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Advances in Molecular Research of Functional and Nutraceutical Food 2017

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 April 2017) | Viewed by 166637

Special Issue Editors


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Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avda Fuentenueva s/n, 18071 Granada, Spain
Interests: bioactive phenolic compounds; metabolomics; analytical techniques; extraction processes; plant and food analysis; bioavailability
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Special Issue Information

Dear Colleagues,

Nowadays, there is an increasing interest in the bioactive molecules, commonly known as "bioactive compounds", which are nutritional constituents that naturally occur in small quantities in foods and plants, and show different health benefits. In recent years, the study of these molecules has been one of the main activities for developing functional foods and nutraceuticals. However, bioactive compounds vary widely in chemical structure and function, which still pose some methodological challenges even for current state-of-the-art technologies.

Indeed, metabolic syndrome is one of the metabolic disorders and it is one of the most serious problems of the last decades. Metabolic syndrome is a multiplex risk factor that produces an increase of blood pressure and blood sugars, an excess body fat, and abnormal cholesterol or triglyceride levels. All these factors contribute to an increase of risk of heart disease, fatty liver, diabetes and several cancers. Lifestyle change and weight loss are considered the most important initial steps in treating metabolic syndrome. However, it has been noticed that some plants, food and food by-products bioactive compounds, such as phenolic compounds, reported strong potential bioactivity against the metabolic syndrome and the effects are strictly related to the bioactive compounds profile, their content and biological activity.

This Special Issue, “Advances in Molecular Research of Functional and Nutraceutical Food”, will cover a selection of recent research topics and current review articles about the composition and content of bioactive compounds in functional food and nutraceuticals, including studies about metabolomic approaches. We are particularly interested in articles describing the new analytical strategies identification of new bioactive compounds, the use of new methodologies for chemical and/or in vitro and in vivo analysis of bioactive compounds guided to the study of diseases related to metabolic syndrome.

Prof. Dr. David Arráez-Román
Dr. Ana Maria Gómez-Caravaca
Guest Editors

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Keywords

  • metabolic syndrome
  • plants, food and food by-products
  • bioactive compounds
  • analytical techniques
  • metabolomics
  • in vivo and in vitro studies
  • functional food
  • nutraceuticals
  • Healthy diet

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Published Papers (15 papers)

