CCl4-induced Liver Damage Research Articles

Ursolic acid alleviates Kupffer cells pyroptosis in liver fibrosis by the NOX2/NLRP3 inflammasome signaling pathway

Pyroptosis has an important role in liver inflammation and fibrosis. The role of KC pyroptosis in liver fibrosis was unclear. Ursolic acid (UA) has antifibrotic effects, but study on the effect and mechanism of UA on KC pyroptosis in liver fibrosis has not been reported. Therefore, we induced KC pyroptosis using Lipopolysaccharide (LPS) and nigericin (Nig) in vitro. C57BL/6J mice were intraperitoneally injected with carbon tetrachloride (CCl4) to establish a liver fibrosis model. We demonstrated that UA attenuated CCl4-induced liver fibrosis, liver damage, and KC pyroptosis of liver tissue. Moreover, KCs were treated with UA and small interfering RNA of NOX2, which showed that inhibiting the NOX2/NLRP3 inflammasome signaling pathway attenuated KC pyroptosis and UA abrogated this effect via suppressing this pathway in vitro. Furthermore, mice were treated with UA, GSK2795039 (a specific inhibitor of NOX2) or MCC950 (a specific inhibitor of NLRP3). Compared with inhibiting NOX2 alone, inhibiting NOX2 in the presence of UA did not markedly ameliorate KC pyroptosis of liver tissue in CCl4-induced liver fibrosis. In addition, when NLRP3 was silenced or inhibited, the result was similar to that of knocking down NOX2 in vivo and in vitro. These results indicate that UA attenuates liver fibrosis in mice via inhibiting KC pyroptosis, which may be through the suppression of NOX2/NLRP3 inflammasome signaling pathway. It may be a new target for treating liver fibrosis and provide a new theoretical basis for the use of UA to treat liver fibrosis.

Pharmacokinetic/Pharmacodynamic Study of Salt-Processed Product of Cuscutae Semen with Hepatoprotective Effects.

Salt-processed product of cuscutae semen (SCS), which is documented in Chinese pharmacopoeia (2020 edition), is one of the processed products of cuscustae semen. SCS possesses hepatoprotective effects. However, Pharmacokinetic/Pharmacodynamic (PK-PD) study of SCS with intervening acute liver injury (ALI) has not been reported yet. Effective constituents are still not well addressed. This study was performed to study PK-PD properties with the purpose of linking SCS hepatoprotective effects to key therapeutic outlines to guide therapeutic use in clinical settings. Rats were orally administered SCS after the acute liver injury model was established. Plasma biochemical analysis, antioxidative analysis, and liver histopathology were measured to evaluate the hepatoprotective effects of SCS. Blood samples were collected at different time points (0 h, 0.083 h, 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 8 h, 12 h, 24 h) for PK/PD study after SCS administration. Contents of chlorogenic acid, hyperoside and astragalin were estimated by UHPLC-ESI-MS. The relationship between concentrations of chlorogenic acid, hyperoside, and astragalin and hepatoprotective effects was assessed by PK-PD modeling. The results showed that SCS ameliorated liver repair and decreased the serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST) markedly. Hepatic oxidative stress was inhibited by SCS, as evidenced by a decrease in malondialdehyde (MDA) and an increase in glutathione (GSH) and superoxide dismutase (SOD) in the liver. PK-PD correlation analysis indicated that concentrations of chlorogenic acid, hyperoside, and astragalin were negatively correlated with level of AST and ALT. The encouraging finding indicates that SCS has beneficial effects on CCl4-induced liver damage. Chlorogenic acid, hyperoside, and astragalin are three effective constituents to exert hepatoprotective effects while astragalin may have maximum pharmacological activity. PK-PD study reveals the positive relationship between drug concentration and action intensity of SCS against liver injury. This research provides a robust foundation for future studies.

