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Lee C.-W.,Chang Gung University | Huang H.-W.,Graduate Institute of Natural Products | Wu T.-H.,Health Bureau of Kaohsiung County Government | Tzeng W.-S.,Chi Mei Foundation Hospital | And 2 more authors.
Journal of Agricultural and Food Chemistry | Year: 2012

Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection. Unfortunately, RES is restricted in clinical application due to poor dissolution property and adsorption. In addition, red wine as a supplement for preventing disease is not recommended for patients with alcohol-related disorders. To address these limitations, we successfully developed a novel RES nanoparticle system (RESN) and demonstrated that RESN could circumvent the physicochemical drawbacks of raw RES with respect to dissolution, such as the reduction of particle size, amorphous transformation, and hydrogen-bond formation. In addition, we employed an animal model of CCl4-induced hepatotoxicity to estimate the potential of the nanoparticle formulation to improve the hepatoprotective effect of orally administered RES. Our results demonstrated that RESN can diminish liver function markers (aspartate aminotransferase and alanine aminotransferase) by decreasing hepatocyte death due to CCl4-induced hepatotoxicity in rats, when compared with RES administration. The effect was achieved by reducing oxidative stress (decreased reactive oxygen species and lipid peroxidation) and lowering inflammatory cytokines (decreased tumor necrosis factor-α and interleukin 1β) and protein expression (cyclooxygenase-2, inducible nitric oxide synthase, cytosolic phospholipase A2, and caspase-3). In conclusion, enhancement of the dissolution of RES through a nanoparticle engineering process can result in increased hepatoprotective effects mediated by antioxidant and anti-inflammatory activities. Consequently, we suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver diseases. © 2012 American Chemical Society.


Lee C.-H.,Kaohsiung Medical University | Yang S.-F.,Kaohsiung Medical University | Peng C.-Y.,Kaohsiung Medical University | Li R.-N.,Kaohsiung Medical University | And 12 more authors.
International Journal of Cancer | Year: 2010

Although cooking emission from high-temperature frying has been deemed a Group 2A carcinogen by the International Agency for Research on Cancer, little is known about its impact on cervical tumorigenesis. To investigate the precancerous consequence of cooking oil fumes on cervical intraepithelial neoplasm (CIN), a community-based case-control study, which takes all known risk factors into consideration, was conducted in Taiwan. From 2003 to 2008, in a Pap smear screening and biopsy examination network, 206 pathology-verified women with inflammations/atypical squamous cells of undetermined significance or CIN grade-1 (CIN1) and 73 with CIN2-3 (defined as low-grade squamous intraepithelial lesions (LGSIL) and high-grade squamous intraepithelial lesions (HGSIL), respectively); and 1,200 area-and-age-matched controls with negative cytology were recruited. Multinomial logistic regression was applied in the multivariate analysis to determine the likelihood of contracting LGSIL or HGSIL. The risks of the two lesions increased with the increase of carcinogenic high-risk human papillomavirus DNA load, with a clear dose-response relationship. Chefs were observed to experience a 7.9-fold elevated HGSIL risk. Kitchens with poor fume ventilation during the main cooking life-stage correlated to a 3.7-fold risk of HGSIL, but not for LGSIL. More than 1 hr of daily cooking in kitchens with poor fume conditions appeared to confer an 8.4-fold HGSIL risk, with an 8.3-fold heterogeneously higher odds ratio than that (aOR = 1.0) for LGSIL. Similar risk pattern has been reproduced among never-smoking women. Our findings demonstrate the association between indoor exposure to cooking fumes from heated oil and the late development of cervical precancerous lesions. This final conclusion needs to be verified by future research. © 2009 UICC.


Yen F.-L.,Kaohsiung Medical University | Wu T.-H.,Health Bureau of Kaohsiung County Government | Tzeng C.-W.,Kaohsiung Medical University | Lin L.-T.,Dalhousie University | Lin C.-C.,Kaohsiung Medical University
Journal of Agricultural and Food Chemistry | Year: 2010

Curcumin (CUR), a natural polyphenol isolated from tumeric (Curcuma longa), has been documented to possess antioxidant and anticancer activities. Unfortunately, the compound has poor aqueous solubility, which results in poor bioavailability following high doses by oral administration. To improve the solubility of CUR, we developed a novel curcumin nanoparticle system (CURN) and investigated its physicochemical properties as well as its enhanced dissolution mechanism. Our results indicated that CURN improved the physicochemical properties of CUR, including a reduction in particle size and the formation of an amorphous state with hydrogen bonding, both of which increased the drug release of the compound. Moreover, in vitro studies indicated that CURN significantly enhanced the antioxidant and antihepatoma activities of CUR (P < 0.05). Consequently, we suggest that CURN can be used to reduce the dosage of CUR and improve its bioavailability and merits further investigation for therapeutic applications. © 2010 American Chemical Society.


Tzeng C.-W.,Kaohsiung Medical University | Yen F.-L.,Kaohsiung Medical University | Wu T.-H.,Health Bureau of Kaohsiung County Government | Ko H.-H.,Kaohsiung Medical University | And 3 more authors.
Journal of Agricultural and Food Chemistry | Year: 2011

Kaempferol (KAE) is a strong antioxidant flavonoid compound, but its clinical application is limited by quantity and poor dissolution property.However, the dissolution mechanismof a kaempferol nanoparticle formulation (KAEN) has not yet been elucidated. The aim of the present study was therefore to use a nanoparticle engineering process to resolve the dissolution problem. Our data indicated that KAEN effectively increased the dissolution percentage by particle size reduction, high encapsulation efficiency, amorphous transformation, and hydrogen-bond formation with excipients. In addition, we used several different antioxidant activity assays to evaluate KAE and KAEN. The data indicated that KAEN retained potent antioxidant activity after the nanoparticle engineering process and showed better antioxidant activity than KAE dissolved in water (P < 0.05). According to these findings, we concluded that KAEN could be a low-dose alternative to KAE in health food and future clinical research. © 2011 American Chemical Society.


Hsu W.-C.,Kaohsiung Medical University | Ng L.-T.,National Taiwan University | Wu T.-H.,Health Bureau of Kaohsiung County Government | Lin L.-T.,Health Center | And 3 more authors.
Journal of Nanoscience and Nanotechnology | Year: 2012

Silymarin, a well known hepatoprotective drug, has been routinely used in treating liver disorders. However, its bioavailability and therapeutic efficiency are limited by the poor aqueous solubility. In this study, we used the nanoprecipitation technique to develop a nanoparticles system to improve the solubility of silymarin. The newly developed silymarin nanoparticles were characterized for mean particle size, morphology, intermolecular interaction, crystalline features and dissolution property, as well as assessing for antioxidant activities. Results indicated that a drastic change in the physiochemical properties of silymarin was noted in the form of nanoparticles, as displayed by the extremely small particle size (46.1±1.73 nm), the formation of intermolecular hydrogen bonding between silymarin and matrix of nanoparticles, and the rendering of amorphous state. These phenomena have contributed to the enhanced dissolution property of silymarin nanoparticles, as well as a greater potency in DPPH radical scavenging, anti-superoxide anion formation, and superoxide anion scavenging activities than the crude silymarin. The present study concludes that silymarin nanoparticles have an improved physicochemical property as demonstrated by an increased solubility and enhanced antioxidant activities. Copyright © 2012 American Scientific Publishers.

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