Laser-Assisted Melt Electrospinning of Poly(L-lactide-co-ε-caprolactone): Analyses on Processing Behavior and Characteristics of Prepared Fibers.

The laser-assisted melt electrospinning (LES) method was utilized for the preparation of poly(L-lactide-co-ε-caprolactone) (PLCL) fibers. During the process, a carbon dioxide laser was irradiated, and voltage was applied to the raw fiber of PLCL. In situ observation of fiber formation behavior revealed that only a single jet was formed from the swelling region under the conditions of low laser power and applied voltage and feeding rate, whereas multiple jets and shots were produced with increases in these parameters. The formation of multiple jets resulted in the preparation of thinner fibers, and under the optimum condition, an average fiber diameter of 0.77 µm and its coefficient of variation of 17% was achieved without the formation of shots. The estimation of tension and stress profiles in the spin-line was also carried out based on the result of in situ observation and the consideration that the forces originated from surface tension, electricity, air friction, and inertia. The higher peak values of tension and stress appearing near the apex of the swelling region corresponded to the formation of thinner fibers for the condition of single-jet ejection. Analyses of the molecular orientation and crystallization of as-spun fibers revealed the formation of a wide variation of higher order structure depending on the spinning conditions.

Planar or Biaxial Stretching of Poly(ethylene terephthalate) Fiber Webs Prepared by Laser-Electrospinning.

In this work, laser-heated electrospinning (LES) process using carbon dioxide laser was explored as an eco-friendly method for producing ultrafine fibers. To enhance the thinning of fibers and the formation of fiber structure, planar or equibiaxial stretching and subsequent annealing processes were applied to poly(ethylene terephthalate) (PET) fiber webs prepared by LES. The structure and properties of the obtained webs were investigated. Ultrafine fiber webs with an average diameter of approximately 1 µm and a coefficient of variation of 20-25% were obtained when the stretch ratios in the MD (machine direction) × TD (transverse direction) were 3 × 1 and 3 × 3 for the planar and equibiaxial stretching, respectively. In the wide-angle X-ray diffraction analysis of the web samples, preferential orientation of crystalline c-axis were confirmed along the MD for planar stretching and only along the web plane for equibiaxial stretching, which was in contrast to the stretching of film samples, where additional preferential orientation of benzene ring along the film plane proceeded. The results obtained suggest that PET fiber webs fabricated through LES and subsequent planar or biaxial stretching processes have potential for a wide variety of applications, such as packaging and battery separator materials.

Effect of environmental conditions on the α-glucosidase inhibitory activity of mulberry leaves.

Mulberry leaves have been used as the sole food for silkworms in sericulture, and also as a traditional medicine for diabetes prevention. Mulberry leaf components, for example 1-deoxynojirimycin (1-DNJ), inhibit the activity of α-glucosidase and prevent increased blood glucose levels, and they are highly toxic to caterpillars other than silkworms. The α-glucosidase inhibitory activity of mulberry leaves changes with the season, but it is unknown which environmental conditions influence the α-glucosidase inhibitory activity. We investigated in this study the relationship between the α-glucosidase inhibitory activity and environmental conditions of temperature and photoperiod. The results demonstrate that low temperatures induced decreasing α-glucosidase inhibitory activity, while the induction of newly grown shoots by the scission of branches induced increasing α-glucosidase inhibitory activity. These results suggest that the α-glucosidase inhibitory activity was related to the defense mechanism of mulberry plants against insect herbivores.

Bamboo Charcoal/Poly(L-lactide) Fiber Webs Prepared Using Laser-Heated Melt Electrospinning.

Although several studies have reported that the addition of bamboo charcoal (BC) to polylactide (PLA) enhances the properties of PLA, to date, no study has been reported on the fabrication of ultrafine BC/poly(L-lactide) (PLLA) webs via electrospinning. Therefore, ultrafine fiber webs of PLLA and BC/PLLA were prepared using PLLA and BC/PLLA raw fibers via a novel laser electrospinning method. Ultrafine PLLA and BC/PLLA fibers with average diameters of approximately 1 µm and coefficients of variation of 13-23 and 20-46% were obtained. Via wide-angle X-ray diffraction (WAXD) analysis, highly oriented crystals were detected in the raw fibers; however, WAXD patterns of both PLLA and BC/PLLA webs implied an amorphous structure of PLLA. Polarizing microscopy images revealed that the webs comprised ultrafine fibers with uniform diameters and wide variations in birefringence. Temperature-modulated differential scanning calorimetry measurements indicated that the degree of order of the crystals in the fibers was lower and the molecules in the fibers had higher mobilities than those in the raw fibers. Transmittance of BC/PLLA webs with an area density of 2.6 mg/cm2 suggested that the addition of BC improved UV-shielding efficiencies.

