Ching-Shu Lai

National Kaohsiung Marine University, Kaohsiung, Kaohsiung, Taiwan

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Publications (40)125.75 Total impact

  • Article: Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors.
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    ABSTRACT: Prostate cancer is one of the most prevalent malignancies and is the second leading cause of cancer-related deaths in men. Fruit and vegetable consumption is a novel, non-toxic therapeutic approach that can be used to prevent and treat prostate cancer. Citrus peels and their extracts have been reported to have potent pharmacological activities and health benefits due to the abundance of flavonoids in citrus fruits, particularly in the peels. Our previous studies demonstrated that oral administration of Gold Lotion (GL), an extract of multiple varieties of citrus peels containing abundant flavonoids, including a large percentage of polymethoxyflavones (PMFs), effectively suppressed azoxymethane (AOM)-induced colonic tumorigenesis. However, the efficacy of GL against prostate cancer has not yet been investigated. Here, we explored the anti-tumor effects of GL using a human prostate tumor xenograft mouse model. Our data demonstrated that treatment with GL by both intraperitoneal (i.p.) injection and oral administration dramatically reduced both the weights (57%-100% inhibition) and volumes (78%-94% inhibition) of the tumors without any observed toxicity. These inhibitory effects were accompanied by mechanistic down-regulation of the protein levels of inflammatory enzymes (inducible nitric oxide synthase, iNOS and cyclooxygenase-2, COX-2), metastasis (matrix metallopeptidase-2, MMP-2 and MMP-9), angiogenesis (vascular endothelial growth factor, VEGF), and proliferative molecules, as well as by the induction of apoptosis in prostate tumors. Our findings suggest that GL is an effective anti-cancer agent that may potentially serve as a novel therapeutic option for prostate cancer treatment.
    Food & function. 05/2013;
  • Article: Epigenetic and diseases targets by polyphenols.
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    ABSTRACT: An epigenetic change is defined as an alteration in gene expression that does not involve a change in the DNA sequence. Epigenetic modifications, including DNA methylation, histone modification (acetylation, methylation and phosphorylation) and miRNA, are critical for regulating developmental events. However, aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD), neurodegenerative disease, obesity, metabolic disorder, bone and skeletal diseases and various cancers. Given that epigenetic modifications are heritable and reversible, in contrast to genetic changes, they have been identified as promising targets for disease prevention strategies. Over the past few decades, polyphenols, which are widely present in foods such as fruits and vegetables, have been shown to exhibit a broad spectrum of biological activities for human health. Polyphenols reverse adverse epigenetic regulation by altering DNA methylation and histone modification, and they modulate microRNA expression or directly interact with enzymes that result in the reactivation of silenced tumor suppressor genes or the inactivation of oncogenes. Therefore, dietary polyphenol-targeted epigenetics becomes an attractive approach for disease prevention and intervention. In this review, we summarize the current knowledge and underlying mechanisms of the most common dietary polyphenols and their influence on major epigenetic mechanisms associated with disease intervention.
    Current pharmaceutical design 02/2013; · 4.41 Impact Factor
  • Article: Effective suppression of azoxymethane-induced aberrant crypt foci formation in mice with citrus peel flavonoids.
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    ABSTRACT: Citrus peel or its extract has been reported to exhibit a broad spectrum of biological activity. Herein, we report the first investigation of inhibitory effects of a formulated product from citrus peel extract, gold lotion (GL), on azoxymethane-induced colonic tumorigenesis. We have demonstrated that oral feeding of GL decreased the number of aberrant crypt foci (ACF), particularly large size of ACF in colonic tissues of mice. Both gene and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were suppressed by GL treatment. The in vivo data have revealed for the first time that the citrus peel extract-GL-is an effective antitumor agent mechanistically downregulating the protein levels of iNOS, COX-2, ornithine decarboxylase, vascular endothelial growth factor, and matrix metallopeptidase 9 in colonic tissues of mice, suggesting that GL is a novel functional natural product capable of preventing inflammation-associated colon tumorigenesis.
    Molecular Nutrition & Food Research 01/2013; · 4.30 Impact Factor
  • Article: Black tea: chemical analysis and stability.
