1.Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts.
Mi CHEN ; Tao WANG ; Zhen-Zhou JIANG ; Chun SHAN ; Hao WANG ; Mei-Juan WU ; Shuang ZHANG ; Yun ZHANG ; Lu-Yong ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2014;12(8):590-598
The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts (AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride (CCl4)-induced hepatitis in mice, D-galactosamine (D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.
Abrus
;
chemistry
;
Animals
;
Anti-Inflammatory Agents
;
pharmacology
;
therapeutic use
;
Biomarkers
;
blood
;
Carbon Tetrachloride
;
Carrageenan
;
Chemical and Drug Induced Liver Injury
;
drug therapy
;
metabolism
;
pathology
;
Edema
;
chemically induced
;
drug therapy
;
Female
;
Flavonoids
;
pharmacology
;
therapeutic use
;
Galactosamine
;
Glycosides
;
pharmacology
;
therapeutic use
;
Inflammation
;
chemically induced
;
drug therapy
;
pathology
;
Liver
;
drug effects
;
metabolism
;
pathology
;
Liver Cirrhosis
;
drug therapy
;
Male
;
Mice, Inbred ICR
;
Monosaccharides
;
Phytotherapy
;
Plant Extracts
;
pharmacology
;
therapeutic use
;
Protective Agents
;
pharmacology
;
therapeutic use
;
Rats, Sprague-Dawley
;
Xylenes
2.Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion.
Martin Humberto MUNOZ-ORTEGA ; Raul Wiliberto LLAMAS-RAMIREZ ; Norma Isabel ROMERO-DELGADILLO ; Tania Guadalupe ELIAS-FLORES ; Edgar DE JESUS TAVARES-RODRIGUEZ ; Maria DEL ROSARIO CAMPOS-ESPARZA ; Daniel CERVANTES-GARCIA ; Luis MUNOZ-FERNANDEZ ; Martin GERARDO-RODRIGUEZ ; Javier VENTURA-JUAREZ
Gut and Liver 2016;10(1):101-108
BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
Adrenergic alpha-1 Receptor Antagonists/*pharmacology
;
Alanine Transaminase/blood
;
Animals
;
Aspartate Aminotransferases/blood
;
Bilirubin/blood
;
Carbazoles/*pharmacology
;
Carbon Tetrachloride
;
Collagen Type I/drug effects/metabolism
;
Cricetinae
;
Doxazosin/*pharmacology
;
Liver/metabolism/pathology
;
Liver Cirrhosis/blood/chemically induced/*drug therapy
;
Liver Function Tests
;
Propanolamines/*pharmacology
;
Serum Albumin/analysis
;
Transforming Growth Factor beta/blood/*drug effects
3.Inhibitory effect of anluohuaxianwan on experimental hepatic fibrosis in rats.
Xing-Hua TAN ; Chang-Qing LI ; Shang-Rong ZOU ; Min XIE ; Ai-Min ZHANG ; Wen-Li LI ; Xiao-Yue LI ; Hui-Fen HUANG ; Chun-Liang LEI
Chinese Journal of Hepatology 2010;18(1):9-12
OBJECTIVETo investigate the effects of anluohuaqianwan on experimental hepatic fibrosis induced by dimethyl nitrosamine (DMN) in rats.
METHODS36 male SD rats were randomly dividied into three groups: model group, normal group, anluohuaqianwan group. The rats in the three groups were treated with DMN daily for 4 weeks. The liver function was detected using auto biochemistry analyzer, the serum HA, LN, IV-C, PIIIP were detected by immunoradiometry, the histopathology was observed in the left liver lobe after HE staining, the expression of matrix metalloproteinase-2 (MMP-2) in liver tissue were detected by immunohistochemistry.
RESULTSThe serum levels of ALT, AST, ALP, TP, ALB and the contents of HA, LN, IV-C in model group were significantly increased compared to these in the normal group (P less than 0.01). The serum levels of ALT, AST and the contents of HA in anluohuaqianwan group were significantly lower than those in the model group (P less than 0.01). The liver MMP-2 in the model group was significantly increased compared to that in the normal group (P less than 0.05). The expression of MMP-2 in liver tissue of model group was lower than that in the anluohuaqianwan group (P less than 0.05).
CONCLUSIONAnluohuaqianwan can inhibit liver fibrosis in rats induced by DMN.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Dimethylnitrosamine ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hyaluronic Acid ; blood ; Hydroxyproline ; metabolism ; Immunohistochemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; metabolism ; pathology ; Liver Function Tests ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley
4.Therapeutic effect of Hongbeiyegen on alcohol-induced rat hepatic fibrosis.
Xiao-Yan LÜ ; Qiang LIU ; Yu-Yao CHEN ; Yu-Hong SONG ; Zhi-Ping LÜ
Journal of Southern Medical University 2007;27(2):153-155
OBJECTIVETo observe the therapeutic effect of Hongbeiyegen [the root of Alchornea trewioides(Benth.) Muell.-Arg.] on alcohol-induced liver fibrosis (AF) in rats and explore its mechanism.