Flavonoid rich extract of Trigonella foenum-graecum leaves ameliorate liver fibrosis

Liver fibrosis is a leading cause of mortality and morbidity globally. For decades, plant secondary metabolites such as flavonoids and saponins have attained much consideration due to their safer therapeutic potential against chronic liver diseases. Trigonella foenum-graecum (Common name “Fenugreek”) is an annual herb used as a spice to increase the taste and aroma of food. Its fresh leaves are used as food and are rich in flavonoids. In the current study antifibrotic potential of Trigonella foenum-graecum flavonoid-rich leaf extract (TF) was evaluated in CCl4-induced hepatic fibrosis in mice. The ALT, AST, MDA, CAT, and GSH analysis illustrated that the treatment group significantly reverses CCl4-induced liver damage. The TF extract was found to be rich in quercetin and kaempferol derivatives analyzed through ESI-MS/MS. After four weeks of the TF treatment, hepatocyte architecture improved and collagen deposition in mice liver tissues reduced considerably. The expression of fibrotic markers, including COL-IA, α-SMA, PDGF, and TIMP1, was downregulated, and MMP3 was upregulated significantly at mRNA and protein levels. Interestingly, TF significantly downregulated NF-κB expression and TGF-β/Smad signaling pathway and upregulated miR-146a and miR-29b. Taking together, these results demonstrated that Trigonella foenum-graecum flavonoid-rich leaf extract ameliorated liver inflammatory and fibrogenic responses through miR-146a/miR-29b/TGF-β/Smad axis.

Therapeutic potential of conditioned medium derived from bone marrow mesenchymal stromal cells cocultured with hepatocytes in alleviation of CCl4-induced liver damage in mice

Терапевтический потенциал среды, кондиционированной стволовыми клетками костного мозга для ослабления повреждения печени у мышей, вызванного CCl4Therapeutic potential of conditioned medium derived from bone marrow mesenchymal stromal cells cocultured with hepatocytes in alleviation of CCl4-induced liver damage in mice

Protective effects of Alstonia congensis Methanolic extract against CCl4 induced liver damage in Wistar rats

The hepatoprotective potential, phytochemical properties, and in vivo antioxidant activities of methanol extract of Alstonia congensis stem bark were investigated against carbon tetrachloride (CCl4) induced hepatic damage in Wistar rats. The animals (thirty) were separated randomly into five groups of each six rats and kept under standard state (temperature 25± 2) and fed standard rat pellets and water ad libitum. Liver toxicity in rats was achieved by the intraperitoneal injection of a single dose of 3 ml/kg of CCl4 in olive oil, after oral treatment of rats with 200 and 400 mg/kg of methanol extract of A. congensis or silymarin (50 mg/kg/day) for fourteen days. Then the rats were sacrificed by cervical dislocation and blood samples collected through cardiac puncture, while the liver tissues were removed for the biochemical tests. Hepatotoxic changes were measured by evaluation of some hepatic enzymes, markers of oxidative stress, and histopathological examination. The phytochemical analysis of the extracts displayed the presence of Alkaloids, Saponins, Tannins, Terpenoids, Steroids, Anthocyanin, Flavonoids, Anthraquinones, and Phenols. Treatment of rats with methanol extracts of A. congensis resulted in a significant (p < 0.05) decrease in the values of serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, tissue lipid peroxidation (LPO), as well as an increase (p < 0.05) in the levels of total protein, albumin, reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) to near normal level relative to the CCl4 intoxicated control group (negative control). These observations were buttressed by the histopathological results. Thus, the results revealed that methanol extracts of A. congensis stem bark possess in vivo antioxidant and hepatoprotective effects against CCL4 induced hepatic damage in rats (dose-dependently), which could be attributed to its phytoconstituents.

Protective effect of Euphorbia thymifolia and Euphorbia hirta against carbon tetrachloride-induced hepatotoxicity in Wistar rats

