounds were identified by GC-MS analysis. The extract exhibited significant free radical scavenging effect at highest concentration. The level of liver function enzymes (AST, ALT and ALP), bilirubin and protein were significantly improved after the administration of 200 and 300 mg/kg of extract. Alterations in SOD, CAT, GSH and lipid peroxidation levels were significantly checked by extract. Compounds propane, 1, 1-dipropoxy- (-5.2); cis-9-hexadecenal (-6.0); 17-octadecen-14-yn-1-ol (-6.0); 6-butyl-1,4-cycloheptadiene (-6.5) exhibited greater docking score as compared to standard silymarin (-5.1). The hepatoprotective potential of C. zeylanica could be due to its antioxidant effect and the synergistic effect of these compounds.

Therapeutic potential of Ni(II) Schiff base complex on CCl4 toxicity

Carbon tetrachloride (CCl4) is a known ecological hazardous xenobiotic that could motivate hepatotoxicity. We aimed to examine, for the first time, the therapeutic potential of nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex versus CCl4-induced hepatotoxicity in rats. We used six rat groups of ten animals each. The negative control, vehicle, normal rats injected i.p. with the complex (2.4 mg/kg/day), positive control rats injected i.p. with CCl4, and treated rats administered complex via injection at low and high concentrations of 1.2 and 2.4 mg/kg/day, respectively at the same time as CCl4 injection for short-term (3-weeks) and long-term (8-weeks) treatment. Intoxicated-rodents exhibited significant elevations in the liver index, hepatic serum markers, and oxidative stress with significant reductions in the hepatic, antioxidants, nucleic acids, and proteins. Complex co-treatment with CCl4 significantly suppressed the elevated liver enzyme activities, attenuated oxidative stress, reactivated antioxidant-system components, and amended the hepatic tissue injury. The complex high dose was more efficient than the low dose. Results of negative control were analogous to those of normal rats injected with the complex high dose. The histopathological analysis also supported the above findings. These results show that complex has good antioxidant and therapeutic properties, which can help in treating and preventing CCl4-induced hepatotoxicity.

Hepatoprotective activity of Phyllanthus niruri Linn. endophytes

BackgroundThe liver is the vital organ which plays a major role in metabolism with numerous functions in the human beings such as protein synthesis, hormone production, and detoxification. Present research work is focused on hepatoprotective potential of chloroform (PNFC) and ethyl acetate (PNFEA) endophytic fractions from Phyllanthus niruri Linn. against CCl4-induced hepatotoxicity in albino Wistar rats. To test our hypothesis, both endophytic fungal fractions were tested for vitro antioxidant and in vivo hepatoprotective activity. Serum biochemical parameters like SGOT, SGOT, SALP, cholesterol, bilirubin, and protein were estimated to assess hepatoprotective activity.ResultsGroup of rats treated with CCl4 possess marked hepatic damage and oxidative stress which indicates that cellular leakage and loss of functional integrity of cell membrane in liver. PNFC and PNFEA fractions of endophyte from Phyllanthus niruri Linn. stem have significantly reduced the elevated levels of biomarkers like SGPT, SGOT, SALP, bilirubin, cholesterol, and total protein in CCl4-induced hepatotoxicity in rats. The results obtained confirm hepatoprotective activity of endophytic fractions (PNFC and PNFEA) mediated through the stabilization of plasma membrane, repair of hepatic tissue damage, return of biochemical marker levels to normal, and regeneration of hepatocytes. Histopathological observations revealed improvement in the liver architecture after the treatment of secondary metabolites of endophytic fractions against CCl4-induced liver damage. Both fungal endophytes PNFC and PNFEA showed DPPH scavenging activity with IC50 of 97.79 μg/ml and 108.40 μg/ml, respectively, and possess antioxidant potential. Presence of flavonoids in the both fractions of endophytes may be a possible reason for its antioxidant potential and identified as Eurotium amstelodami strain.ConclusionBoth fungal endophytes PNFC and PNFEA possess hepatoprotective potential due to the presence of secondary metabolites of fungi, i.e., Eurotiumam stelodami strain which support the claim endophytes and act as a potent biomedicine for treatment of various chronic diseases.

