Evaluation of the Safety of Daily Consumption of Kaempferia parviflora Extract (KPFORCE): A Randomized Double-Blind Placebo-Controlled Trial.

This study's aim was to evaluate the safety of daily consumption of Kaempferia parviflora extract (KPE) using a randomized double-blind placebo-controlled study with 52 recruited healthy Japanese subjects. Each subject received five KPE tablets (containing 150 mg of KPFORCE™/tablet) or placebo daily for 4 weeks. There were no adverse events related to KPE intake or any abnormalities compared with placebo group in anthropometric, cardiovascular, blood, and urine parameters during the course of the study. Thus, daily KPE ingestion was found to be safe in healthy Japanese men and women.

Toxicological evaluation of standardized Kaempferia parviflora extract: Sub-chronic and mutagenicity studies.

Kaempferia parviflora (KP), also known as Krachai-dam in Thailand, belongs to the family Zingiberaceae and has been used traditionally to improve blood flow and treat inflammatory, allergic, and gastrointestinal disorders. The objective of this study was to investigate the safety profile of a standardized hydroalcoholic KP rhizome extract via mutagenicity and sub-chronic toxicity evaluations using in vitro and in vivo techniques. The in vitro mutagenicity of KP extract was assessed via reverse mutation tests using Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2 uvrA. The sub-chronic toxicity profile was evaluated after daily oral administration of KP extract to Sprague-Dawley rats for 90 days. General toxicological parameters were monitored weekly. After the treatment period, blood was collected for hematological and biochemical analyses and certain organs were removed for macroscopic and histopathological analyses. Reverse mutation tests revealed that KP extract did not induce gene mutations at any of the concentrations tested. In the sub-chronic toxicity test, a few changes were observed, including increased salivation in the animals administered high-dose KP extract (249 mg/kg body weight (bw)/day). No toxicologically relevant changes were observed in the biochemical analysis. Sub-chronic administration of KP extract increased platelet levels in animals administered low-dose KP extract (25 mg/kg bw/day). However, the hematological and biochemical parameters remained within normal physiological ranges for the animal species. No toxicological changes were observed in the macroscopic and histopathological analyses performed in this study. These results demonstrate that KP extract is not genotoxic and that 90-day oral administration of the doses tested did not result in toxicity. Therefore, KP extract has a high safety margin for daily use.

Daily intake of Kaempferia parviflora extract decreases abdominal fat in overweight and preobese subjects: a randomized, double-blind, placebo-controlled clinical study.

PURPOSE: Obesity is a serious problem, which is now a worldwide health problem. Kaempferia parviflora extract (KPE) exhibits anti-obesity effects in animals. However, as no clinical trials have evaluated the anti-obesity effects of KPE in humans, we examined the effects of KPE in reducing abdominal fat in overweight and preobese Japanese subjects. MATERIALS AND METHODS: A 12-week, single-center, randomized, double-blind, placebo-controlled clinical trial was conducted. Seventy-six subjects (males and females aged 20 to <65 years) with a body mass index ≥24 and <30 kg/m2 were randomly assigned into two groups. The subjects in each group ingested one capsule of placebo or active KPE (containing 150 mg of KPE) once daily for 12 weeks. The primary outcome was reduction in visceral fat area as determined by computed tomography scanning. The key secondary outcomes were reductions in subcutaneous fat area and total fat area. Subgroup analysis was also performed in healthy subjects without dyslipidemia, hypertension, or hyperglycemia. The safety of KPE ingestion was also evaluated. RESULTS: Compared with the placebo group, the active KPE group exhibited significant reduction in abdominal fat area (visceral, subcutaneous, and total fat) and triglyceride levels after 12 weeks. Subgroup analyses demonstrated a significant reduction in abdominal fat area and triglyceride levels in healthy subjects compared with the placebo group after 12 weeks. Neither group exhibited adverse events related to the test foods or clinically relevant abnormal changes in physical, biochemical, or hematologic parameters, or in urinalysis results and medical interview. CONCLUSION: Daily ingestion of KPE safely reduces body fat, particularly abdominal fat, in Japanese overweight and preobese subjects.

Tilt orientationally disordered hexagonal columnar phase of phthalocyanine discotic liquid crystals.

The structures of the discotic liquid crystalline (LC) phase of metal-free octa-substituted phthalocyanine (Pc) derivatives were investigated using molecular dynamics (MD) simulations. Special attention was paid to the LC phase structure of the non-peripheral octa-hexyl substituted Pc-derivatives that were recently found to show very high carrier mobilities for the discotic LCs. We obtained spontaneous transition to the columnar hexagonal (Col_{h}) LC phase in a melting simulation from the crystal structure obtained using an x-ray diffraction study. In this simulated Col_{h} structure, the Pc-core normal vectors were tilted 47{∘} from the column axis in parallel within each column, but the tilting directions are disordered between columns. We also found that the inter-core distance was not as large as previously suggested (0.4-0.5 nm) but similar to the common value (0.36 nm). This may resolve the contradiction between the high carrier mobility of the non-peripheral substituted Pcs, because larger inter-core separations degrade the mobilities.

