Graduate Institute of Natural Products

Kaohsiung, Taiwan

Graduate Institute of Natural Products

Kaohsiung, Taiwan
Time filter
Source Type

Lin C.-C.,Antai Medical Care Corporation Antai Tian Sheng Memorial Hospital | Whuang T.-Y.,National Dong Hwa University | Su J.-H.,National Dong Hwa University | Hwang T.-L.,Graduate Institute of Natural Products | And 6 more authors.
Natural Product Communications | Year: 2017

A new marine sterol, 4α-methylergosta-22(E),24(28)-dien-3β-ol (1), was isolated from the octocoral Nephthea columnaris. The structure of 1 was elucidated on the basis of spectroscopic and mass spectrometric methods.

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.-C.,Graduate Institute of Natural Products | Lee C.-C.,China Medical University at Taichung | Lin Y.-H.,Graduate Institute of Natural Products | Chang W.-H.,Graduate Institute of Medicine | And 4 more authors.
European Journal of Cancer Prevention | Year: 2012

We purified calactin from the roots of the Chinese herb Asclepias curassavica L. and analyzed its biologic effects in human leukemia cells. Our results showed that calactin treatment caused DNA damage and resulted in apoptosis. Increased phosphorylation levels of Chk2 and H2AX were observed and were reversed by the DNA damage inhibitor caffeine in calactin-treated cells. In addition, calactin treatment showed that a decrease in the expression of cell cycle regulatory proteins Cyclin B1, Cdk1, and Cdc25C was consistent with a G2/M phase arrest. Furthermore, calactin induced extracellular signal-regulated kinase (ERK) phosphorylation, activation of caspase-3, caspase-8, and caspase-9, and PARP cleavage. Pretreatment with the ERK inhibitor PD98059 significantly blocked the loss of viability in calactin-treated cells. It is indicated that calactin-induced apoptosis may occur through an ERK signaling pathway. Our data suggest that calactin is a potential anticancer compound. © 2012 Wolters Kluwer Health | Lippincott Williams &Wilkins.

Yang C.-H.,National Kaohsiung University of Applied Sciences | Cheng Y.-H.,Toko University | Chuang L.-Y.,I - Shou University | Chang H.-W.,Graduate Institute of Natural Products | Chang H.-W.,Kaohsiung Medical University
Bioinformatics | Year: 2013

Many drug or single nucleotide polymorphism (SNP)- related resources and tools have been developed, but connecting and integrating them is still a challenge. Here, we describe a user-friendly web-based software package, named Drug-SNPing, which provides a platform for the integration of drug information (DrugBank and PharmGKB), protein-protein interactions (STRING), tagSNP selection (HapMap) and genotyping information (dbSNP, REBASE and SNP500Cancer). DrugBank-based inputs include the following: (i) common name of the drug, (ii) synonym or drug brand name, (iii) gene name (HUGO) and (iv) keywords. PharmGKB-based inputs include the following: (i) gene name (HUGO), (ii) drug name and (iii) disease-related keywords. The output provides drug-related information, metabolizing enzymes and drug targets, as well as protein- protein interaction data. Importantly, tagSNPs of the selected genes are retrieved for genotyping analyses. All drug-based and protein-protein interaction-based SNP genotyping information are provided with PCR-RFLP (PCR-restriction enzyme length polymorphism) and TaqMan probes. Thus, users can enter any drug keywords/brand names to obtain immediate information that is highly relevant to genotyping for pharmacogenomics research. © The Author 2013.

Hsieh T.J.,Kaohsiung Medical University | Tsai Y.-H.,Graduate Institute of Natural Products | Liu C.-C.,Kaohsiung Medical University | Wu M.-T.,Kaohsiung Medical University | Wu M.-T.,Kaohsiung Municipal Hsiao Kang Hospital
Toxicological Sciences | Year: 2012