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    ABSTRACT: Tea is the most popular flavored and functional drink worldwide. The nutritional value of tea is mostly from the tea polyphenols that are reported to possess a broad spectrum of biological activities, including anti-oxidant properties, reduction of various cancers, inhibition of inflammation, and protective effects against diabetes, hyperlipidemia and obesity. Tea polyphenols include catechins and gallic acid in green and white teas, and theaflavins and thearubigins as well as other catechin polymers in black and oolong teas. Accurate analysis of black tea polyphenols plays a significant role in the identification of black tea contents, quality control of commercial tea beverages and extracts, differentiation of various contents of theaflavins and catechins and correlations of black tea identity and quality with biological activity, and most importantly, the establishment of the relationship between quantitative tea polyphenol content and its efficacy in animal or human studies. Global research in tea polyphenols has generated much in vitro and in vivo data rationally correlating tea polyphenols with their preventive and therapeutic properties in human diseases such as cancer, and metabolic and cardiovascular diseases etc. Based on these scientific findings, numerous tea products have been developed including flavored tea drinks, tea-based functional drinks, tea extracts and concentrates, and dietary supplements and food ingredients, demonstrating the broad applications of tea and its extracts, particularly in the field of functional food.
    Food & function. 10/2012;
  • Article: Pterostilbene, a natural analogue of resveratrol, potently inhibits 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin carcinogenesis.
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    ABSTRACT: We reported previously that pterostilbene, a natural analogue of resveratrol from blueberries, strongly suppressed lipopolysaccharide-induced up-expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further investigated pterostilbene's molecular mechanism of action and its anti-tumor properties. Pretreatment with pterostilbene has resulted in the reduction of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear translocation of the nuclear factor-κB (NFκB) subunits. Pterostilbene also reduced TPA-induced phosphorylation of IκBα and p65 and caused subsequent degradation of IκBα. Moreover, pterostilbene markedly suppressed TPA-induced activation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK)1/2, phosphatidylinositol 3-kinase (PI3K) and Akt, which are upstream of NFκB and activator protein 1 (AP-1). Furthermore, pterostilbene significantly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. The presented data has, for the first time, revealed that pterostilbene is an effective anti-tumor agent that functions by downregulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that pterostilbene is a novel functional agent capable of preventing inflammation-associated tumorigenesis.
    Food & function. 07/2012; 3(11):1185-94.
  • Article: Inotilone suppresses phorbol ester-induced inflammation and tumor promotion in mouse skin.
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    ABSTRACT: Chemoprevention is one of the most feasible approaches to reduce the risk of cancer. Over the past decades, scientists have realized that chronic inflammation is a critical component of cancer development. Inotilone, existing in Inonotus mushroom has been reported to exhibit anti-inflammatory properties in vitro. Hence, we investigated the effects of inotilone on 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated acute inflammation and tumor promotion in mouse skin and the underlying molecular mechanisms. Inotilone was topically applied to mouse skin 30 min prior to TPA treatment. The results have shown that inotilone inhibited the production of inflammatory mediators by attenuating the activation of nuclear factor-κB (NF-κB) and the expression of CCAAT/enhancer binding protein β (C/EBPβ). Furthermore, the ability of inotilone to prevent tumorigenesis at promotion stage was evaluated using a classical two-stage mouse skin carcinogenesis model. After initiation of 7,12-dimethylbenz[a]anthracene (DMBA), applying inotilone topically before each TPA treatment was found to reduce the tumor incidence and tumor multiplicity of papillomas. Based on the results, we concluded that inotilone has potential to be developed into an effective chemopreventive agent for the treatment of a variety of inflammatory diseases, especially the prevention and treatment of epithelial skin cancer.
    Molecular Nutrition & Food Research 05/2012; 56(8):1324-32. · 4.30 Impact Factor
  • Article: Xanthigen suppresses preadipocyte differentiation and adipogenesis through down-regulation of PPARγ and C/EBPs and modulation of SIRT-1, AMPK, and FoxO pathways.
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    ABSTRACT: Xanthigen is a source of punicic acid and fucoxanthin derived from pomegranate seed and brown seaweed, respectively with recognized triacylglycerol-lowering effects in humans, yet the mechanism remains to be fully elucidated. The present study investigated the inhibitory effects of Xanthigen, fucoxanthin, and punicic acid (70% in pomegranate seed oil) on the differentiation of 3T3-L1 preadipocytes. Xanthigen potently and dose-dependently suppressed accumulation of lipid droplets in adipocytes compared to its individual components, fucoxanthin and pomegranate seed oil. Western blot analysis revealed that Xanthigen markedly down-regulated the protein levels of key adipogenesis transcription factors peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP) β, and C/EBPδ as well as a key enzyme involved in adipogenesis, fatty acid synthase (FAS). Xanthigen up-regulated the NAD(+)-dependent histone deacetylases (SIRT1) and activated AMP-activated protein kinase (AMPK) signaling in differentiated 3T3-L1 adipocytes. In addition, Xanthigen may also stimulate insulin trigger signaling and result in Akt-dependent phosphorylation of forkhead/winged helix O (FoxO)1 and FoxO3a. These results indicate that Xanthigen suppresses adipocyte differentiation and lipid accumulation through multiple mechanisms and may have applications for the treatment of obesity.
