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Special Issue "Plant-Derived Pharmaceuticals by Molecular Farming 2012"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 November 2012)

Special Issue Editor

Guest Editor
Prof. Dr. Chang Won Choi

Department of Biology & Medicinal Science, Pai Chai University, 155-40 Baejae-ro, Seo-Gu, Daejeon 35345, Korea
Website | E-Mail
Phone: +82-42-520-5617
Fax: +82-70-4362-6308
Interests: plant-derived biomedicines; plant-made pharmaceuticals; molecular farming; recombinant proteins; plant metabolic engineering; hypoglycaemic; hypolipidemic; antioxidants; antiviral

Keywords

  • edible vaccines
  • antibodies for diagnostic, preventative, and therapeutic applications
  • bioplastics made from simple, biodegradable molecules produced in plants
  • an enzyme used in the treatment of human and animals
  • enzymes for use in food processing
  • proteins for industrial purpose

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Published Papers (19 papers)

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Research

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Open AccessArticle Effects of (−)-Gallocatechin-3-Gallate on Tetrodotoxin-Resistant Voltage-Gated Sodium Channels in Rat Dorsal Root Ganglion Neurons
Int. J. Mol. Sci. 2013, 14(5), 9779-9789; doi:10.3390/ijms14059779
Received: 30 January 2013 / Revised: 10 April 2013 / Accepted: 24 April 2013 / Published: 7 May 2013
Cited by 1 | PDF Full-text (895 KB) | HTML Full-text | XML Full-text
Abstract
The (−)-gallocatechin-3-gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8
[...] Read more.
The (−)-gallocatechin-3-gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant compared to other isoforms and functionally linked to nociception. In this study, the effects of GCG on tetrodotoxin-resistant Na+ currents were investigated in rat primary cultures of dorsal root ganglion neurons via the whole-cell patch-clamp technique. We found that 1 μM GCG reduced the amplitudes of peak current density of tetrodotoxin-resistant Na+ currents significantly. Furthermore, the inhibition was accompanied by a depolarizing shift of the activation voltage and a hyperpolarizing shift of steady-state inactivation voltage. The percentage block of GCG (1 μM) on tetrodotoxin-resistant Na+ current was 45.1% ± 1.1% in 10 min. In addition, GCG did not produce frequency-dependent block of tetrodotoxin-resistant Na+ currents at stimulation frequencies of 1 Hz, 2 Hz and 5 Hz. On the basis of these findings, we propose that GCG may be a potential analgesic agent. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Figures

Open AccessArticle Combinatorial Analysis of Secretory Immunoglobulin A (sIgA) Expression in Plants
Int. J. Mol. Sci. 2013, 14(3), 6205-6222; doi:10.3390/ijms14036205
Received: 3 December 2012 / Revised: 4 January 2013 / Accepted: 27 February 2013 / Published: 18 March 2013
Cited by 11 | PDF Full-text (1063 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Delivery of secretory immunoglobulin A (sIgA) to mucosal surfaces as a passive immunotherapy agent is a promising strategy to prevent infectious diseases. Recombinant sIgA production in plants requires the co-expression of four transcriptional units encoding the light chain (LC), heavy chain (HC), joining
[...] Read more.