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Research

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3267 KiB  
Article
MDG-1, a Potential Regulator of PPARα and PPARγ, Ameliorates Dyslipidemia in Mice
by Xu Wang, Linlin Shi, Sun Joyce, Yuan Wang and Yi Feng
Int. J. Mol. Sci. 2017, 18(9), 1930; https://doi.org/10.3390/ijms18091930 - 8 Sep 2017
Cited by 16 | Viewed by 5650
Abstract
Hyperlipidemia is a serious epidemic disease caused by lipid metabolism disorder, which is harmful to human health. MDG-1, a β-d-fructan polysaccharide extracted from Ophiopogon japonicus, has been shown to improve abnormal blood lipid levels and alleviate diabetes. However, the underlying [...] Read more.
Hyperlipidemia is a serious epidemic disease caused by lipid metabolism disorder, which is harmful to human health. MDG-1, a β-d-fructan polysaccharide extracted from Ophiopogon japonicus, has been shown to improve abnormal blood lipid levels and alleviate diabetes. However, the underlying mechanism on hyperlipidemia is largely unknown. In this study, male C57BL/6 mice were randomly separated into three groups, respectively: low-fat diet (Con), high-fat diet (HFD), and high-fat diet plus 5‰ MDG-1 (HFD + MDG-1). Body weight was measured and the serum lipid levels were analyzed. Using gene microarray, various core pathways, together with levels of gene expression within hepatocytes, were analyzed. RT-PCR was used to confirm the identity of the differentially expressed genes. MDG-1 could prevent obesity in HFD-induced mice and improve abnormal serum lipids. Besides, MDG-1 could regulate hyperlipidemia symptoms, specifically, and decrease fasting blood glucose, improve glucose tolerance, and ameliorate insulin resistance. According to results from gene microarray, most of the identified pathways were involved in the digestion and absorption of fat, biosynthesis, and catabolism of fatty acids as well as the secretion and biological synthesis of bile acids. Furthermore, MDG-1 may act upon peroxisome proliferator-activated receptors (PPAR) α and γ, activating PPARα whilst inhibiting PPARγ, thus having a potent hypolipidemic effect. Full article
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Article
Licochalcone A Inhibits the Proliferation of Human Lung Cancer Cell Lines A549 and H460 by Inducing G2/M Cell Cycle Arrest and ER Stress
by Chenyu Qiu, Tingting Zhang, Wenxin Zhang, Lina Zhou, Bin Yu, Wei Wang, Zhihong Yang, Zhiguo Liu, Peng Zou and Guang Liang
Int. J. Mol. Sci. 2017, 18(8), 1761; https://doi.org/10.3390/ijms18081761 - 12 Aug 2017
Cited by 80 | Viewed by 7389
Abstract
Licochalcone A (LicA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, has wide spectrum of pharmacological activities. In this study, the anti-cancer effects and potential mechanisms of LicA in non-small cell lung cancer (NSCLC) cells were studied. LicA decreased [...] Read more.
Licochalcone A (LicA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, has wide spectrum of pharmacological activities. In this study, the anti-cancer effects and potential mechanisms of LicA in non-small cell lung cancer (NSCLC) cells were studied. LicA decreased cell viability and induced apoptosis in a dose-dependent manner in NSCLC cells. LicA inhibited lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LicA treatment decreased the expression of MDM2, Cyclin B1, Cdc2 and Cdc25C in H460 and A549 cancer cell lines. In addition, LicA induced caspase-3 activation and poly-ADP-ribose polymerase (PARP) cleavage, which displayed features of apoptotic signals. Furthermore, LicA increased the expression of endoplasmic reticulum (ER) stress related proteins, such as p-EIF2α and ATF4. These data provide evidence that LicA has the potential to be used in the treatment of lung cancer. Full article
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2358 KiB  
Article
Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway
by Yu-Tsai Lin, Hung-Chen Wang, Yi-Chiang Hsu, Chung-Lung Cho, Ming-Yu Yang and Chih-Yen Chien
Int. J. Mol. Sci. 2017, 18(7), 1343; https://doi.org/10.3390/ijms18071343 - 23 Jun 2017
Cited by 92 | Viewed by 8205
Abstract
Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in [...] Read more.
Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells. Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest. Western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to measure capsaicin-induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway. Capsaicin induced autophagy by increasing levels of the autophagy markers LC3-II and Atg5, enhancing p62 and Fap-1 degradation and increasing caspase-3 activity to induce apoptosis, suggesting a correlation of blocking the PI3K/Akt/mTOR pathway with the above-mentioned anticancer activities. Taken together, these data confirm that capsaicin inhibited the growth of human NPC cells and induced autophagy, supporting its potential as a therapeutic agent for cancer. Full article
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Article
Hepatoprotective Effect of Aqueous Extract from the Seeds of Orychophragmus violaceus against Liver Injury in Mice and HepG2 Cells
by Xiaowei Huo, Chenqi Liu, Li Gao, Xudong Xu, Nailiang Zhu and Li Cao
Int. J. Mol. Sci. 2017, 18(6), 1197; https://doi.org/10.3390/ijms18061197 - 15 Jun 2017
Cited by 29 | Viewed by 6129
Abstract
Orychophragmus violaceus (O. violaceus) is a kind of edible wild herb in north China and its seeds have medical potential, however, the effect of O. violaceus seeds on liver injury and the mechanism of action remains poorly understood. Thus, the purpose [...] Read more.
Orychophragmus violaceus (O. violaceus) is a kind of edible wild herb in north China and its seeds have medical potential, however, the effect of O. violaceus seeds on liver injury and the mechanism of action remains poorly understood. Thus, the purpose of the present study is to investigate the effect of O. violaceus seeds on liver injury and further explore the molecular mechanism of the beneficial effects using aqueous extract from the seeds of O. violaceus (AEOV). Mice were orally administrated with saline, AEOV, and biphenyldicarboxylate for 4 days, and were then injected subcutaneously with 0.1% carbon tetrachloride (CCl4) dissolved in corn oil. Sixteen hours later, mice were sacrificed and blood samples were collected. Then, the serum was separated and used for biochemical assay. Livers were excised and were routinely processed for histological examinations. Enzyme activities and protein levels in liver homogenates were detected using commercial kits or by western blot analysis. Additionally, the hepatoprotective effect of AEOV in vitro was evaluated using epigoitrin, the major alkaloid compound isolated from AEOV. We found that AEOV attenuated liver injury induced by CCl4 as evidenced by decreased levels of alanine aminotransferase (ALT) and aminotransferase (AST) in serum, improvement of liver histopathological changes, and substantial attenuation of oxidative stress and inflammation via regulation of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor κB (NFκB) pathways. These effects of AEOV were comparable to that of biphenyldicarboxylate which was commonly used as a hepatoprotective reference. Moreover, pretreatment of HepG2 cells with epigoitrin improved cell viability, decreased lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, attenuated the NFκB pathway, and elevated the Nrf2 pathway after exposure to H2O2. These results suggest that AEOV could effectively prevent CCl4-induced liver injury in mice via regulating the Nrf2 and NFκB pathways, and reveal the cytoprotective effects of epigoitrin against H2O2-induced oxidative stress in HepG2 cells. Full article
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Article
Inhibitory Effects of Dimethyllirioresinol, Epimagnolin A, Eudesmin, Fargesin, and Magnolin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes
by Ju-Hyun Kim, Soon-Sang Kwon, Hyeon-Uk Jeong and Hye Suk Lee
Int. J. Mol. Sci. 2017, 18(5), 952; https://doi.org/10.3390/ijms18050952 - 1 May 2017
Cited by 12 | Viewed by 5179
Abstract
Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP) enzyme activities in human liver microsomes were evaluated using [...] Read more.
Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP) enzyme activities in human liver microsomes were evaluated using liquid chromatography–tandem mass spectrometry to determine the inhibition mechanisms and inhibition potency. Fargesin inhibited CYP2C9-catalyzed diclofenac 4’-hydroxylation with a Ki value of 16.3 μM, and it exhibited mechanism-based inhibition of CYP2C19-catalyzed [S]-mephenytoin 4’-hydroxylation (Ki, 3.7 μM; kinact, 0.102 min−1), CYP2C8-catalyzed amodiaquine N-deethylation (Ki, 10.7 μM; kinact, 0.082 min−1), and CYP3A4-catalyzed midazolam 1’-hydroxylation (Ki, 23.0 μM; kinact, 0.050 min−1) in human liver microsomes. Fargesin negligibly inhibited CYP1A2-catalyzed phenacetin O-deethylation, CYP2A6-catalyzed coumarin 7-hydroxylation, CYP2B6-catalyzed bupropion hydroxylation, and CYP2D6-catalyzed bufuralol 1’-hydroxylation at 100 μM in human liver microsomes. Dimethyllirioresinol weakly inhibited CYP2C19 and CYP2C8 with IC50 values of 55.1 and 85.0 μM, respectively, without inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, and CYP3A4 activities at 100 μM. Epimagnolin A, eudesmin, and magnolin showed no the reversible and time-dependent inhibition of eight major CYP activities at 100 μM in human liver microsomes. These in vitro results suggest that it is necessary to investigate the potentials of in vivo fargesin-drug interaction with CYP2C8, CYP2C9, CYP2C19, and CYP3A4 substrates. Full article