Structure and Properties of Poly(ethylene terephthalate) Fiber Webs Prepared via Laser-Electrospinning and Subsequent Annealing Processes.

Melt-electrospinning is an eco-friendly method for producing ultra-fine fibers without using any solvent. We prepared webs of poly(ethylene terephthalate) (PET) through melt-electrospinning using CO2 laser irradiation for heating. The PET webs comprised ultra-fine fibers of uniform diameter (average fiber diameter = 1.66 µm, coefficient of variation = 19%). The co-existence of fibers with high and low molecular orientation was confirmed through birefringence measurements. Although the level of high orientation corresponded to that of commercial highly oriented yarn, crystalline diffraction was not observed in the wide-angle X-ray diffraction (WAXD) analysis of the webs. The crystallinity of the webs was estimated using differential scanning calorimetry (DSC). The fibers with higher birefringence did not exhibit any cold crystallization peak. After annealing the web at 116 °C for 5 min, a further increase in the birefringence of the fibers with higher orientation was observed. The WAXD results revealed that the annealed webs showed crystalline diffraction peaks with the orientation of the c-axis along the fiber axis. In summary, the formation of fibers with a unique non-crystalline structure with extremely high orientation was confirmed.

Cancer preventive agents. Part 8: Chemopreventive effects of stevioside and related compounds.

In a search for potential cancer chemopreventive agents from natural resources, stevioside (1), a sweetener, and six related compounds, including two aglycones steviol (6) and isosteviol (7), were screened in an in vitro assay for inhibitory effects on Epstein-Barr virus early antigen activation. Compounds 1, 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1, as well as 6 and 7, could be valuable as chemopreventive agents for chemical carcinogenesis.

Correlation between oxidation potentials and inhibitory effects on Epstein-Barr virus activation of flavonoids.

The oxidation potentials of fifteen flavonoids in phosphate buffer at pH 7.2 were determined by cyclic voltammetry. A good correlation was found between these oxidation potentials and the ability of flavonoids to inhibit Epstein-Barr virus early antigen (EBV-EA) activation. Furthermore, multiple regression analysis revealed that the solvent-accessible surface area (SASA) was a useful parameter for estimating the inhibitory effects of flavonoids on EBV-EA activation.

Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in mammalian cells.

Because heat shock proteins (Hsps) are involved in protecting cells and in the pathophysiology of diseases such as inflammation, cancer, and neurodegenerative disorders, the use of regulators of the expression of Hsps in mammalian cells seems to be useful as a potential therapeutic modality. To identify compounds that modulate the response to heat shock, we analyzed several natural products using a mammalian cell line containing an hsp promoterregulated reporter gene. In this study, we found that an extract from Fructus Arctii markedly suppressed the expression of Hsp induced by heat shock. A component of the extract arctigenin, but not the component arctiin, suppressed the response at the level of the activation of heat shock transcription factor, the induction of mRNA, and the synthesis and accumulation of Hsp. Furthermore, arctigenin inhibited the acquisition of thermotolerance in mammalian cells, including cancer cells. Thus, arctigenin seemed to be a new suppressive regulator of heat shock response in mammalian cells, and may be useful for hyperthermia cancer therapy.

Anticarcinogenic activity of natural sweeteners, cucurbitane glycosides, from Momordica grosvenori.

To search for cancer chemopreventive agents from natural resources, many phytochemicals and food additives have been screened. Consequently, two natural sweeteners, mogroside V and 11-oxo-mogroside V isolated from the fruits of Momordica grosvenori, exhibited strong inhibitory effect on the primary screening test indicated by the induction of Epstein-Barr virus early antigen (EBV-EA) by a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). These sweet glycosides, having cucurbitane triterpenoid aglycon, exhibited the significant inhibitory effects on the two-stage carcinogenesis test of mouse skin tumors induced by peroxynitrite (ONOO-) as an initiator and TPA as a promoter. Further, 11-oxo-mogroside V also exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

Grandinal, a New Phloroglucinol Dimer from Eucalyptus grandis.

Grandinal, a new dimeric phloroglucinol compound, was isolated from Eucalyptus grandis and characterized by spectral techniques. Tautomeric structures 1, 2, and 3 were assigned to grandinal. Biogenetically, 1 is proposed to be formed from intermediates derived from grandinol and jensenone.

Tyrosinase inhibitors from galls of Rhus javanica leaves and their effects on insects.

As a defense mechanism of the leaves of Rhus javanica (Anacardiaceae) against the aphid Melaphis chinensis (Aphididae) attack, tannic acid is rapidly accumulated and forms galls along the midrib of the leaves resulting in a unique natural medicine Gallae Rhois. Tannic acid was found to inhibit the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase (EC 1.14.18.1) with an IC50 of 22 microM. The aphid would detoxify the ingested toxic tannic acid to relatively nontoxic gallic acid, whereas the non-adapted pink bollworm Pectinophora gossypiella larvae are sensitive to the ingested tannic acid.

