Glycosides of herbal medicines, such as glycyrrhizin, ginsenosides, kalopanaxsaponins, rutin and ponicirin, were studied regarding their metabolic fates and pharmacological actions in relation to intestinal bacteria using germ-free, gnotobiotic and conventional animals. When glycyrrhizin (GL) was orally administered, $18{\beta}-glycyrrhetinic\;acid\;(GA)$, not GL, was detected in plasma and intestinal contents of gnotobiotic and conventional rats. However, GA could not be detected in germ-free rats. When GL was incubated with human intestinal bacteria, it was directly metabolized to GA (>95%) or via $18{\beta}-glycyrrhetinic\;acid-3-{\beta}-D-glucuronide$(>5%). Orally administered GL was effective in gnotobiotic and conventional rats for liver injury induced by carbon tetrachloride, but was not effective in germ-free rats. When ginseng saponins were orally administered to human beings, compound K in the plasma was detected, but the other protopanxadiol saponins were not detected. The compound K was active for tumor metastasis and allergy. When kalopanaxsaponins were incubated with human intestinal microflora, they were metabolized to kalopanaxsaponin A, kalopanaxsaponin I and hederagenin. These metabolites were active for rheumatoid arthritis and diabetic mellitus while the other kalopanxsaponins were not. When flavonoid glycosides were orally administered to animals, aglycones and/or phenolic acids were detected in the urine. The metabolic pathways proceeded by intestinal bacteria rather than by liver or blood enzymes. These metabolites, aglycones and phenolic acids, showed antitumor, antiinflammatory and antiplatelet aggregation activities. These findings suggest that glycosides of herbal medicines are prodrugs.
In the sequence of carbon tetrachloride hepatotoxicity, increased serum levels of a number of enzymes have been demonstrated in experimental animals. These observations, therefore, have served to help in detecting hepatic injury. The serological influence of chlorpromazine (CPZ) and iproniazid on the acute $CCl_4$ poisoning was executed in this investigation taking use of 6 albino rabbits (around 2 kg b.w.) in each group. By measuring of blood sugar level (Nelson-Somogyi method), S-GOT and S-GPT activities (Reitman-Frankel method), the pharmacological effects of the drugs was evaluated setting pretreated groups against the control. The results obtained were summarized as follows: 1. The intramuscular injection of $CCl_4$ led to increase the blood sugar level in first 3 hours and, after that, to decrease reasonably. But CPZ-pretreated group showed a tendency of increasing in compare with the control, and iproniazid-pretreated group inhibited evidently. 2. In S-GOT activity, the increased level was induced by $CCl_4$ in control. And CPZ-pretreated group showed a increased level until first day and decreased rapidly. But this property inhibited inhibited significantly by pretreating with iproniazid. 3. Although a single dose of $CCl_4$ increased the S-GPT activity, the more increasing trend was observed in CPZ-pretreated group. But these tendencies depressed remarkably in the iproniazid-pretreated group. It seemed to be attributed not to defend the $CCl_4$ toxicity but to be suppressed the enzyme systems in the liver by iproniazid that the blood sugar level and serum transaminase activities was decreased significantly in pretreating with iproniazid.
Din, Syafawati Shamsahal;Mamat, Siti Syariah;Ismail, Noor Aisyah;Zainulddin, Wan Noraziemah Wan;Zabidi, Zalina;Yahya, Farhana;Kamisan, Farah Hidayah;Mohtarrudin, Norhafizah;Othman, Fezah;Suhaili, Zarizal;Zakaria, Zainul Amiruddin
CELLMED
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v.2
no.4
/
pp.34.1-34.5
/
2012
The present study aimed to determine the hepatoprotective activity of the chloroform extract of D. linearis leaves (CEDL) using the paracetamol (PCM)- and carbon tetrachloride ($CCl_4$)-induced liver injury models in rats. The rats received $dH_2O$ (negative control), 200 mg/kg of silymarin (positive control) or CEDL (50, 250 and 500 mg/kg) orally once daily for 7 days and then were subjected to the hepatotoxic induction on the $7^{th}$ day. The samples (i.e. blood and liver) were collected and underwent biochemical and microscopical analysis, respectively. From the data obtained, both inducers caused significant (p < 0.05) increase in the levels of AST and ALT when compared to the control group, which were significantly (p < 0.05) reduced by CEDL in a generally dose-dependent manner. These biochemical findings were supported by the histopathological analysis and histological scoring. In conclusion, CEDL possesses potential hepatoprotective activity, which could be associated with its flavonoid and tannin contents with the mechanisms of hepatoprotection linked to either its antioxidant or anti-inflammtory/immunomodulating activities. Further in-depth studies are required to identify the responsible bioactive compound.