Objectives The present study aims to investigate the protective effect of Euphorbia thymifolia and Euphorbia hirta extracts on in vitro antioxidant activity and in vivo analysis on hepatic marker enzyme levels and histopathological changes in the liver of carbon tetrachloride (CCl4) induced hepatotoxicity rats. Materials and methods This study includes 42 adult male Albino Wistar rats randomly divided into seven treatment groups, including control (basal diet, G1), CCl4-induced single dose (1.5 ml/kg, i.p.) as the negative control (G2), G1 supplemented with 300 mg/kg of ethanol extract of E. thymifolia (G3) and E. hirta (G4), G2 supplemented with 300 mg/kg of ethanol extract of E. thymifolia (G5), E. hirta (G6), and silymarin (25 mg/kg b.w.) used as a standard drug (G7) for 21-days experimental period. Results The ethanolic extracts of E. thymifolia and E. hirta exhibited potential in vitro antioxidant activity in a dose-dependent manner (25 μg/ml, 50 μg/ml, 100 μg/ml, 200 μg/ml and 250 μg/ml). Oxidative stress caused by CCl4-induced the liver damage, including changes in liver marker enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase), enzymatic (superoxide dismutase and catalase), non-enzymatic antioxidants (lipid peroxides and glutathione) and hepatocellular alterations such as hydropic degeneration, irregular hepatocytes, and distention of the vein. Administration of E. thymifolia and E. hirta significantly (p < 0.05) restored the enzyme activity along with the histology of the liver. Conclusion The results from the current study demonstrate that E. thymifolia and E. hirta have the property of restoring hepatic redox capacity and antioxidant activities against CCl4-induced acute liver damage.

Hepatoprotective activity of different leaves extracts of Convolvulus pluricaulis against CCl4 induced liver damage

Hepatoprotective activity of different leaves extracts of Convolvulus pluricaulis against CCl4 induced liver damage

Hepatocurative Properties of Eucalyptus camaldulensis Stem Bark Extract

The research investigates the hepatocurative potentials of Eucalyptus camaldulensis solvents extract on CCl4 induced liver damage using albino rats, partial characterization of the most active extract was done using GCMS techniques. Forty-two rats were placed into seven groups of six rats each. Group I and II were normal control and test control respectively. Groups III to VII were induced with liver damage using 120mg/kg of CCl4 and administered with standard drug, n-hexane extract (E1), chloroform extract (E2), ethyl acetate extract (E) and methanol extract (E4) respectively. 24 hours after CCl4 administration, a significant (p&lt;0.05) increase in mean serum level activities of AST, ALT, ALP with decrease in conjugated bilirubin and albumin concentration was recorded in test control group compared to normal control. This was reversed upon administration chloroform and methanol extract with former been most active. Antioxidant analysis reveals a significant (p&lt;0.05) decrease in level of liver tissue antioxidant enzymes (SOD, CAT and GPx) with concomitant increase in MDA of test control compared to normal control rats. After extracts administration, increase in the antioxidants enzymes (SOD, Catalase and GPx) levels was recorded in methanol and standard drug administered groups.

Igf2bp2 knockdown improves CCl4-induced liver fibrosis and TGF-β-activated mouse hepatic stellate cells by regulating Tgfbr1

Progressive liver fibrosis is a dynamic process characterized by the net accumulation of extracellular matrix (ECM), which could eventually develop into cirrhosis, leading to malignant transformation. In this study, insulin-like growth factor 2 mRNA binding protein 2 (Igf2bp2) was found to be up-regulated in carbon tetrachloride (CCl4)-induced liver fibrosis and transforming growth factor-beta 1 (TGF-β)-activated hepatic stellate cells (HSCs). Igf2bp2 knockdown in the CCl4-induced hepatic fibrosis mice model significantly improved CCl4-induced liver damage by decreasing necrosis and fibrotic septa, reducing hydroxyproline levels, and down-regulating fibrotic markers levels. In TGF-β-activated HSCs, Igf2bp2 knockdown partially attenuated TGF-β-induced cellular effects by suppressing HSCs viability and DNA synthesis and reducing the ECM-associated factors such as α-SMA, COLLAGEN I, and COLLAGEN III. Integrative network and signaling analysis revealed that the Igf2bp2 could bind to Tgfbr1. Transforming growth factor-beta receptor 1 (Tgfbr1) was found to be significantly up-regulated in the fibrotic liver and activated HSCs, and positively correlated with Igf2bp2. Tgfbr1 knockdown partially eliminated TGF-β-induced fibrotic changes and Igf2bp2 overexpression effects on TGF-β-activated HSCs in vitro. Moreover, Igf2bp2 overexpression promoted the phosphorylation of SMAD2/SMAD3, AKT, and PI3K, whereas Tgfbr1 knockdown exhibited the opposite effect; Tgfbr1 knockdown also partially attenuated the effects of Igf2bp2 overexpression on the phosphorylation of SMAD2/SMAD3, AKT, and PI3K. In closing, Igf2bp2 and Tgfbr1 are up-regulated in CCl4-induced liver fibrosis and TGF-β-activated mHSCs. Igf2bp2 knockdown improved CCl4-induced liver fibrosis and TGF-β-activated HSCs by targeting Tgfbr1, possibly through the PI3K/Akt pathway.

