OBJECTIVEThe efficiency network is a complicated network for revealing the efficient mechanism of traditional Chinese medicines (TCMs) and relations among efficiencies. The efficiency-property relations were used to establish a warm-pungent-liver efficiency network to explain the principle of treating hepatoma with medicines invigorating blood circulation and eliminating blood stasis. Safflower, a warm-pungent medicine distributing along the live meridian, was taken for example to discuss the efficiency network' s application in the identification of active ingredients of TCMs and the combination.

METHODIn the early stage of this study, combined warm-pungent-liver medicines distributed along the liver meridian and invigorating blood circulation and eliminating blood stasis were taken as the study objects to collect the pharmacological effect data of warm-pungent-liver medicines and obtain the pharmacological effect combinations with the highest blood circulation-invigorating association by the association rules and the chi-square test. The pharmacological target data recorded in the DrugBank database is used to establish the warm-pungent-liver efficiency network according to the principle line of "efficiency-property-pharmacology-target-protein interaction" under the background of the protein interaction network.

RESULTThe blood circulation-invigorating medicines could directly treat hepatoma by impacting protooncogene, cancer suppressor gene, cell apoptosis and anti-inflammation, and indirectly treat hepatoma by resisting coagulation and adhesion, regulating local blood circulation, preventing cancer cell metastasis and enhancing the tissues' sensitivity to the anticancer drugs. Among the active ingredients of safflower screened based on the blood circulation-invigorating network targets, carthamin yellow, quercetin and luteolin have been proved to have the anti-hepatoma effect in literatures, which indicated the reliability of this study's results and the purpose of the efficiency network.

CONCLUSIONThe efficiency network is an effective method for revealing the TCM's mechanism, and lays a foundation for discovering key active ingredients of TCMs for treating specific diseases.

Antineoplastic Agents, Phytogenic ; chemistry ; therapeutic use ; Blood Circulation ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Gene Regulatory Networks ; drug effects ; Humans ; Liver ; blood supply ; drug effects ; Liver Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology

We previously demonstrated that there are acute and delayed phases of renal protection against renal ischemia and reperfusion (IR) injury with renal ischemic preconditioning (IPC). This study assessed whether hepatic IPC could also reduce distant renal IR injury through the blood stream-mediated supply of reactive oxygen species (ROS). Male C57BL/6 mice were randomly divided into four groups: group I, sham operated including right nephrectomy; group II (IR), left renal ischemia for 30 min and reperfusion injury; group III (IPC-IR), hepatic ischemia for 10 min followed by 10 min of reperfusion before left renal IR injury; group IV (MPG - IPC + IR), pretreated with 100 mg/kg N-(2-mercaptopropionyl)-glycine (MPG) 15 min before hepatic IPC and left renal IR injury. Renal function, histopathologic findings, proinflammatory cytokines, and cytoprotective proteins were evaluated 15 min or 24 hr after reperfusion. Hepatic IPC attenuated the expression of proinflammatory cytokines, tumor necrosis factor alpha, intercellular adhesion molecule 1, and induced inducible nitric-oxide synthase, and the phosphorylation of Akt in the murine kidney. Renal function was better preserved in mice with hepatic IPC (group III) than groups II or IV. Hepatic IPC protects against distant renal IR injury through the blood stream-delivery of hepatic IPC-induced ROS, by inducing cytoprotective proteins, and by inhibiting inflammatory reactions.
Animals ; Intercellular Adhesion Molecule-1/genetics/metabolism ; *Ischemic Preconditioning ; Kidney/drug effects/metabolism/pathology/physiopathology ; Liver/blood supply/drug effects/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide Synthase Type II/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Reactive Oxygen Species/metabolism ; Reperfusion Injury/*metabolism/pathology/prevention & control ; Tiopronin/pharmacology ; Tumor Necrosis Factor-alpha/genetics/metabolism

Animals ; Colon ; blood supply ; pathology ; Colonic Diseases ; drug therapy ; etiology ; physiopathology ; Hemodynamics ; Hepatic Veins ; pathology ; physiopathology ; Hypertension, Portal ; complications ; physiopathology ; Intestinal Mucosa ; blood supply ; drug effects ; pathology ; Liver Cirrhosis, Experimental ; complications ; Losartan ; administration & dosage ; therapeutic use ; Male ; Microscopy ; Portal Pressure ; drug effects ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo study the protective function and pathophysiology of cystathionine gamma-lyase (CSE)/hydrogen sulfide (H(2)S) system in hepatic ischemia-reperfusion injury (HIRI) in rats.

