Antioxidant and hepatoprotective effects of Ginkgo biloba phytosomes in carbon tetrachloride‐induced liver injury in rodents (original) (raw)

CCl4 INDUCED LIVER INJURY; AQUEOUS EXTRACT OF GINKGO BILOBA (GKBE) AMELIORATES CYTOPLASMIC AND MITOCHONDRIAL ENZYMES

THE PROFESSIONAL MEDICAL JOURNAL, 2017

ORIGINAL PROF-3762 ABSTRACT… Objectives: Evaluate the mitigating effect of aqueous extract of Ginkgo biloba (GkbE) on liver enzymes and histology in carbon tetrachloride (CCl 4) induced liver injury in albino rat. Study design: Experimental study. Setting and Duration: Animal house, Bhitai Dental and Medical College Mirpurkhas and Agriculture University Tando Jam from Animal house from May 2015-August 2016. Subjects and Methods: Sixty rats were equally divided into 3 groups Group 1-Controls (0.9% isotonic saline), Group 2-(CCl 4 CCl 4 1.0mg/ kg intraperitoneal) and Group 3-(CCl 4 + GkbE). Blood samples were collected at end of experiment from tail veins. Liver was obtained after rat sacrifice by cervical dislocation. Tissue was fixed in formaldehyde and embedded in paraffin. Microscopy of 3μ tissue sections was performed after H & E staining. Statistix 10.0 (USA) software was used for data analysis at 95% confidence interval. Results: Four weeks GkbE administration in CCl 4 rat showed significant amelioration of liver enzymes and improved liver histology (p=0.0001). In GkbE treated rats, the histological changes of degeneration, fatty change, inflammatory cell infiltration, sinusoid congestion and necrosis was minimal (p=0.0001). GkbE was proved of mitigating the hepatocellular injury inflicted by carbon tetrachloride. Conclusion: GkbE mitigates the carbon tetrachloride induced liver injury in rat model. GkbE may be used in drug and chemical induced liver injury.

Comparative analysis of the antihepatotoxic effects of Ginkgo biloba leaf extract and Legalon using histological and biochemical techniques

Journal of Microbiology & Experimentation, 2022

Drugs, alcohol, and poor nutrition all contribute to the overproduction of free radicals, which linked to numerous diseases and resulted in a high number of cases of liver injury. Antioxidants have shown to play a significant role in reducing the harm caused by these compounds in recent studies. Treatment of liver disease with plants from the natural world has received considerable attention for quite some time. This study compared Ginkgo biloba leaf extract (GbE) with a commonly used drug in Egypt called Legalon for treating liver disorders, in order to assess GbE's hepato-protective effect against hepatotoxicity induced experimentally by CCl4. Before the first dose of CCl4, animals given GbE (100 ml/kg) and Legalon drug (100 ml/kg) orally, once a day, for a week. After that, CCl4 given orally at a dose of (2.5 ml/kg) in olive oil daily for 8 weeks to induce liver fibrosis, and the administration of GbE and Legalon maintained at the same dose and duration. The protective effect...

Hepatoprotective effect of< i> Ginkgoselect Phytosome® in rifampicin induced liver injurym in rats: Evidence of antioxidant activity

Fitoterapia, 2008

The protective effects of Ginkgoselect Phytosome ® (GBP) on Rifampicin (RMP) induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. Liver damage was induced in Wistar rats by administering rifampicin (500 mg/kg, p.o.) daily for 30 days. Simultaneously, GBP at 25 mg/kg and 50 mg/kg, and the reference drug silymarin (100 mg/kg) were administered orally for 30 days/daily to RMP treated rats. Levels of marker enzymes (SGOT, SGPT and SALP), albaumin (Alb) and total proteins (TP) were assessed in serum. The effects of GBP on lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were assayed in liver homogenates to evaluate antioxidant activity. GBP (25 and 50 mg/kg) and silymarin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPX, GR, Alb and TP in a dose dependant manner. The present findings suggest that the hepatoprotective effect of GBP in RMP induced oxidative damage may be related to its antioxidant and free radical scavenging activity.

