CCl4-induced Liver Injury In Rats Research Articles

Augmented reparative potential of adipose-derived stem cells with silver nanoparticles against CCl4-induced liver injury in rats

Cymbopogon citratus (lemongrass) is a widely used medicinal plant. The previous literature studies demonstrated its diverse pharmacological activities such as anti-inflammatory, anti-diabetic, antibacterial and antifungal properties. The present study involves the green synthesis of silver nanoparticles from lemongrass and their characterization by X-ray diffraction (XRD), scanning electron microscope (SEM) and Fourier transmission infrared (FTIR). The purpose of this study is to evaluate the hepatoprotective potential of silver nanoparticles derived from the aqueous extract of lemongrass (LG-NPs) in comparison with the rat adipose-derived mesenchymal stem cells (ASCs) treated with lemongrass-derived silver nanoparticles (LG-NPs + ASCs). To assess the hepatoprotective effect of LG-NPs + ASCs, CCl4-induced fibrosis model rats were employed and it was revealed that transplanting LG-NPs + ASCs decreased fibrosis development compared to transplanting naive ASCs and LG-NPs, as demonstrated by improved hepatic architecture and functions. Additionally, the liver parenchyma's expression of fibrosis-associated gene markers Interleukin 1 beta (IL-1β), Cytochrome P450 2E1 (CYP2E1), Transforming Growth Factor Beta 1 (TGF-β1), collagen type I alpha 1(Col1α1), α-smooth muscle actin (α-SMA) reduced after LG-NPs + ASCs transplantation. These results suggest that pretreating ASCs with LG-NPs increase their effectiveness.

Oleuropein, a phenolic component of Olea europaea L. ameliorates CCl4-induced liver injury in rats through the regulation of oxidative stress and inflammation.

This study aimed to assess the hepatoprotective role of oleuropein (Olp), a phenolic compound found in olive, against carbon tetrachloride (CCl4)-induced liver damage in rats. The research involved male albino rats, which received intraperitoneal injections of 100 mg/kg b.w. of oleuropein for 8 consecutive weeks before being subjected to carbon tetrachloride (CCl4) at a dosage of 1.0 ml/kg b.w. Changes induced by CCl4 in antioxidant and inflammatory marker levels were assessed using ELISA assay kits. Moreover, CCl4-induced liver tissue architecture alteration, fibrosis, and expression pattern of protein were evaluated by performing H&E, Sirius red, Masson trichrome, and immunohistochemistry staining. Increased serum transaminases and massive hepatic damage were observed by this liver toxicant. The hepatic injury was further evidenced by a significant decrease in antioxidant enzyme activity [superoxide dismutase (SOD), glutathione peroxidase (GPx), Glutathione (GSH) and Total Antioxidant Capacity (T-AOC)]. The administration of CCl4 resulted in an increased inflammatory response, which was measured by C-reactive protein, interleukin-6, as well as tumor necrosis factor-alpha. Olp as a curative regimen led to significant attenuation in the inflammatory response and oxidative/nitrosative stress. This polyphenol treatment improved the hepatic tissue architecture and decreased fibrosis. In the CCl4 treatment group, the expression pattern of IL-6 protein was high, whereas expression was decreased after Olp, as evidenced by immunohistochemistry staining. The study suggests that oleuropein treatment has the potential to reduce liver damage caused by CCl4 induction by inhibiting oxidative stress and inflammation and maintaining liver tissue architecture. This could make it a promising treatment option for liver pathogenesis.