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18954 KiB  
Article
Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury
by Xiaodan Han, Xiaolei Xue, Yu Zhao, Yuan Li, Weili Liu, Junling Zhang and Saijun Fan
Int. J. Mol. Sci. 2017, 18(5), 942; https://doi.org/10.3390/ijms18050942 - 29 Apr 2017
Cited by 27 | Viewed by 6168
Abstract
Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with [...] Read more.
Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress. Full article
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2807 KiB  
Article
Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells
by Jui-Hung Yen, Pei-Shan Wu, Shu-Fen Chen and Ming-Jiuan Wu
Int. J. Mol. Sci. 2017, 18(4), 852; https://doi.org/10.3390/ijms18040852 - 17 Apr 2017
Cited by 54 | Viewed by 7105
Abstract
Background: Fisetin (3,7,3′,4′-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study [...] Read more.
Background: Fisetin (3,7,3′,4′-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells. Methods: Cell viability was assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptotic and autophagic markers were analyzed by Western blot. Gene expression of unfolded protein response (UPR) and Phase II enzymes was further investigated using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) by a fluorometer. The effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1 (Sirtuin 1) signaling pathways were examined using Western blotting and specific inhibitors. Results: Fisetin (<20 µM) restored cell viability and repressed apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2-targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38 MAPK. Addition of JNK and p38 MAPK inhibitor significantly antagonized its cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm-inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor) significantly blocked fisetin-mediated cytoprotection. In conclusion, this result shows that fisetin activates Nrf2, MAPK and SIRT1, which may elicit adaptive cellular stress response pathways so as to protect cells from Tm-induced cytotoxicity. Full article
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2548 KiB  
Article
Permeation of Polymethoxyflavones into the Mouse Brain and Their Effect on MK-801-Induced Locomotive Hyperactivity
by Satoshi Okuyama, Kohei Miyazaki, Rie Yamada, Yoshiaki Amakura, Morio Yoshimura, Atsushi Sawamoto, Mitsunari Nakajima and Yoshiko Furukawa
Int. J. Mol. Sci. 2017, 18(3), 489; https://doi.org/10.3390/ijms18030489 - 24 Feb 2017
Cited by 21 | Viewed by 5227
Abstract
Accumulating data have indicated that citrus polymethoxyflavones (PMFs) have the ability to affect brain function. In the present study, we showed that 3,5,6,7,8,3′,4′-heptamethoxy- flavone (HMF) given intraperitoneally to mice was immediately detected in the brain and that the permeability of the brain tissues [...] Read more.
Accumulating data have indicated that citrus polymethoxyflavones (PMFs) have the ability to affect brain function. In the present study, we showed that 3,5,6,7,8,3′,4′-heptamethoxy- flavone (HMF) given intraperitoneally to mice was immediately detected in the brain and that the permeability of the brain tissues to it was significantly higher than that of other citrus PMFs (nobiletin, tangeretin, and natsudaidain). The permeation of these PMFs into the brain well correlated with their abilities to suppress MK-801-induced locomotive hyperactivity, suggesting that HMF had the ability to act directly in the brain. We also obtained data suggesting that the suppressive effect of HMF on MK-801-induced locomotive hyperactivity was mediated by phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the hippocampus. Full article
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12999 KiB  
Article
d,l-Sulforaphane Induces ROS-Dependent Apoptosis in Human Gliomablastoma Cells by Inactivating STAT3 Signaling Pathway