Although several reports have failed to observe adverse subchronic renal effects following relatively high melamine exposure, the safety of low and continuous melamine exposure is still debatable. Recent studies suggest that long-term, low-dose melamine exposure is associated with an increased risk of urolithiasis, which has been linked to chronic kidney disease (CKD). CKD is a consequence of nephron loss and is associated with the interaction of inflammation, oxidative stress, and transforming growth factor-β (TGF-β), which increases extracellular matrix genes and cell apoptosis with progression to fibrosis and end-stage renal disease. Thus far, information is still lacking regarding the influence of melamine at the gene and protein levels, which are activated at a much earlier phase than the occurrence of the renal morphological change. In this study, we stimulated human renal proximal tubular HK-2 cells with melamine (0, 125, 250, 500, or 1000 μg/ml) for different time intervals and observed its effects on several well-documented molecular mechanisms of CKD. Here, we demonstrate that melamine can activate mitogen-activated protein kinases, NFkB, and reactive oxygen species, which results in the upregulation of interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, and TGF-β1 in HK-2 cells. The melamine-stimulated overexpression of TGF-β1 not only promotes fibronectin production but also leads to decreased antiapoptotic (bcl-2, bcl-xl)/proapoptotic (bad, bax) protein ratio, increased caspase-3 and caspase-9 activities, and eventually HK-2 cell apoptosis. Our study suggests that melamine exposure may be a risk factor for the chronic loss of tubular cells and may ultimately lead to tubulointerstitial damage. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.

Hwang T.-L.,Graduate Institute of Natural Products | Hwang T.-L.,Chang Gung University | Aljuffali I.A.,King Saud University | Lin C.-F.,Chang Gung University | And 3 more authors.
International Journal of Nanomedicine | Year: 2015

This report compares the effect of lipid and polymeric nanoparticles upon human neutrophils in the presence of cationic surfactants. Nanostructured lipid carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory mediators such as lactate dehydrogenase (LDH), elastase, O2 •-, and intracellular Ca2+ were examined. The nanoparticles showed a size of 170–225 nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium ethosulfate, the cationic surfactant, converted zeta potential from a negative to a positive charge. Nanoparticles without cationic surfactants revealed a negligible change on immune and inflammatory responses. Cationic surfactants in both nanoparticulate and free forms induced cell death and the release of mediators. Lipid nanoparticles generally demonstrated a greater response compared to poly­meric nanoparticles. The neutrophil morphology observed by electron microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating material showed more significant activation of neutrophils than soyaethyl morpholinium ethosulfate. Confocal microscope imag­ing displayed a limited internalization of nanoparticles into neutrophils. It is proposed that cationic nanoparticles interact with the cell membrane, triggering membrane disruption and the following Ca2+ influx. The elevation of intracellular Ca2+ induces degranulation and oxidative stress. The consequence of these effects is cytotoxicity and cell death. Caution should be taken when selecting feasible nanoparticulate formulations and cationic additives for consideration of applicability and toxicity. © 2015 Hwang et al.

Liu Y.-K.,Chang Gung University | Chen K.-H.,Chang gung Memorial hospital | Leu Y.-L.,Graduate institute of natural Products | Leu Y.-L.,Chang Gung University | And 7 more authors.
OncoTargets and Therapy | Year: 2014

Inducing apoptosis to susceptible cells is the major mechanism of most cytotoxic anticancer drugs in current use. Cinnamomum kanehirai Hayata (Lauraceae), a unique and native tree of Taiwan, is the major host for the medicinal fungus Antrodia cinnamomea which exhibits anti-cancer activity. Because of the scarcity of A. cinnamomea, C. kanehirai Hayata instead, is used as fork medicine in liver cancer. Here we observed the C. kanehirai Hayata ethanol extract could inhibit the cellular viability of both HepG2 and HA22T/VGH human hepatoma cell lines in a dose- and time-dependent manner. We found the mode of cell death was apoptosis according to cell morphological changes by Liu’s stain, oligonucleosomal DNA fragmentation by gel electrophoresis, externalization of phosphotidyl serine by detecting Annexin V and hypoploid population by cell cycle analysis. Our results showed that the extracts caused cleavage of caspase-3 and increased enzyme activity of caspase-8 and caspase-9. Caspase 3 inhibitor partially reversed the viability inhibition by the extract. Furthermore, the up-regulation of Bax and down-regulation of Bcl-2 were also noted by the extract treatment. In conclusion, C. kanehirai Hayata ethanol extract induced intrinsic pathway of apoptosis through caspase-3 cascade in human hepatoma HA22T/VGH and HepG2 cells, which might shed new light on hepatoma therapy. © 2015 Liu et al.