Delivery of secretory immunoglobulin A (sIgA) to mucosal surfaces as a passive immunotherapy agent is a promising strategy to prevent infectious diseases. Recombinant sIgA production in plants requires the co-expression of four transcriptional units encoding the light chain (LC), heavy chain (HC), joining chain (JC) and secretory component (SC). As a way to optimize sIgA production in plants, we tested the combinatorial expression of 16 versions of a human sIgA against the VP8* rotavirus antigen in Nicotiana benthamiana, using the recently developed GoldenBraid multigene assembly system. Each sIgA version was obtained by combining one of the two types of HC (α1 and α2) with one of the two LC types (k and λ) and linking or not a KDEL peptide to the HC and/or SC. From the analysis of the anti-VP8* activity, it was concluded that those sIgA versions carrying HCα1 and LCλ provided the highest yields. Moreover, ER retention significantly increased antibody production, particularly when the KDEL signal was linked to the SC. Maximum expression levels of 32.5 μg IgA/g fresh weight (FW) were obtained in the best performing combination, with an estimated 33% of it in the form of a secretory complex. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle PG-2, a Potent AMP against Pathogenic Microbial Strains, from Potato (Solanum tuberosum L cv. Gogu Valley) Tubers Not Cytotoxic against Human Cells
Int. J. Mol. Sci. 2013, 14(2), 4349-4360; doi:10.3390/ijms14024349
Received: 16 December 2012 / Revised: 16 January 2013 / Accepted: 6 February 2013 / Published: 21 February 2013
Cited by 2 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text
Abstract
In an earlier study, we isolated potamin-1 (PT-1), a 5.6-kDa trypsin-chymotrypsin protease inhibitor, from the tubers of a potato strain (Solanum tuberosum L cv. Gogu Valley). We established that PT-1 strongly inhibits pathogenic microbial strains, but not human bacterial strains, and that
[...] Read more.
In an earlier study, we isolated potamin-1 (PT-1), a 5.6-kDa trypsin-chymotrypsin protease inhibitor, from the tubers of a potato strain (Solanum tuberosum L cv. Gogu Valley). We established that PT-1 strongly inhibits pathogenic microbial strains, but not human bacterial strains, and that its sequence shows 62% homology with a serine protease inhibitor. In the present study, we isolated an antifungal and antibacterial peptide with no cytotoxicity from tubers of the same potato strain. The peptide (peptide-G2, PG-2) was isolated using salt-extraction, ultrafiltration and reverse-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) showed the protein to have a molecular mass of 3228.5 Da, while automated Edman degradation showed the N-terminal sequence of PG-2 to be LVKDNPLDISPKQVQALCTDLVIRCMCCC-. PG-2 exhibited antimicrobial activity against Candida albicans, a human pathogenic yeast strain, and Clavibacter michiganensis subsp. michiganensis, a plant late blight strain. PG-2 also showed antibacterial activity against Staphylococcus aureus, but did not lyse human red blood cells and was thermostable. Overall, these results suggest PG-2 may be a good candidate to serve as a natural antimicrobial agent, agricultural pesticide and/or food additive. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Expression of a Functional Recombinant Human Basic Fibroblast Growth Factor from Transgenic Rice Seeds
Int. J. Mol. Sci. 2013, 14(2), 3556-3567; doi:10.3390/ijms14023556
Received: 29 November 2012 / Revised: 22 January 2013 / Accepted: 31 January 2013 / Published: 7 February 2013
Cited by 13 | PDF Full-text (4113 KB) | HTML Full-text | XML Full-text
Abstract
Basic fibroblast growth factor (FGF-2) is an important member of the FGF gene family. It is widely used in clinical applications for scald and wound healing in order to stimulate cell proliferation. Further it is applied for inhibiting stem cell differentiation in cultures.
[...] Read more.
Basic fibroblast growth factor (FGF-2) is an important member of the FGF gene family. It is widely used in clinical applications for scald and wound healing in order to stimulate cell proliferation. Further it is applied for inhibiting stem cell differentiation in cultures. Due to a shortage of plasma and low expression levels of recombinant rbFGF in conventional gene expression systems, we explored the production of recombinant rbFGF in rice grains (Oryza sativa bFGF, OsrbFGF). An expression level of up to 185.66 mg/kg in brown rice was obtained. A simple purification protocol was established with final recovery of 4.49% and resulting in a yield of OsrbFGF reaching up to 8.33 mg/kg OsrbFGF. The functional assay of OsrbFGF indicated that the stimulating cell proliferation activity on NIH/3T3 was the same as with commercialized rbFGF. Wound healing in vivo of OsrbFGF is equivalent to commercialized rbFGF. Our results indicate that rice endosperm is capable of expressing small molecular mass proteins, such as bFGF. This again demonstrates that rice endosperm is a promising system to express various biopharmaceutical proteins. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application
Int. J. Mol. Sci. 2013, 14(2), 3656-3670; doi:10.3390/ijms14023656
Received: 8 October 2012 / Revised: 5 December 2012 / Accepted: 30 January 2013 / Published: 7 February 2013
Cited by 1 | PDF Full-text (435 KB) | HTML Full-text | XML Full-text
Abstract
A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS). TA-III and the IS were detected in MRM mode with a negative ionization
[...] Read more.