    Journal of Agricultural and Food Chemistry 02/2012; 60(4):1094-101. · 2.82 Impact Factor
  • Article: Molecular mechanisms for anti-aging by natural dietary compounds.
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    ABSTRACT: Aging is defined as a normal decline in survival with advancing age; however, the recent researches have showed that physiological functions of the body change during the aging process. Majority of the changes are often subject to a higher risk of developing diseases, such as cardiovascular disease, type II diabetes, Alzheimer's disease, Parkinson's disease, as well as the dysregulated immune and inflammatory disorders. Aging process is controlled by a complicated and precise signaling network that involved in energy homeostasis, cellular metabolism and stress resistance. Over the past few decades, research in natural dietary compounds by various organism and animal models provides a new strategy for anti-aging. Natural dietary compounds act through a variety mechanisms to extend lifespan and prevent age-related diseases. This review summarizes the current understanding on signaling pathways of aging and knowledge and underlying mechanism of natural dietary compounds that provide potential application on anti-aging and improve heath in human.
    Molecular Nutrition & Food Research 11/2011; 56(1):88-115. · 4.30 Impact Factor
  • Article: Tetrahydrocurcumin, a major metabolite of curcumin, induced autophagic cell death through coordinative modulation of PI3K/Akt-mTOR and MAPK signaling pathways in human leukemia HL-60 cells.
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    ABSTRACT: Autophagy (type II programmed cell death) is crucial for maintaining cellular homeostasis. Several autophagy-deficient or knockout studies indicate that autophagy is a tumor suppressor. Tetrahydrocurcumin (THC), a major metabolite of curcumin, has been demonstrated with anti-colon carcinogenesis and antioxidation in vivo. In the present study, we found that treatment with THC induced autophagic cell death in human HL-60 promyelocytic leukemia cells by increasing autophage marker acidic vascular organelle (AVO) formation. Flow cytometry also confirmed that THC treatment did not increase sub-G1 cell population whereas curcumin did with strong apoptosis-inducing activity. At the molecular levels, the results from Western blot analysis showed that THC significantly down-regulated phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinase signalings including decreasing the phosphorylation of mammalian target of rapamycin, glycogen synthase kinase 3β and p70 ribosomal protein S6 kinase. Further molecular analysis exhibited that the pretreatment of 3-methyladenine (an autophagy inhibitor) also significantly reduced acidic vascular organelle production in THC-treated cells. Taken together, these results demonstrated the anticancer efficacy of THC by inducing autophagy as well as provided a potential application for the prevention of human leukemia.
    Molecular Nutrition & Food Research 09/2011; 55(11):1646-54. · 4.30 Impact Factor
  • Article: Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis.
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    ABSTRACT: Tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR), has been demonstrated to be anti-cancerogenic and anti-angiogenic and prevents type II diabetes. In this present study, we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of CUR and THC in azoxymethane (AOM)-induced colon carcinogenesis in mice. All mice were sacrificed at 6 and 23 wk, and colonic tissue was collected and examined. We found that dietary administration of both CUR and THC could reduce aberrant crypt foci and polyps formation, while THC showed a better inhibitory effect than CUR. At the molecular level, results from Western blot analysis and immunohistochemistry staining showed that dietary CUR and THC exhibited anti-inflammatory activity by decreasing the levels of inducible NOS and COX-2 through downregulation of ERK1/2 activation. In addition, both dietary CUR and THC significantly decreased AOM-induced Wnt-1 and β-catenin protein expression, as well as the phosphorylation of GSK-3β in colonic tissue. Moreover, dietary feeding with CUR and THC markedly reduced the protein level of connexin-43, an important molecule of gap junctions, indicating that both CUR and THC might interfer with the intercellular communication of crypt cells. Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary THC against AOM-induced colonic tumorigenesis.
    Molecular Nutrition & Food Research 09/2011; 55(12):1819-28. · 4.30 Impact Factor
  • Article: Flavonoid glycosides from Microtea debilis and their cytotoxic and anti-inflammatory effects.