Evaluation of hepatoprotective effect of Trametes gibbosa on CCl4-induced liver injury in rats

Evaluation of hepatoprotective effect of Trametes gibbosa on CCl4-induced liver injury in rats

Hepatoprotective study of Indonesian water kefir against CCl4-induced liver injury in rats

Context: Water kefir is a fermented beverage that is typically made in the home by inoculating a sugar-rich solution with a microbial community (water kefir grains). Several studies on the metabolite content and hepatoprotective effects of water kefir have been published, but carbon tetrachloride (CCl4)-induced acute liver injury has not been studied. Aims: To evaluate the efficacy of water kefir in vivo against hepatoprotective CCl4-induced acute liver injury and to in silico investigate metabolites that play an important role in hepatoprotective mechanisms. Methods: The present study aimed to investigate the hepatoprotective activity of water kefir in an animal model caused by CCl4. Furthermore, using molecular docking, the metabolites found in water kefir were evaluated for their role in the NF-κB and Nrf2 signaling pathways. Results: Water kefir significantly and dose-dependently alleviated acute liver injury caused by CCl4. Water kefir administration at all doses produced results comparable to the positive control (Curcuma extract). Molecular docking simulations showed that, compared to Nrf2, the 25 metabolites were more likely to interact with the NF-B receptor. Fumaric acid is the strong metabolite that interacts with the NF-κB receptor with a free energy of binding and an inhibition constant of -6.66 kcal/mol and 13.22 µM, respectively. Conclusions: Water kefir administration improved the condition of liver damage, characterized by a decrease in serum levels of AST, ALT, TNF-, TGF-, and an improvement in the liver tissue profile. In silico evaluation showed that the metabolites in water kefir were able to interact with target proteins in the NF-B and Nrf2 pathways. It was concluded that water kefir improves the condition of the liver by reducing the level of necrosis and fibrosis.

A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury

Ethnopharmacological relevanceShicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. Aim of studyTo explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. MethodsA rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. ResultsCompared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. ConclusionThis study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.

The Protective Rolls of Taraxacum officinale against Carbone Tetrachloride Infarction in the Liver

Carbon tetrachloride (CCl4) is a liquid that is colorless, transparent, inflammable, and volatile. Its central carbon atom is surrounded by four Cl- atoms. As a result, the objective of this effort was to estimate the anti-oxidant properties of silver nanoparticles (AgNPs) made utilizing aqueous plant extracts from Taraxacum officinale leaves. A green synthesis of AgNPs using a synergistic aqueous extract from T. officinale leaves was tested against liver damage in rats caused by CCl4. The rats were randomly distributed into seven groups: Group 1: Control group, Group 2: Olive oil group, Group 3: AgNPs-treated group (100 mg/kg BW.), Group 4: AgNPs-treated group (200 mg/kg BW.), Group 5: CCl4 + Olive oil group, Group 6: (CCl4 + Olive Oil) + 100 mg/kg of AgNPs-treated group, and Group 7: (CCl4 + Olive oil) + 200 mg/kg of AgNPs-treated group one a week for 6 weeks. This study demonstrated a sustainable method for synthesizing AgNPs utilizing T. officinale leaf (TOL) extract. To characterize the synthesized T. officinale leaf-silver nanoparticles (TOL-AgNPs), various microscopic and spectroscopic methods were used. The effectiveness of the biosynthesized TOL-AgNPs against CCl4 was tested to assess their antioxidant potential. The antioxidant properties of synthetic TOL-AgNPs were also evaluated. Histopathological research showed that all groups treated with nano-extract had less severe inflammatory responses. Our findings demonstrated that AgNPs synthesized using the leaves of T. officinale possess a potential anti-oxidant activity against CCl4-induced liver injury in rats.

Amelioration of CCL4-induced liver injury in rats by antioxidant Citrus extract

Amelioration of CCL4-induced liver injury in rats by antioxidant Citrus extract

Effect of Gypenosides on the composition of gut microbiota and metabolic activity in the treatment of CCl4-induced liver injury in rats