A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS). TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ) was 11.14 ng/mL. Intra-day and inter-day precisions (RSD) were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Figures

Open AccessArticle Antioxidant, Analgesic, Anti-Inflammatory, and Hepatoprotective Effects of the Ethanol Extract of Mahonia oiwakensis Stem
Int. J. Mol. Sci. 2013, 14(2), 2928-2945; doi:10.3390/ijms14022928
Received: 17 November 2012 / Revised: 7 January 2013 / Accepted: 10 January 2013 / Published: 30 January 2013
Cited by 12 | PDF Full-text (839 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOSEtOH). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOSEtOH was analyzed by high-performance
[...] Read more.
The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOSEtOH). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOSEtOH was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOSEtOH exhibited antioxidative activity using the DPPH assay (IC50, 0.743 mg/mL). The DPPH radical scavenging activity of MOSEtOH was five times higher that that of vitamin C. MOSEtOH was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOSEtOH (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl4-treated group. Histological evaluation showed that MOSEtOH reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOSEtOH were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOSEtOH has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOSEtOH for relieving pain and inflammation in folk medicine. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Yeast α-Glucosidase Inhibitory Phenolic Compounds Isolated from Gynura medica Leaf
Int. J. Mol. Sci. 2013, 14(2), 2551-2558; doi:10.3390/ijms14022551
Received: 10 December 2012 / Revised: 16 January 2013 / Accepted: 21 January 2013 / Published: 28 January 2013
Cited by 11 | PDF Full-text (198 KB) | HTML Full-text | XML Full-text
Abstract
Gynura medica leaf extract contains significant amounts of flavonols and phenolic acids and exhibits powerful hypoglycemic activity against diabetic rats in vivo. However, the hypoglycemic active constituents that exist in the plant have not been fully elaborated. The purpose of this study
[...] Read more.
Gynura medica leaf extract contains significant amounts of flavonols and phenolic acids and exhibits powerful hypoglycemic activity against diabetic rats in vivo. However, the hypoglycemic active constituents that exist in the plant have not been fully elaborated. The purpose of this study is to isolate and elaborate the hypoglycemic activity compounds against inhibition the yeast α-glucosidase in vitro. Seven phenolic compounds including five flavonols and two phenolic acids were isolated from the leaf of G. medica. Their structures were identified by the extensive NMR and mass spectral analyses as: kaempferol (1), quercetin (2), kaempferol-3-O-β-D-glucopyranoside (3), kaempferol-3-O-rutinoside (4), rutin (5), chlorogenic acid (6) and 3,5-dicaffeoylquinic acid methyl ester (7). All of the compounds except 1 and 3 were isolated for the first time from G. medica. Compounds 17 were also assayed for their hypoglycemic activity against yeast α-glucosidase in vitro. All of the compounds except 1 and 6 showed good yeast α-glucosidase inhibitory activity with the IC50 values of 1.67 mg/mL, 1.46 mg/mL, 0.38 mg/mL, 0.10 mg/mL and 0.53 mg/mL, respectively. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle The Combination of Catechin and Epicatechin Gallate from Fructus Crataegi Potentiates β-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus (MRSA) in Vitro and in Vivo
Int. J. Mol. Sci. 2013, 14(1), 1802-1821; doi:10.3390/ijms14011802
Received: 8 October 2012 / Revised: 29 November 2012 / Accepted: 8 January 2013 / Published: 16 January 2013
Cited by 14 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fructus crataegi (hawthorn) is the common name of all plant species in the genus Crataegus of the Rosaceae family. In the present study, three monomers of (+)-catechin (C), (−)-epicatechin gallate (ECg) and (−)-epigallocatechin (EGC) were isolated from the hawthorn under the guide of
[...] Read more.