Antioxidant and Hepatoprotective Effects of Garcinia Indica Choisy Fruits in Carbon Tetrachloride-Induced Liver Injury in Rats

Journal of Food Biochemistry, 2012

The present study was undertaken to investigate the in vitro and the in vivo antioxidant and hepatoprotective effects of Ginkgo biloba leave extracts. Qualitative analysis of different leaves extracts [ethanol 70% (Et), ethyl acetate (EA), and water (W)] revealed the presence of flavonoids, phenolic compounds, saponins, tannins, terpenes, and carbohydrates. The quantitative analysis of the leaves extracts revealed that the Et extract contains the highest amounts of tannins, saponins, flavonoids and phenolic compounds. The EA extract contains higher amounts of flavonoids and phenolic compounds and lower amounts of tannins and saponins compared to the W extract. The in vitro studies revealed that all the Ginkgo biloba leave extracts have a high antioxidant activity. The Et extract showed the highest activity followed by the EA extract then the W extract. Moreover, the in vivo studies revealed that all the Ginkgo biloba leave extracts have hepatoprotective activity, which evidenced by the effect of these extracts on the antioxidant enzymes activities [superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione-S-transferase (GST)], the liver marker enzymes [alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT)], the lipid peroxidation as well as inhibitory effects on nitric oxide (NO) release. The administration of these extracts significantly restored the elevated activities of the liver marker enzymes, and the antioxidant enzymes, which increase during hepatotoxicity. Also, they inhibit the release of NO. The treatment with the Et extract gave the best results for hepatoprotective effects. Moreover, the administration with this extract did not significantly affect the normal values of blood glucose (BG), total proteins (T.P), total lipids (T.L), total cholesterol (T.C), low and high density lipoprotein cholesterol (LDL-c and HDL-c). From this study it can conclude that the treatment with Ginkgo biloba leave extracts can inhibit the hepatotoxicity without toxic effect.

Cytotoxicity, genotoxicity and gene expression changes elicited by exposure of human hepatic cells to Ginkgo biloba leaf extract

Food and Chemical Toxicology, 2017

The use of Ginkgo biloba leaf extract as nutraceutical is becoming increasingly common. As a consequence, the definition of a reliable toxicological profile is a priority for its safe utilization. Recently, contrasting data have been reported on the carcinogenic potential of Ginkgo biloba extract in rodent liver. We measured viability, Reactive Oxygen Species (ROS), apoptosis, colony-forming efficiency, genotoxicity by comet assay, and gene expression changes associated with hepato-carcinogenicity in human cells of hepatic origin (HepG2 and THLE-2) treated with different concentrations (0.0005-1.2 mg/mL) of Ginkgoselect®Plus*. Our analyses highlighted a decrease of cell viability, not due to apoptosis, after treatment with high doses of the extract, which was likely due to ROS generation by a chemical reaction between extract polyphenols and some components of the culture medium. Comet assay did not detect genotoxic effect at any extract concentration. Finally, the array analysis detected a slight decrease in the expression of only one gene (IGFBP3) in Ginkgo-treated THLE-2 cells as opposed to changes in 28 genes in Aflatoxin B1 treated-cells. In conclusion, our results did not detect any significant genotoxic or biologically relevant cytotoxic effects and gross changes in gene expression using the Ginkgo extract in the hepatic cells tested.

Protective effect of Ginkgo biloba extract on CCI4-induced liver damage

Hepatology Research, 1999

In this study, the protective effect of Ginkgo biloba extract (EGb 761), an antioxidant, on carbon tetrachloride (CCI 4 )-induced liver damage were investigated in rats. Malondialdehyde (MDA, a breakdown product of lipid peroxidation) levels, histopathological findings and serum enzyme activities were evaluated. Rats were divided into two groups: The first group (CCI 4 plus EGb 761) was composed of 18 rats, whereas the second group (CCI 4 ) had 14 rats. A total of 0.15 ml/100 g body weight CCI 4 were injected subcutaneously for 3 days/week to the rats in both groups. In the first group, 200 mg/kg per day EGb 761 were added to drinking water. The second group of rats received only tap water. After the 4-week treatment, rats were sacrificed, blood samples were collected for determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and plasma MDA levels. Liver tissue samples were used for histopathological examinations and measurement of MDA levels. Plasma MDA levels, ALT, AST and ALP activities were significantly higher in CCI 4 group compared to the CCI 4 plus EGb 761 group (PB 0.05, PB0.01, PB0.01, PB0.05, respectively). The level of liver MDA was significantly decreased in the CCI 4 plus EGb 761 group than CCI 4 group (PB 0.001). In histopathological