• To explore the mechanism of GPs in the treatment of liver injury from a microbiome-metabolomics perspective. • 13 differential genera were found to be associated with the development of liver injury and the treatment with GPs. • The biomarkers were mainly involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. Long-term chronic liver damage can lead to serious consequences of cirrhosis or liver failure, so it is crucial to find effective therapeutic drugs. Gypenosides (GPs) has been proved to have therapeutic effects on various liver diseases. To provide an overall description of GPs for the treatment of liver injury, we conducted a combined study of gut microbiota and host metabolism based on metabolomic analysis and 16S rRNA high-throughput sequencing. The results showed that GPs treatment significantly improved the disorder of liver function index, inflammatory index, intestinal barrier index and oxidative damage index induced by liver injury. H&E staining showed that GPs treatment could significantly alleviate liver injury in rats. Metabolomics analysis identified 25, 27 and 31 endogenous metabolites in feces, plasma and urine, respectively. Gut microbiota analysis revealed increased diversity in the model group and significant differences between groups. Metastats analysis identified 13 differential genera. Spearman’s correlation analysis was found that the increase of liver injury-related pathological indices or metabolite showed positive correlation with the genera with increased relative abundance, while the genera with decreased relative abundance showed negative correlation with them. The above results suggest that GPs modulates gut microbiota dysbiosis-metabolic activity disorder to achieve the treatment of liver injury.

Antioxidant and hepatoprotective potentials of olive (Olea europaea L. var. Sigoise) leaves against carbon tetrachloride-induced hepatic damage in rats, and investigation of its constituents by high-performance liquid chromatography-mass spectrometry

The present work explored the preventive potential of ethanolic extract of Olea europaea L. (EEOE) leaves against CCl4-induced liver injury in rats. The fingerprint chromatogram of EEOE was determined by HPLC-MS analysis. The antioxidative potential of EEOE was determined by adopting three approved in vitro methods. The EEOE was orally given at a dose of 400 mg/kg, once a day, for 15 days continuously, succeeded by intraperitoneal (i.p.) injection of CCl4 (0.2%). The hepatoprotective potential was evaluated by estimating biochemical parameters including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total cholesterol, and triglycerides in the bloodstream. In vivo, the antioxidant ability against CCl4-induced liver injury in rats was assessed by estimating the levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total reduced glutathione, and lipid peroxidation in the liver tissues. Further, histological analyses were performed to evaluate the degree of hepatic damage. Nine compounds were identified in the EEOE, principally oleuropein, luteolin-7-O-glucoside, and apigenin. The EEOE exhibited strong radical scavenging activity in DPPH assay. The EEOE significantly decreased the augmentation of serum cholesterol, TG, ALT, AST, ALP, and total bilirubin contents. It also restored hepatic SOD, CAT, GSH-Px activities, and glutathione (GSH) amount, and lowered lipid peroxidation amount comparable to the standard silymarin. The biochemical data were complemented with histological conclusions. These findings are indicative of the protective potential of the EEOE against CCl4-induced hepatotoxicity, which is possibly related to the potent antioxidative capacity of its phenolic compounds.

Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats.

The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl4) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl4 (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl4-induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl4 was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl4-induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.

Cajanus cajan ameliorated CCl4-induced oxidative stress in Wistar rats via the combined mechanisms of anti-inflammation and mitochondrial-membrane transition pore inhibition

Ethnopharmacological relevanceLiver diseases is a public health issue in sub-saharan Africa and has been reported to be the major cause of many hospital admissions. Oxidative stress, mitochondrial dysfunction and inflammation play important roles in several diseases including liver injury. Cajanus cajan is an indigenous medicinal plant useful in the traditional treatment of jaundice, inflammation and liver injury. Aim of studyThis study assessed the effects of methanol extract Cajanus cajan (MECC) on mitochondrial permeability transition (mPT) pore opening, biomarkers of oxidative stress and inflammation in CCl4-induced liver injury in rats. MethodsWistar albino rats (200–210g) were completely randomized into five (5) groups of six animals each. Group I (control) was given distilled water orally once daily. Animals in group II were administered CCl4 in parafin (1:1) at a dose of 0.5 mL/kg i.p on the seventh day. Animals in groups III, IV and V were administered methanol extract of Cajanus cajan (MECC) at doses of 100, 200 mg/kg and silymarin (100 mg/kg) respectively for 7 days prior to a single intraperitoneal dose of CCl4. After 24 h of CCl4 treatment, serum and liver tissues were collected. Mitochondrial permeability transition (mPT) pore opening, mitochondrial ATPase activities and biomarkers of oxidative stress were determined spectrophotometrically. Tumor necrosis factor (TNFα), NF-κB and COX-2 were determined by immunohistochemistry and the phytochemicals present in the extract were determined by GC-MS. ResultsLiver enzyme (AST, ALP, ALT and γGT) activities and MDA levels were significantly decreased in rats pretreated with MECC at the dose of 100, 200 and silymarin (100 mg/kg) when compared to the rats administered CCl4 alone (p < 0.05). GSH, GST, CAT and SOD increased and the expressions of TNFα, NF-κB and COX- 2 were also reduced when compared to the CCl4- treated animals.In addition, the liver histopathological analyses revealed that MECC markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. GC-MS analysis yielded 23 compounds including flavonoids, terpenoids and fatty acids. ConclusionCajanus cajan leaf extract elicited hepatoprotective action on CCl4-induced liver injury via inhibition of mPT pore opening, prevention of CCl4-induced hepatic oxidative stress and suppression of inflammatory response thus it may become useful for chemoprevention of liver injury. This supports its traditional use.

