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Hepatoprotective and antioxidant activity of methanolic extract of flowers of Nerium oleander against CCl_4-induced liver injury in rats

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Asian Pacific Journal of Tropical Medicine 2012年第9期5卷 677-685页

作者： Kumar Gaurav Singhal Ghanshyam Das Gupta Pharmacology & Toxicology Research Lab Department of PharmacologyASBASJSM College of PharmacyBelaRopar-140111PunjabIndia ASBASJSM College of Pharmacy BelaRopar-140111PunjabIndia

Objective:To investigate the antioxidant and hepatoproteetive activity of methanolic flower extract of Nerium oleander against CCl4—induced hepatotoxicity in ***:In vitro antioxidant activity of methanolic extract of dowers of Nerium oleander（MENO-F） was evaluated by various assays,including reducing power,lipid ***,superoxide anion,hydroxyl radicals and metal *** hepatoproteetive and in vivo antioxidant activity of MENO-F were evaluated against CCl4-induced hepatic damage in *** MENO-F at dose of 100.200 and 400 mg/kg were administered orally once daily for seven *** enzymatic levels of serum glutamate oxaloacetate transaminase（AST）,serum glutamate pyruvate transaminase（ALT）,serum alkaline phosphatase（ALP） and total bilirubin were estimated along with estimation of superoxide dismutase（SOD） and malondialdehvde（MDA） levels in liver *** histopathological examination of the liver sections was carried out to support the induction of hepalotoxicity and hepatoproteetive ***:The extract showed potent activities on reducing power,lipid *** anion,hydroxyl radical and metal *** substantially elevated serum enzymatic levels of AST,*** and total bilirubin were found to he restored towards normalization significantly by the MENO-F in a dose dependent manner with maximum hepatoprotection at 400 mg/kg dose *** histopathological observations supported the biochemical evidences of *** level of SOD and decreased level of MDA further strengthen the hepatoproteetive observations. The results of the present study strongly reveal that MENO-F has potent antioxidant activity and hepatoproteetive activity against CCl4—induced hepatic damage in experimental animals.

关键词： Hepatoprotective Antioxidant Carbon tetrachloride Nerium oleander Silymarin

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Lygodium flexuosum extract down regulates the expression of proinflammatory cytokines in CCl_4 -induced hepatotoxicity

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Asian Pacific Journal of Tropical Medicine 2012年第6期5卷 421-426页

作者： Pallara Janardhanan Wills Velikkakathu Vasumathi Asha Plant Based Bioactives and Disease Biology Laboratory Rajiv Gandhi Centre for BiotechnologyThiruvananthapuramKerala 695014India MIMS Research Foundation Malabar Institute of Medical SciencesCalicut-673007KeralaIndia

Objective:To examine the downregulalion of proinflammatory cytokines in a time dependant manner on carbon tetrachloride induced toxicity in experimental ***:CCl4（150μL/100 g） was dissolved in com oil（1:1 v/v%） and administered orally,GroupⅠwas treated as normal control and received corn oil on 8th ***Ⅱwas toxic control and was given a single dose of CCl4 on 8th ***Ⅲwas treated with Lygodium flexuosum（***） n-hexane extract（200 mg/kg） for 8 days and on 8th day a single dose of CCl4 was ***Ⅳ（negative contnil） received *** n-hexane extract（200 mg/kg） alone for 8 ***:Treatment with n-hexane extract prior to the administration of CCl4 significantly prevented an increase in serum AST,ALT,LDH activity and lipid peroxidation and prevented the depletion of glutathione （GSH）.Rats treated with *** had reduced mRNA levels of TGF-β1,TNF-αand IL-1βgenes in liver of CCl4 intoxicated rats when compared to CCl4 control as evidenced by RT-PCR. Conclusions:The data suggest that ***,a widely available fem,significantly reduces CCl4 induced acute hepatotoxicily by down-regulating the expression of pro-inflammatory cytokines in rats.