These studies were carried out to observe the effect of Aqua-acupuncture with Woolgum extract on the recovery from liver injury of rats. The liver injury of rats induced with 0.5ml/200g carbon tetrachloride. The Aqua-acupuncture with Woolgum extract solution inserted into corresponding locus of the Kansu(BL18.) in Rats. Experimental group was divided into 4 groups: Normal group, $CCI_4$-intoxicated group, Saline treated group after $CCI_4$-intoxicated and Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. Biochemical assays for each serum enzyme activity of GOT, GPT, LDH, total protein, triglyceride, albumin, WBC, neutrophils, lymphocyte were performed. The results were as follows : 1. GOT was decreased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. In GOT activity, the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated showed higher level significant compared with the saline aqua-acupuncture treated group after $CCI_4$-intoxicated. 2. GPT was decreased with statistical significance in the Woolgum aqua-acupuncture treated after $CCI_4$-intoxicated. In GOT activity, the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated showed higher level significant compared with the saline aqua-acupuncture treated group after $CCI_4$-intoxicated. 3. LDH was decreased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. 4. Total protein increased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. 5. Albumin was increased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. The saline aqua-acupuncture treated group after $CCI_4$-intoxicated was not recognized as compared with $CCI_4$-intoxicated group. 6. Triglyceride was increased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. 7. WBC was decreased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. In WBC count, the Woolgum aqua-acupuncture higher level significant compared with the saline aqua-acupuncture treated group after $CCI_4$-intoxicated. 8. Lymphocyte was decreased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. 9. Neutrophils was increased with statistical significance in the Woolgum aqua-acupuncture treated group after $CCI_4$-intoxicated. The saline aqua-acupuncture treated group after $CCI_4$-intoxicated was not recognized as compared with $CCI_4$-intoxicated group. From above results, it is suggested that the Woolgum aqua-acupuncture had significant effects on the injury induced by $CCI_4$.
The purpose of present study is to observe the hepato-protective effect of ginger aqueous extracts on carbon tetrachloride($CCl_4$)-induced mouse. Ginger groups received ginger aqueous extracts (500 mg/kg) orally for 3 days and given a single dose of $CCl_4$ (4 mL/kg). Silymarin group was treated with silymarin (50 mg/kg) orally for 3 days and then aministration of $CCl_4$ (4 mL/kg). Control group was only administered $CCl_4$ (4 mL/kg). In the ginger groups, the AST, ALT levels were significantly (p < 0.05) decreased compared to the control groups. Histopathological evaluation, hepatic parenchyma and kidney parenchyma of ginger groups were significantly (p < 0.05) decreased compared to control group. The results obtained in this study suggest that ginger aqueous extracts are able to protect the liver $CCl_4$-induced injury.
This study was conducted to investigate the hepatoprotective effects of fermented Smilax china leaf ethylacetate extracts by Aspergillus oryzae on carbon tetrachloride-induced liver injury in mice. Experimental mice were divided into four groups (five mice/group) (NC; normal control group, CB; basic diet supplemented before $CCl_4$ treatment group, NS ; basic diet mixed with 0.5% Smilax china leaf ethyl acetate extract supplemented before $CCl_4$ treatment group, FS; basic diet mixed with 0.5% fermented Smilax china leaf ethyl acetate extract supplemented before $CCl_4$ treatment group) fed for 4 weeks each. In the $CCl_4$-treated groups (CB, NS and FS) compared with the NC group, liver weights, activities of alanine aminotransferase, aspartate aminotransferase, xanthine oxidase and aldehyde oxidase, contents of triglycerides, total cholesterol and LDL-cholesterol in serum, and hepatic lipid peroxide levels increased, whereas body weight gain and contents of glutathione and HDL-cholesterol decreased. Furthermore, in the FS groups compared with the NS and CB groups, increased or decreased indicators by $CCl_4$ treatment significantly decreased or increased, respectively. This study suggests that fermented Smilax china L. leaf extracts may regulate xanthine oxidase and aldehyde oxidase inhibitory activities and hepatoprotective effects due to flavonoid aglycone derived from its glycoside in leaves of Smilax china by fermentation of A. oryzae.