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    ABSTRACT: Two new 5-O-glucosylflavones, 5-O-β-D-glucopyranosyl cirsimaritin (1) and 5, 4'-O-β-D-diglucopyranosyl cirsimaritin (2), four known flavonoids, cirsimarin (3), cirsimaritin (4), salvigenin (5), 4', 5-dihydroxy-7-methoxyflavone (6), and a norisoprenoid, vomifoliol (7), have been isolated from the aerial parts of Microtea debilis. All isolates were tested for cytotoxicity in human cancer cell lines (Hep G2, COLO 205, and HL-60) and anti-inflammatory activities in LPS-treated RAW264.7 macrophages. Compound 6 was found to be a potent inhibitor to nitrite production in macrophages. Compounds 2, 4, 6, and 7 showed moderate anti-proliferative activity against COLO-205 cells with IC(50) values of 7.1, 13.1, 6.1, and 6.8 μM, respectively.
    Fitoterapia 03/2011; 82(2):168-72. · 1.85 Impact Factor
  • Article: Rosmanol potently induces apoptosis through both the mitochondrial apoptotic pathway and death receptor pathway in human colon adenocarcinoma COLO 205 cells.
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    ABSTRACT: Rosemary (Rosmarinus officinalis), a culinary spice and medicinal herb, has been widely used in European folk medicine to treat numerous ailments. Many studies have shown that rosemary extracts play important roles in anti-inflammation, anti-tumor, and anti-proliferation in various in vitro and in vivo settings. The roles of tumor suppression of rosemary have been attributed to the major components, including carnosic acid, carnosol, and rosmarinic acid, rosmanol, and ursolic acid. This study was to explore the effect of rosmanol on the growth of COLO 205 human colorectal adenocarcinoma cells and to delineate the underlying mechanisms. When treated with 50 μM of rosmanol for 24h, COLO 205 cells displayed a strong apoptosis-inducing response with a 51% apoptotic ratio (IC(50) ∼42 μM). Rosmanol increased the expression of Fas and FasL, led to the cleavage and activation of pro-caspase-8 and Bid, and mobilized Bax from cytosol into mitochondria. The mutual activation between tBid and Bad decreased the mitochondrial membrane potential and released cytochrome c and apoptosis-inducing factor (AIF) to cytosol. In turn, cytochrome c induced the processing of pro-caspase-9 and pro-caspase-3, followed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45). These results demonstrate that the rosmanol-induced apoptosis in COLO 205 cells is involvement of caspase activation and involving complicated regulation of both the mitochondrial apoptotic pathway and death receptor pathway.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2011; 49(2):485-93. · 2.99 Impact Factor
  • Article: Chemoprevention of colonic tumorigenesis by dietary hydroxylated polymethoxyflavones in azoxymethane-treated mice.
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    ABSTRACT: Hydroxylated polymethoxyflavones (PMFs), existing exclusively in citrus genus, have been reported to exhibit a broad spectrum of biological activity. Here we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of hydroxylated PMFs in an azoxymethane (AOM)-induced colonic tumorigenesis model. Male, Institute of Cancer Research (ICR), mice at age of 6 wk were injected with AOM twice weekly at a dose of 5 mg/kg for 2 wk and continuously fed control diet or diets containing 0.01 and 0.05% hydroxylated PMFs, respectively. Mice were then sacrificed at 6 and 20 wk, and colonic tissues were collected and examined. Hydroxylated PMFs feeding dose-dependently decreased the number of aberrant crypt foci in colonic tissues of mice. More importantly, we found that hydroxylated PMFs caused a strong reduction in numbers of large aberrant crypt foci and tumors in colonic tissue. Molecular analysis exhibited the anti-proliferative, anti-inflammatory, anti-angiogenic and pro-apoptotic activities of hydroxylated PMFs by significantly decreasing the levels of inducible nitric oxide synthase, cyclooxygenase, cyclin D1 and vascular endothelial growth factor through interfering with Wnt/β-catenin and epidermal growth factor receptor/Ras/mitogen-activated protein kinase signaling pathways as well as the activation of transcription factors NF-κB and STAT3 in colonic tissue, thus resulting in suppression of colonic tumorigenesis. Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary hydroxylated PMFs against AOM-induced colonic tumorigenesis.
    Molecular Nutrition & Food Research 02/2011; 55(2):278-90. · 4.30 Impact Factor
  • Article: Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds.