关键词： Lygodium flexuosum Carbon tetrachloride mRNA TGF-β1 TNF-α IL-1β

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Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl_4-induced liver injury

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Chinese Journal of Natural Medicines 2017年第7期15卷 525-533页

作者： GUO Qing ZHANG Qian-Qian CHEN Jia-Qing ZHANG Wei QIU Hong-Cong ZHANG Zun-Jian LIU Bu-Ming XU Feng-Guo MOE Key Laboratory of Drug Quality Control and Pharmacovigilance China Pharmaceutical University Nanjing 210009 China State key laboratory of natural medicine China Pharmaceutical University Nanjing 210009 China State Key Laboratory for Quality Research in Chinese Medicines Macao University of Science & Technology Avenida Wai Long Taipa Macao China Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards Nanning 530022 China

Phyllanthus Urinaria L.(PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl_4-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl_4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl_4-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis(OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl_4-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

关键词： Metabolomics Hepatic protection Phyllanthus Urinaria Carbon tetrachloride

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Yiguanjian decoction enhances fetal liver stem/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state

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World Journal of Gastroenterology 2018年第42期24卷 4759-4772页

作者： Ying Xu Wei-Wei Fan Wen Xu Shi-Li Jiang Gao-Feng Chen Cheng Liu Jia-Mei Chen Hua Zhang Ping Liu Yong-Ping Mu Department of Hepatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Liver Diseases Shanghai University of Traditional Chinese MedicineShanghai 201203China Key Laboratory of Liver and Kidney Disease of the Ministry of Education Shanghai 201203China Clinical Key Laboratory of TCM of Shanghai Shanghai 201203China

AIM To investigate whether Yiguanjian decoction(YGJ) has an anti-liver cirrhotic effect and whether it regulates hepatic stem cell *** A rat model of liver cirrhosis was established via subcutaneous injection of carbon tetrachloride(CCl4) for8 wk. From the beginning of the ninth week, the rats received 2-acetylaminofluorene(2-AAF) by oral gavage and a DLK-1+ fetal liver stem/progenitor cell(FLSPC)transplant or an FLSPC transplant in combination with YGJ treatment for 4 wk. In vitro, lipopolysaccharide(LPS)-activated macrophages were co-cultured with WB-F344 cells, and the differentiation of WB-F344 cells was observed in the presence and absence of YGJ *** FLSPC transplantation improved liver function and histopathology, and inhibited the activation of the noncanonical Wnt signaling pathway, while activating the canonical Wnt signaling pathway. YGJ enhanced the therapeutic effects of FLSPCs and also promoted the liver regeneration differentiation of FLSPCs into *** vitro, LPS-activated macrophages promoted the differentiation of WB-F344 cells into myofibroblasts, and the canonical Wnt signaling was inhibited while the noncanonical Wnt signaling was activated in WB-F344 *** suppressed the activation of macrophages and then inhibited non-canonical Wnt signaling and promoted canonical Wnt *** YGJ enhances FLSPC-mediated repair of liver cirrhosis through regulation of macrophage activation state, and YGJ in combination with stem cell transplantation may be a suitable treatment for end-stage liver cirrhosis.

关键词： Cirrhosis Hepatic progenitor cells Wnt signaling pathway Macrophage 2-acetylaminofluorene Carbon tetrachloride Yiguanjian decoction

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Hemodynamic changes in hepatic sinusoids of hepatic steatosis mice

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World Journal of Gastroenterology 2019年第11期25卷 1355-1365页

作者： Jing Fan Chong-Jiu Chen Yu-Chen Wang Wei Quan Jian-Wei Wang Wei-Guang Zhang Department of Anatomy Histology and EmbryologySchool of Basic Medical SciencesPeking University Health Science Center

BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the *** To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic *** Eight-week-old male C57 BL/6 mice were divided into three groups randomly(control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin(HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic *** Oil red O staining indicated lipid accumulation in the liver after CCl_4 *** staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice onmorphological examination. Hemorheological tests included whole blood viscosity(mPas, γ = 10 s-1/γ = 100 s-1)(8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ±1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume(%)(51.00 ± 4.00, 42.00 ±5.00, and 40.00 ± 3.00), the content of plasma fibrinase(g/L)(3.80 ± 0.50, 2.90 ±0.80, and 2.30 ± 0.70), erythrocyte deformation index(%)(44.49 ± 5.81, 48.00 ±15.29, and 44.36 ± 15.01), eryt

