Asiatic acid (AA), a pentacyclic triterpene compound in the medicinal plant Centella asiatica, was evaluated for antinociceptive and anti-inflammatory effects. Treatment of male ICR mice with AA significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, AA decreased the paw edema at the 4th and 5th h after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. AA decreased the nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels on serum level at the 5th h after Carr injection. Western blotting revealed that AA decreased Carr-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and nuclear factor-κB (NF-κB) expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with AA also diminished neutrophil infiltration into sites of inflammation as did indomethacin (Indo). The anti-inflammatory mechanisms of AA might be related to the decrease in the level of MDA, iNOS, COX-2, and NF-κB in the edema paw via increasing the activities of CAT, SOD, and GPx in the liver.

Hispolon, an active ingredient in the fungi Phellinus linteus was evaluated with analgesic and anti-inflammatory effects. Treatment of male ICR mice with hispolon (10 and 20 mg/kg) significantly inhibited the numbers of acetic acid-induced writhing response. Also, our result showed that hispolon (20 mg/kg) significantly inhibited the formalin-induced pain in the later phase (P<.01). In the anti-inflammatory test, hispolon (20 mg/kg) decreased the paw edema at the fourth and fifth hour after λ-carrageenin (Carr) administration, and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver tissue. We also demonstrated that hispolon significantly attenuated the malondialdehyde (MDA) level in the edema paw at the fifth hour after Carr injection. Hispolon (10 and 20 mg/kg) decreased the nitric oxide (NO) levels on both the edema paw and serum level at the fifth hour after Carr injection. Also, hispolon (10 and 20 mg/kg) diminished the serum TNF-α at the fifth hour after Carr injection. The anti-inflammatory mechanisms of hispolon might be related to the decrease in the level of MDA in the edema paw by increasing the activities of SOD, GPx and GRx in the liver. It probably exerts anti-inflammatory effects through the suppression of TNF-α and NO.

The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.

No abstract

In the present study, we investigated the hepatoprotective and antioxidant capacities of ethanol extract of Phellinus merrillii (PM) on carbon tetrachloride-induced hepatotoxicity. In high-performance liquid chromatography (HPLC) analysis, the finger print chromatogram of PM was established. Both hispolon and PM showed a similar peak at the retention time of 6 min. This implied that PM did contain the active ingredient of hispolon. Treatment with PM (0.5, 1 and 2 g/kg) prior to the administration of carbon tetrachloride (1.5 ml/kg in olive oil, 20%) significantly prevented the increased serum alanine aminotransferase (s-GOT) and serum aspartate aminotransferase (s-GPT) in a dose-dependent manner. We also found that the incidences of ballooning degeneration, necrosis and portal triaditis were lowered in the group pretreated with PM. Carbon tetrachloride induces up-regulation of antioxidant enzymes, including superoxide dismutase (SOD) (86.6%), catalase (58.8%) and glutathione peroxidase (GPx)(64.7%) in the liver. Pretreatment with PM significantly reduced the all these antioxidant enzyme activities. Therefore, we verified that ethanol extract of PM has the hepatoprotective and antioxidant capacities on rats.

According to the known effects of each ingredient, Gan-Lu-Yin (GLY), a traditional Chinese herbal formula, has the potential to be an antiangiogenic agent. The purpose of this study was to explore the putative effect of GLY on antiangiogenesis. An ethanol extract of GLY was tested on chicken chorioallantoic membrane (CAM) and human umbilical vein endothelial cells (HUVEC) to evaluate the effects of GLY extract on cell proliferation, migration, and tube formation. The results showed that treatment with 1.0 mg/mL of GLY extract could markedly reduce cell migration and in vitro tube formation of HUVEC, and 1.5 mg/mL of GLY extract was sufficient to inhibit proliferation of HUVEC. The expression level of vascular endothelial growth factor (VEGF) of HUVEC was significantly decreased by 1.5 and 2.0 mg/mL of GLY extract. In chicken CAM assay, all tested concentrations of GLY extract were found to reduce the capillary mesh on the CAM of fertilized eggs. The inhibitory effects of GLY extract (1 mg/mL) were also found on tumor cell-induced HUVEC proliferation and tube formation. These observations suggested that GLY extract has an inhibitory effect on angiogenesis, which in turn may prevent tumor growth, and its mechanism might be partially associated with blocking VEGF protein expression of HUVEC.

We investigated whether midazolam administration influenced morphine-induced antinociception and tolerance and dependence in the rat. Antinociception was assessed by the tail-flick (TF) and the hot-plate test (HP 52 degrees C). Morphine tolerance developed after daily single injections of morphine for 11 days. The effect of midazolam on morphine-induced antinociception and tolerance was assessed by giving daily injections of various doses of midazolam for 11 days. The first injection of saline or midazolam was given intraperitoneally and 30 min later morphine (10 mg/kg body weight) was administered subcutaneously. Antinociception was monitored by measuring TF and HP latencies 60 min after the second injection. Midazolam was injected at four different concentrations: 0.03, 0.1, 0.3, and 3 mg/kg body weight. Chronic administration of morphine resulted in the development of tolerance to antinociception in both TF and HP tests, with rats exhibiting baseline antinociception on Day 9. Animals treated with midazolam alone showed little antinociception on Days 3-9. However, midazolam administration in morphine-treated animals attenuated morphine-induced tolerance to antinociception on Days 1-11 as measured by the tail-flick test. Midazolam also decreased the jumping behavior following naloxone injections in morphine-dependent rats. These results suggest that midazolam may prolong the effects of morphine by delaying morphine-induced development of tolerance to antinociception. Midazolam also attenuated a decrease in weight gain induced by chronic injections of morphine.

The present study demonstrated that alpinumisoflavone exerts the significant effects of anti-inflammatory and anti-oxidative in both LPS-induced RAW264.7 macrophages and a mouse model of acute lung injury.