Protective Effects of Geniposide on Hepatic Ischemia/Reperfusion Injury.

BACKGROUND: Geniposide (GEN) is the major ingredient of Gardenia jasminoides Ellis, which has anti-inflammatory and anti-apoptotic activities and is widely used to treat ischemia disease. Inflammation and apoptosis play an important role in hepatic ischemia/reperfusion (I/R) injury. The current study was conducted to explore the effects of geniposide on hepatic I/R injury and its potential molecular mechanism in mice. METHODS: Fifty Sprague-Dawley rats were randomly divided into 5 groups: the sham group (sham), the hepatic I/R injury group (IRI) and the GEN groups (low, middle, and high). In the GEN and IRI groups, hepatic IRI by was induced by means of clamping the left and median liver lobes for 30 minutes with noninvasive endoclips. The GEN groups were pretreated with GEN (5, 10, 20 mg/kg) at 30 minutes before ischemia by use of intraperitoneal injection. Rats in the IRI group and sham group were administrated with same dosage of saline at the same time. After reperfusion for 6 hours, the hepatic pathology and the expression of alanine aminotransferase (ALT), AST aspartate aminotransferase, LDH lactic acid dehydrogenase, PI3K, AKT, p-AKT, m-TOR, Bax, BCL-2, interleukin (IL)-6, MCP-1, and tumor necrosis factor (TNF)-α were examined. RESULTS: Compared with the sham group, the IRI group had higher expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and lower expression of BCL-2, PI3K, p-AKT, and mammalian target of rapamycin (mTOR), with more inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. Compared with the IRI group, the GEN group had lower expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and higher expression of BCL-2, PI3K, p-AKT, and mTOR, with less inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. There were no differences in the expression of AKT among several groups. CONCLUSIONS: GEN can protect rats against hepatic I/R injury and partly relies on suppressing inflammation and apoptosis by inducing the activation of the PI3K/Akt/mTOR signaling pathway.

Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis.

Glucocorticoid hormones induce apoptosis in lymphoid cells. This process is transcriptionally regulated and requires de novo RNA/protein synthesis. However, the full spectrum of glucocorticoid-regulated genes mediating this cell death process is unknown. Through gene expression profiling we discovered that the expression of thioredoxin-intereacting protein (txnip) mRNA is significantly induced by the glucocorticoid hormone dexamethasone not only in the murine T-cell lymphoma line WEHI7.2, but also in normal mouse thymocytes. This result was confirmed by Northern blot analysis in multiple models of dexamethasone-induced apoptosis. The induction of txnip mRNA by dexamethasone appears to be mediated through the glucocorticoid receptor as it is blocked in the presence of RU486, a glucocorticoid receptor antagonist. Deletion and mutation analysis of the txnip promoter identified a functional glucocorticoid response element in the txnip promoter. Reporter assays demonstrated that this glucocorticoid response element was necessary and sufficient for induction of txnip by dexamethasone. Expression of a GFP-TXNIP fusion protein was sufficient to induce apoptosis in WEHI7.2 cells, and repression of endogenous txnip by RNA interference inhibited dexamethasone-induced apoptosis in WEHI7.2 cells. Together, these findings indicate that txnip is a novel glucocorticoid-induced primary target gene involved in mediating glucocorticoid-induced apoptosis.

[Studies on lipase production from Candida rugosa].

We studied some factors affecting the lipase production from candida rugosa, they mainly included medium compositions and culture condition. The result showed that the optimal medium compositions for lipase production are 0.1% glucose 4.0% olive oil (carbon source), 0.3% NH4NO3(nitrogen source), 1.2% K2HPO4 and 0.4% MgSO4.7H2O. And the optimal culture condition is initial pH6.5, temperature 30 degrees C, agitation 180 r/min and time 60 h. As a result, and the lipase activity could reach 19.5 u/mL. Meanwhile we found that the surfactant could be helpful to the lipase production, and the optimal surfactant concentration was 0.03% GPE. The lipase activity was improved by more than 170% after we optimized the medium compositions and culture condition. While in a 5L fermentator, the lipase activity of fermentation broth could reach 33.5 u/mL within 48 hours.