The mechanism of hepatoprotective effect of sesquiterpene rich fraction from Cichorum glandulosum Boiss. et Huet on immune reaction-induced liver injury in mice

Ethnopharmacological relevance

Cichorum glandulosum Boiss. et Huet is a traditional Uygur herbal medicine that has been used as a cholagogic and diuretic agent to improve liver function. However, the mechanism is not known for the liver-protective function. We investigated the antioxidant effects of plant extraction (CGE60) in vitro and in vivo, and find the mechanism of liver protection in Bacille Calmette-Guerin vaccine (BCG)+Lipopolysaccharides (LPS) induced liver injury in mice.

Materials and methods

CGE60 was made, and the antioxidant activity was investigated by comparing the ability of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2-azinobis(3-ehtylbenzothiazolin-6-sulfnicAcid) diammonium salt (ABTS) free radicals in vitro. Then, CGE60 was administrated in mice of liver damage model which was induced in mice using the BCG+LPS protocol. The CGE 60 extract was tested at three dosages: 50 mg/kg, 100 mg/kg, and 200 mg/kg. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX,), nitric oxide (NO), nitric oxide synthetase (NOS), hydroxyproline and alkaline phosphatase (ALP) contents were evaluated in liver to determine the CGE60 activity in the hepatic injury model. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) proteins were determined in the liver tissues using ELSIA. The signaling activities were evaluated in Western blot.

Results

CGE60 exhibited strong antioxidant ability in vitro. With oral administration, CGE60 significantly increased the activity of CAT, SOD, GSH-PX, and decreased the level of NO, NO synthase, hydroxyproline, ALP and lipid peroxidation liver of in the BDG+ LPS model. CGE60 attenuated hepatic inflammation via down- regulation of TNF-α, IL-6 and TGF-β. CGE60 blocked protein expression of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa-B (NF-κB), phosphorylation of extracellular signal-regulated kinase (p-ERK1/2), and cyclooxygenase-2 (COX-2),but activated the expression of p-P38 MAPK.

Conclusion

This study suggests that CGE60 possesses antioxidant activity and this activity associates with hepatoprotective effect in the mice of BCG +LPS model, and the mechanisms underlying these effects may involve antioxidant actions and anti-inflammation activities.     

Hepatoprotective and antioxidant activity of pentagamavunon-0 against carbon tetrachloride-induced hepatic injury in rats

ObjectiveTo investigate the hepatoprotective and antioxidant activity of pentagamavunon-0(PGV-0) against CCl₄-induced hepatic injury in rats.MethodsThe groups of animals were administered with PGV-0 at the doses 2.5, 5, 10, and 20 mg/kgb.w., p.o. once in a day for 6 days and at day 7 the animals were administrated with carbon tetrachloride (CCl) (20%, 2 mL/kgb.w. in liquid paraffin (i.p.). The effect of PGV-0 on serum transaminase (SGPT), alkaline phosphates (ALP) and total bilirubin were determined in CCl₄-induced hepatotoxicity in rats. Further, the effects of PGV-0 on glutathione (GSH) content, catalase (CAT) and NO free radical scavenging activity also were investigated.ResultsThe results demonstrated that PGV-0 significantly reduced the activity of SGPT, serum ALP and total bilirubin in CCl₄induced rat hepatotoxicity. PGV-0 has effect on the antioxidant and free radical defense system. It prevented the depletion level of GSH and decrease activity of CAT in CCl₄-induced liver injury in rats. PGV-0 also demonstrated the free radical scavenger effects on NO free radical scavenging activity with ES value of 32.32μM.ConculsionAll of our findings suggests that PGV-0 could protect the liver cells from CCl₄-induced liver damages and the mechanism may through the antioxidative effect of PGV-0 to prevent the accumulation of free radicals and protect the liver damage.     

Protective effect of Sida cordata leaf extract against CCl4 induced acute liver toxicity in rats

ObjectiveTo investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim.MethodsWister albino rats were divided into 6 groups: Group I served as control; Group II served as hepatotoxic (CCl₄ treated) group; Group III, IV and V served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group VI served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies.ResultsObtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl₄ induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies.ConclusionsThe results of this study strongly indicate the protective effect of SCLE against CCl₄ induced acute liver toxicity in rats and thereby scientifically support its traditional use.     