METHODSIn rats with AF, the serum levels of transforming growth factor beta1 (TGFbeta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected along with examination of the changes in serum hyaluronic acid (HA), laminin (LN), procolagen type III (PC III), collagen type IV (C IV), glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) levels.
RESULTSCompared with the control group, Hongbeiyegen could significantly reduce the levels of TGFbeta1, TIMP-1, HA, LN, PC III, CIV, ALT and AST in rats with AF.
CONCLUSIONHongbeiyegen can relieve and ameliorate liver fibrosis possibly by inhibiting the expression of TGFbeta1 and TIMP-1.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Collagen Type III ; blood ; Collagen Type IV ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Ethanol ; Euphorbiaceae ; chemistry ; Female ; Hyaluronic Acid ; blood ; Laminin ; blood ; Liver Cirrhosis, Experimental ; blood ; chemically induced ; drug therapy ; Male ; Phytotherapy ; Plant Roots ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Transforming Growth Factor beta1 ; blood
5.Experimental study of saikosaponin-D (SSd) on lipid peroxidation of hepatic fibrosis on rat.
Yan HE ; Zhi-Feng HU ; Ping LI ; Cheng XIAO ; Yu-Wu CHEN ; Ke-Ming LI ; Jing-Zhen GUO ; Lin PAN ; Jia-Peng XIONG
China Journal of Chinese Materia Medica 2008;33(8):915-919
OBJECTIVETo study the effect of SSd on lipid peroxidation during experimental hepatic fibrosis progression.
METHODThe experimental models of hepatic fibrosis were induced by intraperitoneal injection of dimethylnitrosamine (DMN) on rats. SSd was administered by intraperitoneal injection for 4 weeks. Serum was analyzed for alanine and aspartate aminotransferase (ALT and AST), hyaluronic acid (HA), laminin (LN), collagen IV (IV-C), malonaldehyde (MDA) and superoxide dismutase (SOD) activities. Liver samples were measured for MDA contents and SOD activities in normal group, model group and SSd group.
RESULTSSd significantly decreased ALT and AST activities and lowered HA, LN and IV-C contents. It enhanced SOD activities in liver, while reduced MDA contents both in serum and liver.
CONCLUSIONSSd has obvious effects of protecting hepatocytes and resisting hepatic fibrosis, and the mechanism may be associated with its anti-lipid peroxidation effect.
Animals ; Aspartate Aminotransferases ; blood ; Collagen Type IV ; blood ; Dimethylnitrosamine ; adverse effects ; Hyaluronic Acid ; blood ; Laminin ; blood ; Lipid Peroxidation ; drug effects ; Liver Cirrhosis ; blood ; chemically induced ; drug therapy ; metabolism ; Malondialdehyde ; blood ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; therapeutic use ; Rats ; Saponins ; pharmacology ; therapeutic use ; Superoxide Dismutase ; blood
6.Experimental study of the therapeutic effect of interferon-alpha on liver fibrosis.
Yiqun HUANG ; Chongguo WANG ; Shuqing LI ; Mingxing ZHOU
Chinese Journal of Hepatology 2002;10(1):71-71
Animals
;
Carbon Tetrachloride
;
Collagen Type IV
;
blood
;
Disease Models, Animal
;
Hyaluronic Acid
;
blood
;
Inflammation
;
drug therapy
;
etiology
;
Interferon-alpha
;
therapeutic use
;
Laminin
;
blood
;
Liver Cirrhosis
;
blood
;
chemically induced
;
complications
;
drug therapy
;
pathology
;
Rats
;
Rats, Sprague-Dawley
;
Transforming Growth Factor beta
;
blood
7.Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome.
Hae Rim KIM ; Young Sun LEE ; Hyung Joon YIM ; Hyun Joo LEE ; Ja Young RYU ; Hyun Jung LEE ; Eileen L. YOON ; Sun Jae LEE ; Jong Jin HYUN ; Sung Woo JUNG ; Ja Seol KOO ; Rok Sun CHOUNG ; Sang Woo LEE ; Jai Hyun CHOI
Clinical and Molecular Hepatology 2013;19(4):417-420
Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.
Bilirubin/blood
;
Creatinine/blood
;
Electrocardiography
;
Fatal Outcome
;
Hepatorenal Syndrome/*drug therapy
;
Humans
;
Intestinal Mucosa/pathology
;
Intestines/surgery
;
Liver Cirrhosis/diagnosis/therapy
;
Lypressin/adverse effects/*analogs & derivatives/therapeutic use
;
Male
;
Middle Aged
;
Necrosis/*chemically induced/surgery
;
Tomography, X-Ray Computed
;
Vasoconstrictor Agents/*adverse effects/*therapeutic use
8.A Case of Osteomalacia Related to Adefovir in a Patient with Chronic Hepatitis B.