Protective effect of Alchornea cordifilia leaf extract on carbon tetrachloride-induced liver damage in Wistar rats

The effect of aqueous extract of the leaves of Alchornea cordifolia on Carbon tetrachloride (CCl4)-induced liver damage was investigated in experimental rats. Treatment of separate groups of rats with 100mg/kg, 150mg/kg and 200mg/kg aqueous leaf extracts of Alchornea cordifolia for 2 weeks after establishment of CCl4 induced liver damage, resulted in significantly (P&lt;0.05) less hepatotoxicity when compared to the CCl4-induced group, as measured by serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. The effect of extract was statistically significant (P&lt;0.05) and was dose dependent. Histopathological study also showed significant reduction and even reversal of liver damage in the rats. The results of this study show that aqueous leaf extract of Alchornea cordifolia has a potent anti-hepatotoxic action against CCl4 induced liver damage in rats.

Liposomal Drug Delivery of Blumea lacera Leaf Extract: In-Vivo Hepatoprotective Effects.

Background: Blumea lacera (B. lacera) is a herbaceous plant commonly found in south-east Asia. It shows significant therapeutic activities against various diseases. The objectives of this study were to evaluate hepatoprotective effects of Blumea lacera leaf extract and also to investigate the comparative effectiveness between a liposomal preparation and a suspension of B. lacera leaf extract against carbon tetrachloride (CCl4)-induced liver damage. Methods: B. lacera leaf extract was characterized using a GC-MS method. A liposomal preparation of B. lacera leaf extract was developed using an ethanol injection method and characterized using dynamic light scattering (DLS) and electronic microscopic systems. The hepatoprotective effects of B. lacera leaf extracts and its liposomal preparation were investigated using CCl4-induced liver damage in Long Evan rats. Results: GC-MS data showed the presence of different components (e.g., phytol) in the B. lacera leaf extract. DLS and microscopic data showed that a liposomal preparation of B. lacera leaf extracts was in the nano size range. In vivo study results showed that liposomal preparation and a suspension of B. lacera leaf extract normalized liver biochemical parameters, enzymes and oxidative stress markers which were elevated due to CCl4 administration. However, a liposomal formulation of B. lacera leaf extract showed significantly better hepatoprotective effects compared to a suspension of leaf extract. In addition, histopathological evaluation showed that B. lacera leaf extract and its liposomal preparation treatments decreased the extent of CCl4-induced liver inflammations. Conclusion: Results demonstrated that B. lacera leaf extract was effective against CCl4-induced liver injury possibly due to the presence of components such as phytol. A liposomal preparation exhibited significantly better activity compared to a B. lacera suspension, probably due to improved bioavailability and stability of the leaf extract.

Influence of hepatotropic and metabiotic correction on the spectrum of free fatty acids in experimental toxic liver damage