Fructus crataegi (hawthorn) is the common name of all plant species in the genus Crataegus of the Rosaceae family. In the present study, three monomers of (+)-catechin (C), (−)-epicatechin gallate (ECg) and (−)-epigallocatechin (EGC) were isolated from the hawthorn under the guide of antibacterial sensitization activity. The bioactivity of the composite fraction in enhancing the antibacterial effect of oxacillin against methicillin-resistant Staphylococcus aureus (MRSA) was greater than that of the individual monomer of the hawthorn extract in vitro. Two-fold dilution and checkerboard methods were used to analyze antibacterial activity and screen for the combination and proportion of monomers with the best bioactivity. The result showed that C (128 mg/L) combined with ECg (16 mg/L) had the greatest effect and the combination also reduced the bacterial load in blood of septic mice challenged with a sublethal dose of MRSA, increased daunomycin accumulation within MRSA and down-regulated the mRNA expression of norA, norC and abcA, three important efflux pumps of MRSA. In summary, C and ECg enhanced the antibacterial effect of β-lactam antibiotics against MRSA in vitro and in vivo, which might be related to the increased accumulation of antibiotics within MRSA via suppression of important efflux pumps’ gene expression. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Enhancement of Palmarumycins C12 and C13 Production in Liquid Culture of Endophytic Fungus Berkleasmium sp. Dzf12 after Treatments with Metal Ions
Int. J. Mol. Sci. 2013, 14(1), 979-998; doi:10.3390/ijms14010979
Received: 12 November 2012 / Revised: 15 December 2012 / Accepted: 25 December 2012 / Published: 7 January 2013
Cited by 11 | PDF Full-text (776 KB) | HTML Full-text | XML Full-text
Abstract
The influences of eight metal ions (i.e., Na+, Ca2+, Ag+, Co2+, Cu2+, Al3+, Zn2+, and Mn4+) on mycelia growth and palmarumycins C12 and C
[...] Read more.
The influences of eight metal ions (i.e., Na+, Ca2+, Ag+, Co2+, Cu2+, Al3+, Zn2+, and Mn4+) on mycelia growth and palmarumycins C12 and C13 production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12 were investigated. Three metal ions, Ca2+, Cu2+ and Al3+ were exhibited as the most effective to enhance mycelia growth and palmarumycin production. When calcium ion (Ca2+) was applied to the medium at 10.0 mmol/L on day 3, copper ion (Cu2+) to the medium at 1.0 mmol/L on day 3, aluminum ion (Al3+) to the medium at 2.0 mmol/L on day 6, the maximal yields of palmarumycins C12 plus C13 were obtained as 137.57 mg/L, 146.28 mg/L and 156.77 mg/L, which were 3.94-fold, 4.19-fold and 4.49-fold in comparison with that (34.91 mg/L) of the control, respectively. Al3+ favored palmarumycin C12 production when its concentration was higher than 4 mmol/L. Ca2+ had an improving effect on mycelia growth of Berkleasmium sp. Dzf12. The combination effects of Ca2+, Cu2+ and Al3+ on palmarumycin C13 production were further studied by employing a statistical method based on the central composite design (CCD) and response surface methodology (RSM). By solving the quadratic regression equation between palmarumycin C13 and three metal ions, the optimal concentrations of Ca2+, Cu2+ and Al3+ in medium for palmarumycin C13 production were determined as 7.58, 1.36 and 2.05 mmol/L, respectively. Under the optimum conditions, the predicted maximum palmarumycin C13 yield reached 208.49 mg/L. By optimizing the combination of Ca2+, Cu2+ and Al3+ in medium, palmarumycin C13 yield was increased to 203.85 mg/L, which was 6.00-fold in comparison with that (33.98 mg/L) in the original basal medium. The results indicate that appropriate metal ions (i.e., Ca2+, Cu2+ and Al3+) could enhance palmarumycin production. Application of the metal ions should be an effective strategy for palmarumycin production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Chemical Constituents from Andrographis echioides and Their Anti-Inflammatory Activity
Int. J. Mol. Sci. 2013, 14(1), 496-514; doi:10.3390/ijms14010496
Received: 12 November 2012 / Revised: 11 December 2012 / Accepted: 17 December 2012 / Published: 27 December 2012
Cited by 4 | PDF Full-text (341 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigation of the whole plants of Andrographis echioides afforded two new 2'-oxygenated flavonoids (1) and (2), two new phenyl glycosides (3) and (4), along with 37 known structures. The structures of new compounds were elucidated
[...] Read more.