METHODSWistar rats were randomly distributed into sham group (n = 18), ischemia-reperfusion (IR) group (n = 18), IR + NaHS group (n = 18) and IR + DL-propargylglycine (PAG) group (n = 18). The hepatic IR model was established by Pringle's hepatic vascular occlusion. At each of the indicated time points (1, 3 and 6 hours after IR), the serum levels of H(2)S and the hepatic CSE activity were measured. The serum levels of inflammatory factors, including TNF-α, IL-10 were determined by ELISA methods. The expression of apoptotic protein, TNF-α, in liver tissue was tested by Western blot assay, cell apoptosis was examined by TUNEL and the histological changes were examined in each group.

RESULTSThe serum levels of H(2)S and CSE activity were significantly increased in group IR compared with group sham at all indicated time points (P < 0.05). The serum level of inflammatory factors (P < 0.01) and the hepatic expression of TNF-α protein (P < 0.05) were elevated obviously in group IR than that in group sham. Administration of NaHS could reduce the production of inflammatory factors in serum (P < 0.01), inhibit hepatic protein expression of TNF-α (P < 0.05) and attenuate the liver histological scores of IR injury (P < 0.05), whereas PAG aggravated them.

CONCLUSIONThe endogenous CSE/H(2)S system maybe involved in the pathogenesis of hepatic IR injury, which suggests that CSE/H(2)S system can protect liver from IR injury in rats by intervening in inflammatory reaction, attenuating the injury severity and inhibiting expression of apoptotic protein TNF-α.

Animals ; Apoptosis ; drug effects ; Cystathionine gamma-Lyase ; blood ; physiology ; Disease Models, Animal ; Hydrogen Sulfide ; blood ; Interleukin-10 ; blood ; Liver ; blood supply ; metabolism ; pathology ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology ; physiopathology ; prevention & control ; Sulfides ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo observe the effect of umbilical sticking therapy (UST) with Qitou Xiaugu Plaster (QXP) on hemodynamics of portal system in patients with liver cirrhosis.

METHODSOne hundred and twenty patients of liver cirrhosis with portal hypertension were assigned to two groups. On the basis of conventional therapy, UST was applied in the 66 patients in treated group, which was exchanged once every 3 days with an interval of 1-day rest. The 54 patients in the control group were orally administered with propanolol. The therapeutic course for both groups was 1 month. Before and after treatment, the hemodynamic changes in portal or splenic veins were observed by color Doppler ultrasonograph, and the changes of liver function, blood coagulation and patients' subjective symptoms were observed as well.

RESULTSAfter treatment, portal vein diameter and splenic vein diameter significantly decreased (P < 0.05, portal venous flow velocity and splenic venous flow velocity apparently increased (P < 0.05), and portal venous flow apparently decreased in both groups (P < 0.05), while no significant change was found in the splenic venous flow (P > 0.05). The liver function and blood coagulation indexes in both groups were improved. The improvement of clinical symptoms in the treated group was superior to that in the control group.

CONCLUSIONUST with QXP could decrease the portal vein pressure in a short time, with the therapeutic effect comparable to propanolol, and with no adverse reaction.

Adult ; Aged ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hemodynamics ; drug effects ; Humans ; Hypertension, Portal ; drug therapy ; physiopathology ; Liver Cirrhosis ; drug therapy ; physiopathology ; Male ; Middle Aged ; Portal Pressure ; drug effects ; Portal Vein ; drug effects ; physiopathology ; Splenic Vein ; drug effects ; physiopathology ; Umbilicus ; blood supply ; Young Adult

OBJECTIVETo study whether ginsenoside (GS) can regulate the glucocorticoid receptor (GR) in mice with ischemic liver damage, and to preliminarily observe its dose-effect relationship for providing an experimental bases in seeking a new way to relieve the damage from view of GR.

METHODSAdult male SD mouse was used to establish liver ischemia model, and different doses (100, 50, and 25 mg/kg) of GS was given via gastric infusion before modeling. The maximal GR binding capacity (Bmax) of liver and the level of GR mRNA expression in liver were dynamically determined at various time points (2 h, 6 h, 12 h and 24 h) after modeling.

