No abstract available.
Anti-Infective Agents/*therapeutic use ; Fatty Alcohols/*therapeutic use ; Female ; Humans ; Male ; Osteoarthritis/*drug therapy

Panax ginseng roots have long been used as a medicinal herb in oriental countries. We have investigated anti-proliferative effects of lipid soluble Panax ginseng components on human renal cancer cell lines. Petroleum ether extract of Panax ginseng roots (GX-PE) or its partially purified preparation (7:3 GX) was added to cultures of three human renal cell carcinoma (RCC) cell lines, A498, Caki-1, and CURC II. Proliferation of RCC cells was estimated by a [3H]thymidine incorporation assay and cell cycle distribution was analyzed by flow cytometry. GX-PE, 7:3 GX, panaxydol and panaxynol inhibited proliferation of all three RCC cell lines in a dose dependent manner in vitro with an order of potency, 7:3 GX > panaxydol > panaxynol = GX-PE. Additive effect of interleukin 4 was also demonstrated, most prominently in Caki-1 which responded poorly to GX-PE alone. Analysis of cell cycle in CURC II and Caki-1 treated with GX-PE demonstrated increase in G1 phase population and corresponding decrease in S phase population. The present study demonstrated that proliferation of human RCC cell lines were inhibited by lipid soluble components of Panax ginseng roots by blocking cell cycle progression at G1 to S phase transition.
Alkanes ; Alkynes/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Phytogenic/therapeutic use* ; Carcinoma, Renal Cell/drug therapy* ; Cell Cycle/drug effects ; Fatty Alcohols/therapeutic use ; Ginseng/therapeutic use* ; Ginseng/chemistry ; Human ; Interleukin-4/therapeutic use ; Kidney Neoplasms/drug therapy* ; Plant Extracts/therapeutic use ; Plant Roots/therapeutic use ; Plant Roots/chemistry

BACKGROUNDGingerol is the generic term for pungent constituents in ginger, which has been reported to be effective for inhibiting vomiting. We attempted to investigate the antiemetic effect of gingerol and its effective mechanism on substance P and NK(1) receptors in minks.

METHODSThe antiemetic effect of gingerol was investigated during a 6-hour observation on a vomiting model in minks induced by cisplatin, (7.5 mg/kg, intraperitoneal). The distribution of substance P and NK(1) receptors in the area postrema and ileum were measured by immunohistochemistry, and the expression of NK(1) receptor in the area postrema and ileum were measured by Western blotting.

RESULTSThe frequency of cisplatin induced retching and vomiting was significantly reduced by pretreatment with gingerol in a dose-dependent manner (P < 0.05). Substance P-immunoreactive was mainly situated in the mucosa and submucosa of the ileum as well as in the neurons of the area postrema. The immunoreactive production of NK(1) receptor was mainly situated in the muscular and submucosa of ileum and the neurons of area postrema, gingerol markedly suppressed the increased immunoreactivity of substance P and NK(1)1 receptor induced by cisplatin in a dose-dependent manner (P < 0.05), and exhibited effective inhibition on the increased expression levels of NK(1) receptor in both the ileum and area postrema dose-dependently (P < 0.05).

CONCLUSIONSGingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of substance P and NK(1) receptors.

Animals ; Area Postrema ; metabolism ; Blotting, Western ; Catechols ; therapeutic use ; Disease Models, Animal ; Fatty Alcohols ; therapeutic use ; Ileum ; metabolism ; Immunohistochemistry ; Male ; Mink ; Receptors, Neurokinin-1 ; metabolism ; Substance P ; metabolism ; Vomiting ; chemically induced ; drug therapy