Bioactive Compounds from Mango peels (Mangifera indica .Tommy Atkins) And Demonstration of its Cytotoxicity and CCl4 Induced Hepatotoxicity in Rat

Mangifera indica (Tommy Atkins) peels, commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Peels is a major by-product during processing of mango fruit into pulp. In the present study, Thirteen pure bioactive compounds were isolated from methanolic peels extract. Six of them are new ellagitannins,namely,1,2,3,4,6 -Penta-O-galloyl-s-4C1-glupyranose (3); 2,3,6-Tri-O-galloyl-(α/β)-4C1-glucopyranose(4); 2,3-Di-O-galloyl-(α/β)-4C1-glucopyranose,Nilocitin(6);3,6-Di-O-galloyl-(α/β)-4C1-glucopyranose(8);1,6 -Di-O-galloyl- β-4C1-glucopyranose (9) ; 1,3-Di-O-galloyl-β-4C1- glucose (11), which were analyzed for the first time from M. indica (Tommy Atkins) peels. The ameliorative effect of the methanolic extract of M. indica (Tommy Atkins) peels towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. The CCl4-treated rats showed a significant decline in the studied the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain metabolic alterations. The work was extended to investigate tissue histopathology. Thus, results suggest that the peels extract can be a potential source of an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture.

Effects of Aqueous Stem Bark Extract of Stereospermum kunthianum on Carbon Tetrachloride - Induced Hepatotoxicity in Rats

Aim: This study is aimed at evaluating the effects of the aqueous stem bark extract of Stereospermum kunthianum on CCl4-induced hepatotoxicity in rats.&#x0D; Methodology: Analysis of qualitative phytochemical components and antioxidant activity were carried out. Experimental rats were randomly divided into six groups of five rats each. Group 1: served as the normal control group. Group 2: was administered with CCl4 only at a dose of 3 ml/kg b.wt by single intraperitoneal administration. Group 3: served as the standard control group. Group 4: was administered with 200 mg/kg b.wt of the aqueous stem bark extract + CCl4. Group 5: was administered with 400 mg/kg b.wt of the aqueous stem bark extract + CCl4. Group 6: was administered with 600 mg/kg b.wt of the aqueous stem bark extract+ CCl4.&#x0D; Results: The phytochemical analysis showed the presence of flavonoid, phenols, saponins, and terpenoid while tannins and alkaloids were absent. The antioxidant activity showed that the extract significantly (P&lt;0.05) inhibits Ferric Reducing Antioxidant Power (FRAP) and Thiobarbituric Acid Reactive Substances (TBARS), giving high activity as the concentration of the extract increases. The elevated levels of ALT and AST coupled with Conjugated bilirubin, Total bilirubin, and total protein caused by CCl4 administration were all reduced significantly (P&lt;0.05) by the extract in dose dependent manner.&#x0D; Conclusion: These findings demonstrated that stem bark extract of Stereospernmum kunthianum could be an alternative medication for liver injury.

A study to evaluate the hepatoprotective activity of prebiotics, probiotics, and synbiotic in CCl4 induced hepatotoxicity in rats

The current study was evaluated for the hepatoprotective activity of probiotics, prebiotics alone, and synbiotic of them. Animals were grouped into 12 groups (n = 6), i.e. normal control (NC), disease control (DC), treatment with prebiotics, probiotics alone, and synbiotic of them, and standard marketed hepatoprotective Silymarin along with Synbiotic 2000. All treatments were orally administered daily for 28 days. On the 28th day, all animals except the NC group received carbon tetrachloride (CCl4) (1 ml/kg, i.p.). Levels of serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, total protein, lactate dehydrogenase, and urea were evaluated. The tissues were evaluated for oxidative markers levels of catalase (CAT), lipid peroxidation (LPO), and glutathione (GSH), and total protein. Histopathology of tissues was carried out. Compositional analysis of intestinal microbiota was done by 16S amplicon sequencing. CCl4 caused elevation in SGPT, SGOT, ALP, total bilirubin, urea, and lactate dehydrogenase in the DC group which was prevented with pretreatment of prebiotics, probiotics, and synbiotics. Total protein was decreased in serum and tissues after administration of CCl4 which was restored with pretreatment of test substances. Oxidative marker LPO was increased in the DC group and catalase (CAT) and GSH were also depleted in liver tissue. These changes were prevented in pretreated test groups. The histological change in hepatic parenchyma and hepatocytes was minimal in test groups compared to DC. The 16S amplicon sequencing indicated that Lactobacillus acidophilus and prebiotic treatment effectively displaced Staphylococcus. Results suggested that the use of prebiotics, probiotics alone, and synbiotic of them has a protective effect against CCl4-induced hepatotoxicity in rats.