Su Young AHN ; Soon Young KO ; Yun Mi JANG ; Yong Hoon CHOI ; Byung Kook KIM ; Won Hyeok CHOE ; Chang Hong LEE ; So Young KWON
The Korean Journal of Gastroenterology 2010;56(2):117-120
Adefovir dipivoxil, an acyclic nucleoside analogue, has been approved for the treatment of patients with chronic hepatitis B. This agent is efficacious particularly in those who have developed lamivudine resistance. The report according to hypophosphatemia induced by low dose adefovir therapy is very rare. We report one case in which osteomalacia with hypophosphatemia developed in a patient with chronic hepatitis B on adefovir dipivoxil at a low dose, 10 mg daily. A 66-year-old man, who had been taking adefovir for more than 4 years due to lamivudine resistance, presented with muscle weakness and bone pain in both thighs. After 3 years of adefovir therapy, hypophosphatemia and elevated serum alkaline phosphatase levels had been noted. A bone scan showed multiple hot uptakes. All the image findings and clinical symptoms, such as bone pain and muscle weakness were improved after correcting the hypophosphatemia with oral phosphorous supplementation.
Adenine/adverse effects/*analogs & derivatives/therapeutic use
;
Aged
;
Alkaline Phosphatase/blood
;
Antiviral Agents/*adverse effects/therapeutic use
;
DNA, Viral/blood
;
Dietary Supplements
;
Hepatitis B, Chronic/*drug therapy
;
Humans
;
Hypophosphatemia/*chemically induced/complications
;
Liver Cirrhosis/diagnosis
;
Male
;
Osteomalacia/*diagnosis/etiology
;
Phosphates/blood
;
Phosphonic Acids/*adverse effects/therapeutic use
;
Whole Body Imaging
9.Protective effect of isoorientin on alcohol-induced hepatic fibrosis in rats.
Yong-Xin CHEN ; Quan-Fang HUANG ; Xing LIN ; Jin-Bin WEI
China Journal of Chinese Materia Medica 2013;38(21):3726-3730
OBJECTIVETo observe the effect and mechanism of isoorientin from Gypsophila elegans on alcohol-induced hepatic fibrosis in rats.
METHODninety healthy male Wistar rats were randomly divided into six groups: the normal control group, the model control group, the colchicines group (positive control, 1.0 mg x kg(-1) x d(-1)), the high, middle and low-dose isoorientin groups (20, 50, 100 mg x kg(-1) x d(-1)). The normal control group received normal saline, while other groups received alcohol to cause hepatic fibrosis. After 24-weeks treatment, the alanine aminotransferase (ALT), aspartate aminotransferase (AST), Interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), hyaluronic acid (HA), laminin (LN), type III precollagen (PCIII), hydroxyproline (Hyp), Myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were assayed according to the manufacturer's instructions, the alpha-SMA and TGF-beta1 were detected by western blotting, and the histopathological changes was observed by H&E staining.
RESULTIsoorientin could improve the liver function by decreasing the activity of ALT, AST, IL-6, TNF-alpha, MDA, MPO, HA, LN, PCIII and Hyp (P < 0.05), increasing the activity of SOD and GSH-Px (P < 0.05), and reducing the expression of alpha-SMA and TGF-beta1 (P < 0.05). In addition, the high and middle-dose isoorientin groups showed more remarkable effect
CONCLUSIONIsoorientin from G. elegans can protect hepatic fibrosis induced by alcohol.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Drugs, Chinese Herbal ; administration & dosage ; Ethanol ; adverse effects ; Glutathione Peroxidase ; blood ; Humans ; Liver Cirrhosis ; chemically induced ; drug therapy ; enzymology ; prevention & control ; Luteolin ; administration & dosage ; Male ; Protective Agents ; administration & dosage ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; metabolism
10.A Case of Ischemic Skin Necrosis after Glypressin Therapy in Liver Cirrhosis.
Ji Eun OH ; Jung Soo HA ; Dae Hyeon CHO ; Gil Jong YU ; Sang Goon SHIM
The Korean Journal of Gastroenterology 2008;51(6):381-384
Terlipressin is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion. Thus, it has a less adverse reaction than vasopressin. We report a case of ischemic skin complication in a cirrhotic patient treated with terlipressin. A 71-year-old man with liver cirrhosis was admitted because of hematemesis and melena. He was commenced on terlipressin at a dose 1 mg every 6 hours for the treatment of varicieal bleeding. After 36 hours of treatment, skin blistering and ecchymosis was noted on the skin of his upper thigh, scrotal area and trunk. We found that terlipressin was a possible cause of ischemic skin complication based on the skin biopsy finding. Terlipressin may induce a complication of the ischemic event. In spite of rarity, special attention needs to paid on the peripheral ischemic complication of terlipressin.
Aged
;
Fatal Outcome
;
Hematemesis/diagnosis
;
Hemorrhage/drug therapy
;
Humans
;
Ischemia/*chemically induced/*pathology
;
Liver Cirrhosis/*complications
;
Lysine Vasopressin/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use
;
Male
;
Melena/diagnosis
;
Necrosis
;
Skin/*blood supply/drug effects/*pathology
;
Vasoconstrictor Agents/administration & dosage/*adverse effects/therapeutic use