This study aimed to determine whether or not glycoprotein isolated from Cudrania tricuspidata Bureau fruit(CTB glycoprotein) exerts a hepatoprotective effect on liver injury induced by the administration of carbon tetrachloride($CCl_4$, 1.0mL/kg) to A/J mice. Following the administration of CTB glycoprotein(0-20mg/kg), the activities of antioxidant enzymes (superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase(GPx)), and the quantities of measured thiobarbituric acid reactive substances(TBARS), lactate dehydrogenase(LDH), and nitric oxide(NO) were evaluated from the murine liver tissues and plasma. Additionally, the activity of nuclear factor-kappa B(NF-${\kappa}B$) was assessed after pretreatment with $CCl_4$. When the mice were treated with $CCl_4$ alone, the activities of antioxidative enzymes reduced but amounts of TBARS, LDH, and NO increased. However, the results of treatment with CTB glycoprotein(10 and 20 mg/kg) revealed significantly increased activities of antioxidant enzymes(SOD, CAT, and GPx), as compared with $CCl_4$ alone. On the other hand, the result showed significant diminutions of the quantities of TBARS, LDH, and NO after treatment with CTB glycoprotein(10 and 20 mg/kg), as compared to $CCl_4$ alone. The activity of NF-${\kappa}B$ also declined after pretreatment with CTB glycoprotein, as compared with $CCl_4$ treatment alone. Thus, it is suggested that the CTB glycoprotein exerts a protective effect against $CCl_4$-induced liver injury in A/J mice.
Ha, Tae-Young;Jeong, Won-Il;Park, Sang-Joon;Jeong, Kyu-Shik;Lee, Cha-Soo
Korean Journal of Veterinary Pathology
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v.5
no.1
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pp.9-16
/
2001
To investigate the effects of safflower seed supplementation diet on the hepatic injury of rats administered with carbon tetrachloride (CCI$_4$), histopathological changes were assessed following acute and chronic administration in rats. In acute cases, all rats in group fed with 10% safflower seed supplementation diet survived despite the administration of lethal doses of $CCl_4$. However, most rats in group fed with control diet died. The hepatic injuries of survived rats, in the histopathological findings, were mild compared to those of dead rats. In the chronic cases, livers of group 2 fed with control diet were more progressive in fatty changes and centrilobular necrosis than those of group 3 fed with 20%safflower seed diet. However, after six weeks, livers of group 2 and 3 showed severe necrosis and mild fibrosis at the same time. Group 5 fed with 10% safflower seed supplementation diet and water containing 0.05% phenobarbital sodium showed mild fatty changes and necrosis compared with group 4 fed with control diet and water containing 0.05% phenobarbital sodium at sixth week. At 8 to 10 wee71s after the administration of $CCl_4$, severe fibrosis. fatty changes and marked necrosis were observed in group 4, but hepatic injuries were less severe in group 5. The present results suggested that safflower seed has some protective effect in hepatic lesions and consequently delay the progression of hepatic fibrosis.
Journal of the Korea Academia-Industrial cooperation Society
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v.20
no.2
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pp.520-526
/
2019
The purpose of this experiment is to investigate the feasibility of extracts (sample extract, MSE) mixed with hot - water extracts as health functional nutritional foods for prevention and treatment of liver damage. The experimental method was to investigate the effects of carbon tetrachloride on liver damage in rats by 60% of liver cirrhosis level. The effect of mixed extracts (MSE) was investigated by measuring the physiological functions, biochemical functions, and molecular biologic TGF - ${\beta}$ and P53 levels in liver - injured rats. with MSE doses administered differently(0.50ml, 0.75ml). A total of 30 rats were used for normal group, control group, positive control group, experimental group 1, and experimental group 2. The rats were given 6 times a week for 6 weeks at a fixed time once a day. The results of the experiment were statistically significantly higher in the control group than in the normal group and the positive control group, and statistically significantly lower in the experimental group (1 and 2) than the control group. There were some significant differences in the comparison between the experimental groups (1 and 2), but no significant changes were found. In conclusion, the results of this study are expected to be useful as functional food, and the variation of physiological activity and the degree of liver molecular biotechnology will be used for the research of the same field.
This study investigated the hepatoprotective effects of mesangi (Capsosiphon fulvecens) in carbon tetrachloride $(CCI_4)$-induced liver injury. Thirty healthy male Sprague-Dawley rats were divided into three groups : the normal (Normal), $CCI_4$-treated $(CCI_4)$, and mesangi-treated (Exp-CF) groups. Administration of $CCI_4$ increased the levels of GOT, GPT, and LDH in serum, while the levels were significantly decreased by the addition of mesangi. Higher levels of HDL-cholesterol were found in the Normal and Exp-CF groups, which has lower levels of total and LDL-cholesterol. Administration of $CCI_4$ also increased IGFBP-1 expression in serum, but it was decreased in the Exp-CF group. This suggests that $CCI_4$ is involved in the change in IGFBP-1 expression via its hepatotoxicity. The results indicate that mesangi has a hepatoprotective effect in rats given $CCI_4$.
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