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Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2022

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 2022) | Viewed by 6042

Special Issue Editors


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Guest Editor
1. Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche—Sez, Biochimica, Università Politecnica delle Marche, Ancona, 60131 Ancona, Italy
2. Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain
Interests: phytochemicals; antioxidants; natural product chemistry; food chemistry; reactive oxygen species; chromatography
Special Issues, Collections and Topics in MDPI journals

grade E-Mail Website
Guest Editor
Department of Odontostomatologic and Specialized Clinical Sciences, Sez-Biochimica, Faculty of Medicine, Università Politecnica delle Marche, Via Ranieri 65, 60100 Ancona, Italy
Interests: nutrition; periodontal diseases/periodontitis; oxidative stress; nutrition; aging; mitochondrial function and diseases; berries (strawberry, blueberry, bilberry, cranberry, etc.); olive oil (dietary fats); honey; polyphenols; flavonoids; antioxidants; apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The importance of diet for human health and well-being has been widely recognized. Dietary guidelines around the world recommend the increased consumption of fruits and vegetables as good sources of dietary fiber, essential nutrients, and phytochemicals, to improve global health and reduce chronic disease risk. A diet rich in fruits and vegetables is indeed associated with a lower incidence of several degenerative pathologies, including obesity, diabetes, cardiovascular diseases, and cancer. In the last few years, numerous studies have demonstrated a wide range of biological properties and healthy benefits exerted by dietary phytochemicals, highlighting their beneficial role both in the prevention and in the treatment of several diseases. At the same time, functional foods have gained an enormous interest all around the world, as shown by the annual increase of their market of about 15%. Indeed, many now embrace the idea that functional foods play specific roles at different times throughout life and accept that certain foods may help to maintain a good health and prevent diseases.

The main aims of the Special Issue on "Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2022" is to be an open forum where researchers may share their investigations and findings in this promising field and, thanks to the open access platform, increase their visibility and the chances to interact with industries and the production systems.

Dr. Francesca Giampieri
Prof. Dr. Maurizio Battino
Guest Editors

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Keywords

  • dietary guideline
  • dietary fiber
  • essential nutrients
  • phytochemicals
  • functional food
  • degenerative pathologies

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Published Papers (33 papers)

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Editorial

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4 pages, 186 KiB  
Editorial
Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables
by Francesca Giampieri and Maurizio Battino
Int. J. Mol. Sci. 2020, 21(9), 3278; https://doi.org/10.3390/ijms21093278 - 6 May 2020
Cited by 6 | Viewed by 3713
Abstract
Today, it is widely accepted that a plant-based diet produces wellbeing and prevents the onset of several human diseases [...] Full article