by Ziwei Miao, Fei Yu, Yahao Ren and Jun Yang
Int. J. Mol. Sci. 2017, 18(1), 72; https://doi.org/10.3390/ijms18010072 - 4 Jan 2017
Cited by 30 | Viewed by 6977
Abstract
d,l-Sulforaphane (SFN), a synthetic analogue of broccoli-derived isomer l-SFN, exerts cytotoxic effects on multiple tumor cell types through different mechanisms and is more potent than the l-isomer at inhibiting cancer growth. However, the means by which SFN impairs [...] Read more.
d,l-Sulforaphane (SFN), a synthetic analogue of broccoli-derived isomer l-SFN, exerts cytotoxic effects on multiple tumor cell types through different mechanisms and is more potent than the l-isomer at inhibiting cancer growth. However, the means by which SFN impairs glioblastoma (GBM) cells remains poorly understood. In this study, we investigated the anti-cancer effect of SFN in GBM cells and determined the underlying molecular mechanisms. Cell viability assays, flow cytometry, immunofluorescence, and Western blot results revealed that SFN could induced apoptosis of GBM cells in a dose- and time-dependent manner, via up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2. Mechanistically, SFN treatment led to increase the intracellular reactive oxygen species (ROS) level in GBM cells. Meanwhile, SFN also suppressed both constitutive and IL-6-induced phosphorylation of STAT3, and the activation of upstream JAK2 and Src tyrosine kinases, dose- and time-dependently. Moreover, blockage of ROS production by using the ROS inhibitor N-acetyl-l-cysteine totally reversed SFN-mediated down-regulation of JAK2/Src-STAT3 signaling activation and the subsequent effects on apoptosis by blocking the induction of apoptosis-related genes in GBM cells. Taken together, our data suggests that SFN induces apoptosis in GBM cells via ROS-dependent inactivation of STAT3 phosphorylation. These findings motivate further evaluation of SFN as a cancer chemopreventive agent in GBM treatment. Full article
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9322 KiB  
Article
Vitamin C Protects Chondrocytes against Monosodium Iodoacetate-Induced Osteoarthritis by Multiple Pathways
by Pu-Rong Chiu, Yu-Chen Hu, Tzu-Ching Huang, Bau-Shan Hsieh, Jou-Pei Yeh, Hsiao-Ling Cheng, Li-Wen Huang and Kee-Lung Chang
Int. J. Mol. Sci. 2017, 18(1), 38; https://doi.org/10.3390/ijms18010038 - 27 Dec 2016
Cited by 44 | Viewed by 10809
Abstract
Osteoarthritis (OA) is the most prevalent joint disease. Dietary intake of vitamin C relates to a reduction in cartilage loss and OA. This study examined the efficacy of vitamin C to prevent OA with the in vitro chondrosarcoma cell line (SW1353) and the [...] Read more.
Osteoarthritis (OA) is the most prevalent joint disease. Dietary intake of vitamin C relates to a reduction in cartilage loss and OA. This study examined the efficacy of vitamin C to prevent OA with the in vitro chondrosarcoma cell line (SW1353) and the in vivo monosodium iodoacetate (MIA)-induced OA rat. Results demonstrated that, in SW1353 cells, treatment with 5 μM MIA inhibited cell growth and increased oxidative stress, apoptosis, and proteoglycan loss. In addition, the expression levels of the pro-inflammatory cytokines IL-6, IL-17A, and TNF-α and matrix metalloproteinases (MMPs) MMP-1, MMP-3, and MMP-13 were increased. All of these MIA-induced changes could be prevented with treatment of 100 μM vitamin C. In an animal model, intra-articular injection of MIA-induced cartilage degradation resembled the pathological changes of OA, and treatment of vitamin C could lessen these changes. Unexpectedly, vitamin C’s effects did not strengthen with the increasing dosage, while the 100 mg/kg dosage was more efficient than the 200 or 300 mg/kg dosages. Vitamin C possessed multiple capacities for prevention of OA progress, including a decrease in apoptosis and in the expression of pro-inflammatory cytokines and MMPs in addition to the well-known antioxidation. Full article
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493 KiB  
Article
A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients
by Giuseppe Derosa, Angela D’Angelo, Davide Romano and Pamela Maffioli
Int. J. Mol. Sci. 2016, 17(11), 1802; https://doi.org/10.3390/ijms17111802 - 28 Oct 2016
Cited by 59 | Viewed by 9147
Abstract
The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 [...] Read more.
The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers. Full article
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Review