Hepatoprotective and Curative Activities of Daphne Gnidium L. Aqueous Extract Against CCl4-Induced Liver Injury in Rats

Background: The liver is one of the largest organs of the human body and the main site for intense metabolism and excretion. Liver injury or dysfunction is recognized as a serious worldwide health problem. Daphne gnidium L., a medicinal plant widely distributed in Algeria and used by populations in traditional medicine to treat hepatitis and other diseases. Objective: Protective and curative effects of aqueous extract of Daphne gnidium L. leaves were investigated against Carbon Tetrachloride (CCl4) induced hepatic damage in rats (Wistar Albino). Method: This study was conducted on 32 Albino rats, which were divided into four groups; the first served as control. Group II animals were treated intraperitoneally with CCl4solution (3ml/ kg). Group III animals were treated intraperitoneally with CCl4solutions (3ml/kg) on the first day, and given aqueous Daphne extract orally at a dose level of (300 mg/kg) daily for 7 days (curative activity test). Animals of group IV were orally administered aqueous Daphne extract at a dose level of (300 mg/kg) daily, and on the seventh day treated intraperitoneally with CCl4solution (3ml/ kg) 3 hours after the latest extract administration (preventive activity test). Results: Our results show that CCl4significantly increases the relative liver weight, serum values of ALT, AST, ALP, GGT, and Total bilirubin, as well as the hepatic rate of oxidative stress parameters; MDA and CAT activities, and significantly decreases hepatic GSH levels compared to the control group. These results were confirmed by liver lesions observed in histological analyses. Pretreatment and curative treatment of dose 300 mg/kg of aqueous Daphne gnidium L. extract significantly reduced relative weight, serum levels of ALT, AST, ALP, GGT and Total bilirubin liver rate, CAT activity, and increases GSH level. In addition, normal liver architecture has been restored. Conclusion: The present study demonstrates the hepatoprotective and curative effects of aqueous extract Daphne gnidium leaves against CCl4-induced liver injury in rats by improving the antioxidant status in tissues (liver) and ameliorating the harmful effects induced by CCl4

Govaniadine Ameliorates Oxidative Stress, Inflammation, and Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

