Hepatoprotective effect of the ethanol extract of Vitis thunbergii on carbon tetrachloride-induced acute hepatotoxicity in rats through anti-oxidative activities

Ethnopharmacological relevance

Vitis thunbergii var. taiwaniana are traditionally used for the treatment of diarrhea, fracture and injury, jaundice, and hepatitis in Taiwan.

Aim of the study

The hepatoprotective activity of its plant extracts seems to be been associated with its antioxidant activity. This paper aims to investigate the in vitro and in vivo antioxidant effects of the ethanol extract of Vitis thunbergii (EVT).

Materials and methods

In HPLC analysis, the fingerprint chromatogram of EVT was established. Antioxidant ability of EVT was investigated by employing several established in vitro methods. In vivo antioxidant activity was tested against CCl₄-induced toxicity in mice. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected in the blood to indicate hepatic injury. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed for the degree of hepatic injury.

Results

EVT exhibited strong antioxidant ability in vitro. After oral administration of EVT significantly decreased ALT and AST, and ameliorated the oxidative stress in hepatic tissue and increased the activity of CAT, SOD, GPx, and GSH. Serum tumor necrosis factor-alpha (TNF-α), interleukin−1β (IL-1β), and nitric oxide (NO) were decreased in the group treated with CCl₄ plus EVT. Western blotting revealed that EVT blocked protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in CCl₄-treated rats, significantly. Histopathological examination of livers showed that EVT reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl₄-treated rats.

Conclusion

This study suggests that EVT possesses antioxidant effects in vitro and hepatoprotective effect on acute liver injuries induced by CCl₄in vivo, and the results suggested that the effect of EVT against CCl₄-induced liver damage is related to its antioxidant properties.     

灯盏花素对四氯化碳小鼠肝损伤的保护作用

目的探讨灯盏花素对四氯化碳(CCl4)肝脏损伤的保护作用.方法小鼠腹腔注射0.1% CCl4 10ml/kg 造成肝损伤模型,以血清丙氨酸氨基转移酶(ALT)、肝匀浆谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量为指标观察灯盏花素对肝脏损伤的保护作用.结果灯盏花素50mg、100mg/kg·d ig×7d能明显降低CCl4中毒小鼠的血清ALT含量和肝匀浆MDA含量,提高肝脏GSH-Px活性.结论灯盏花素具有明显的保护肝作用,可通过增强抗氧化能力拮抗四氯化碳的肝毒性.     

Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats

AIM OF THE STUDY: To investigate the protective effects of dehydrocavidine (DC), a main active ingredient of Corydalis saxicola Bunting (Yanhuanglian), on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms involved in male Sprague-Dawley rats. MATERIALS AND METHODS: Acute hepatotoxicity was induced by CCl4 intoxication in rats. Serum biological analysis, lipid peroxides and antioxidants estimation, histopathological studies were carried out. RESULTS: Both pre-treatment with DC prior to CCl4 administration and post-treatment with DC after CCl4 administration significantly prevented increases in serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and total bilirubin (TBIL). In addition, pre- and post-treatment with DC also significantly prevented formation of hepatic malondialdehyde (MDA), depletion of glutathione peroxidase (GPx) and depression of superoxide dismutase (SOD) in the liver of CCl4-intoxicated rats. ALT, AST, LDH, ALP and TBILL levels, as well as MDA, SOD and GPx activities were unaffected in normal rats by treatment with DC alone. GST, a phase II enzyme, had no significant changes during our experiments. Histopathological changes induced by CCl4 were also significantly attenuated by DC treatment in both preventive and curative experiments. CONCLUSIONS: DC has a potent hepatoprotective effect on CCl4-induced liver injury in rats through its antioxidant activity.     