关键词： Hepatic steatosis Hemodynamics Hepatic sinusoids Two-photon fluorescence microscopy Carbon tetrachloride

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Efficacy evaluation of the protein isolated from Peganum harmala seeds as an antioxidant in liver of rats

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Asian Pacific Journal of Tropical Medicine 2013年第4期6卷 285-295页

作者： Amel M Soliman Helal S Abu-El-Zahab Gamiaa A Alswiai Zoology Department Faculty of ScienceCairo University Zoology Department Faculty of Science

Objective:To evaluate the curative effect of the 132 KD protein isolated from the seeds of Peganum harmala（***） L against carbon tetrachloride（CCl4） induced oxidative stress in ***:Animals were post treated intraperitoneally with 132 KO isolated protein at doses of 4 and 8 mg/kg body weight and bovine serum albumin（BSA）（8 mg/kg body weight） as well as vitamin C（250 mg/kg body weight p.o.） for 7 d after they challenged with CCl4 orally（1 ml/Ag body weight） in olive oil（50%） for 2 ***:The purified protein from seeds of *** plant showed in vitro antioxidant activity with DPPH *** of CCl4 induced induction in serum aminotransferases（AST,ALT）,alkaline phosphatase（ALP）,lipid profile parameters and liver malondialdehyde（MDA） and decrease in serum total protein,liver superoxide dismutase （SOD）,catalase（CAT）,and reduced glutathione（GSH） levels.132 KD protein treatment of rats post CCl4 intoxication successfully alleviated the toxic effects of CCl4.Conclusions:The isolated protein possessed strong antioxidant activity comparable to that of BSA（negative control） and vitamin C（positive control）.

关键词： Carbon tetrachloride Peganum harmala Oxidative stress 132 KD isolated protein

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In vitro and in vivo antioxidative and hepatoprotective activity of aqueous extract of Cortex Dictamni

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World Journal of Gastroenterology 2017年第16期23卷 2912-2927页

作者： Lin Li Yun-Feng Zhou Yan-Lin Li Li-Li Wang Hiderori Arai Yang Xu Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100193China Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine Ministry of EducationBeijing 100193China Department of Human Health Sciences Kyoto University Graduate School of MedicineKyoto 606-8507Japan

AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in *** The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl(DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate(FTC) and thiobarbituric acid(TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1(CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinine oxidoreductase 1(NQO1), and γ-glutamylcysteine synthetase catalytic subunit(γ-GCSc) protein expression was measured by Western *** Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation(P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE(160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes(P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities

关键词： Cortex Dictamni Antioxidant activity Hepatoprotective Carbon tetrachloride Nrf2

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In vivo antioxidant effect of aqueous root bark,stem bark and leaves extracts of Vitex doniana in CCl_4 induced liver damage rats

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Asian Pacific Journal of Tropical Biomedicine 2013年第5期3卷 395-400页

作者： Kadejo Olubukola Adetoro James Dorcas Bolanle Sallau Balarebe Abdullahi Ozigi Abdulrahaman Ahmed Department of Biochemistry Ahmadu Bello University

Objective:The antioxidant effects of aqueous root bark,stem bark and leaves of Vitex doniana(***)were evaluated in carbon tetrachloride(CCl_4)induced liver damage and non induced liver damage albino ***:A total of 60 albino rats(36 induced liver damage and 24 non induced liver damage)were assigned into liver damage and non liver damage groups of 6 rats in a *** animals in the CCl_4 induced liver damage groups,were induced by intraperitoneal injection with a single dose of CCl_4(148mg·ml^(-1)·kg^(-1)body weight)as a 1:1(v/v)solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark,stem bark and leaves extracts of *** and vitamin E as standard drug(100 mg/kg body weighy per day)for 21 d,while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same *** administration of CCl_4 was done once a week for a period of three ***:The liver of CCl_4 induced not treated group showed that the induction with CCl_4,significantly(P0.05)difference between TBARS,SOD and CAT in the liver of the induced treated groups and normal control *** the *** showed no significant(P>0.05)difference between the normal and the induced groups,SOD was significantly(P0.05)change in the liver and kidney level of TBARS,SOD and CAT compared with the normal control except in the kidney of animals treated with stem extract where TBARS was significantly(P<0.05)lowered compare

