Huanglian Jiedutang Alleviates Liver Injury in Septic Mice by Inducing Autophagy / 中国实验方剂学杂志

ObjectiveTo explore effect of Huanglian Jiedutang （HLJDT） on autophagy-related protein expression in septic mice with liver injury induced by cecal ligation and puncture （CLP）. MethodSixty eight-week-old C57BL/6 mice were randomly divided into four groups， namely， the sham operation group， model group， and low- （1.44 g∙kg-1） and high-dose （2.88 g∙kg-1） HLJDT groups， with 15 in each group. The septic model was established by CLP after the last administration of HLJDT for three successive days. The survival rate of mice with 24 h was observed. The mice were sacrificed 12 h after operation for collecting the serum and liver tissue. The levels of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） were detected by enzyme-linked immunosorbent assay （ELISA）， and the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum by biochemical method. The pathological changes in liver tissue were observed by hematoxylin-eosin （HE） staining， and the apoptosis index （AI） of hepatocytes by TdT-mediated dUTP-biotin nick end-labeling （TUNEL）. The expression levels of protein high-mobility group box 1 protein （HMGB1）， Beclin1， and microtubule-associated protein 1 light chain 3 （LC3）-Ⅱ/Ⅰ in the liver tissue were assayed by Western blot. ResultCompared with the sham operation group， the model group showed reduced survival rate at 12 and 24 h， elevated IL-6， TNF-α， and IL-1β levels， enhanced AST and ALT activities （P<0.05）， hepatocyte swelling， inflammatory cell infiltration， and apoptosis， and up-regulated HMGB1 （P<0.05）， Beclin1， and LC3-Ⅱ/Ⅰ （P<0.05）. Compared with the model group， each medication group exhibited increased survival rate at 12 and 24 h， lowered IL-6 and TNF-α levels， weakened AST and ALT activities （P<0.05）， alleviated liver injury and apoptosis （P<0.05）， down-regulated HMGB1 expression （ P<0.05）， and up-regulated Beclin1 and LC3-Ⅱ/Ⅰ （P<0.05）. ConclusionHLJDT alleviates the liver injury of septic mice possibly by inducing autophagy and inhibiting apoptosis.

A new triterpenoid from Pittosporum glabratum Lindl / 药学学报

The roots of Pittosporum glabratum Lindl. (Pittosporaceae) have been used as a folk medicine for the treatment of rheumatic arthritis, insomnia and hypertension. Only a few chemical or biological studies on P. glabratum have been reported. As part of our ongoing phytochemical research on this plant, four compounds were isolated. Their structures were identified as 3beta, 6beta, 19alpha, 21alpha, 24-pentahydroxy-12-en-28-oleanolic acid (1), 3-O-beta-D-glucuronopyranosyl-28-O-beta-D-glucopyranosyl siaresinolic acid (2), 3, 4, 5-trimethoxyphenyl-1-O-beta-D-(5-O-syringoyl)-apiofuranosyl-(1 --> 6)-beta-D-glucopyranoside (3) and 3, 4, 5-trimethoxyphenol-1-O-beta-D-apiofuranosyl-(1 --> 6)-beta-D-glucopyranoside (4) on the basis of physical evidence and spectroscopic analysis. Among them, compound 1 is a new triterpenoid, and compounds 2-4 are isolated from the genus Pittosporum for the first time.

The up-regulation of hypoxia inducible factor-1α by hypoxic postconditioning reduces hypoxia/reoxygenation-induced injury in heart-derived H9c2 cells / 生理学报

The aim of the present study was to explore the effects of hypoxic postconditioning (PostC) on heart-derived H9c2 cells injury induced by hypoxia/reoxygenation (H/R) and the expression of hypoxia inducible factor-1α (HIF-1α), and to analyze the relationship between them. Cultured H9c2 cardiac muscle cells were subjected to 3-hour hypoxia and 2-hour reoxygenation to simulate ischemia and reperfusion, or underwent 3 cycles of 5-min reoxygenation and 5-min hypoxia preceding the long reoxygenation to simulate ischemic postconditioning. Cell viability, lactate dehydrogenase (LDH) activity, and caspase-3 activity were detected respectively to investigate the cell injury induced by H/R. The level of HIF-1α mRNA was measured by real-time PCR. Western blot was used to determine HIF-1α protein level. The results showed that postconditioning significantly increased H9c2 cell viability, reduced the activity of LDH and caspase-3. Simultaneously, postconditioning up-regulated the HIF-1α protein level. Moreover, after DMOG, an inhibitor of proline hydroxylase (PHD) which targeted to HIF-1α degradation, was used to stabilize HIF-1α protein level, the reduction of H9c2 cells injury was comparable to that by postconditioning. There was a significant linear positive relationship between HIF-1α protein level and cell viability (r = 0.743, P < 0.01). After HIF-1α gene was silenced by siRNA, the cardio-protective effects of postconditioning was significantly weakened. These data suggest that up-regulation of HIF-1α plays an important role in the cardio-protection of postconditioning.

The attenuation of myocardial susceptibility to ischemia/reperfusion injury by ischemic postconditioning in hypercholesteremia rats and the role of hypoxia inducible factor-1alpha / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore whether ischemic postconditioning can attenuate the myocardial injury induced by ischemia/reperfusion (I/R) in hypercholesteremic rats and whether hypoxia inducible factor-1alpha (HIF-1alpha) play a role in the protection.</p><p><b>METHODS</b>Adult male Wistar rats received a high fat diet for 8 weeks to prepare the hypercholesteremic models. Myocardial damage induced by ischemia/reperfusion was evaluated by infarct size, creatine kinase (CK) activity and myocardial apoptosis. HIF-1alpha mRNA level was detected by real time-RT-PCR and the protein level was detected by Western blot.</p><p><b>RESULTS</b>Myocardial infarct size, CK activity, and caspase-3 activity induced by I/R were markedly increased in hypercholesteremic rats compared with those in normal rats. Ischemic postconditioning attenuated the myocardial injury in both normal rats and hypercholesteremic rats, and increased HIF-1alpha protein level. There was a significant linear inverse relationship between HIF-1alpha protein level and infarct size (r = -0.802, P <0.01).</p><p><b>CONCLUSION</b>Hypercholesteremia enhanced the susceptibility of myocardia to ischemia/reperfusion injury. While ischemic postconditioning markedly attenuated the increase of myocardial susceptibility to I/R induced by hypercholesteremia. HIF-1alpha might be one of the mechanisms of protection by ischemic postconditioning.</p>