Preliminary studies on antihepatotoxic effect of Physalis peruviana Linn. (Solanaceae) against carbon tetrachloride induced acute liver injury in rats

Physalis peruviana is a medicinal herb used by Muthuvan tribes and Tamilian native who reside in the shola forest regions of Kerala, India against jaundice. It was evaluated for its antihepatotoxic, phytochemical analysis and the acute toxicity of the most promising extract in rats. Water, ethanol and hexane extracts of Physalis peruviana (500mg/kg body weight) showed antihepatotoxic activities against CCl(4) induced hepatotoxicity. The ethanol and hexane extracts showed moderate activity compared to water extract, which showed activity at a low dose of 125mg/kg. The results were judged from the serum marker enzymes. Histopathological changes induced by CCl(4) were also significantly reduced by the extract. Further, the extract administration to rats resulted in an increase in hepatic GSH and decrease in MDA. Preliminary phytochemical analysis revealed the presence of various components in the crude aqueous extract. The extract was found to be devoid of any conspicuous acute toxicity in rats.     

Protective effect of Smilax glabra extract against lead-induced oxidative stress in rats

Ethnopharmacological relevance

Smilax glabra Roxb. is a traditional Chinese herb, the rhizome of Smilax glabra has been used in folk medicine for the treatment of lead poisoning.

Aims of the study

The present study was conducted to investigate the protective role of Smilax glabra extract (SGE) individually or combined with meso-2,3-dimercaptosuccinic acid (DMSA) against the effects of lead acetate on oxidative stress and lead burden in rats.

Materials and methods

The biochemical parameters and enzymes in different treated rats were determined by commercial kits. The metal concentrations were measured using atomic absorption spectrophotometer.

Results

SGE (300 mg/kg) showed very low toxicity to organs in non-lead exposed rats. Administration of SGE individually had no effect on blood zinc protoporphyrin (ZPP) level but significantly enhanced the glutathione (GSH) content and δ-aminolevulinic acid dehydratase (ALAD), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in lead exposed rats. The co-treatment of SGE and DMSA had a synergism in increasing brain, liver and kidney superoxide dismutase (SOD), catalase (CAT) activities and GSH level, and decreasing oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS) levels. Moreover, the co-treatment could improve the hepatic and renal histopathology changes. SGE as chelating agent showed significant efficiency in reducing blood and tissue lead burden.

Conclusions

The in vivo results suggested that SGE individually or combined with DMSA exhibited remarkable protective effects on lead-induced oxidative stress and lead burden in rats.     

Hepatoprotective effect of Trichosanthes cucumerina Var cucumerina L. on carbon tetrachloride induced liver damage in rats

Ethnopharmacological relevance

Different parts of the plant Trichosanthes cucumerina Var cucumerina L. (cucurbitaceae) are used to treat liver disorders, traditionally. It is one among the constituents in various Ayurvedic formulations used for the treatment of liver disorders and other diseases.

Aims of study

The aim of the present study is to evaluate the protective effect of Trichosanthes cucumerina against experimentally induced liver injury.

Materials and methods

The methanolic extract of whole plant of Trichosanthes cucumerina (TCME) was evaluated for the hepatoprotective activity against carbon tetrachloride (CCl₄) induced hepatotoxicity in rats. Various biochemical parameters like alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), total protein (TP) and albumin (ALB) levels were estimated in serum as well as the glutathione (GSH) and malondialdehyde (MDA) levels in the liver were determined. Histopathological changes in the liver of different groups were also studied.

Results

The pre-treatment of TCME at dose levels of 250 and 500 mg/kg b.w.p.o. had controlled the raise of AST, ALT, ALP, TB and MDA levels and the effects were comparable with standard drug (silymarin 100 mg/kg b.w.p.o.). The GSH, TP and ALB levels were significantly increased in the animals received pre-treatment of the extract. The animals received pre-treatment of the extract shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl₄ intoxication alone. Thus the histopathalogical studies also supported the protective effect of the extract.

Conclusion

This study demonstrates the hepatoprotective activity of Trichosanthes cucumerina and thus scientifically supports the usage of this plant in various Ayurvedic preparations and traditional medicine for treatment of liver disorders.     

