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Chou Y.-C.,National Taiwan University | Chou Y.-C.,China Medical University at Taichung | Su H.-M.,National Taiwan University | Lai T.-W.,China Medical University at Taichung | And 2 more authors.
Nutrition | Year: 2012

Objective: The aim of this study was to investigate the adipogenic effect of cis-9, trans-11, trans-13-conjugated linolenic acid (c9, t11, t13-CLN), a fatty acid naturally present in bitter melon. Methods: The 3T3-L1 murine preadipocyte cell line was used to test the effect of saponifiables from whole bitter melon and of commercially prepared pure c9, t11, t13-CLN on adipocyte differentiation. The effect of c9, t11, t13. -CLN on 3T3-L1 cell viability was also tested at proliferation, mitotic clonal expansion, and terminal differentiation stages. Results: Compared to the free fatty acid control mixture, the proadipogenic effect on 3T3-L1 was less potent using saponifiables obtained from bitter melon. C9, t11, t13-CLN, unlike its non-conjugated counterpart linolenic acid (LN) or other common fatty acids such as oleic acid or linoleic acid, exerted no proadipogenic effect on 3T3-L1. In contrast to LN displaying no cytotoxic effect at a concentration ≤100 μM, c9, t11, t13-CLN caused a dose-dependent reduction in the viability of pre- and postconfluent preadipocytes associated with apoptosis. Sustained ERK/MAPK activation, accompanied by increased peroxisome proliferator-activated receptor γ phosphorylation, was seen in c9, t11, t13-CLN-treated cells at initiation of differentiation. Conclusion: C9, t11, t13-CLN is less adipogenic for 3T3-L1 cells than LN and this is partly due to its apoptotic effect on proliferating preadipocytes and to the sustained ERK phosphorylation seen during mitotic clonal expansion. © 2012 Elsevier Inc.


Weng C.-Y.,Chia Nan University of Pharmacy and Science | Chiou S.-Y.,Hualien District Agricultural Research and Extension Station | Wang L.,Chia Nan University of Pharmacy and Science | Kou M.-C.,Chia Nan University of Pharmacy and Science | And 2 more authors.
Archives of Toxicology | Year: 2014

Chronic arsenic exposure has been linked to endothelial dysfunction and apoptosis. We investigate the involvement of unfolded protein response (UPR) signaling in the arsenic-mediated cytotoxicity of the SVEC4-10 mouse endothelial cells. The SVEC4-10 cells underwent apoptosis in response to As 2O3 dose- and time-dependently, accompanied by increased accumulation of calcium, and activation of caspase-3. These phenomena were completely inhibited by α-lipoic acid (LA), which did not scavenge ROS over-production, but were only partially or not ameliorated by tiron, a potent superoxide scavenger. Moreover, arsenic activated UPR, leading to phosphorylation of eukaryotic translation initiation factor 2 subunit α (eIF2α), induction of ATF4, and processing of ATF6. Treatment with arsenic also triggered the expression of endoplasmic reticulum (ER) stress markers, GRP78 (glucose-regulated protein), and CHOP (C/EBP homologous protein). The activation of eIF2α, ATF4 and ATF6 and expression of GRP78 and CHOP are repressed by both LA and tiron, indicating arsenic-induced UPR is mediated through ROS-dependent and ROS-independent pathways. Arsenic also induced ER stress-inducible genes, BAX, PUMA (p53 upregulated modulator of apoptosis), TRB3 (tribbles-related protein 3), and SNAT2 (sodium-dependent neutral amino acid transporter 2). Consistent with intracellular calcium and cell viability data, ROS may not be important in arsenic-induced death, because tiron did not affect the expression of these pro-apoptotic genes. In addition, pretreatment with salubrinal, a selective inhibitor of eIF2α dephosphorylation, enhanced arsenic-induced GRP78 and CHOP expression and partially prevented arsenic cytotoxicity in SVEC4-10 cells. Taken together, these results suggest that arsenic-induced endothelial cytotoxicity is associated with ER stress, which is mediated by ROS-dependent and ROS-independent signaling. © 2013 Springer-Verlag Berlin Heidelberg.