Phytochemical investigation of the whole plants of Andrographis echioides afforded two new 2'-oxygenated flavonoids (1) and (2), two new phenyl glycosides (3) and (4), along with 37 known structures. The structures of new compounds were elucidated by spectral analysis and chemical transformation studies. Among the isolated compounds, (12) and (619) were subjected into the examination for their iNOS inhibitory bioactivity. The structure-activity relationships of the flavonoids for their inhibition of NO production were also discussed. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Apoptosis Induction of Human Prostate Carcinoma DU145 Cells by Diallyl Disulfide via Modulation of JNK and PI3K/AKT Signaling Pathways
Int. J. Mol. Sci. 2012, 13(11), 14158-14171; doi:10.3390/ijms131114158
Received: 24 September 2012 / Revised: 22 October 2012 / Accepted: 26 October 2012 / Published: 2 November 2012
Cited by 15 | PDF Full-text (1060 KB) | HTML Full-text | XML Full-text
Abstract
Diallyl disulfide (DADS), a sulfur compound derived from garlic, has various biological properties, such as anticancer, antiangiogenic and anti-inflammatory effects. However, the mechanisms of action underlying the compound's anticancer activity have not been fully elucidated. In this study, the apoptotic effects of DADS
[...] Read more.
Diallyl disulfide (DADS), a sulfur compound derived from garlic, has various biological properties, such as anticancer, antiangiogenic and anti-inflammatory effects. However, the mechanisms of action underlying the compound's anticancer activity have not been fully elucidated. In this study, the apoptotic effects of DADS were investigated in DU145 human prostate carcinoma cells. Our results showed that DADS markedly inhibited the growth of the DU145 cells by induction of apoptosis. Apoptosis was accompanied by modulation of Bcl-2 and inhibitor of apoptosis protein (IAP) family proteins, depolarization of the mitochondrial membrane potential (MMP, ΔΨm) and proteolytic activation of caspases. We also found that the expression of death-receptor 4 (DR4) and Fas ligand (FasL) proteins was increased and that the level of intact Bid proteins was down-regulated by DADS. Moreover, treatment with DADS induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular-signal regulating kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). A specific JNK inhibitor, SP600125, significantly blocked DADS-induced-apoptosis, whereas inhibitors of the ERK (PD98059) and p38 MAPK (SB203580) had no effect. The induction of apoptosis was also accompanied by inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt and the PI3K inhibitor LY29004 significantly increased DADS-induced cell death. These findings provide evidence demonstrating that the proapoptotic effect of DADS is mediated through the activation of JNK and the inhibition of the PI3K/Akt signaling pathway in DU145 cells. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Ethyl Gallate Induces Apoptosis of HL-60 Cells by Promoting the Expression of Caspases-8, -9, -3, Apoptosis-Inducing Factor and Endonuclease G
Int. J. Mol. Sci. 2012, 13(9), 11912-11922; doi:10.3390/ijms130911912
Received: 10 August 2012 / Revised: 29 August 2012 / Accepted: 11 September 2012 / Published: 20 September 2012
Cited by 6 | PDF Full-text (1273 KB) | HTML Full-text | XML Full-text
Abstract
Many phytochemicals have been recognized to have potential therapeutic efficacy in cancer treatment. In this study, we investigated ethyl gallate (EG) for possible proapoptotic effects in the human promyelocytic leukemia cell line, HL-60. We examined cell viability, morphological changes, DNA content and fragmentation,
[...] Read more.