Hepatoprotective effects of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced acute liver hepatotoxicity in rats

Aim of the study

Coptidis rhizoma (CR, Chinese name is Huanglian) has been used in treating infectious and inflammatory diseases for two thousand years in Traditional Chinese Medicine (TCM). Its related pharmacological basis for the therapeutics has been studied intensively, but CR can also be used for vomiting of “dampness-heat type or acid regurgitation” due to “liver-fire attacking stomach” in TCM, whose symptoms seem to link the hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. To clarify this ethnopharmacological relevance, hepatoprotective effect of Coptidis rhizoma aqueous extract (CRAE) and its possible mechanism were studied in rats intoxicated with carbon tetrachloride (CCl₄) in the present study.

Materials and methods

Sprague–Dawley (SD) rats aged 7 weeks old were intraperitoneally injected with CCl₄ at a dose of 1.0 ml/kg as a 50% olive oil solution. The rats were orally given the CRAE at doses of 400, 600, 800 mg/kg and 120 mg/kg berberine body weight (BW) after 6 h of CCl₄ treatment. At 24 h after CCl₄ injection, samples of blood and liver were collected and then biochemical parameters and histological studies were carried out.

Results

The results showed that CRAE and berberine inhibited significantly the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and increased the activity of superoxide dismutase (SOD). Observation on the hepatoprotective effect of berberine was consistent to that of CRAE.

Conclusion

The study is the first time to demonstrate that CRAE has hepatoprotective effect on acute liver injuries induced by CCl₄, and the results suggest that the effect of CRAE against CCl₄-induced liver damage is related to antioxidant property.     

Evaluation of hepatoprotective effect of Zhi-Zi-Da-Huang decoction and its two fractions against acute alcohol-induced liver injury in rats

Aim of the study

To investigate the hepatoprotective effect of Zhi-Zi-Da-Huang decoction (ZZDHD) and its two fractions (one is extracted with diethyl ether as a solvent from the water extract and is called ZD-DE for short, the other is the remained aqueous fraction after extracted with diethyl ether and is abbreviated as ZD-AQ) against acute alcohol-induced liver injury in rats.

Materials and methods

Animals were administered orally with alcohol 6 g/kg at 2 h after the doses of ZZDHD and two fractions everyday for eight consecutive days except rats in normal group. The protective effect was evaluated by biochemical parameters including aspartate transaminase (AST), alanine transferase (ALT), reduced glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD). The biochemical observations were supplemented by histopathological examination. HPLC-UV was used for phytochemical analysis of the ZZDHD and its two fractions.

Results

The high dose of ZZDHD exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes. ZD-DE and ZD-AQ demonstrated different protective action in biochemical examination. Partly assayed indexes were ameliorated after administrated the media dose of ZZDHD. HPLC analysis indicated that ZZDHD contained flavonoids, anthraquinones and iridoids, which might be the active chemicals.

Conclusions

This study demonstrated the hepatoprotective activity of ZZDHD thus scientifically supported the usage of this formula.     

Hepatoprotective effect and its possible mechanism of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced chronic liver hepatotoxicity in rats

Ethnopharmacological relevance

Coptidis rhizoma is traditionally used for heat-clearing and toxic-scavenging and it belongs to liver meridian in Chinese medicine practice. Clinically, Coptidis rhizoma can be used for hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. Our previous study demonstrated that Coptidis rhizoma aqueous extract (CRAE) against CCl₄-induced acute liver damage was related to antioxidant property. In the present study, the protection of CRAE on chronic liver damage induced by carbon tetrachloride (CCl₄) in rats and its related mechanism were explored.

Materials and methods

The CCl₄-induced chronic liver damage model was established, and CRAE's protective effect was examined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, serum and liver superoxide dismutase (SOD) activity were then measured. The histological changes were observed under microscopy and then computed in numerical score. The normal or damaged cells were isolated and related signaling pathway was evaluated.

