METHODS: The extract was analyzed quantitatively by performing a validated reversed phase high performance liquid chromatography (RP-HPLC). Zerumbone was isolated by chromatographic technique while the essential oil was acquired through hydro-distillation of the rhizomes and further analyzed by gas chromatography (GC) and GC-MS. Chemotaxis assay was assessed by using a 24-well cell migration assay kit, while CD18 integrin expression and phagocytic engulfment were measured using flow cytometry. The reactive oxygen species (ROS) production was evaluated by applying lucigenin- and luminol-enhanced chemiluminescence assays.
RESULTS: Zerumbone was found to be the most abundant compound in the extract (242.73 mg/g) and the oil (58.44%). Among the samples tested, the oil revealed the highest inhibition on cell migration with an IC50 value of 3.24 μg/mL. The extract, oil and zerumbone showed moderate inhibition of CD18 integrin expression in a dose-dependent trend. Z. zerumbet extract showed the highest inhibitory effect on phagocytic engulfment with percentage of phagocytizing cells of 55.43% for PMN. Zerumbone exhibited strong inhibitory activity on oxidative burst of zymosan- and PMA-stimulated neutrophils. Zerumbone remarkably inhibited extracellular ROS production in PMNs with an IC50 value of 17.36 μM which was comparable to that of aspirin.
CONCLUSION: The strong inhibition on the phagocytosis of neutrophils by Z. zerumbet extract and its essential oil might be due the presence of its chemical components particularly zerumbone which was capable of impeding phagocytosis at different stages.
METHODS: Six healthy male Malaysian subjects were given a single oral dose of 200 mg artemether. Blood samples were collected to 72 h. Plasma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electro-chemical detection in the reductive mode.
RESULTS: Mean (+/- s.d.) maximum concentrations of ARM, 310 +/- 153 micrograms l-1, were reached 1.88 +/- 0.21 h after drug intake. The mean elimination half-life was 2.00 +/- 0.59 h, and the mean AUC 671 +/- 271 micrograms l-1 h. The mean Cmax of DHA, 273 +/- 64 micrograms l-1 was observed at 1.92 +/- 0.13 h. The mean AUC of DHA was 753 +/- 233 micrograms h l-1'. ARM and DHA were stable at < or = -20 degrees C for at least 4 months in plasma samples.
CONCLUSIONS: The relatively short half-life of ARM may be one of the factors responsible for the poor radical cure rate of falciparum malaria with regimens employing daily dosing. In view of the rapid loss of DHA in plasma samples held at room temperature (26 degrees C) it is recommended to store them at a temperature of < or = -20 degrees C as early as possible after sample collection.
METHODS AND RESULTS: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels.
CONCLUSION: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.