Background. Today most of the scientists are studying the processes of hepatocyte damage under the influence of free fatty acids (FFA) in vitro conditions. Therefore, in vivo studies of the spectrum of FFA in liver pathologies of different genesis, including toxic ones, are of considerable interest. Materials and methods. Toxic liver damage was simulated by subcutaneous injection of CCl4 solution in olive oil into rats. The following groups were formed: control (healthy; n=15); I— CCl4-induced liver damage without drug correction (n=6); III— CCl4-induced liver damage + metadoxin (Liveria IC; n=8); III— CCl4-induced liver damage + metabiotic (Hilac forte) (n=7). For morphological assessment of steatosis and fibrosis we used three-color qualitative staining of liver samples by Mallory-Slinchenko. Quantitative content of monounsaturated fatty acids (MUFA) in liver homogenate was determined by gas chromatography. Results. Evaluation of hepatobioptates in group I rats revealed tissue disorganization with macrovesicular steatosis in the cytoplasm of hepatocytes, the formation of interparticle multiple fibrous septa and inflammatory cell infiltration. The use of metadoxin (group II) and metabiotic (group III) improved the morphological picture of the liver, which was damaged by CCl4. Total MUFA content increased significantly in 118 (p&lt;0.001), 34 (p&lt;0.001) and 99 times (p&lt;0.001), respectively, for groups I–III animals relative to control, but in group II— tended to decrease in 3.5 (p=0.430) and 2.9 times (p=0.064), compared to groups I and III, respectively. Conclusions. It was found that correction with methadoxin and metabioticreduced the manifestations of protein-fatty dystrophy in hepatocytes. In all animal research groups, the content of PUFA increased mainly due to significant concentrations of cis-10-pentadecenoic, cis-10-heptadecenoic, trans- and cis-9-octadecenoic and cis-11-eicosenoic acids. MUFA content decreased more under the influence of methadoxin than metabiotic.

Effect of Aqueous Extract of Moringa oleifera Leaves on Some Serum Enzymes of Wistar Rats with Carbon Tetrachloride-Induced Liver Damage

Introduction: The study was aimed at evaluating the hepatoprotective effect of Moringa oleifera leaf extract against liver damage induced by carbon tetrachloride (CCl4).&#x0D; Methods: 25 Wistar rats were used. They were administered orally with CCl4 in a ratio of 1:1 at a dose of 1500mg/kg and allowed for five days before treated with Moringa oleifera leaf extract at concentrations of 50mg/kg, 100mg/kg, and 150mg/kg daily for one week. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and total protein (TP) in the blood cells were determined. The study lasted for 18 days. The liver enzyme, ALT, and TP were increased after injection with CCl4.&#x0D; Results: Treatment with Moringa oleifera leave at various dose reveals a significant reduction (p&lt;0.05). AST was increased after treatment with CCl4. Treatment with Moringa oleifera leaf reveals a dose-dependent significant reduction (p≤ 0.05). No significant reduction occurred for ALP in comparison to only CCl4 -treated group, but in comparison with the normal control.&#x0D; Conclusions: The result of this study showed that aqueous Moringa oleifera leaf extract may have hepatoprotective action against CCl4-induced liver damage in rats.

Hepatoprotective Activity of Methanolic Extract of Leaves Parts of Chenopodium Album Linn on Carbon Tetrachloride Induced Hepatotoxicity in Waster Rats.

The liver is among the most complex and important organ in the human body. Its primary function is to control the flow and safety of substances absorbed from the digestive system before distribution of these substances to the systemic circulatory system. Carbon tetra chloride is well- known hepatotoxin which is widely used to induce hepatotoxicity in laboratory animals. Chenopodium album Linn also known as frost Bilte, Pigweed (Canada), found to have antipruritic and antinociceptic, sperm immoblizing agent, cryptomeridiol and 8- alpha-acetoxycryryptomeridiol as growth promoting activity, (patak and pandey) Chenopodium album has reported hepatoprotective activity, antifungal, antihelminitic, contraceptive, antipyretic and antinoceipetive activity. The present study was aimed to investigate hepatoprotective activity of alcoholic extract of leaves parts of Chenopodium album Linn on carbon tetrachloride induced hepatotoxicity in waster rats. The leaves of plant was dried under shed and then powdered. The Powder was packed into a Soxhlet apparatus, extract was concentrated in steam bath till the complete evaporation of the solvent. Administration of Carbon tetra chloride subcutanously (SC) in the lower abdomen, in a suspension of liq. paraffin (LP, 1:1 v\v) at the dose of 1ml\kg B.W. on alternate days of week showed significant increase in SGOT and SGPT. Methanol extract of Chenopodium album Linn. at dose of 200mg\kg B.W. P.O. (Group III) in a carbon tetra chloride treated groups cause significant decrease in SGOT and SGPT. Result of biochemical parameters of Chenopodium album Linn. (400 mg\kg B.W. P. O.), showed significantly arrestedin in rise of level of SGOT, SGPT was found in group IV. The standard drug Liv2R showed significant reduction in all parameters when compared to CCl4 treated groups. This study concluded that methanolic extract of Chenopodium album Linn. has hepatotprotective effect in CCl4 induced liver damage. This effect is evident especially with high dose of Chenopodium album Linn. (400 mg\kg B.W. p.o) because it caused drastic fall in serum markers as compared to other doses of Doses of Chenopodium Album Linn.&#x0D; Abbreviations- serum glutamate oxaloacetatae transaminase (SGOT) and serum Glutamate Pyruvate Transaminase (SGPT)&#x0D; Keywords- Chenopodium album Linn., methanolic extract, carbon tetrachloride (CCl4), hepatotoxicity