Result

Serum AST and ALT activities were significantly decreased in rats treated with different doses of CRAE, indicating its protective effect against CCl₄-induced chronic liver damage. Observation on serum SOD activity revealed that CRAE might act as an anti-oxidant agent against CCl₄-induced chronic oxide stress. Histological study supported these observations. Erk1/2 inhibition may take part into CRAE's effect on preventing hepatocyte from apoptosis when exposed to oxidative stress.

Conclusion

CRAE showed protective effect against CCl₄-induced chronic liver damage in rats and its potential as an agent in the treatment of chronic liver diseases by protecting hepatocyte from injury.     

Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats

Terminalia belerica Roxb. is one of the oldest medicinal herb of India, is an ingredient of Indian Ayurvedic drug 'triphala' used for the treatment of digestion and liver disorders. Present study is aimed to evaluate the protective effect of Terminalia belerica fruit extract and its active principle, gallic acid (3,4,5-trihydroxybenzoic acid) at different doses against carbon tetrachloride intoxication. Toxicant caused significant increase in the activities of serum transaminases and serum alkaline phosphatase. Hepatic lipid peroxidation level increased significantly whereas significant depletion was observed in reduced glutathione level after carbon tetrachloride administration. A minimum elevation was found in protein content on the contrary a significant fall was observed in glycogen content of liver and kidney after toxicant exposure. Activities of adenosine triphosphatase and succinic dehydrogenase inhibited significantly in both the organs after toxicity. Treatment with TB extract (200, 400 and 800mg/kg, p.o.) and gallic acid (50, 100 and 200mg/kg, p.o.) showed dose-dependent recovery in all these biochemical parameters but the effect was more pronounced with gallic acid. Thus it may be concluded that 200mg/kg dose of gallic acid was found to be most effective against carbon tetrachloride induced liver and kidney damage.     

In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice

Aim of the study

This study aimed to evaluate in vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. (AEAA), which has been used for the treatment of liver disorders in Traditional Uighur Medicine.

Materials and methods

Qualitative and quantitative phytochemical analysis of the AEAA was performed by means of thin layer chromatography and spectrophometric assays. Aqueous extract (50, 100 or 200 mg/kg body weight/day) was administered orally to experimental mice. Liver injury was induced chemically, by a single CCl₄ administration (0.1% in olive oil, 10 ml/kg, i.v.), or immunologically, by injection of endotoxin (LPS, 10 μg, i.v.) in BCG-primed mice. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in mouse sera, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) in mouse liver tissues were measured. The biochemical observations were supplemented by histopathological examination.

Results

Obtained results demonstrated that the pretreatment with AEAA significantly (P < 0.001) and dose-dependently prevented chemically or immunologically induced increase in serum levels of hepatic enzymes. Furthermore, AEAA significantly (P < 0.05) reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes SOD and GPx towards normal levels. In the BCG/LPS model, increase of the levels of important pro-inflammatory mediators TNF-α and IL-1 was significantly (P < 0.01) suppressed by AEAA pretreatment. Histopathology of the liver tissue showed that AEAA attenuated the hepatocellular necrosis and led to reduction of inflammatory cells infiltration. Phytochemical analyses revealed the presence of sesquiterpene lactones, flavonoids, phenolic acids and tannins in the AEAA.

Conclusions

The results of this study strongly indicate the protective efect of AEAA against acute liver injury which may be attributed to its antioxidative and/or immunomodulatory activity, and thereby scientifically support its traditional use.     

Anti-fibrosis and anti-cirrhosis effects of Rhizoma paridis saponins on diethylnitrosamine induced rats

Ethnopharmacological relevance

Paris polyphylla var. yunnanensis as a traditional Chinese medicine has been used in the treatment of liver disease for thousands of years. Rhizoma paridis saponins (RPS), as the main active components of Paris polyphylla, have been used to treat liver injury. Anti-cirrhosis effect of Rhizoma paridis saponins (RPS) has not been known.