New 6-amino-6-deoxy-glycoglycerolipids derived from 2-O-ß-D-glucopyranosylglycerol: insights into the structure-activity relationship of glycoglycerolipids as anti-tumor promoters.

As part of a project aimed at obtaining compounds capable of inhibiting tumor promotion, new 6-amino-6-deoxyglycoglycerolipids (AGGLs) derived from 2-O-ß-D-glucopyranosyl-sn-glycerol were synthesized and tested for their anti-tumor-promoting activity using a short-term in vitro assay of the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The corresponding 6-amino-6-deoxy-ß-D-octylglucosides were also prepared as simplified aminoglycolipid models and tested. Comparison with the activity of a series of previously studied glycoglycerolipids showed that replacing the 6-oxygen of the glucose moiety by a nitrogen atom greatly reduced the in vitro activity of the compounds. A two-stage mouse skin carcinogenesis test of two representative aminoglycoglycerolipids confirmed their reduced activity also in this in vivo model.

Oral chemoprevention of skin cancer in mice by benzophenone sunscreens dioxybenzone and octabenzone in drinking water.

BACKGROUND: Sunscreen compounds with added benefit of skin cancer prevention have both public and commercial interests. Our earlier study using the Epstein-Barr virus early antigen in vitro assay reported on skin cancer chemoprevention potential of benzophenone sunscreens. We now report the in vivo antitumor activity of two of the benzophenone sunscreens which tested positively in the in vitro assay, octabenzone (UV-1) and dioxybenzone (UV-2), in the two-stage mouse skin carcinogenesis model using (±)-(E)-4-methyl-2-[-(E)-hydroxyamino]-5-nitro-6-methoxy-3-hexanamide (NOR-1) as inducer and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as promoter. MATERIALS AND METHODS: Pathogen-free, female hairless mice of HOS:HR-1 strain, 15 animals per control and test groups, were used. Skin tumors were induced by a single dose of NOR-1 (390 nmol in 100 µl of acetone). One week later, TPA (1.7 nmol in 100 µl of acetone) was applied to skin twice weekly for 20 weeks as tumor a promoter. The test compounds UV-I or UV-2 were administered at 0.0025% to mice through drinking water ad libitum, starting one week prior to and stopping one week after tumor initiation. All animals were examined weekly for the development of skin papillomas. RESULTS: In both UV-1- and UV-2-treated mice, a two-week delay in tumor appearance, and significant inhibition (p<0.001) of tumor incidence (50% and 60%, respectively) and tumor burden (papilloma inhibition/mouse, 50% and 70%, respectively) were observed when compared to the positive control group. UV-2 (dihydroxy derivative) was a more potent inhibitor of skin tumor than UV-1 (monohydroxy derivative), which followed their antioxidant activity ranking. CONCLUSION: The results affirm the skin cancer chemoprevention potential of orally-ingested benzophenone sunscreens in mice and warrant studies in humans to validate synergistic protection achievable by complementation of oral and topical sunscreen usage.

Chemoprevention of skin cancer: effect of Lawsonia inermis L. (Henna) leaf powder and its pigment artifact, lawsone in the Epstein- Barr virus early antigen activation assay and in two-stage mouse skin carcinogenesis models.

In continuation of our studies with chemoprevention potential of plant-derived naphthoquinone derivatives, leaf powder of the medicinal plant Lawsonia inermis L, commonly known as 'henna', was evaluated by its inhibition of the Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Lawsone (2-hydroxy- 1,4-naphthoquinone), the reddish orange pigment artifact formed during the extraction or preparation of the dye from henna leaves and believed to be the active component, was also assessed in this in vitro assay. Both showed a profound inhibition (>88%) of EBV-EA activation. In the in vivo two-stage mouse skin carcinogenesis study using UV-B radiation for initiation and TPA for tumor promotion, oral feeding of henna (0.0025%) in drinking water ad libitum decreased tumor incidence by 66% and multiplicity by 40% when compared to the positive control at 10 weeks of treatment. Similarly, in the above mouse model, orally fed lawsone (0.0025%) decreased tumor incidence by 72% and multiplicity by 50%. The tumor inhibitory trend continued throughout the 20-week test period. Similar antitumor activities were observed when henna (0.5 mg/ml) was applied topically on the back skin in the UV-B initiated, TPA promoted and peroxynitrite initiated, TPA promoted mouse skin carcinogenesis models. Topically applied lawsone (0.015 mg/ml) also exhibited similar protection against tumor formation in the 7,12-dimtehylbenz(a)anthracene induced and TPA promoted skin cancer in mice. Also, there was a delay of 1 to 2 weeks in tumor appearance in both henna and lawsone treated groups compared to control in all three test models. This study ascertains the skin cancer chemopreventive activity of henna leaf powder and lawsone when administered by either oral (through drinking water) or topical (by application on the back skin) routes. Further, it emphasizes the need for the evaluation of these henna-derived green chemopreventive candidates in combination with currently used sunscreen agents for complementary anticancer potential against UV-induced skin carcinogenesis.