口服齐墩果酸对D-氨基半乳糖致小鼠急性肝损伤的保护作用

目的 研究口服齐墩果酸(OA)对D-氨基半乳糖诱导小鼠急性肝损伤的保护作用.方法 将♂昆明种小鼠随机分为对照组、OA给药组、模型组、OA预处理组.采用ig给予OA给药组和OA预处理组小鼠200 μmol· kg-1 OA,ig给予对照组、模型组等体积菜籽油,每天2次,连续3d,末次给药1h后,ip给予对照组、OA给药组等体积生理盐水,ip给予模型组和OA预处理组800 mg· kg-1D-氨基半乳糖溶液造模,造模8h后,收集各组小鼠的血液和肝脏组织,测定小鼠血清中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和肝脏中丙二醛(MDA)的含量,观察肝组织病理学的改变,并应用实时定量RT-PCR检测肝毒性相关基因的表达水平.结果 OA预处理能降低D-氨基半乳糖所致小鼠血清中AST、ALT的活性及肝组织中MDA的含量,明显改善肝细胞坏死病变的程度,并逆转小鼠急性肝损伤所致的生长停滞及DNA损伤诱导基因153(Chop10)、生长停滞及DNA损伤诱导基因45、Egr1、mKC、TNF-α mRNA表达的增高.结论 OA对D-氨基半乳糖所致小鼠急性肝损伤具有保护作用,其机制可能与缓解急性内质网应激、减轻炎症和抗氧化有关.     

Hepatoprotective and antioxidant activity of Amaranthus spinosus against CCl4 induced toxicity

Aim

50% ethanolic extract (ASE) of Amaranthus spinosus (whole plant) was evaluated for in vitro antioxidant and hepatoprotective activity.

Methods

The total phenolics and reducing capacity of ASE was determined using standard curve of gallic acid (0–1.0 mg/ml) and butylated hydroxy anisole. In vitro antioxidant activity was determined by DPPH, superoxide, hydroxyl radicals, hydrogen peroxide and nitric oxide scavenging methods. The hepatoprotective activity of ASE was evaluated at 6, 7, 8, 9 and 10 μg/ml concentration against CCl₄ (1%) induced toxicity in freshly isolated rat hepatocytes and HepG2 cells.

Results

ASE was found to contain 336 ± 14.3 mg/g total polyphenolics expressed as gallic acid equivalent while the reducing capacity was 2.26 times of BHA. ASE showed significant antioxidant activity in DPPH assay (IC₅₀ 29 μg/ml), scavenges superoxide (IC₅₀ ∼ 66–70 μg/ml), hydrogen peroxide (IC₅₀ ∼120–125 μg/ml), hydroxyl radicals (IC₅₀ ∼140–145 μg/ml) and nitric oxide (IC₅₀ ∼ 135–140 μg/ml). ASE (6, 7, 8, 9 and 10 μg/ml) was able to normalise the levels of biochemical parameters in isolated rat hepatocytes intoxicated with CCl₄. A dose dependent increase in percentage viability was observed in CCl₄ intoxicated HepG2 cells.

Conclusions

ASE possesses significant hepatoprotective activity which might be due to antioxidant defence factors and phenolics might be the main constituents responsible for activity.     

The hepatoprotective and antifibrotic effects of Saururus chinensis against carbon tetrachloride induced hepatic fibrosis in rats

Ethnopharmacological relevance

Saururus chinensis (Lour.) Baill (Saururaceae) has been used in Chinese folk medicine for treatment of various diseases, such as edema, jaundice, gonorrhea, antipyretic, diuretic, and antiinflammatory agents.

Aim of the study

Our aim was to evaluate the hepatoprotective and antifibrotic effects of Saururus chinensis extract (SC-E) in carbon tetrachloride (CCl₄) induced liver fibrosis rats.

Materials and methods

The SC-E (70 mg/kg) was administrated via gavage once a day starting from the onset of CCl₄ treatment (14 weeks) for subsequent 8 weeks. Evaluated with liver index, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), hepatic malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity, total cholesterol (TC), triglyceride (TG), total lipoprotein (TP), albumin (ALB), hydroxyproline (HYP), total antioxidant capacity (T-AOC), laminin (LN), type III collagen terminal peptide (PC-IIINP), and type IV collagen (IV-C), as well as with histopathologic changes of liver.

Results

SC-E effectively reduced the elevated levels of liver index, serum ALT, AST, HA, and hepatic MDA contents, enhance the reduced hepatic SOD activity in CCl₄-treated rats. The histopathological analysis suggested that SC-E obviously alleviated the degree of liver fibrosis induced by CCl₄.

Conclusions

Those results suggest SC-E has protective and therapeutic effects on liver fibrosis induced by CCl₄.     