Chen P.-H.,China Medical University at Taichung | Chen G.-C.,China Medical University at Taichung | Yang M.-F.,China Medical University at Taichung | Hsieh C.-H.,China Medical University at Taichung | And 5 more authors.
Journal of Nutrition | Year: 2012

The aim of this study was to investigate the antiadiposity effect of bitter melon seed oil (BMSO), which is rich in the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid. In Expt. 1, C57BL/6J mice were fed a butter-based, high-fat diet [HB; 29% butter + 1% soybean oil (SBO)] for 10 wk to induce obesity. They then continued to receive that diet or were switched to an SBO-based, high-fat diet alone (HS; 30%SBO) or containing bitter melon seed oil (BMSO) (HBM; 15%SBO+ 15% BMSO) for 5 wk. The body fat percentage was significantly lower in mice fed the HBM diet (21%), but not the HS diet, compared with mice fed the HB diet. In Expt. 2, mice were fed an SBO-based, high-fat diet containing 0 (HS), 5 (LBM), 10 (MBM), or 15% (HBM) BMSO for 10 wk. In the LBM, MBM, and HBM groups, the body fat percentage was significantly lower by 32, 35, and 65%, respectively, compared with the HS control. The reduction in the HBM group was significantly greater than that in the LBM or MBM group. BMSO administration increased phosphorylation of acetyl-CoA carboxylase, cAMP-activated protein kinase (PKA), and signal transducer and activator of transcription 3 in the white adipose tissue (WAT), suggesting that PKA and leptin signaling might be involved in the BMSO-mediated reduction in lipogenesis and increase in thermogenesis and lipolysis. However, compared with the HS control, the HBM group had a significantly higher TNFa concentration in the WAT accompanied by TUNEL-positive nuclei. We conclude that BMSO is effective in attenuating body fat accumulation through mechanisms associated with PKA activation and programmed cell death in the WAT, but safety concerns need to be carefully addressed. © 2012 American Society for Nutrition.


Lu K.-H.,National Taiwan University of Science and Technology | Tseng H.-C.,National Taiwan University of Science and Technology | Liu C.-T.,National Taiwan University of Science and Technology | Huang C.-J.,National Taiwan University of Science and Technology | And 3 more authors.
Food and Function | Year: 2014

Bitter gourd (Momordica charantia L.) is a common vegetable grown widely in Asia that is used as a traditional medicine. The objective of this study was to investigate whether wild bitter gourd possessed protective effects against chronic alcohol-induced liver injury in mice. C57BL/6 mice were fed an alcohol-containing liquid diet for 4 weeks to induce alcoholic fatty liver. Meanwhile, mice were treated with ethanol extracts from four different wild bitter gourd cultivars: Hualien No. 1′, Hualien No. 2′, Hualien No. 3′ and Hualien No. 4′. The results indicated that the daily administration of 500 mg kg body weight-1 of a Hualien No. 3′ extract (H3E) or a Hualien No. 4′ extract (H4E) markedly reduced the steatotic alternation of liver histopathology. In addition, the activation of serum aminotransferases (AST and ALT) and the accumulation of hepatic TG content caused by alcohol were ameliorated. The hepatoprotective effects of H3E and H4E involved the enhancement of the antioxidant defence system (GSH, GPx, GRd, CAT and SOD), inhibition of lipid peroxidation (MDA) and reduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in the liver. Moreover, H3E and H4E supplementation suppressed the alcohol-induced elevation of CYP2E1, SREBP-1, FAS and ACC protein expression. These results demonstrated that ethanol extracts of Hualien No. 3′ and Hualien No. 4′ have beneficial effects against alcoholic fatty liver, in which they attenuate oxidative stress and inflammatory responses. © 2014 the Partner Organisations.


Kou M.-C.,Chia Nan University of Pharmacy and Science | Chiou S.-Y.,Hualien District Agricultural Research and Extension Station | Weng C.-Y.,Chia Nan University of Pharmacy and Science | Wang L.,Chia Nan University of Pharmacy and Science | And 2 more authors.
Molecular Nutrition and Food Research | Year: 2013

Scope: Curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) have been demonstrated as having antioxidant, anticarcinogenic, and hypocholesterolemic activities. We report the diverse antiatherogenic effects and mechanisms of curcuminoids. Methods and results: We found that CUR was the most potent antioxidant against copper-mediated LDL oxidation as measured by thiobarbituric acid-reactive substances assay, oxidized LDL (oxLDL) ELISA, and electrophoretic mobility. CUR upregulated heme oxygenase-1, modifier subunit of glutamate-cysteine ligase (GCLM), and CD36 expression in undifferentiated THP-1 cells, supporting the possible involvement of Nrf2 pathway in CD36 expression. Monocyte-to-macrophage differentiation plays a vital role in early atherogenesis. BDMC reduced oxLDL uptake most effectively, while CUR was the best inhibitor for CD36, scavenger receptor A, and lectin-like oxidized LDL receptor-1 expression during phorbol 12-myristate 13-acetate (PMA)-induced THP-1 differentiation. In PMA-differentiated THP-1 macrophages, CUR and DMC effectively induced heme oxygenase-1 expression, but attenuated oxLDL-induced CD36 expression, leading to decreased oxLDL uptake. Conclusion: This result indicates curcuminoids, despite structural similarities, exert different atheroprotective effects. Curcuminoids, especially CUR and DMC, are hormetic compounds, which induce Phase II enzyme expression and confer resistance to PMA- and oxLDL-induced scavenger receptor expression and activity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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