Research

Jump to: Editorial, Review

21 pages, 10440 KiB  
Article
Protective Effects of Currants (Vitis vinifera) on Corticolimbic Serotoninergic Alterations and Anxiety-like Comorbidity in a Rat Model of Parkinson’s Disease
by Martha Tsarouchi, Eleni Fanarioti, Vaios T. Karathanos and Catherine R. Dermon
Int. J. Mol. Sci. 2023, 24(1), 462; https://doi.org/10.3390/ijms24010462 - 27 Dec 2022
Cited by 4 | Viewed by 2032
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigral dopaminergic neurons. Increasing evidence supports that PD is not simply a motor disorder but a systemic disease leading to motor and non-motor symptoms, including memory loss and neuropsychiatric conditions, [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigral dopaminergic neurons. Increasing evidence supports that PD is not simply a motor disorder but a systemic disease leading to motor and non-motor symptoms, including memory loss and neuropsychiatric conditions, with poor management of the non-motor deficits by the existing dopaminergic medication. Oxidative stress is considered a contributing factor for nigrostriatal degeneration, while antioxidant/anti-inflammatory properties of natural phyto-polyphenols have been suggested to have beneficial effects. The present study aimed to determine the contribution of monoaminergic neurotransmission on the anxiety-like phenotype in a rat rotenone PD model and evaluate the possible neuroprotective effects of black Corinthian currant, Vitis vinifera, consisting of antioxidant polyphenols. Rotenone-treated rats showed anxiety-like behavior and exploratory deficits, accompanied by changes in 5-HT, SERT and β2-ARs expression in the prefrontal cortices, hippocampus and basolateral amygdala. Importantly, the motor and non-motor behavior, as well as 5-HT, SERT and β2-ARs expression patterns of the PD-like phenotype were partially recovered by a supplementary diet with currants. Overall, our results suggest that the neuroprotective effects of Corinthian currants in rotenone-induced anxiety-like behavior may be mediated via corticolimbic serotonergic transmission. Full article
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12 pages, 1493 KiB  
Article
Changes in the Phytochemical and Bioactive Compounds and the Antioxidant Properties of Wolfberry during Vinegar Fermentation Processes
by Ting Xia, Xiao Qiang, Beibei Geng, Xiaodong Zhang, Yiming Wang, Shaopeng Li, Yuan Meng, Yu Zheng and Min Wang
Int. J. Mol. Sci. 2022, 23(24), 15839; https://doi.org/10.3390/ijms232415839 - 13 Dec 2022
Cited by 7 | Viewed by 2286
Abstract
Wolfberry (Lycium barbarum L.), as a kind of functional fruit, has various nutritional and bioactive components, which exhibit healthy benefits. However, wolfberry is not easy to preserve, and the intensive processing of wolfberry needs to be developed. In the present study, the [...] Read more.
Wolfberry (Lycium barbarum L.), as a kind of functional fruit, has various nutritional and bioactive components, which exhibit healthy benefits. However, wolfberry is not easy to preserve, and the intensive processing of wolfberry needs to be developed. In the present study, the changes in the phytochemical and bioactive compounds, as well as the antioxidant properties of wolfberry, were evaluated in the brewed processes. We found that the sugar contents were significantly decreased, and the total acids values were significantly increased during the fermentation processes. The sugar and fat contents were low in the wolfberry fruit vinegar after fermentation, which is of benefit to human health. In addition, amino acids were examined during the fermentation processes, and histidine, proline, and alanine were found to be the main amino acids in vinegar. The total phenolics and flavonoids contents were significantly increased by 29.4% and 65.7% after fermentation. 4-Hydroxy benzoic acid, 3-hydroxy cinnamic acid, and chlorogenic acid were the primary polyphenols in the wolfberry fruit vinegar. Moreover, the antioxidant activity of wolfberry fruit vinegar was significantly increased compared with that of wolfberry fruit after the fermentation processes. Polysaccharides and polyphenolics were strongly correlated with the antioxidant activity during the fermentation processes. The findings suggest that wolfberry fruit vinegar has a high antioxidant capability, and could be a beneficial food in the human diet. Full article
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19 pages, 2554 KiB  
Article
Phytochemical Molecules from the Decarboxylation of Gomphrenins in Violet Gomphrena globosa L.—Floral Infusions from Functional Food
by Natalia Drobnicka, Katarzyna Sutor, Agnieszka Kumorkiewicz-Jamro, Aneta Spórna-Kucab, Michał Antonik, Ewa Dziedzic, Tomasz Świergosz, Joanna Ortyl and Sławomir Wybraniec