Dynamics of discotic fluoroalkylated triphenylene molecules studied by proton NMR relaxometry.

The Larmor frequency and temperature dependence of the proton nuclear magnetic resonance (NMR) spin-lattice relaxation time was measured in the isotropic and columnar phases of both chain-end fluorinated triphenylene disk-like and fully hydrogenated molecules. In the columnar phase, the results are interpreted in terms of the collective motions, due to the deformations of the columns, and individual molecular translational self-diffusion displacements and rotations/reorientacions. In the isotropic phase, local molecular motions and order fluctuations as a pretransitional effect were considered. The activation energies of the molecular motions of the partially fluorinated molecule were found to be higher than those corresponding to the hydrocarbon homologue. Our findings show a clear difference in the relaxation dispersion between the two liquid crystals homologues. In particular it is observed that the columnar undulations have a much stronger contribution to the relaxation rate in the low frequency regime in the case of the fully hydrogenated triphenylene. The effect of fluorination of the pheripheral chain enhances the columnar mesophase's stability.

Molecular cloning and expression of starfish protein kinase C isoforms.

To investigate the roles of protein kinase C (PKC) isoforms in Echinoderms, we cloned starfish cDNAs for novel, atypical, and conventional PKCs. They showed highest homology with PKCdelta, iota, and alpha isoforms respectively. It was predicted from the whole genome sequence and by RT-PCR that sea urchin has only one isoform of each PKC subgroups. It is thus likely that these isoforms are the prototypes or ancestors of the PKC subgroups. The phylogenetic tree suggests that atypical PKC was first formed by evolution from the common prototype of AGC protein kinase family, and novel and conventional PKCs next. RT-PCR analysis indicated that novel and atypical PKC mRNAs are expressed ubiquitously in all tissues of adult starfish, whereas conventional PKC mRNA is expressed mainly in the ovary and oocytes, and only slightly in the tube foot and stomach. Upon heterologous expression, only atypical PKC was expressed in the functional form in insect cells.

Remineralization of enamel subsurface lesions by xylitol chewing gum containing funoran and calcium hydrogenphosphate.

The aim of the present study was to determine the remineralization effects of xylitol chewing gum containing funoran and calcium hydrogenphosphate on enamel subsurface lesions in humans. The study was a double-blind, randomized, cross-over design, with 4 types of gum: (1) xylitol gum, (2) xylitol gum containing funoran and calcium hydrogenphosphate, (3) sugar gum, and (4) gum base as a control. Seven subjects were instructed to wear removable lingual appliances, with half-slab insets of human enamel containing demineralized subsurface lesions. They were told to chew gum for 20 minutes 4 times per day for 7 days. Upon completion of each treatment the enamel half-slabs were paired with their respective demineralized control half-slabs, embedded, sectioned, and subjected to microradiography and densitometric image analysis, for measurement of the level of remineralization. The mean area of remineralization (deltaZd-deltaZr) and mean percent remineralization (%R) in those chewing xylitol gum containing funoran and calcium hydrogenphosphate were significantly higher than the corresponding values for xylitol gum, sugar gum and gum base. Chewing xylitol gum containing funoran and calcium hydrogenphosphate has a significant effect on the remineralization of initial caries-like lesions of the teeth.

Heterologous expression and catalytic properties of the C-terminal domain of starfish cdc25 dual-specificity phosphatase, a cell cycle regulator.

The 3'-terminal region of starfish Asterina pectinifera cdc25 cDNA encoding the C-terminal catalytic domain was overexpressed in Escherichia coli. The C-terminal domain consisted of 226 amino acid residues containing the signature motif HCxxxxxR, a motif highly conserved among protein tyrosine and dual-specificity phosphatases, and showed phosphatase activity toward p-nitrophenyl phosphate. The enzyme activity was strongly inhibited by SH inhibitors. Mutational studies indicated that the cysteine and arginine residues in the conserved motif are essential for activity, but the histidine residue is not. These results suggest that the enzyme catalyzes the reaction through a two-step mechanism involving a phosphocysteine intermediate like in the cases of other protein tyrosine and dual-specificity phosphatases. The C-terminal domain of Cdc25 activated the histone H1 kinase activity of the purified, inactive form of Cdc2.cyclin B complex (preMPF) from extracts of immature starfish oocytes. Synthetic diphosphorylated di- to nonadecapeptides mimicking amino acid sequences around the dephosphorylation site of Cdc2 still retained substrate activity. Phosphotyrosine and phosphothreonine underwent dephosphorylation in this order. This is the reverse order to that reported for the in vivo and in vitro dephosphorylation of preMPF. Monophosphopeptides having the same sequence served as much poorer substrates. As judged from the results with synthetic phosphopeptides, the presence of two phosphorylated residues was important for specific recognition of substrates by the Cdc25 phosphatase.