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    ABSTRACT: Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. This review focuses on preventing the initiation and promotion of neoplastic growth in colorectal cancer, particularly with natural dietary compounds. Chemoprevention is defined as the use of natural dietary compounds and/or synthetic substances that can delay, prevent, or even reverse the development of adenomas, as well as the progression from adenoma to carcinoma. The molecular mechanisms of their chemopreventive action are associated with the modulation of signaling cascades, gene expressions involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of chronic inflammation, metastasis, and angiogenesis. Here, we summarize the currently known targets and signaling pathways whereby natural dietary compounds interfere with the development of colorectal cancer, and thus providing evidence for these substances in colonic cancer chemopreventive action.
    Molecular Nutrition & Food Research 01/2011; 55(1):32-45. · 4.30 Impact Factor
  • Article: Hexavalent chromium induced ROS formation, Akt, NF-kappaB, and MAPK activation, and TNF-alpha and IL-1alpha production in keratinocytes.
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    ABSTRACT: In certain cell types, it has been found that, hexavalent chromium could increase ROS formation, activate cell signaling and stimulate the release of cytokines. But, in keratinocytes, these effects have not yet fully been demonstrated. Our aim is to observe the above effects of hexavalent chromium on keratinocytes. By utilizing HaCaT cells and the skin of albino guinea pigs, we showed that hexavalent chromium could increase ROS formation, activate the Akt, NF-kB, and MAPK pathways as well as increase the production of cytokines, including TNF-alpha and IL-1alpha. The release of these cytokines from keratinocytes is considered to be a key participant in the pathogenesis of contact hypersensitivity. Among cement workers, chromium hypersensitivity is an important occupational skin disease issue. Therefore, the observations of our study help us better understand the role of hexavalent chromium on the development of chromium hypersensitivity, which might provide clues for clinicians in the development of chemopreventative agents for the prevention of chromium hypersensitivity among cement workers.
    Toxicology Letters 10/2010; 198(2):216-24. · 3.23 Impact Factor
  • Article: Flavonoids and phenolic compounds from Rosmarinus officinalis.
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    ABSTRACT: A new flavonoid, 6''-O-(E)-feruloylhomoplantaginin (1), and 14 known compounds, 6''-O-(E)-feruloylnepitrin (2), 6''-O-(E)-p-coumaroylnepitrin (3), 6-methoxyluteolin 7-glucopyranoside (4), luteolin 3'-O-beta-D-glucuronide (5), luteolin 3'-O-(3''-O-acetyl)-beta-D-glucuronide (6), kaempferol (7), luteolin (8), genkwanin (9), and ladanein (10), together with 1-O-feruloyl-beta-D-glucopyranose (11), 1-O-(4-hydroxybenzoyl)-beta-D-glucopyranose (12), rosmarinic acid (13), carnosic acid (14), and carnosol (15), were isolated from the leaves of Rosmarinus officinalis . The structures were established on the basis of NMR spectroscopic methods supported by HRMS. All isolated compounds were tested for cytotoxicity in human cancer cell lines (HepG2, COLO 205, and HL-60) and for anti-inflammatory activities in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. Among them, compounds 14 and 15 were modestly active in the inhibition of nitrite production in macrophages, followed by compounds 8 and 5. Compounds 14 and 15 were more effective as an antiproliferative agent in HL-60 cells with IC(50) values of 1.7 and 5.5 microM, followed by compounds 8 and 7 with IC(50) of 39.6 and 82.0 microM, respectively. In addition, compounds 14 and 15 showed potent antiproliferative effects on COLO 205 cells with IC(50) values of 32.8 and 29.9 microM, respectively.
    Journal of Agricultural and Food Chemistry 05/2010; 58(9):5363-7. · 2.82 Impact Factor
  • Article: Anti-inflammatory activity of natural dietary flavonoids.
    Min-Hsiung Pan, Ching-Shu Lai, Chi-Tang Ho
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    ABSTRACT: Over the past few decades, inflammation has been recognized as a major risk factor for various human diseases. Acute inflammation is short-term, self-limiting and it's easy for host defenses to return the body to homeostasis. Chronic inflammatory responses are predispose to a pathological progression of chronic illnesses characterized by infiltration of inflammatory cells, excessive production of cytokines, dysregulation of cellular signaling and loss of barrier function. Targeting reduction of chronic inflammation is a beneficial strategy to combat several human diseases. Flavonoids are widely present in the average diet in such foods as fruits and vegetables, and have been demonstrated to exhibit a broad spectrum of biological activities for human health including an anti-inflammatory property. Numerous studies have proposed that flavonoids act through a variety mechanisms to prevent and attenuate inflammatory responses and serve as possible cardioprotective, neuroprotective and chemopreventive agents. In this review, we summarize current knowledge and underlying mechanisms on anti-inflammatory activities of flavonoids and their implicated effects in the development of various chronic inflammatory diseases.