Phenolic compounds and hepatoprotective potential of Anastatica hierochuntica ethanolic and aqueous extracts against CCl4-induced hepatotoxicity in rats.

To investigate the effect of Anastatica hierochuntica ethanolic (KEE), aqueous (KAE) extracts, and their combination against CCl4-induced hepatotoxicity in rats. The HPLC analysis for KEE and KAE was quantitatively carried out. Biochemical liver markers, antioxidant enzymes, and histopathologicalalterations were examined then total hepatoprotection potential was calculated. Among 9 identified phenolic compounds (PC) in KEA, sinapic acid was the highest while syringic acid was the highest among 21 identified PC in KAE. Six flavonoids were identified in KEE and two in KAE using HPLC, respectively. Oral administration of KEE, KAE, and KEE + KAE at 250 mg/kg body weight significantly reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, alkaline phosphatase (ALP), total bilirubin (TBILI), and also attenuated histopathological changes. Additionally, they reduced malondialdehyde (MOD), restored reduced-glutathione (GSH), and enhanced superoxide dismutase (SOD) levels. KEE, KAE, and KEE+KAE protected the liver from CCl4-hepatotoxicity as they mainly attenuating oxidative stress. Total hepatoprotection was about 128.3%, 114.5%, and 103.8% for KEE, KAE, and KEE+KAE, respectively. Biochemical observations, supplemented by histopathological examination revealed thatAH affords extract-depending protection against CCl4-hepatotoxicity.

Isolation of biologically active metabolites from Bougainvillea spectabilis Willd. cultivated in Egypt

Bougainvillea spectabilis Willd. is an ornamental plant cultivated in tropical, subtropical regions and other places as Egypt. The present study aimed to perform bioassay guided fractionation and isolation of some of the bioactive compounds from the Egyptian cultivate. The total ethanol extracts of the leaves (T.ET.L.), stems (T.ET.S.) and flowers (T.ET.F.) were screened for some pharmacological activities viz. in vivo anti-oxidant and anti-hepatotoxic, in addition to in vitro cytotoxic activities. The anti-oxidant effect was assessed by measuring serum glutathione level (GSH) in alloxan-induced diabetic rats. The anti-hepatotoxic activity was evaluated via measuring serum markers level viz . alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl4-induced hepatotoxicity in rats. In vitro cytotoxicity of the different extracts was estimated for liver cancer cell line (HEPG2) adopting Sulforhodamine B stain assay. T.ET.L. exhibited significantly potent anti-oxidant and anti-hepatotoxic activities, while T.ET.S. showed the highest cytotoxic activity. Through biological guided fractionation, leaves and stems were subjected to successive solvent extraction, whereas the leaves ethyl acetate (Et.Ac.L.) and the stems ethanol 70% (Et.70%S.) extracts showed highly potent activities. Thus, different chromatographic techniques were performed on Et.Ac.L. and Et.70%S. extracts leading to the isolation of five bioactive metabolites. Three flavonoids were isolated from Et.Ac.L.; genistein-7-O-rutinoside (1) , formononetin-7-O-rutinoside (2) and myricetin (3) , while orobol-7-O-glucoside (4) and hesperidin (5) were isolated from Et.70%S. This work demonstrated the importance of the plant as a promising anti-oxidant, anti-hepatotoxic and cytotoxic product for nutraceutical use.

Suaeda vermiculata Aqueous-Ethanolic Extract-Based Mitigation of CCl4-Induced Hepatotoxicity in Rats, and HepG-2 and HepG-2/ADR Cell-Lines-Based Cytotoxicity Evaluations.