RESULTSCompared with the normal control group, GR Bmax and GR mRNA expression in model rats were lower obviously (P < 0.01). As compared with the control group, GR Bmax and GR mRNA expression in model rats treated with 50 mg/kg GS significantly raised at 2 h, 6 h, 12 h (P < 0.01), while the changes in modeling rats treated with other two doses of GS were of no statistical significance.

CONCLUSIONGS in dose of 50 mg/kg can elevate the GR Bmax of liver and the level of GR mRNA expression in liver of rats with ischemic damage.

Animals ; Gene Expression Regulation ; drug effects ; Ginsenosides ; pharmacology ; Ischemia ; physiopathology ; Liver ; blood supply ; drug effects ; metabolism ; Male ; Mice ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Receptors, Glucocorticoid ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors

OBJECTIVETo investigate the protective effects of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs) their and mechanisms in liver ischemic preconditioning.

METHODSIn rat models of liver ischemia-reperfusion (IR) and ischemic preconditioning (IP), the liver function was evaluated by examining serum alanine aminotransferase and aspartate aminotransferase levels, and the morphological changes of the liver cells were observed under microscope. PKC activator phorbol 12-myristate 13-acetate(PMA) and inhibitor chelerythrine(CHE), as well as MEK inhibitor PD98059, were utilized to analyze the phosphorylation of PKC and P44/42 MAPKs.

RESULTSCompared with the control rats, the liver function was best protected in rats of IP group, but not in those of IP group with PD98059 or CHE treatment. The rats in IR group showed improved liver function after PMA treatment. Similarly, the phosphorylation of PKC and P44/42 MAPKs was correlated with the liver function, and highly enhanced PKC and P44/42 MAPKs activity was observed in IP and IR+PMA groups, but decreased activity in IR and IP+CHE groups.

CONCLUSIONPhosphorylation of PKC and MAPKs plays a pivotal role in the preservation of the hepatocytes during IP.

Alanine Transaminase ; blood ; Alkaloids ; pharmacology ; Animals ; Aspartate Aminotransferases ; blood ; Benzophenanthridines ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Flavonoids ; pharmacology ; Ischemic Preconditioning ; Liver ; blood supply ; enzymology ; Male ; Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism ; Phosphorylation ; drug effects ; Protein Kinase C ; antagonists & inhibitors ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; physiopathology ; Tetradecanoylphorbol Acetate ; pharmacology

OBJECTIVETo observe the effect of prostaglandin E(1) (PGE(1)) on the expression of monocyte chemotactic protein-1 (MCP-1) in Kupffer cells (KCs) of rats with hepatic ischemia-reperfusion injury (IRI).

METHODSSeventy-two SD rats were randomized into sham operation group, ischemia-reperfusion group (I/R group) and PGE(1) treatment group (PGE(1) group). Rat models of partial warm ischemia-reperfusion injury of the liver was established, and in PGE(1) group, PGE(1) were given 10 min before the operation. At 1, 6, 12 and 24 h after the reperfusion, blood sample was taken from the inferior vena cava for measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The KCs were isolated and incubated in vitro, and tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the supernatant were measured by enzyme-linked immunosorbent assay. MCP-1 expression in the KCs was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSALT and AST levels of the PGE(1) group were significantly lower than I/R group (P<0.01). The mRNA and protein expression of MCP-1 and the TNF-alpha and IL-1beta levels in the I/R group significantly increased in the course of reperfusion and slightly decreased at 24 h, but were still significantly higher than those in the sham operation group (P<0.05). The expression of these factors were markedly decreased after PGE(1) treatment as compared with the I/R group (P<0.05).

CONCLUSIONPGE(1) can protect against ischemia-reperfusion injury of the rat liver partially by suppressing KCs activation, reducing excessive release of TNF-alpha and IL-1beta from KCs and decreasing the high expression of MCP-1 protein and mRNA.

Alanine Transaminase ; blood ; Alprostadil ; pharmacology ; Animals ; Aspartate Aminotransferases ; blood ; Chemokine CCL2 ; biosynthesis ; genetics ; Enzyme-Linked Immunosorbent Assay ; Immunohistochemistry ; Kupffer Cells ; drug effects ; metabolism ; Liver ; blood supply ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; physiopathology ; Reverse Transcriptase Polymerase Chain Reaction