Research progress in application and mechanism of Schisandrae Chinensis Fructus for prevention and treatment of liver diseases / 中国中药杂志

Schisandra is the mature fruit of Schisandra chinensis(known as "north Schisandra") or S. shenanthera(known as "south Schisandra"). S. chinensis contains a variety of lignans, volatile oils, polysaccharides, organic acids and other chemical constituents; among them, lignans are recognized as the characteristic active components. Clinical studies have found that Schisandra and Schisandra-related products have a better effect in the prevention and treatment of viral hepatitis, drug-induced liver injury, liver cirrhosis, liver failure and other liver diseases. Modern pharmacological studies have demonstrated that Schisandra has a variety of pharmacological activities, such as anti-inflammation, antioxidation, anticancer, regulation of nuclear receptor, antivirus, regulation of cytochrome P450 enzyme, inhibition of liver cell apoptosis and promotion of liver regeneration. This paper reviews the studies about the applications and mechanism of Schisandra in the prevention and treatment of liver diseases, in the expectation of providing guidance for the development of hepatoprotective drugs from Schisandra and the clinical applications of Schisandra-related products.

Inhibitory effect of flavonoids from Scutellariae Radix on human cytochrome P450 1A / 中国中药杂志

This study investigated the inhibitory effect of eight natural flavonoids in Chinese herb Scutellariae Radix on huamn cytochrome P450 1 A(CYP1 A), a key cancer chemo-preventive target. In this study, phenacetin was used as a probe substrate for CYP1 A, while human liver microsomes and recombinant human CYP1 A enzymes were used as enzyme sources. Liquid chromatography-tandem mass spectrometry was used to monitor the formation rates of acetaminophen, the O-deethylated metabolite of phenacetin. The dose-dependent inhibition curves were depicted based on the changes of the formation rates of acetaminophen, while the IC_(50) were determined. Inhibition kinetic analyses and docking simulations were used to investigate the inhibition modes and mechanism of wogonin(the most potent CYP1 A inhibitor in this herb), while the inhibition constants(K_i) of wogonin against both CYP1 A1 and CYP1 A2 were determined. Among all tested flavonoids, wogonin, 7-methoxyflavanone and oroxylin A displayed a strong inhibitory effect on CYP1 A(IC_(50)100 μmol·L~(-1)). Further investigations demonstrated that wogonin had a weak inhibitory effect on other human CYP enzymes, suggesting that it could be used as a lead compound for the development of specific inhibitors of CYP1 A. Furthermore, the inhibition kinetic analyses clearly demonstrated that wogonin could strongly inhibit phenacetin O-deethylation in both CYP1 A1 and CYP1 A2 in a competitive manner, with K_i values at 0.118 and 0.262 μmol·L~(-1), respectively. Molecular docking demonstrated that wogonin could strongly interact with CYP1 A1 and CYP1 A2 via hydrophobic and π-π interactions, as well as Ser120 and Ser116 in CYP1 A1 via hydrogen-bonding. In conclusion, this study found that some flavonoids in Scutellariae Radix displayed a strong inhibitory effect on CYP1 A, while wogonin is the most potent CYP1 A inhibitor with a relatively high selectivity towards CYP1 A over other human CYPs.

Protective effects of salubrinal on liver injury in rat models of brain death / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats. In this study, we observed the effect of salubrinal (Sal, Sigma, USA) on liver cells in BD rats and explored its relevant mechanisms.</p><p><b>METHODS</b>Thirty Sprague-Dawley rats were equally randomized into three groups: BD group, Sal group, and DMSO group. The BD models were established by increasing intracranial pressure in a modified, slow, and intermittent way. In the drug groups, Sal was administered 1 h before the induction of BD. After modeling was completed, the blood and liver samples were harvested. CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction. PKR-like ER kinase (PERK), P-eukaryotic translation initiation factor 2α (eIF2α), eIF2α, CHOP and caspase-12 expression was detected using western blotting (WB). CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC). Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer. Hepatic cell apoptosis was detected using TUNEL. The results were analyzed using Quantity-one v4.62 software (Bio-Rad, USA).</p><p><b>RESULTS</b>CHOP and caspase-12 expression and PERK, eIF2α, and P-eIF2α protein expression showed no significant difference between BD group and DMSO group. Compared with BD group, Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05). However, eIF2α expression showed no significant difference (P > 0.05). After the Sal treatment, CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05). WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment. Sal was associated with improved liver function and decreased hepatic cell apoptosis.</p><p><b>CONCLUSIONS</b>Sal can significantly reduce apoptosis in hepatic cells of BD rats. This protective effect may be achieved via the PERK-eIF2α signaling pathway.</p>

Extracorporeal membrane oxygenation for severe acute respiratory and heart failure in a child with severe pneumonia / 中华儿科杂志

<p><b>OBJECTIVE</b>To report clinical application of Extracorporeal membrane oxygenation for severe acute respiratory and heart failure in a child with severe pneumonia.</p><p><b>METHOD</b>A seven-year old male patient with severe pneumonia complicated with heart and lung function failure was admitted to PICU in 28th of December, 2008.Veno-artery access was set up via euthyphoria cannulation in operative incision. Blood was drained from the right atrium through a cannula introduced via femoral veins, and returned via femoral artery. The inter-surface of the ECMO equipment system was completely coated with heparin-coating technique. Anticoagulation was maintained with heparin to keep the activated clotting time (ACT) between 150 and 200 seconds and heparin usage dose was 10 U/(kg.h), mean blood flow was 1/2-2/3 of 80-120 ml/(kg.min) during ECMO assistant period. During ECMO, ventilator settings were gradually reduced to allow lung rest, i.e. peak inspiratory pressure less than 25 cm H2O (1 cm H2O=0.098 kPa), end expiratory pressure 8-10 cm H2O, rate 10-15 breaths per minute and FiO2 30%-40%.</p><p><b>RESULTS</b>In management of ECMO, the incipient blood flow was set at 0.8 L/min, the radio of oxygen and blood flow was 1:1, FiO2 60%. After ten minutes of ECMO working, the blood oxygen saturation of radial artery increased from 40 mm Hg (1 mm Hg=0.133 kPa) to 177 mm Hg, Lac decreased from 3.5 mmol/L to 2.8 mmol/L. Four hours later, blood gas analysis of radial artery showed PaO2 202 mm Hg, PCO2 44 mm Hg, Lac 1.5 mmol/L, blood flow was set at 0.6 L/min, FiO2 60%, PaO2 kept above 150 mm Hg. 96 hours after ECMO supporting, the blood flow was set at 0.4 L/min [20 ml/(kg.min)], the results of blood gas analysis of radial artery was PaO2 190 mm Hg, PaCO2 36 mm Hg, SaO2 100%, Lac 0.9 mmol/L, then the child weaned off successfully from ECMO. Two days later, the child was successfully extubated. After two weeks treatment, the patient was discharged. The main complication associated with extracorporeal membrane oxygenation were bleeding.</p><p><b>CONCLUSION</b>ECMO is an effective mechanical assistant therapy method for severe pulmonary and cardiac failure in a child.</p>