Therapeutic potential of mouse bone marrow mesenchymal stromal cells transplantation in ameliorating of CCL4-induced liver damage (in vivo study)

Терапевтический потенциал трансплантации мышам мезенхимных клеток костного мозга для ослабления повреждения печени, вызванного CCL4 (исследование in vivo)Therapeutic potential of mouse bone marrow mesenchymal stromal cells transplantation in ameliorating of CCL4-induced liver damage (in vivo study)

Evaluation of Hepatoprotective Activity of Whole Fruit Extracts of Luffa Acutangula. Var. Amara and Rhizome Extracts of Rheum Emodi in CCl4 - Induced Chronic Hepatotoxicity

To investigate the hepatoprotective activity of whole fruit extracts of Luffa acutangula.var. amara and rhizome extracts of Rheum emodi in CCl4 treated rats. The dried powders of L. amara and R. emodi were extracted successively with petroleum ether, ethanol and distilled water. The hepatoprotective capacity of the extract of the whole fruits of L. amara and the rhizomes of R. emodi was analyzed in liver injured CCl4- treated male rats. The present study explored the possibilities of using low doses of both plant extracts (150mg/kg, and 300mg/kg bw, po route) to treat CCL4 intoxicated albino rats in both acute and chronic models of hepatic damage, evident by increased serum levels of glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), direct bilirubin, total bilirubin, cholesterol and triglycerides, all being implicated in considerable hepatic damage.&#x0D; Histopathological examination in CCl4 treated rats revealed collapse of liver parenchyma with early fibrosis and chronic inflammatory cell infiltration in patchy areas around central vein (Pic.group-2) when compared to the control group. Histopathological and physical examinations also indicated their effectiveness with their dose tolerability and liver protection.&#x0D; Ethanolic and aqueous extracts of the whole fruits of L. amara and rhizomes of R. emodi were indicative of more hepatoprotective properties when compared to the petroleum ether extracts of both plants against CCl4 induced liver damage as confirmed from hepatic serum marker enzyme activities and histopathological studies.

Synergistic hepatoprotective effects of ω-3 and ω-6 fatty acids from Indian flax and sesame seed oils against CCl4-induced oxidative stress-mediated liver damage in rats

Flaxseed (FS) and sesame seed (SS) are traditional and functional foods in traditional Indian medicine for treating various disorders. The present study investigated the hepatoprotective effects of bioactive-fatty acids (FAs) from FS and SS against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Pre and post-treatments for 28 consecutive days significantly increased the activities of in vivo antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and peroxidase (POX), whereas, lipid peroxidation (LPO) activity was markedly decreased in a dose-dependent manner in liver and kidneys. A significant reduction was observed in the hematological parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin in the serum of post-treated animals compared to the negative control. The results were confirmed histopathologically. The results suggested that the ω-3 and ω-6 FAs from flaxseed oil (FSO) and sesame seed oil (SSO), respectively, showed potential synergistic hepatoprotective and antioxidant effects that were mediated mainly by ω-3 and ω-6 FAs present in the respective seed oils.