Liver diseases such as hepatic carcinoma are one of the main health problems worldwide. Herbal drugs are largely used to treat liver injury in the indigenous system of medicine and may provide lead compounds for hepatoprotective drug discovery. The present study is investigated to test the Corydalis govaniana Wall. extract, fraction, and isolate therapeutically active constituents to explore their hepatoprotective, anti-inflammatory, and antioxidant activities. For this purpose, the antioxidant activity of govaniadine, caseadine, caseamine, and protopine was performed by assessing the scavenging events of the stable 2,2-diphenyl-1-picrylhydrazyl. Hepatoprotection of govaniadine was assessed in terms of reduction in serum enzymes (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) caused by CCl4-induced liver injury in rats and by histopathological techniques. All the compounds showed significant antioxidant activity with a percentage inhibition of 92.2, 86.7, 85.3, and 79.7, respectively, compared to propyl gallate 90.3%. Treatment with govaniadine reduced the serum enzyme level down to normal levels in the CCl4-treated group while inhibiting the increase of malondialdehyde, and the induction of superoxide dismutase and the glutathione level was upregulated. Histopathology showed ∼47% damage to the liver cells in the CCl4-treated group; reduction in this damaged area was found to be better upon using govaniadine. Immunohistochemistry results showed that govaniadine as compared to silymarin has exceedingly decreased the inflammation by halting the CCl4-induced activation of hepatic macrophages. In carrageenan-induced paw edema assay, govaniadine significantly alleviated the edema after 1–5 h at a dose of 20 mg/kg (26.00 and 28.5%), 50 mg/kg (22.05 and 27.0%), and 100 mg/kg (20.02 and 25.30%), respectively. The results of our experiments suggest that govaniadine showed antioxidant and hepatoprotective activity in liver injury. The hepatoprotective function of govaniadine may be associated to the scavenging of the free radical and attenuation of oxidative stress as well as inflammatory responses in the liver. Hence, govaniadine may be a lead compound for the hepatoprotective drug discovery process and further research is needed to find out their molecular mechanism of protection.

Hepatoprotective effect of different combinations of 18α-and 18β-Glycyrrhizic acid against CCl4-induced liver injury in rats

The purpose of the current study was to evaluate the optimal compatibility proportion of 18α-Glycyrrhizic acid (18α-GA) and 18β-Glycyrrhizic acid (18β-GA) against carbon tetrachloride (CCl4)-induced hepatic damage in rats, and further explored the underlying mechanism. Rats were injected with CCl4 (0.1%, 0.3 ml/kg) once a week and were orally administrated with different proportions of 18α-, and 18β-GA daily for 4 weeks. Rats were then sacrificed and blood samples were collected for biochemical assay. Liver tissues were assessed histologically for severity of liver injury. Enzyme activities in liver homogenate were determined using commercial kits. The mRNA levels of associated proteins were evaluated by RT-PCR. The data showed that the combination of 18α-, and 18β-GA, especially at proportion of 4:6, obviously alleviated CCl4-induced liver injury as evidenced by the improvement of liver histopathological changes, and decreased levels of ALT and AST in serum. Moreover, 18α- and 18β-GA at all proportions substantially improved glucose tolerance, and markedly reversed the decrease of SOD, MDA, and GSH, and increase of lipid markers (TG, TC, HDL, LDL) induced by CCl4 via regulating the mRNA levels of SREBP-1c, ACC, PPAR-α, and CPT-1a. Collectively, these results suggested that 18α-GA in combination with 18β-GA, especially at proportion of 4:6, effectively reduced liver injury induced by CCl4, comparable to the positive control silibinin, and the mechanism may be associated with reduced marker of liver oxidative stress and improvement of lipid metabolism via regulation of ACC, CTP-1A, PPARα, and SREBP1.

Berberine ameliorates CCl4‑induced liver injury in rats through regulation of the Nrf2‑Keap1‑ARE and p53 signaling pathways.

Berberine (BBR) is an isoquinoline alkaloid, reported to have multiple pharmacological functions. However, its effects against CCl4-induced oxidative damage remain poorly studied. Therefore, the present study investigated the protective action of BBR, and its antioxidant mechanisms, against CCl4-induced liver injury in rats. A total of 48 rats were randomly arranged into six groups: Control; model; positive control (PC); BBR low-dose (BL); BBR middle-dose (BM); and BBR high-dose (BH). The BL, BM and BH animals received BBR (5, 10 and 15 mg/kg by weight, respectively) orally for 7 consecutive days. Rats in the PC group were given silymarin (150 mg/kg), and the control and model groups were administered distilled water orally. At the end of the experiment, blood samples and livers were collected. To measure the liver biochemical indices, the reactive oxygen species (ROS) generation and the expression levels of related genes and protein, the following methods were used: An automatic biochemical analyzer; flow cytometry; spectrophotometry; reverse transcription-quantitative PCR; western blotting; and hematoxylin and eosin staining. The results revealed that BBR significantly decreased the serum levels of alanine transaminase, aspartate transaminase and alkaline phosphatase, and increased those of glutathione and superoxide dismutase, but decreased malondialdehyde activity in hepatic tissue, and significantly decreased the reactive oxygen species level in hepatocytes. In hepatic tissue, the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (Keap-1), NAD(P)H quinone dehydrogenase 1 (NQO-1), heme oxygenase 1 (HO-1), Bcl-2 and Bcl-xL mRNA, and HO-1 protein were elevated, and the expression of p53 mRNA was decreased, particularly in the BH group (15 mg/kg). In conclusion, BBR exerts a protective action against CCl4-induced acute liver injury in rats via effectively regulating the expression of Nrf2-Keap1-antioxidant responsive element-related genes and proteins, and inhibiting p53 pathway-mediated hepatocyte apoptosis.

