OBJECTIVETo observe the effect of Gingerol on endotoxemia mouse induced by heatstroke.

METHODSForty mice were randomly divided into five groups, the endotoxemia model group (A), the normal temperature group (B), the Gingerol treated group (C), the solvent control group (D), and the saline control group (E), 8 mice in each group. Group B to E was administered with saline, Gingerol, solvent and saline respectively. Mice in group B were placed at room temperature 25 +/- 0.5 degrees C , relative humidity 43 +/- 5 % for 2 hrs, while mice in the other groups were exposed under 35 +/- 0.5 degrees C and relative humidity 65 +/- 5 % for 2 hrs in an artificial hot-climate mimic cabin to establish heatstroke endotoxemia model. The energy metabolic level of celiomacrophage was detected with MTT; the phagocytic ability was examined with neutral red chromometry; the hepatocyte ultrastructure was observed with transmission electron microscopy, as well as the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in plasma was tested.

RESULTSAs compared with Group A, D and E, in Group C, energy metabolic levels of macrophage, phagocytic ability, and activity of SOD were significantly higher (P < 0.01), and the level of MDA was significantly lower respectively (P < 0.01), with the levels of SOD and MDA approaching to those in Group B (P >0.05). The pathologic changes of hepatocyte ultrastructure in group C were less than those in the other three endotoxemia groups.

CONCLUSIONGingerol could raise the energy metabolic level of celio-macrophage to enhance its phagocytic ability, increase the activity of SOD and reduce the production of MDA in mouse with heatstroke endotoxemia, so as to alleviate the liver damage.

Animals ; Catechols ; Endotoxemia ; drug therapy ; etiology ; Fatty Alcohols ; isolation & purification ; pharmacology ; therapeutic use ; Female ; Ginger ; chemistry ; Heat Stroke ; complications ; Macrophages ; immunology ; Male ; Mice ; Phagocytosis ; drug effects ; Phytotherapy ; Random Allocation

[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild- type (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21(cip1), was p53-independent. [6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53- expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53- expressing cells by inducing temporal growth arrest.
Tumor Suppressor Protein p53/*genetics/metabolism ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; Pancreatic Neoplasms/*drug therapy ; Mutation ; Humans ; Gene Expression Regulation, Neoplastic/drug effects ; Fatty Alcohols/*pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Cell Cycle/*drug effects ; Apoptosis/*drug effects ; Antineoplastic Agents/*pharmacology/therapeutic use

OBJECTIVETo evaluate the effect of panaxynol (PAN) on delayed type hypersensitivity and possible mechanism.

METHODAllergic contact dermatitis (ACD) was induced by DNCB as a delayed type hypersensitivity (DTH) model to observe effect of PAN on auricle inflammation including pathological injury. Proliferation of T lymphocytes was induced by ConA and measured by MTf method. IFN-gamma secretion of splenocyte induced by ConA was detected by ELISA.

RESULTThe swelling degree of auricle and pathological injury in ACD mice was reduced significantly by treated with PAN in induction phase. Proliferation of T lymphocytes induced by ConA in vitro was inhibited significantly by PAN, By contrast, no detectable effect was observed in resting splenocyte. IFN-y induced by ConA in splenocytes was inhibited markedly by PAN from 10 micromol x L(-1) and from 6 h.

CONCLUSIONThe results showed that DTH was inhibited by PAN mainly in induction phase and this effect may be related with the inhibition on T lymphocytes proliferation and secretion of IFN-gamma.

Animals ; Cell Proliferation ; drug effects ; Concanavalin A ; metabolism ; Dermatitis, Allergic Contact ; drug therapy ; immunology ; metabolism ; Diynes ; pharmacology ; therapeutic use ; Fatty Alcohols ; pharmacology ; therapeutic use ; Female ; Interferon-gamma ; secretion ; Male ; Mice ; Mice, Inbred ICR ; Spleen ; drug effects ; pathology ; secretion ; T-Lymphocytes ; drug effects ; pathology

AIMAnnonaceous acetogenin 89-2 was obtained from atemoya plant. To investigate the effect of 89-2 on experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells.

METHODSCytotoxicity was determined by tetrazolium (MTT) assay. The models of KB and KBv200 xenografts in nude mice were established to investigate the effect of 89-2 on experimental chemotherapy against cancer in vivo. Mechanistic experiments were conducted to examine the function of P-gp by Fura 2-AM assay.

RESULTSThe compound 89-2 showed potent cytotoxicity in KBv200 and KB cells, and the mean IC50 of 89-2 to KBv200 and KB cells was 48.7 and 64.6 nmol.L-1, respectively. The IC50 of 89-2 to multidrug resistant (MDR) cells was similar to that to the parental drug-sensitive cells (P < 0.05). In the models of KBv200 and KB cell xenografts in nude mice, 89-2 (0.90 mg.kg-1, q2d x 6) exhibited 52.3% and 56.5% in inhibiting the growth of xenografts, respectively. The toxicity was endurable. The intracellular accumulation of Fura-2 in KBv200 cells increased to 1.66, 2.03, and 2.74-fold, respectively, by addition of 12.8, 64 and 320 nmol.L-1 of 89-2.

CONCLUSIONBoth MDR KBv200 cells and parental drug-sensitive KB cells were sensitive to the treatment of 89-2 in vitro and in vivo. The mechanism of overcoming MDR was associated with the decrease of P-gp function MDR cells.

4-Butyrolactone ; analogs & derivatives ; isolation & purification ; pharmacology ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Annona ; chemistry ; Antineoplastic Agents, Phytogenic ; isolation & purification ; therapeutic use ; Cell Division ; drug effects ; Disease Models, Animal ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Fatty Alcohols ; isolation & purification ; pharmacology ; Humans ; KB Cells ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental ; drug therapy ; Plants, Medicinal ; chemistry ; Xenograft Model Antitumor Assays