Many phytochemicals have been recognized to have potential therapeutic efficacy in cancer treatment. In this study, we investigated ethyl gallate (EG) for possible proapoptotic effects in the human promyelocytic leukemia cell line, HL-60. We examined cell viability, morphological changes, DNA content and fragmentation, and expression of apoptosis-related proteins for up to 48 h after EG treatment. The results showed that EG induced morphological changes and DNA fragmentation and reduced HL-60 cell viability in a dose-dependent and time-dependent manner. Western blotting analysis indicated that EG-mediated HL-60 apoptosis mainly occurred through the mitochondrial pathway, as shown by the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G (Endo G), as well as the upregulation of Bcl-2-associated X protein (Bax). EG also activated the death receptor-dependent pathway of apoptosis by enhancing the expression of caspases-8, -9, and -3 and the Bcl-2 interacting domain (Bid). Collectively, our results showed that EG induces apoptosis in HL-60 via mitochondrial-mediated pathways. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Determination and Analysis of Ustiloxins A and B by LC-ESI-MS and HPLC in False Smut Balls of Rice
Int. J. Mol. Sci. 2012, 13(9), 11275-11287; doi:10.3390/ijms130911275
Received: 20 July 2012 / Revised: 10 August 2012 / Accepted: 6 September 2012 / Published: 10 September 2012
Cited by 16 | PDF Full-text (530 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ustiloxins are cyclopeptide mycotoxins produced by the pathogenic fungus Villosiclava virens of rice false smut. Ustiloxins A and B as two main mycotoxins were determined conveniently by LC-ESI-MS in the water extract from rice false smut balls which were mostly composed of the
[...] Read more.
Ustiloxins are cyclopeptide mycotoxins produced by the pathogenic fungus Villosiclava virens of rice false smut. Ustiloxins A and B as two main mycotoxins were determined conveniently by LC-ESI-MS in the water extract from rice false smut balls which were mostly composed of the chlamydospores and mycelia of the pathogen. Both ustiloxins A and B in the water extract were also quantitatively analyzed by HPLC. This is the first report on the determination and analysis of ustiloxins A and B simultaneously by LC-ESI-MS and HPLC in false smut balls of rice. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessCommunication Neuroprotective Effects of Triterpene Glycosides from Glycine max against Glutamate Induced Toxicity in Primary Cultured Rat Cortical Cells
Int. J. Mol. Sci. 2012, 13(8), 9642-9648; doi:10.3390/ijms13089642
Received: 7 June 2012 / Revised: 16 July 2012 / Accepted: 23 July 2012 / Published: 2 August 2012
Cited by 2 | PDF Full-text (246 KB) | HTML Full-text | XML Full-text
Abstract
To examine the neuroprotective effects of Glycine max, we tested its protection against the glutamate-induced toxicity in primary cortical cultured neurons. In order to clarify the neuroprotective mechanism(s) of this observed effect, isolation was performed to seek and identify active fractions and
[...] Read more.