Hepatoprotective activity of ethanolic and aqueous extract of Turnera aphrodisiaca leaves against CCl4-induced liver injury in rats

Background: The botanical Latin name of the plant, Turnera aphrodisiaca, describes its ancient use as an aphrodisiac.Methods: The aim of the present study is to evaluate the protective effect of ethanolic and aqueous extract of Turnera aphrodisiaca leaves against carbon tetrachloride (CCl4)-induced liver damage in male Wistar rats.Results: Administration with ethanolic and aqueous extract of Turnera aphrodisiaca leaves (200 and 400 mg/kg) for 7 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in a dose dependent matter. In addition, treatment of both the extracts resulted in markedly increased the levels of superoxide dismutase and catalase enzymes in rats. The histopathological studies in the liver of rats also supported that both extracts markedly reduced the toxicity of CCL4 and preserved the histoarchitecture of the liver tissue to near normal.Conclusion: Thus, the results suggest that ethanolic and aqueous extract of Turnera aphrodisiaca leaves acts as a potent hepatoprotective agent against CCl4 induced hepatotoxicity in rats.

Combination of cut-log cultivated fruiting body and solid-state cultured mycelia of Taiwanofungus camphoratus ameliorates CCl4-induced liver injury in rats

Taiwanofungus camphoratus, a medicinal mushroom indigenous to Taiwan, possesses various pharmacological functions. The most recognized ethnopharmacological relevance of T. camphoratus is hepatoprotection since it was traditionally used for treating liver disorders by Taiwan aborigines. The aim of this study is to evaluate the hepatoprotective effect of the combination of fruiting body and solid-state cultured mycelia of T. camphoratus (LDAC) on carbon tetrachloride (CCl4)-induced chronic liver damage in rats. We treated Wistar rats daily with low, medium and high [87.5, 175 and 437.5 mg/kg body weight (bw), respectively] doses of LDAC for 9 weeks. After the first week of treatment, rats were administered 20% CCl4 (0.5 mL/0.3 kg bw) twice a week to induce liver damage until the treatment ended. The results showed that administration of LDAC by oral gavage significantly reduced the absolute weight of the liver and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in CCl4-treated rats. The activities of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GRd) and catalase (CAT) were increased by LDAC treatment. Moreover, LDAC improved CCl4-induced hepatic vacuolization, necrosis and fibrosis in a dose-dependent manner, and no adverse effects were observed in the LDAC-treated groups. Based on the results, LDAC is a promising hepatoprotective agent for preventing and ameliorating CCl4-induced chronic liver injury, and this effect might be exerted through activation of the antioxidant defense system.

A New Polyoxygenated Flavonol Gossypetin-3-O-β-d-Robinobioside from Caesalpinia gilliesii (Hook.) D. Dietr. and In Vivo Hepatoprotective, Anti-Inflammatory, and Anti-Ulcer Activities of the Leaf Methanol Extract.

A hitherto unknown polyoxygenated flavonol robinobioside (gossypetin-3-O-β-d-robinobioside) was isolated from the leaves of Caesalpinia gilliesii along with thirteen known phenolic secondary metabolites. The isolated compounds were characterized using spectroscopic analysis, including 1D and 2D NMR and mass spectrometry (MS) analyses. The extract reduced the level of liver damage in CCl4-induced liver injury in rats. A decrease of the liver biomarkers—aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and an increase of total antioxidant capacity (TAC) levels—were observed similar to the liver protecting drug silymarin. In addition, the extract showed promising activity against carrageenan-induced paw edema in rats and protected their stomachs against ethanol-induced gastric ulcers in a concentration dependent fashion. The observed activities could be attributed to the high content of antioxidant polyphenols. Our results suggest that the C. gilliesii has the capacity to scavenge free radicals and can protect against oxidative stress, and liver and stomach injury.