Materials and methods

We analyzed diethylnitrosamine (DEN)-induced metabonomic changes in multiple biological matrices (plasma and urine) of rats by using ¹H-NMR spectroscopy together with clinical biochemistry assessments, oxidative stress test and DNA fragmentation assay.

Results

Mechanisms of RPS that participated in the inhibition of the fibrotic process included anti-oxidant, anti-apoptosis, and metabolic disturbance such as decreasing lipid oxidation, regulation of TCA cycle, carbohydrate, and amino acid metabolisms in DEN-induced liver tissues.

Conclusions

Integrated NMR analysis of serum and urine samples, together with traditional clinical biochemical assays provided a holistic method for elucidating mechanisms of potential anti-fibrotic agent, RPS.     

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats

Ethnopharmacological relevance

The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties.

Materials and methods

Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration.

Results

Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity.

Conclusion

The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This antihypertensive activity is associated with an improvement of antioxidant status. Overall, results justify and support the use of Kalanchoe pinnata as antihypertensive medicine.     

Mechanism of protective effects of Danshen against iron overload-induced injury in mice

Ethnopharmacological relevance

Danshen (Salvia miltiorrhiza) has been widely prescribed in traditional folk medicine for treatment of hepatic and cardiovascular diseases in China and other Asian countries for several hundred years.

Materials and methods

Sixty male mice were randomly divided into five groups: control, iron overload, low-dose Danshen (L-Danshen, 3 g/kg/day), high-dose Danshen (H-Danshen, 6 g/kg/day) and deferoxamine (DFO) groups (n=12 per group). Iron dextran was injected intraperitoneally (i.p.) at 50 mg/kg body weight/day to establish the iron overload model. While control mice received saline, mice of the treated groups simultaneously received (i.p.) injections of L-Danshen, H-Danshen or DFO daily for 2 weeks. At the end of the experiment, changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), glutathione peroxidase (GSH-Px), superoxide desmutase (SOD) and malondialdehyde (MDA) were measured, and histological changes were observed by Prussian blue or hematoxylin and eosin staining of the liver. Apoptosis was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling.

Results

Treatment of iron overloaded mice with either low or high doses of Danshen not only significantly attenuated the hepatic dysfunction (ALT/AST levels), decreased the content of MDA and increased the activities of GSH-Px and SOD, it also suppressed apoptosis in hepatocytes. Histopathological examination showed that treatment with Danshen reduced iron deposition and ameliorated pathological changes in the liver of iron overloaded mice.

Conclusions

Danshen demonstrated significant protective effects in the liver of iron overloaded mice, which were at least partly due to the decrease of iron deposition and inhibition of lipid peroxidation and hepatocyte apoptosis.     

Antioxidative and hepatoprotective effect of CGX, an herbal medicine, against toxic acute injury in mice

Aim

CGX, a modified traditional Chinese herbal drug whose name means “liver cleaning,” is used to treat various liver disorders. This study investigated the protective effects of CGX and its mechanisms.

Material and methods

After pretreating ICR mice twice daily with CGX (po, 50 or 100 mg/kg) or distilled water for three consecutive days, acute liver injury was induced by a single injection of CCl₄ (ip, 10 mL/kg of 0.2% in olive oil) (n = 8 per group).

Results

Pretreatment with CGX significantly attenuated the elevation in biochemical parameters, such as alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) in serum, and the malondialdehyde concentrations in liver tissue. Pretreatment with CGX significantly restored the reduction of catalase activity and glutathione (GSH) content, but not superoxide dismutase (SOD) activity, and it inhibited the CCl₄-induced high expression of iNOS and TNF-α in hepatic tissue.

Conclusion

This study showed that CGX has hepatoprotective effects against free radical-induced acute injury via primarily antioxidative properties.     

Acute toxicity and sub-chronic toxicity of steroidal saponins from Dioscorea zingiberensis C.H.Wright in rodents

Ethnopharmacological relevance

Steroidal saponins from Dioscorea zingiberensis are widely used in China for curing cardiovascular diseases. However, there was little toxicological information available on them.