Histological effect of Ginkgo Biloba on liver and heart of adult male albino rat

the egyptian journal of histology, 2020

Ginkgo biloba (EGb) is a dietary supplement used for various purported therapeutic benefits. It contains powerful antioxidants, can help to fight inflammation, induces psychic disorders, and improves brain function. Some researchers recommended using Ginkgo Biloba as a protective agent. The study aims are to evaluate the histological effect of chronic administration with different doses of Ginkgo Biloba on the liver and heart of adult male albino rats. Material and methods: the study was performed on a total number of 30 adult male albino rats; weighing 170–200 g. Rats were divided into three equal groups (10 rats each) and treated once a day. Group I (control group; n=10), each one received distilled water (1ml/day). Group II (low dose group; n=10): received EGb at a dose of 100 mg/kg BW. Group III (high dose; n=10): received a dose of EGb 200 mg/kg BW; orally by daily gavage for 4 weeks. Rats were sacrificed and prepared for histological study. Result: In specimens of liver tissue...

Protective effects of Ginkgo biloba against rat liver carcinogenesis

Chemico-Biological Interactions, 2008

Ginkgo biloba (EGb) has been proposed as a promising candidate for cancer chemoprevention and has shown protective effects on the liver against chemically induced oxidative injury and fibrosis. The potential beneficial effects of EGb were investigated in two rat liver carcinogenesis bioassays induced by diethylnitrosamine (DEN). In a short-term study for anti-initiating screening, male Wistar rats were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb and initiated 14 days later with a single dose of DEN (100 mg/kg i.p.). The respective groups were killed 24 h or 2 weeks after DEN-initiation. Liver samples were collected for the analysis of proliferating cell nuclear antigen (PCNA), transforming growth factor alpha (TGF-␣), p53, apoptosis and induction of single hepatocytes and minifoci positive for the enzyme glutathione S-transferase P-form (GST-P). In a medium-term study for anti-promoting screening, the animals received a single dose of DEN (200 mg/kg i.p.) and, 2 weeks later, were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb for 6 weeks. All animals underwent 70% partial hepatectomy (PH) at week 3 and killed at week 8. Liver samples were colleted to analyze development of preneoplastic foci of altered hepatocytes (FAH) expressing GST-P. In the short-term study, pretreatment of rats with 1000 ppm EGb significantly reduced the rates of cell proliferation, apoptosis and p53, TGF-␣ immunoreactivity and the number of GST-P-positive hepatocytes. In the medium-term study, EGb treatment during the post-initiation stage failed to reduce the development of DEN-induced GST-P-positive foci. Thus, EGb presented inhibitory actions during initiation but not promotion of rat liver carcinogenesis induced by DEN.

Toxicity and Carcinogenicity Studies of Ginkgo biloba Extract in Rat and Mouse

Toxicologic Pathology, 2013

Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program’s Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic ...

Ginkgo biloba L. Leaf Extract Protects HepG2 Cells Against Paraquat-Induced Oxidative DNA Damage

Plants

Ginkgo biloba L. leaf extracts and herbal infusions are used worldwide due to the health benefits that are attributed to its use, including anti-neoplastic, anti-aging, neuro-protection, antioxidant and others. The aim of this study was to evaluate the effect of an aqueous Ginkgo biloba extract on HepG2 cell viability, genotoxicity and DNA protection against paraquat-induced oxidative damage. Exposure to paraquat (PQ), over 24 h incubation at 1.0 and 1.5 µM, did not significantly reduce cell viability but induced concentration and time-dependent oxidative DNA damage. Ginkgo biloba leaf extract produced dose-dependent cytotoxicity (IC50 = 540.8 ± 40.5 µg/mL at 24 h exposure), and short incubations (1 h) produced basal and oxidative DNA damage (>750 and 1500 µg/mL, respectively). However, lower concentrations (e.g., 75 µg/mL) of Ginkgo biloba leaf extract were not cytotoxic and reduced basal DNA damage, indicating a protective effect at incubations up to 4 h. On the other hand, lon...