Effect of Apricot kernel on Some Hematological,Histological and Biochemical Parameters in CCl4-induced Liver Injury in rats

The purpose of the present study was to find out the effect of apricot kernel on carbon tetrachloride (CCl4) induced liver injury in male albino rats. To achieve this purpose and to explain, the histological, hematological and biochemical parameters were included. Thirty male albino rats were used and randomly divided to in to three groups. The first group represented control group which received normal diet and intraperitoneal injection with oil (0.5 ml/kg). The second group injected with CCl4(1 ml/kg), represented the CCl4(1 ml/kg)model,the third groupwere treated like the second group with 15%/ day apricot kernelfor a month . The apricot kernel extracts treated group showed significant differences in AST, ALT, ALP, direct bilirubin, , GSH, liver SOD, WBC, LYM and PLT when compared to CCl4 treated rats. In the current study histological section through the liver of control rats showed normal architecture of hepatocytes.Although Paraffin section of the rat liver treated with CCl4 most of the hepatocytes were degenerated, congestion of blood and inflammatory leukocyte infiltration were observed,the results showed that CCl4 injection caused significant alterations in histological and biochemical parameters but our study showed that the apricot kernel administration showed improvement of histological analysis for four weeks (March to April 2015).

Effect of bone marrow mesenchymal stem cell transplantation on CCl₄-induced liver injury in rats and intervention effects of Yiguanjian

The aim of this paper was to observe the function of bone marrow mesenchymal stem cell (BMSC) transplantation in process of liver injury induced by carbon tetrachloride (CCl₄) in vivo and the intervention effect of Yiguanjian (YGJ), a compound of Chinese herbal medicine. Wistar rats were randomly divided into five groups: normal group, model group, cell transplantation (CT) group, YGJ group and cell transplantation plus Yiguanjian (CTY) group. Liver injury was induced through subcutaneous injection with CCl₄ at a dose of 3 mL·kg⁻¹ body weight for 4 weeks, twice a week. They were injected for a total of 9 times. After the first injection with CCl₄, rats in the CT group and CTY group were injected with the third-generation BMSCs at dose 1×10⁶ (suspended in 1 mL saline solution) via tail vein. Rats in the YGJ and CTY groups were also intragastrically administered with Yiguanjian once a day. Rat serum ALT and AST activities were increased significantly on the second day after injection with CCl₄, while BMSC transplantation and Yiguanjian decreased their activities. After 4 weeks of injection with CCl₄, serum ALT, AST and γ-GT activities, and serum TNF-α and IL-6 expressions were increased, while TBIL were decreased in model rats compared with normal rats. Meanwhile, liver cells edema, plasmatic loose, and numerous lipid droplets were observed in rats of the model group. BMSC transplantation aggravated liver injury compared with model rats, which was manifested by decreasing SOD activity, increased MDA, TG, TNF-α and IL-6 levels, and aggravated necrosis level of hepatocytes, fusion of lipid droplets, and collagen deposition in liver tissue. Yiguanjian decreased liver injury induced by CCl₄ alone and CCl₄ plus BMSC transplantation. SRY gene in situ hybridization method was used to detect the positive SRY expressions in heart, liver, spleen, lung and kidney, especially in liver, while Yiguangjian decreased liver SRY expression. Wnt and β-catenin showed high expressions in rats of normal group, which were decreased significantly in rats of models group, while Yiguanjian increased their expressions. In conclusion, BMSC transplantation could exacerbate liver injury, while Yiguanjian could protect liver injury induced by CCl₄ and BMSC transplantation, which was related to decreasing the homing of BMSCs to liver and up-regulating Wnt/β-catenin signaling pathway.