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

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is intimately related to insulin resistance and ranges from a benign course to liver fibrosis and cirrhosis. NAFLD management mainly involves dietary modification and weight loss. Although no fully successful pharmacological intervention is available, alternative therapies to treat NAFLD have shown promising results. Experimental studies have shown that D-002, a mixture of beeswax alcohols with antioxidant effects, is hepatoprotective. The aim of this study was to investigate the efficacy and safety of D-002 in patients with NALFD. METHODS: Fifty patients with NAFLD were randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks. The primary endpoint was a significant ultrasonography-detected reduction of liver fat infiltration versus a placebo. Secondary endpoints were decreases in the homeostatic model assessment (HOMA) index, insulin levels, serum liver enzymes, increases in plasma total antioxidant status (TAS) and improved clinical symptoms versus the placebo recipients. RESULTS: At randomization, all indicators were comparable in both groups. At study completion, seven (28.0%) D-002-patients, but none of the placebo recipients, exhibited a normal liver echo pattern on ultrasonography (p < 0.01). Also, D-002 significantly reduced (p < 0.01 vs. baseline and placebo) the HOMA index and insulin levels and increased the TAS, but did not affect other parameters. The proportion of D-002-patients (12/25, 48.0%) showing symptom improvement was higher (p < 0.001) than that of the placebo group (1/25, 4.0%). The treatment was safe and well tolerated. Three patients in each group withdrew from the study. CONCLUSIONS: D-002 (100 mg/day) improved ultrasonographic findings, indicators of insulin resistance, plasma TAS and clinical evolution on NAFLD patients. Further studies, however, are needed to confirm these results.
Adult ; Aged ; Antioxidants/adverse effects/isolation & purification/*therapeutic use ; Biological Markers/blood ; Blood Glucose/metabolism ; Cuba ; Double-Blind Method ; Enzymes/blood ; Fatty Alcohols/adverse effects/isolation & purification/*therapeutic use ; Fatty Liver/blood/*drug therapy/ultrasonography ; Female ; Humans ; Insulin/blood ; Lipids/blood ; Liver/*drug effects/enzymology/ultrasonography ; Male ; Middle Aged ; Prospective Studies ; Time Factors ; Treatment Outcome ; Waxes/*chemistry

BACKGROUND/AIMS: Nonsteroidal anti-inflammatory drugs relieve osteoarthritis (OA) symptoms but cause adverse effects. D-002, a mixture of beeswax alcohols, is effective against experimental OA. A pilot study found that D-002 (50 mg/day) for 8 weeks improves OA symptoms. The aim of this study was to investigate the effects of D-002 (50 to 100 mg/day) administered for 6 weeks on OA symptoms. METHODS: Patients with OA symptoms were double-blindly randomized to D-002 (50 mg) or placebo for 6 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the visual analog scale (VAS) scores. Patients without symptom improvement at week 3 were titrated to two daily tablets. The primary outcome was the total WOMAC score. WOMAC pain, joint stiffness and physical function scores, VAS score, and use of rescue medications were secondary outcomes. RESULTS: All randomized patients (n = 60) completed the study, and 23 experienced dose titration (two in the D-002 and 21 in the placebo groups). At study completion, D-002 reduced total WOMAC (65.4%), pain (54.9%), joint stiffness (76.8%), and physical function (66.9%) WOMAC scores, and the VAS score (46.8%) versus placebo. These reductions were significant beginning in the second week, and became enhanced during the trial. The use of rescue medication by the D-002 (6/30) group was lower than that in the placebo (17/30) group. The treatment was well tolerated. Seven patients (two in the D-002 and five in the placebo group) reported adverse events. CONCLUSIONS: These results indicate that D-002 (50 to 100 mg/day) for 6 weeks ameliorated arthritic symptoms and was well tolerated.
Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Anti-Infective Agents/administration & dosage/adverse effects/*therapeutic use ; Cuba ; Double-Blind Method ; Drug Administration Schedule ; Fatty Alcohols/administration & dosage/adverse effects/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis/diagnosis/*drug therapy/physiopathology ; Pain Measurement ; Questionnaires ; Tablets ; Time Factors ; Treatment Outcome ; Young Adult

[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