To examine the neuroprotective effects of Glycine max, we tested its protection against the glutamate-induced toxicity in primary cortical cultured neurons. In order to clarify the neuroprotective mechanism(s) of this observed effect, isolation was performed to seek and identify active fractions and components. From such fractionation, two triterpene glycosides, 3-O-[α-L-rhamnopyranosyl(1-2)-β-D-glucopyranosyl(1-2)-β-D-glucuronopyranosyl]olean-12-en-3β,22β,24-triol (1) and 3-O-[β-D-glucopyranosyl(1-2)-β-D-galactopyranosyl(1-2)-β-D-glucuronopyranosyl]olean-12-en-3β,22β,24-triol (2) were isolated with the methanol extracts with of air-dried Glycine max. Among these compounds, compound 2 exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viability of about 50% at concentrations ranging from 0.1 μM to 10 μM. Therefore, the neuroprotective effect of Glycine max might be due to the inhibition of glutamate-induced toxicity by triterpene glycosides. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization
Int. J. Mol. Sci. 2012, 13(7), 9097-9109; doi:10.3390/ijms13079097
Received: 20 June 2012 / Revised: 11 July 2012 / Accepted: 16 July 2012 / Published: 20 July 2012
Cited by 7 | PDF Full-text (369 KB) | HTML Full-text | XML Full-text
Abstract
Curcumin, one of the major constituents of Curcuma longa, has been shown to inhibit depolarization-evoked glutamate release from rat prefrontocortical nerve terminals by reducing voltage-dependent Ca2+ entry. This study showed that curcumin inhibited ionomycin-induced glutamate release and KCl-evoked FM1-43 release, suggesting
[...] Read more.
Curcumin, one of the major constituents of Curcuma longa, has been shown to inhibit depolarization-evoked glutamate release from rat prefrontocortical nerve terminals by reducing voltage-dependent Ca2+ entry. This study showed that curcumin inhibited ionomycin-induced glutamate release and KCl-evoked FM1-43 release, suggesting that some steps after Ca2+ entry are regulated by curcumin. Furthermore, disrupting the cytoskeleton organization using cytochalasin D abolished the inhibitory action of curcumin on ionomycin-induced glutamate release. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of curcumin on ionomycin-induced glutamate release. Western blot analyses showed that curcumin decreased the ionomycin-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, the main presynaptic target of ERK. These results show that curcumin-mediated inhibition of glutamate release involves modulating downstream events by controlling synaptic vesicle recruitment and exocytosis, possibly through a decrease of MAPK/ERK activation and synapsin I phosphorylation, thereby decreasing synaptic vesicle availability for exocytosis. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)

Review

Jump to: Research

Open AccessReview Improving Pharmaceutical Protein Production in Oryza sativa
Int. J. Mol. Sci. 2013, 14(5), 8719-8739; doi:10.3390/ijms14058719
Received: 21 January 2013 / Revised: 14 April 2013 / Accepted: 15 April 2013 / Published: 24 April 2013
Cited by 15 | PDF Full-text (247 KB) | HTML Full-text | XML Full-text
Abstract
Application of plant expression systems in the production of recombinant proteins has several advantages, such as low maintenance cost, absence of human pathogens, and possession of complex post-translational glycosylation capabilities. Plants have been successfully used to produce recombinant cytokines, vaccines, antibodies, and other
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Application of plant expression systems in the production of recombinant proteins has several advantages, such as low maintenance cost, absence of human pathogens, and possession of complex post-translational glycosylation capabilities. Plants have been successfully used to produce recombinant cytokines, vaccines, antibodies, and other proteins, and rice (Oryza sativa) is a potential plant used as recombinant protein expression system. After successful transformation, transgenic rice cells can be either regenerated into whole plants or grown as cell cultures that can be upscaled into bioreactors. This review summarizes recent advances in the production of different recombinant protein produced in rice and describes their production methods as well as methods to improve protein yield and quality. Glycosylation and its impact in plant development and protein production are discussed, and several methods of improving yield and quality that have not been incorporated in rice expression systems are also proposed. Finally, different bioreactor options are explored and their advantages are analyzed. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessReview Natural Products as a Source for Treating Neglected Parasitic Diseases
Int. J. Mol. Sci. 2013, 14(2), 3395-3439; doi:10.3390/ijms14023395
Received: 21 December 2012 / Revised: 12 January 2013 / Accepted: 16 January 2013 / Published: 6 February 2013
Cited by 38 | PDF Full-text (341 KB) | HTML Full-text | XML Full-text
Abstract