Hepatoprotective effects of Ganoderma lucidum peptides against d-galactosamine-induced liver injury in mice

Ganoderma lucidum (GL), a traditional Chinese medicinal mushroom, has been widely used for the treatment of chronic hepatopathy of various etiologies. The hepatoprotective activity of peptides from Ganoderma lucidum (GLP) was evaluated against d-galactosamine (d-GalN)-induced hepatic injury in mice. GLP was administered via gavage daily for 2 weeks at doses of 60, 120 and 180 mg/kg, respectively. Control groups were given the same amount of physiological saline synchronously. Then the mice from d-GalN control and GLP-treated groups were treated with d-GalN (750 mg/kg) suspended in normal saline by intraperitoneal injection. d-GalN-induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (AST, ALT) in serum and MDA level in liver (P<0.01), and by a significant decrease in activity of SOD and GSH level in liver (P<0.01). Pretreatment of mice with GLP reversed these altered parameters to normal values. The biochemical results were supplemented by histopathological examination of liver sections. The best hepatoprotective effects of GLP were observed after treatment with the dose of 180 mg/kg as it was evidenced from biochemical parameters and liver histopathological characters which were similar to those of normal control group. Results of this study revealed that GLP could afford a significant protection in the alleviation of d-GalN-induced hepatocellular injury.     

Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against d-galactosamine induced acute liver damage in rats

Ethnopharmacological relevance

The whole plant of Enicostemma axillare Raynal (Family: Gentianaceae) is used in variety of diseases in traditional Indian system of medicine including hepatic ailments.

Aim of the study

Swertiamarin isolated from Enicostemma axillare Raynal was evaluated for antioxidant and hepatoprotective activity.

Materials and methods

Swertiamarin was isolated from successive ethyl acetate extract of the plant Enicostemma axillare belongs to the family Gentianaceae. The concentration of swertiamarin was determined by high performance thin layer chromatography (HPTLC). The hepatoprotective and antioxidant activity of swertiamarin (100 and 200 mg/kg body weight) was carried out against d-Galactosamine (d-GalN) (200 mg/kg body weight intraperitoneally i.p.) induced liver injury in rats.

Results

Swertiamarin a secoiridoid glycoside was found to contain a major constituent of the extract. d-GalN caused significant hepatotoxicity by alteration of several hepatic parameters. It also caused significant lipid peroxidation and reduced the levels of antioxidant defense mechanisms. The treatment with swertiamarin at 100 and 200 mg/kg body weight when administered orally for 8 days prior to d-GalN caused a significant restoration of all the altered biochemical parameters due to d-GalN towards the normal, indicating the potent antioxidant and hepatoprotective nature of swertiamarin.

Conclusions

Swertiamarin isolated from Enicostemma axillare possesses significant antioxidant and hepatoprotective properties against d-GalN induced hepatotoxicity given at 100 and 200 mg/kg body weight orally for 8 days, which might be due to its in vitro antioxidant activity.     

Protective and Therapeutic Effect of the Indonesian Medicinal Herb Curcuma xanthorrhiza on β-D-Galactosamine-induced Liver Damage

The present study was carried out to investigate the hepatoprotective effects of a dose of C. xanthorrhiza on acute hepatotoxicity induced in rats by a single dose of β-D -galactosamine (288 mg/kg, i.p.), and its mechanism of action. C. xanthorrhiza (100 mg/kg) was administered p.o. to experimental animals according to the protocol followed by the i.p. administration of a single dose of hepatotoxin. Hepatoprotective activity was monitored by estimating serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels and histopathological changes in the livers of C. xanthorrhiza -treated and untreated groups of animals. The results clearly indicated that the extract of C. xanthorrhiza significantly reduced the acute elevation of serum transaminases induced by hepatotoxin, and alleviated the degree of liver damage at 24 h after the intraperitoneal administration of the hepatotoxins.     

Hepatoprotective activity of ethanolic extracts of bark of Zanthoxylum armatum DC in CCl4 induced hepatic damage in rats

Aim of the study

Zanthoxylum armatum DC is described as a hepatoprotective in Ayurveda, the Indian system of medicine. However, there is no scientific basis or reports in the modern literature regarding its usefulness as a hepatoprotective agent. The present study was carried out to evaluate the hepatoprotective activity of ethanolic extract of bark of Zanthoxylum armatum DC in CCl₄ induced hepatotoxicity in male Wistar rats.

Materials and methods

Ethanolic extracts at doses of 100, 200, and 400 mg/kg were administered orally once daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum bilirubin, total protein and serum antioxidant enzymes along with histopathological studies of liver tissue.

Results

The substantially elevated serum enzymatic levels of serum transaminases, alkaline phosphatase and total bilirubin were significantly restored towards normalization by the extracts. Bark extracts significantly increased the levels of antioxidant enzymes: superoxide dismutase, catalase and glutathione. Phytochemical analysis revealed presence of isoquinoline alkaloid, berberine, as well as flavonoids and phenolic compounds, which have been known for their hepatoprotective activities.

Conclusions

Zanthoxylum armatum DC possesses significant protective effect against hepatotoxicity induced by CCl₄ which may be attributed to the individual or combined action of phytoconstituents present in it.