Aim of the study

The study evaluated potential toxicity of the steroidal saponins and analyzed the metabolites in rats.

Materials and methods

For the acute study, the steroidal saponins were administered to kunming mice in single doses of 112.5–9000 mg/kg given by gavage. General behavior adverse effects, mortality and liver histopathological changes were examined. For the sub-chronic toxicity study, Sprague–Dawley rats were gavaged at doses of 127.5, 255 and 510 mg/kg/day for 30 days, then examined the biochemical and hematological parameters. Metabolites in serum were analyzed by HPLC–MS.

Results

The steroidal saponins caused dose-dependent general behavior adverse effects, mortality and liver histopathological changes in the acute toxicity study. In the sub-chronic toxicity study, 510 mg/kg/day of steroidal saponins increased total bilirubin (TBIL) in serum and decreased protein content in liver significantly. The metabolic process of TBIL in liver includes TBIL intaking, conjugated bilirubin forming, conjugated bilirubin excreting to biliary passage. Treatment with high dose of the steroidal saponins in vivo may lead to vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis. In all doses used in the experiment, the steroidal saponins decreased aspartate aminotransferase (GOT), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) in serum and increased reduced glutathione hormone (GSH), glutathione reductase (GR) and glutathione S-transferases (GST) in liver. Diosgenin was the main metabolite in serum.

Conclusions

The steroidal saponins did not show any sign of toxicity up to oral dose of 562.5 mg/kg in mice. No significant changes of biochemical and hematological parameters in rats (except at 510 mg/kg/day), it was concluded that the steroidal saponins did not appear to have significant toxicity in their traditional uses.     

Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice

Aims of study

Although Artemisia sacrorum Ledeb. (Compositae) has long been used as one kind of oriental folk medicine to treat some liver diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. This study was designed to investigate the hepatoprotective effects of 50% ethanol eluate precipitation of Artemisia sacrorum Ledeb. (EEP) on acetaminophen (APAP)-induced toxicity in mice.

Materials and methods

The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-α (TNF-α) levels in mouse sera, and glutathione (GSH), malondialdehyde (MDA) in mouse liver tissues were measured. In addition, apoptosis and necrosis were evaluated by liver histopathological analysis and DNA laddering. Moreover, caspase-3 and -8 protein expressions in mouse livers were observed by Western blot analysis.

Results

Pretreated with EEP prior to the administration of APAP significantly prevented the increases of AST, ALT, and TNF-α levels in sera, and suppressed the GSH depletion, MDA accumulation in liver tissues markedly. In addition, EEP prevented APAP-induced apoptosis and necrosis, as indicated by liver histopathological analysis, immunohistochemical analysis, and DNA laddering. Furthermore, according to the results from Western blot analysis, EEP decreased APAP-induced caspase-3 and caspase-8 protein expressions in mouse livers markedly.

Conclusion

All these results suggest that the protective effects of EEP against APAP-induced liver injury may involve mechanisms associated with its inhibitive effects of lipid peroxidation and the down-regulation of TNF-α mediated apoptosis. In a word, EEP could be a valuable candidate for further development for prevention and treatment of hepatic injury.     

The protective effect of Schisandra lignans on stress-evoked hepatic metastases of P815 tumor cells in restraint mice

Aim of the study

The present study was conducted to investigate the effects of schisandra lignans extract (SLE) on stress-evoked hepatic metastases of mastocytoma P815 tumor cells, which was closely related with immune function.

Materials and methods

The high-performance liquid chromatography (HPLC) fingerprint of SLE was recorded and the percentage composition of schisandra lignans was determined as 82.63%. The contributions of the immunomodulatory properties of SLE to the protective effects on stress-induced hepatic metastases were studied.

Results

Our results found that restraint stress significantly promoted hepatic metastases of P815 tumor cells. However, oral administration of SLE (100 and 200 mg/kg/d, 14 d) significantly reduced the number of metastatic colonies in liver of restrained mice. SLE was further found to be significantly improving T lymphocyte proportions and increasing cytotoxic T lymphocyte (CTL) activity of immunized spleen cells in stressed mice.