    Food & function. 01/2010; 1(1):15-31.
  • Article: Differential inhibitory effects of inotilone on inflammatory mediators, inducible nitric oxide synthase and cyclooxygenase-2, in LPS-stimulated murine macrophage.
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    ABSTRACT: The inhibitory effects of inotilone and methylinotilone on the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with LPS were investigated. The results show that both hydroxyl groups on the benzene ring of the inotilone molecule are required for better anti-inflammatory effect. Western blotting and RT-PCR analyses demonstrated that inotilone blocked protein and mRNA expression of iNOS but not COX-2. Instead, inotilone inhibited prostaglandin E(2) production through decreasing the enzyme activity of COX-2. The repression of iNOS but not COX-2 expression may come from the differential effect of inotilone on nuclear factor-kappaB (NFkappaB) and CCAAT/enhancer-binding protein beta Treatment with inotilone resulted in the reduction of LPS-induced nuclear translocation of NFkappaB subunit and the NFkappaB-dependent transcriptional activity by blocking phosphorylation of inhibitor kappaB(IkappaB)alpha and p65 and subsequent degradation of inhibitor kappaBalpha. Inotilone also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. Our results suggest that inotilone may have potential to be developed into an effective anti-inflammatory agent.
    Molecular Nutrition & Food Research 10/2009; 53(11):1386-95. · 4.30 Impact Factor
  • Article: Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways.
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    ABSTRACT: Rosmanol is a natural polyphenol from the herb rosemary (Rosmarinus officinalis L.) with high antioxidant activity. In this study, we investigated the inhibitory effects of rosmanol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells induced by lipopolysaccharide (LPS). Rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as the downstream products, NO and PGE2. Treatment with rosmanol also reduced translocation of the nuclear factor-kappaB (NF-kappaB) subunits by prevention of the degradation and phosphorylation of inhibitor kappaB (IkappaB). Western blot analysis showed that rosmanol significantly inhibited translocation and phosphorylation of NF-kappaB, signal transducer and activator of transcription-3 (STAT3), and the protein expression of C/EBPbeta and C/EBPdelta. We also found that rosmanol suppressed LPS-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Our results demonstrate that rosmanol downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-kappaB and STAT3 through interfering with the activation of PI3K/Akt and MAPK signaling. Taken together, rosmanol might contribute to the potent anti-inflammatory effect of rosemary and may have potential to be developed into an effective anti-inflammatory agent.
    Journal of Agricultural and Food Chemistry 10/2009; 57(22):10990-8. · 2.82 Impact Factor
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    Article: Modulation of inflammatory genes by natural dietary bioactive compounds.
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    ABSTRACT: Several epidemiologic studies have shown that chronic inflammation predisposes individuals to various types of cancer. Many cancers arise from sites of infection, chronic irritation, and inflammation. Conversely, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumors. Natural bioactive compounds in dietary plant products including fruits, vegetables, grains, legumes, tea, and wine are claimed to help prevent cancer, degenerative diseases, and chronic and acute inflammation. Modern methods in cell and molecular biology allow us to understand the interactions of different natural bioactive compounds with basic mechanisms of inflammatory response. The molecular pathways of this cancer-related inflammation are now unraveled. Natural bioactive compounds exert anti-inflammatory activity by modulating pro-inflammatory gene expressions have shown promising chemopreventive activity. This review summarizes current knowledge on natural bioactive compounds that act through the signaling pathways and modulate inflammatory gene expressions, thus providing evidence for these substances in cancer chemopreventive action.
    Journal of Agricultural and Food Chemistry 07/2009; 57(11):4467-77. · 2.82 Impact Factor

Institutions

  • 2005–2013
    • National Kaohsiung Marine University
      Kaohsiung, Kaohsiung, Taiwan
    • National Pingtung University of Education
      Pingtung, Taiwan, Taiwan
  • 2006–2012
    • Rutgers, The State University of New Jersey
      • Department of Food Science
      New Brunswick, NJ, USA
  • 2008–2011
    • Chang Jung Christian University
      Tainan, Taiwan, Taiwan
  • 2008–2010
    • National Cheng Kung University Hospital
      Tainan, Taiwan, Taiwan
  • 2007
    • Toko University
      Taipei, Taipei, Taiwan
    • Taipei Medical University
      Taipei, Taipei, Taiwan