Thymus fontanesii attenuates CCl4-induced oxidative stress and inflammation in mild liver fibrosis

Liver injury is a major public health problem all over the world that raises the demand of developing novel effective and safe remedies. Traditionally, Thyme (Thymus fontanesii) has a therapeutic potential against different organs toxicity due to its antioxidant activity. The present study aimed to evaluate the antioxidant activities in vitro and the possible hepato-protective effects of T. fontanesii aqueous extract (TFAE) against CCl4 induced liver damage (mild fibrosis) in male albino mice and annotate its phytochemical constituents as well. The extract displayed substantial antioxidant activities in vitro and high content of flavonoids and other phenolic compounds. Oral administration of TFAE (especially high dose) significantly suppressed (but with different degrees) the incidence and severity of CCl4 liver toxicity by activating the hepatic antioxidant defense mechanisms, modulating hepatic functions, and decreasing the production of lipid peroxidation, pro-inflammatory mediators, and pro-fibrotic proteins expression including COL1A1, Fn, and TGF-β1. These activities might be attributed to the presence of 58 secondary metabolites (identified by LC-MS), mainly phenolic acids, flavonoids and diterpenoids that were able, according to molecular docking, to bind to the inhibitor’s binding site of three protein targets involved in liver inflammation and fibrosis. These results showcase the antioxidant and anti-inflammatory properties of Thyme (Thymus fontanesii), illustrate the protective and beneficial effects of the plant against CCl4-induced hepatic toxicity in mice, and support its consumption, traditional uses and promotes its valorization as nutraceutical product.

Ginger (Zingiber officinale Roscoe), Lemon (Citrus limon L.) Juices as Preventive Agents from Chronic Liver Damage Induced by CCl4: A Biochemical and Histological Study.

Zingiber officinale Roscoe and Citrus limon L. are well known for their multi-use and for their pharmacological effect in the treatment of many illnesses. This study aims to investigate the chemical composition of the ginger and lemon juice extracts and in addition, to evaluate their antioxidant properties and their hepatoprotective effect against the liver damage of Wistar rats induced by the injection of CCl4 to treated animals. The obtained effects were completed by a histological study for better confirmation of the registered pharmacological effects. The ginger juice extract was found to be rich in 4-gingerol, 6-gingediol, and 6-gingerol, while the lemon juice extract chemical composition was highlighted by the presence of eriodyctiol, rutin, hesperidin, and isorhamnetin. Concerning the antioxidant activity, the ginger, lemon juice extracts, and their formulation showed an important antioxidant potential using TAC (total antioxidant capacity), an antiradical activity against the radical DPPH• (2,2-diphenyl-1-picrylhydrazil), and a ferric reducing power. Finally, the ginger, lemon, and their formulation at different doses were able to prevent CCl4 induced liver damage. Indeed, these different bioactive compounds could be used as alternative agents for the treatment of chronic liver diseases.

Methanol Stem Bark Extract of Ficus platyphylla Protects Against Carbon Tetrachloride-Induced Liver Damage in Wistar Rats

Ficus platyphylla (Gutta percha tree) is used in Nigerian traditional medicine for treating pain and psychosis. This study evaluated the protective effect of methanol stem bark extract of Ficus platyhylla (MEFP) against carbon tetrachloride (CCl4)-induced liver injury in Wistar rats. Rats were allotted into six groups namely normal control, negative control, standard drug (silymarin) and extract treated (100, 200 and 400 mg/kg p.o. respectively) groups. Treatment was administered for 7 days. Animals in groups II-VI received a single dose of CCl4 (1:1) p.o. in olive oil at 1.5 ml/kg body weight after last treatment. Experimental rats were sacrificed after 24 hours of CCl4 administration and blood samples collected for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Supernatant of liver homogenate was used to determine activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Results indicate increased activities (p &lt; 0.05) in CAT, SOD and GPx in samples of MEFP treated rats while levels of ALT and AST in serum samples of treated groups differ significantly (p&lt;0.05) when compared with negative control group (Group III). Treatment with methanol stem bark extract of Ficus platyphylla may have offered protection against CCl4 induced liver damage in experimental rats.