Conclusion

These results indicated that the protective effects of SLE on hepatic metastases were related to its alleviation of the adverse effects of stressors for bio-homeostasis and immunoprotection. The obtained data provided evidences to elucidate the traditional use of Fructus schisandrae as a tonic or sedative.     

Antidiarrheal and antioxidant activities of chamomile (Matricaria recutita L.) decoction extract in rats

Ethnopharmacological relevance

Matricaria recutita L. (Chamomile) has been widely used in the Tunisian traditional medicine for the treatment of digestive system disorders. The present work aims to investigate the protective effects of chamomile decoction extract (CDE) against castor oil-induced diarrhea and oxidative stress in rats.

Methods

The antidiarrheal activity was evaluated using castor oil-induced diarrhea method. In this respect, rats were divided into six groups: Control, Castor oil, Castor oil+Loperamide (LOP) and Castor oil+various doses of CDE. Animals were per orally (p.o.) pre-treated with CDE during 1 h and intoxicated for 2 or 4 h by acute oral administration of castor oil.

Results

Our results showed that CDE produced a significant dose-dependent protection against castor oil-induced diarrhea and intestinal fluid accumulation. On the other hand, we showed that diarrhea was accompagned by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level and depletion of antioxidant enzyme activities as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Castor oil also increased gastric and intestinal mucosa hydrogen peroxide (H₂O₂) and free iron levels. Importantly, we showed that chamomile pre-treatment abrogated all these biochemical alterations.

Conclusion

These findings suggested that chamomile extract had a potent antidiarrheal and antioxidant properties in rats confirming their use in traditional medicine.     

Polyprenols from Taxus chinensis var. mairei prevent the development of CCl4-induced liver fibrosis in rats

Ethnopharmacological relevance

The aim of this study was to investigate the anti-fibrotic effects and the possible underlying mechanisms of taxus polyprenols (TPs) isolated from the needles of Taxus chinensis var. mairei.

Materials and methods

The animals were randomly divided into normal control with vehicles only (olive oil), rat model given CCl₄ only, CCl₄+low TPs (48 mg/kg), CCl₄+medium TPs (120 mg/kg), CCl₄+high TPs (300 mg/kg), and CCl₄+Polyene phosphatidylcholine (PP, 120 mg/kg). The rat model of liver fibrosis was induced by subcutaneous injection of 40% (v/v) of CCl₄ diluted in olive oil (3 mL/kg body weight) twice per week for 8 weeks. Liver histopathological study was performed. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and albumin (ALB) of the serum were determined for evaluating the liver function. In order to reveal the possible mechanisms of the anti-fibrotic effects, oxidative stress level, hepatic collagen metabolism, and hepatic stellate cells (HSCs) activation were investigated. Furthermore, the mRNA expression of the fibrotic-related factors was measured by the quantitative real-time RT-PCR.

Results

TPs successfully attenuated liver injury induced by CCl₄ shown by histopathological sections of livers and improved liver function as indicated by decreased ALT, AST and ALP levels and increased ALB levels in serum of the rats. TPs significantly increased the hepatic Cu/Zn SOD and GSH-Px activities along with GSH content while a remarkable decrease in MDA content. Both immunohistochemical staining and mRNA expression levels of α-SMA indicated a profound suppression of HSCs activation. Furthermore, it significantly inhibited the mRNA expression of the pro-fibrotic cytokines Col α1(I), Col α1(Ш), MMP-2, TIMP-1, TIMP-2, PDGF-β, TGF-β1, CTGF and TNF-α and restored the hepatoprotective factor HGF.

Conclusion

These results suggest that the protective effects of TPs in chronic CCl₄-induced liver fibrosis might be related with the reduction of oxidative damage, the inhibition of HSCs activation, the down-regulation of pro-fibrogenic stimuli and the protection of hepatocytes.