Infectious diseases caused by parasites are a major threat for the entire mankind, especially in the tropics. More than 1 billion people world-wide are directly exposed to tropical parasites such as the causative agents of trypanosomiasis, leishmaniasis, schistosomiasis, lymphatic filariasis and onchocerciasis, which
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Infectious diseases caused by parasites are a major threat for the entire mankind, especially in the tropics. More than 1 billion people world-wide are directly exposed to tropical parasites such as the causative agents of trypanosomiasis, leishmaniasis, schistosomiasis, lymphatic filariasis and onchocerciasis, which represent a major health problem, particularly in impecunious areas. Unlike most antibiotics, there is no “general” antiparasitic drug available. Here, the selection of antiparasitic drugs varies between different organisms. Some of the currently available drugs are chemically de novo synthesized, however, the majority of drugs are derived from natural sources such as plants which have subsequently been chemically modified to warrant higher potency against these human pathogens. In this review article we will provide an overview of the current status of plant derived pharmaceuticals and their chemical modifications to target parasite-specific peculiarities in order to interfere with their proliferation in the human host. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessReview Production of Pharmaceutical Proteins in Solanaceae Food Crops
Int. J. Mol. Sci. 2013, 14(2), 2753-2773; doi:10.3390/ijms14022753
Received: 3 December 2012 / Revised: 11 January 2013 / Accepted: 22 January 2013 / Published: 29 January 2013
Cited by 12 | PDF Full-text (232 KB) | HTML Full-text | XML Full-text
Abstract
The benefits of increased safety and cost-effectiveness make vegetable crops appropriate systems for the production and delivery of pharmaceutical proteins. In particular, Solanaceae edible crops could be inexpensive biofactories for oral vaccines and other pharmaceutical proteins that can be ingested as minimally processed
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The benefits of increased safety and cost-effectiveness make vegetable crops appropriate systems for the production and delivery of pharmaceutical proteins. In particular, Solanaceae edible crops could be inexpensive biofactories for oral vaccines and other pharmaceutical proteins that can be ingested as minimally processed extracts or as partially purified products. The field of crop plant biotechnology is advancing rapidly due to novel developments in genetic and genomic tools being made available today for the scientific community. In this review, we briefly summarize data now available regarding genomic resources for the Solanaceae family. In addition, we describe novel strategies developed for the expression of foreign proteins in vegetable crops and the utilization of these techniques to manufacture pharmaceutical proteins. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessReview The Twenty-Year Story of a Plant-Based Vaccine Against Hepatitis B: Stagnation or Promising Prospects?
Int. J. Mol. Sci. 2013, 14(1), 1978-1998; doi:10.3390/ijms14011978
Received: 17 December 2012 / Revised: 7 January 2013 / Accepted: 14 January 2013 / Published: 21 January 2013
Cited by 14 | PDF Full-text (591 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years. Plants were considered as alternative sources of vaccines, to be mainly orally administered. Despite 20-year attempts, no real anti-HBV plant-based vaccine has been developed. Immunization
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Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years. Plants were considered as alternative sources of vaccines, to be mainly orally administered. Despite 20-year attempts, no real anti-HBV plant-based vaccine has been developed. Immunization trials, based on ingestion of raw plant tissue and conjugated with injection or exclusively oral administration of lyophilized tissue, were either impractical or insufficient due to oral tolerance acquisition. Plant-produced purified HBV antigens were highly immunogenic when injected, but their yields were initially insufficient for practical purposes. However, knowledge and technology have progressed, hence new plant-derived anti-HBV vaccines can be proposed today. All HBV antigens can be efficiently produced in stable or transient expression systems. Processing of injection vaccines has been developed and needs only to be successfully completed. Purified antigens can be used for injection in an equivalent manner to the present commercial vaccines. Although oral vaccines require improvement, plant tissue, lyophilized or extracted and converted into tablets, etc., may serve as a boosting vaccine. Preliminary data indicate also that both vaccines can be combined in an effective parenteral-oral immunization procedure. A partial substitution of injection vaccines with oral formulations still offers good prospects for economically viable and efficacious anti-HBV plant-based vaccines. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)

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