Suaeda vermiculata, an edible halophytic plant, used by desert nomads to treat jaundice, was investigated for its hepatoprotective bioactivity and safety profile on its mother liquor aqueous-ethanolic extract. Upon LC-MS (Liquid Chromatography-Mass Spectrometry) analysis, the presence of several constituents including three major flavonoids, namely quercetin, quercetin-3-O-rutinoside, and kaempferol-O-(acetyl)-hexoside-pentoside were confirmed. The aqueous-ethanolic extract, rich in antioxidants, quenched the DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, and also showed noticeable levels of radical scavenging capacity in ABTS (2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) assay. For the hepatoprotective activity confirmation, the male rat groups were fed daily, for 7 days (n = 8/group, p.o.), either carboxyl methylcellulose (CMC) 0.5%, silymarin 200 mg/kg, the aqueous-ethanolic extract of the plant Suaeda vermiculata (100, 250, and 500 mg/kg extract), or quercetin (100 mg/kg) alone, and on day 7 of the administrations, all the animal groups, excluding a naïve (250 mg/kg aqueous-ethanolic extract-fed), and an intact animal group were induced hepatotoxicity by intraperitoneally administering carbon tetrachloride (CCl4). All the animals were sacrificed after 24 h, and aspartate transaminase and alanine transaminase serum levels were observed, which were noted to be significantly decreased for the aqueous-ethanolic extract, silymarin, and quercetin-fed groups in comparison to the CMC-fed group (p < 0.0001). No noticeable adverse effects were observed on the liver, kidney, or heart’s functions of the naïve (250 mg/kg) group. The aqueous-ethanolic extract was found to be safe in the acute toxicity (5 g/kg) test and showed hepatoprotection and safety at higher doses. Further upon, the cytotoxicity testings in HepG-2 and HepG-2/ADR (Adriamycin resistant) cell-lines were also investigated, and the IC50 values were recorded at 56.19 ± 2.55 µg/mL, and 78.40 ± 0.32 µg/mL (p < 0.001, Relative Resistance RR 1.39), respectively, while the doxorubicin (Adriamycin) IC50 values were found to be 1.3 ± 0.064, and 4.77 ± 1.05 µg/mL (p < 0.001, RR 3.67), respectively. The HepG-2/ADR cell-lines when tested in a combination of the aqueous-ethanolic extract with doxorubicin, a significant reversal in the doxorubicin’s IC50 value by 2.77 folds (p < 0.001, CI = 0.56) was noted as compared to the cytotoxicity test where the extract was absent. The mode of action for the reversal was determined to be synergistic in nature indicating the role of the aqueous-ethanolic extract.

A search for protective activity of aqueous extract of Punica granatum var. pleniflora against CCl4-induced hepatotoxicity in rats

A search for protective activity of aqueous extract of Punica granatum var. pleniflora against CCl4-induced hepatotoxicity in rats

Effect of Roasted Date Palm Rich Oil Extracts in Liver Protection and Antioxidant Restoration in CCl4-induced Hepato Toxicity in Rats

Effect of Roasted Date Palm Rich Oil Extracts in Liver Protection and Antioxidant Restoration in CCl4-induced Hepato Toxicity in Rats

Antioxidant and hepatoprotective activity of Flemingia tuberosa Dalzell in CCl4-induced hepatotoxicity in rats

Micro-morphology of Achillea clypeolata: contribution to the pharmacognostical profileAnely Nedelcheva

Hepatoprotective Effects of Standardized Extracts from an Ancient Italian Apple Variety (Mela Rosa dei Monti Sibillini) against Carbon Tetrachloride (CCl4)-Induced Hepatotoxicity in Rats.

The aim of this research was to examine the effect of the hydroalcoholic extracts from the peel (APE) and pulp (APP) of a traditional apple cultivar from central Italy (Mela Rosa dei Monti Sibillini) on CCl4-induced hepatotoxicity in rats. Phytoconstituents were determined by liquid chromatography–mass spectrometry (LC-MS) analysis showing an abundance of proanthocyanidins and flavonol derivatives together with the presence of annurcoic acid in APE. Wistar rats received APE/APP (30 mg/kg oral administration) for three days before CCl4 injection (2 mL/kg intraperitoneal once on the third day). Treatment with both APE and APP prior to CCl4 injection significantly decreased the serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) compared to the CCl4 group. Besides, pretreatment with APE reversed the CCl4 effects on superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) and interleukin-1beta (IL-1β) levels in liver tissue in rats and reduced tissue damage as shown in hematoxylin and eosin staining. These results showed that this ancient Italian apple is worthy of use in nutraceuticals and dietary supplements to prevent and/or protect against liver disorders.