Lin I.-Y.,National Yang Ming University | Yen C.-H.,Graduate Institute of Natural Products | Yen C.-H.,Center for Infectious Disease and Cancer Research | Lin S.-E.,Taipei Medical University Hospital | And 4 more authors.
Anticancer Research | Year: 2013

Background: Glycine N-methyltransferase (GNMT) is a tumor suppressor of hepatocellular carcinoma (HCC). High proportions of GNMT knockout mice developed HCC. We previously identified a potential novel marker from Gnmt knockout mice, FK506 binding protein 11 (FKBP11). Here, we determined the clinical usefulness of FKBP11. Patients and Methods: FKBP11 expression levels were analyzed in 123 paired tumor and tumor-Adjacent non-tumorous (TA) tissue samples from patients with HCC and in 29 benign liver samples from patients with hemangioma using quantitative real-time polymerase-chain-reaction. Results: FKBP11 was expressed at a higher level in tumor tissues compared to TA tissues (p<0.01). Moreover, we observed a significantly higher level of FKBP11 in TA tissues than in benign liver samples (p<0.01). Interestingly, expression of FKBP11 was higher in hepatitis viral-infected TA and benign tissues than in samples without viral etiology (p<0.05). Conclusion: These results suggest a progressively elevated expression of FKBP11 during the development of HCC and FKBP11 has the potential to be an early marker for HCC.

Chen H.-M.,E DA Hospital | Chen H.-M.,Graduate Institute of Natural Products | Chang F.-R.,Graduate Institute of Natural Products | Chang F.-R.,Kaohsiung Medical University | And 11 more authors.
Free Radical Biology and Medicine | Year: 2011

The protoapigenone analogue WYC02-9, a novel synthetic flavonoid, has been shown to act against a variety of experimental tumors. However, its effects on prostate cancer and its mechanism of action are unknown. Thus, WYC02-9 was investigated for its cytotoxicity against DU145 prostate cancer cells, as was the underlying mechanisms by which WYC02-9 might induce DNA damage and apoptotic cell death through reactive oxygen species (ROS). WYC02-9 inhibited the cell growth of three prostate cancer cell lines, especially DU145 cells. In DU145 cells, WYC02-9 increased the generation of intracellular ROS, followed by induction of DNA damage and activation of the ATM-p53-H2A.X pathway and checkpoint-related signals Chk1/Chk2, which led to increased numbers of cells in the S and G2/M phases of the cell cycle. Furthermore, WYC02-9 induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9, caspase-3, and PARP. The above effects were all prevented by the ROS scavenger N-acetylcysteine. Administration of WYC02-9 in a nude mouse DU145 xenograft model further identified the anti-cancer activity of WYC02-9. These findings therefore suggest that WYC02-9-induced DNA damage and mitochondria-dependent cell apoptosis in DU145 cells are mediated via ROS generation. © 2010 Elsevier Inc. All rights reserved.

Liu C.-S.,Changhua Christian Hospital | Chang C.-C.,Kaohsiung Medical University | Du Y.-C.,Graduate Institute of Natural Products | Chang F.-R.,Graduate Institute of Natural Products | And 6 more authors.
Journal of Cardiovascular Pharmacology | Year: 2012

Chalcone is a class of flavonoid compounds that are widely biosynthesized in plants. Epidemiological studies suggest that increased intake of flavonoids from fruits and vegetables reduces the risk of cardiovascular disease. However, the effect of chalcone on cardiovascular diseases has not been fully investigated. The aims of this study were to evaluate the antiatherosclerotic effect of 2-hydroxy-4-methoxychalcone (AN07, a synthetic chalcone derivate) and to investigate its potential pharmacological mechanisms. Oxidized low-density lipoprotein (Ox-LDL) has been reported to stimulate proliferation of human aortic smooth muscle cells and that is one of the mechanisms resulting in atherosclerosis. In this study, we demonstrate that AN07 significantly inhibits the Ox-LDL-induced proliferation of human aortic smooth muscle cells. This effect is mediated via the inhibition of p44/42 mitogen-activated protein kinase and E-twenty six 1 phosphorylations. In the effect of anti-inflammation, AN07 decreases the Ox-LDL-stimulated upregulation of interleukin (IL) 1β and IL-6. In addition, AN07 acts synergistically with rosiglitazone and pioglitazone to inhibit the Ox-LDL-induced proliferation of human aortic smooth muscle cells and upregulation of cyclin D1, cyclin D3, IL-1β, and IL-6. These effects are a result of an increase in peroxisome proliferator-activated receptor gamma mRNA and protein expression stimulated by AN07 in human aortic smooth muscle cells. In conclusion, the chalcone derivate AN07 has versatile therapeutic potential against atherosclerosis by acting as peroxisome proliferator-activated receptor gamma inducer, p44/42 mitogen-activated protein kinase inhibitor, and cell cycle blocker. © 2012 by Lippincott Williams & Wilkins.

Loading Graduate Institute of Natural Products collaborators
Loading Graduate Institute of Natural Products collaborators