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1190 KiB  
Review
Flavonoids, Thyroid Iodide Uptake and Thyroid Cancer—A Review
by Carlos F. L. Gonçalves, Mariana L. De Freitas and Andrea C. F. Ferreira
Int. J. Mol. Sci. 2017, 18(6), 1247; https://doi.org/10.3390/ijms18061247 - 12 Jun 2017
Cited by 42 | Viewed by 11876
Abstract
Thyroid cancer is the most common malignant tumor of the endocrine system and the incidence has been increasing in recent years. In a great part of the differentiated carcinomas, thyrocytes are capable of uptaking iodide. In these cases, the main therapeutic approach includes [...] Read more.
Thyroid cancer is the most common malignant tumor of the endocrine system and the incidence has been increasing in recent years. In a great part of the differentiated carcinomas, thyrocytes are capable of uptaking iodide. In these cases, the main therapeutic approach includes thyroidectomy followed by ablative therapy with radioiodine. However, in part of the patients, the capacity to concentrate iodide is lost due to down-regulation of the sodium-iodide symporter (NIS), the protein responsible for transporting iodide into the thyrocytes. Thus, therapy with radioiodide becomes ineffective, limiting therapeutic options and reducing the life expectancy of the patient. Excessive ingestion of some flavonoids has been associated with thyroid dysfunction and goiter. Nevertheless, studies have shown that some flavonoids can be beneficial for thyroid cancer, by reducing cell proliferation and increasing cell death, besides increasing NIS mRNA levels and iodide uptake. Recent data show that the flavonoids apingenin and rutin are capable of increasing NIS function and expression in vivo. Herein we review literature data regarding the effect of flavonoids on thyroid cancer, besides the effect of these compounds on the expression and function of the sodium-iodide symporter. We will also discuss the possibility of using flavonoids as adjuvants for therapy of thyroid cancer. Full article
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410 KiB  
Review
Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions
by Francisca Echeverría, Macarena Ortiz, Rodrigo Valenzuela and Luis A. Videla
Int. J. Mol. Sci. 2017, 18(5), 930; https://doi.org/10.3390/ijms18050930 - 28 Apr 2017
Cited by 92 | Viewed by 7937
Abstract
Hydroxytyrosol (HT) ((3,4-Dihydroxyphenyl)ethanol) is a polyphenol mainly present in extra virgin olive oil (EVOO) but also in red wine. It has a potent antioxidant effect related to hydrogen donation, and the ability to improve radical stability. The phenolic content of olive oil varies [...] Read more.
Hydroxytyrosol (HT) ((3,4-Dihydroxyphenyl)ethanol) is a polyphenol mainly present in extra virgin olive oil (EVOO) but also in red wine. It has a potent antioxidant effect related to hydrogen donation, and the ability to improve radical stability. The phenolic content of olive oil varies between 100 and 600 mg/kg, due to multiple factors (place of cultivation, climate, variety of the olive and level of ripening at the time of harvest), with HT and its derivatives providing half of that content. When consumed, EVOO’s phenolic compounds are hydrolyzed in the stomach and intestine, increasing levels of free HT which is then absorbed in the small intestine, forming phase II metabolites. It has been demonstrated that HT consumption is safe even at high doses, and that is not genotoxic or mutagenic in vitro. The beneficial effects of HT have been studied in humans, as well as cellular and animal models, mostly in relation to consumption of EVOO. Many properties, besides its antioxidant capacity, have been attributed to this polyphenol. The aim of this review was to assess the main properties of HT for human health with emphasis on those related to the possible prevention and/or treatment of non-communicable diseases. Full article
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824 KiB  
Review
Health Effects of Psidium guajava L. Leaves: An Overview of the Last Decade
by Elixabet Díaz-de-Cerio, Vito Verardo, Ana María Gómez-Caravaca, Alberto Fernández-Gutiérrez and Antonio Segura-Carretero
Int. J. Mol. Sci. 2017, 18(4), 897; https://doi.org/10.3390/ijms18040897 - 24 Apr 2017
Cited by 120 | Viewed by 31615
Abstract
Today, there is increasing interest in discovering new bioactive compounds derived from ethnomedicine. Preparations of guava (Psidium guajava L.) leaves have traditionally been used to manage several diseases. The pharmacological research in vitro as well as in vivo has been widely used [...] Read more.
Today, there is increasing interest in discovering new bioactive compounds derived from ethnomedicine. Preparations of guava (Psidium guajava L.) leaves have traditionally been used to manage several diseases. The pharmacological research in vitro as well as in vivo has been widely used to demonstrate the potential of the extracts from the leaves for the co-treatment of different ailments with high prevalence worldwide, upholding the traditional medicine in cases such as diabetes mellitus, cardiovascular diseases, cancer, and parasitic infections. Moreover, the biological activity has been attributed to the bioactive composition of the leaves, to some specific phytochemical subclasses, or even to individual compounds. Phenolic compounds in guava leaves have been credited with regulating blood-glucose levels. Thus, the aim of the present review was to compile results from in vitro and in vivo studies carried out with guava leaves over the last decade, relating the effects to their clinical applications in order to focus further research for finding individual bioactive compounds. Some food applications (guava tea and supplementary feed for aquaculture) and some clinical, in vitro, and in vivo outcomes are also included. Full article
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3007 KiB  
Review
Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease
by Yunqi Weng, Jian Yao, Sawyer Sparks and Kevin Yueju Wang
Int. J. Mol. Sci. 2017, 18(3), 523; https://doi.org/10.3390/ijms18030523 - 28 Feb 2017
Cited by 143 | Viewed by 35583
Abstract
Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK), a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of [...] Read more.
Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK), a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting) capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II) in the USA for atherothrombotic prevention. Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed. Full article
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