关键词： Antioxidant Vitex doniana Carbon tetrachloride

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Hepatocurative potential of Vitex doniana root bark,stem bark and leaves extracts against CCl_4-induced liver damage in rats

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Asian Pacific Journal of Tropical Biomedicine 2014年第6期4卷 480-485页

作者： James Dorcas Bolanle Kadejo Olubukola Adetoro Sallau Abdullahi Balarabe Owolabi Olumuyiwa Adeyemi Department of Biochemistry Ahmadu Bello University

Objective:To evaluate the hepatocurative effects of aqueous root bark,stem bark and leaves of Vitex doniana in carbon tetrachloride(CCl_4)induced liver damage and non induced liver damage albino ***:A total of 60 albino rats(36 induced liver damage and 24 non induced liver damage)were assigned into liver damage and non liver damage groups of 6 rats in a *** animals in the CCl_4 induced liver damage groups,were induced by intraperitoneal injection with a single dose of CCl_4(1 mL/kg body weight)as a 1:1(v/v)solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark,stem bark and leaves extracts of Vitex doniana and vitamin E as standard drug(100 mg/kg body weight per day)for 21 d,while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same *** administration of CCl_4 was done once a week for a period of 3 ***:There was significant(P<0.05)increase in concentration of all liver marker enzymes,alanine aminotransferase,aspartate aminotransferase and alkaline aminotransferase(ALT,AST and ALP)and significant(P<0.05)decrease in albumin in the CCl_4 induced liver damage control when compared to the normal *** extracts caused a significant(P<0.05)reduction in the serum activities of liver marker enzymes(ALT,AST and ALP)and a significant(P<0.05)increase in albumin of all the induced treated *** stem bark extract and vitamin E significantly(P<0.05)increased total *** the extracts significantly(P<0.05)lowered serum creatinine whereas only root bark extract significantly(P<0.05)lowered serum level of urea in the rats with CCl_4 induced liver ***:Hepatocurative study shows that all the plant parts(root bark,stem bark and leaves)possess significant hepatocurative properties among other therapeutic values justifying their use in folklore medicine.

关键词： Vitex doniana Hepatocurative Liver damage Creatinine Carbon tetrachloride

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Protective effect of Tetracera scandens *** extract against CCl_4-induced acute liver injury in rats

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Asian Pacific Journal of Tropical Biomedicine 2015年第3期5卷 221-227页

作者： Tung Bui Thanh Hai Nguyen Thanh Hue Pham Thi Minh Huong Le-Thi-Thu Huong Duong Thi Ly Loi Vu Duc School of Medicine and Pharmacy Vietnam National University Hanoi University of Pharmacy

Objective:To investigate the protective potential of ethanolic extracts of Tetracera scandens L.(***) against CCl_4 induced oxidative stress in liver ***:Dried leaf powder of *** was extracted with ethanol and concentrated to yield a dry *** were administered with 100 mg/kg of ethanolic extracts orally once daily for one *** were subsequently administered with a single dose of CCl_4(I mL/kg body weight,intraperitoneal injection).Various assays,such as serum levels of alanine aminotransferase,aspartate aminotransferase,lipid peroxidation,protein oxidation(carbonyl protein group),tumor necrosis factor alpha,catalase,superoxide dismutase,and glutathione peroxidase,were used to assess damage caused by CCl_4 and the protective effects of the ethanol extract on liver ***:Hepatotoxicity induced by CCl_4 was evidenced by a significant increase in serum aspartate aminotransferase and alanine aminotransferase level,lipid peroxidation,protein carbonyl group,and tumor necrosis factor alpha,as well as decreased activity of the hepatic antioxidant enzymes(*** *** glutathione peroxidase).Treatment with ethanolic *** extracts prevented all of these typically observed changes in CCl_4-treated ***:Our findings indicate that *** has a significant protective effect against CCl_4 induced hepatotoxicity in *** may be due to its antioxidant properties.

关键词： Tetracera scandens L Antioxidant Carbon tetrachloride Liver toxicity Lipid peroxidation

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