Electrospray ionization-mass spectrometric measurement of sake, a traditional Japanese alcohol beverage, for characterization.

A rapid method for the characterization of sake by measuring the ratio of the peak intensities of taste components in sake, using electrospray ionization/mass spectrometry (ESI/MS) has been developed. Twenty-six different kinds of sake samples were collected and analyzed by ESI/MS. The ESI/MS ion peaks were assigned to amino acids, organic acids, and sugars. Principal component analysis was performed using the respective peak intensities obtained by ESI/MS measurements. As a result, the cumulative proportion of the two first principal components was over 70%, and these components could be used for the characterization of sake.

Cancer chemopreventive activity of the prenylated coumarin, umbelliprenin, in vivo.

Umbelliprenin is a prenylated compound, which belongs to the class of sesquiterpene coumarins. In continuation of our earlier in-vitro finding, we determined to assess the cancer chemopreventive activity of umbelliprenin in vivo by using a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite as an initiator and TPA (12-O-tetradecanoylphorbol-13-acetate) as a promoter. In this assay, treatment with umbelliprenin along with peroxynitrite/TPA delayed the formation of papillomas up to week 9, and approximately 33.3 and 86.6% of the mice bore papillomas after 11 and 20 weeks of promotion, respectively. Umbelliprenin reduced the number of tumors per mouse by 45% after 20 weeks of promotion compared with the control group. Interestingly, this is equal to the corresponding value (45%) for curcumin, used as a reference standard compound in our study. In addition, the pattern of tumor promotion was slower in mice treated with umbelliprenin compared with the curcumin. Therefore, umbelliprenin might be valuable as a cancer chemopreventive agent.

Cowaniin, a C-glucosidic ellagitannin dimer linked through catechin from Cowania mexicana.

A new complex tannin, cowaniin (1) was isolated from the leaves and stems of Cowania mexicana (Rosaceae), and its structure was characterized as novel C-glucosidic tannin dimer linked through (+)-catechin on the basis of spectral and chemical evidence. The inhibitory effect on activation of the Epstein-Barr virus early antigen was assessed for cowaniin. Six known polyphenols and related compounds, including a nitrile glucoside, purshianin, were also characterized.

Five phloroglucinol-monoterpene adducts from Eucalyptus grandis.

Five new euglobals possessing the phloroglucinol-monoterpene structure, euglobals G8-G12, together with a known euglobal-IIc were isolated from the hexane fraction of the methanol extract of the leaves of Eucalyptus grandis. Euglobal-G8 is an adduct of formyl-isovaleroyl-phloroglucinol and gamma-terpinene whereas -G9, -G10 and -G11 have the same phloroglucinol moiety fused with alpha-terpinene, while Euglobal-G12 has terpinolene fused with the same phloroglucinol moiety. The structures of these compounds were elucidated on the basis of spectral evidences. Biomimetic synthesis of euglobals suggests that these compounds are derived biogenetically by the Diels-Alder type cycloaddition of the corresponding terpenes with an ortho-quinone methide generated from grandinol.

Quantification of sideroxylonals in Eucalyptus foliage by high-performance liquid chromatography.

This paper describes the extraction and quantification of sideroxylonals, a group of formylated phloroglucinol compounds found in the foliage of some eucalypt species. Samples of dry, ground foliage were Soxhlet-extracted with light petroleum spirit:acetone (4:1) and the resultant extract analysed (in the presence of internal standard) by reversed-phase HPLC without further purification. The yield of sideroxylonals was exponential with time and showed an inflection at ca. 4 h of extraction. It is recommended that samples be extracted for 6 h, giving a 92% recovery of the sideroxylonals. The title compounds deteriorate under various conditions, e.g. 10% are lost when foliage is oven-dried at 40 degrees C compared to freeze-drying. Storing samples in mobile phase led to a slow deterioration of sideroxylonals with a 7% loss after 4 days, while 22% of these compounds were lost from dry, ground eucalypt leaf stored at room temperature for 20 months.

Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse skin tumor model. The anti-oxidant capabilities of these compounds could not solely explain the observed anti-cancer characteristics. Resveratrol is present in grapes. Sesamol, a constituent of sesame oil and sunflower oil are regularly consumed dietary natural products. The observed chemopreventive effect of these products particularly warrants more attention since they already exist in the population with no known adverse effects.