Int. J. Mol. Sci. 2020, 21(22), 8834; https://doi.org/10.3390/ijms21228834 - 22 Nov 2020
Cited by 2 | Viewed by 3067
Abstract
Herein, the generation of decarboxylated derivatives of gomphrenin pigments exhibiting potential health-promoting properties and the kinetics of their extraction during tea brewing from the purple flowers of Gomphrena globosa L. in aqueous and aqueous citric acid solutions were investigated. Time-dependent concentration monitoring of [...] Read more.
Herein, the generation of decarboxylated derivatives of gomphrenin pigments exhibiting potential health-promoting properties and the kinetics of their extraction during tea brewing from the purple flowers of Gomphrena globosa L. in aqueous and aqueous citric acid solutions were investigated. Time-dependent concentration monitoring of natural gomphrenins and their tentative identification was carried out by LC-DAD-ESI-MS/MS. The high content of acylated gomphrenins and their principal decarboxylation products, 2-, 15-, 17-decarboxy-gomphrenins, along with minor levels of their bidecarboxylated derivatives, were reported in the infusions. The identification was supported by the determination of molecular formulas of the extracted pigments by liquid chromatography coupled with high-resolution mass spectrometry (LCMS-IT-TOF). The influence of plant matrix on gomphrenins’ stability and generation of their derivatives, including the extraction kinetics, was determined by studying the concentration profiles in the primary and diluted infusions. Isolated and purified acylated gomphrenins from the same plant material were used for the preliminary determination of their decarboxylated derivatives. The acylated gomphrenins were found to be more stable than nonacylated ones. Citric acid addition had a degradative influence on natural gomphrenins mainly during the longer tea brewing process (above 15 min); however, the presence of plant matrix significantly increased the stability for betacyanins’ identification. Full article
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17 pages, 3489 KiB  
Article
Tellimagrandin II, A Type of Plant Polyphenol Extracted from Trapa bispinosa Inhibits Antibiotic Resistance of Drug-Resistant Staphylococcus aureus
by Yu-Wei Chang, Wan-Chun Huang, Chun-Yu Lin, Wen-Hung Wang, Ling-Chien Hung and Yen-Hsu Chen
Int. J. Mol. Sci. 2019, 20(22), 5790; https://doi.org/10.3390/ijms20225790 - 18 Nov 2019
Cited by 17 | Viewed by 4730
Abstract
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new candidates of anti-S. aureus agents is urgently required because the therapeutic strategies for infected patients are limited currently. Therefore, the present study investigated whether Tellimagrandin II (TGII), [...] Read more.
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new candidates of anti-S. aureus agents is urgently required because the therapeutic strategies for infected patients are limited currently. Therefore, the present study investigated whether Tellimagrandin II (TGII), a pure compound extracted from the shells of Trapa bispinosa, exhibits antibacterial effects against MRSA. We first showed that TGII exerted potent inhibitory activity against MRSA with a minimum inhibitory concentration of 128 μg/mL. The obtained fractional inhibitory concentration suggested that TGII could alone exert antistaphylococcal activity, and TGII combined with low doses of antibiotics displayed synergistic effects against MRSA. Moreover, we found that TGII exerted bactericidal activity by reducing the expression of mecA followed by the negative regulation of the penicillin-binding protein 2a (PBP2a) of MRSA. Transmission electron microscopy (TEM) images further confirmed that TGII destroyed the integrity of the cell wall of MRSA and caused the loss of cytoplasm content. In conclusion, we evidenced the antibacterial effects of TGII against MRSA, which enables the effective dose of current antibiotics to be reduced and the predicament of drug-resistant S. aureus isolates to be overcome. Full article
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15 pages, 6816 KiB  
Article
Quercetin Exposure Suppresses the Inflammatory Pathway in Intestinal Organoids from Winnie Mice
by Manuela Dicarlo, Gabriella Teti, Giulio Verna, Marina Liso, Elisabetta Cavalcanti, Annamaria Sila, Sathuwarman Raveenthiraraj, Mauro Mastronardi, Angelo Santino, Grazia Serino, Antonio Lippolis, Anastasia Sobolewski, Mirella Falconi and Marcello Chieppa
Int. J. Mol. Sci. 2019, 20(22), 5771; https://doi.org/10.3390/ijms20225771 - 16 Nov 2019
Cited by 37 | Viewed by 5732
Abstract
Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine [...] Read more.
Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses. Full article
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16 pages, 7473 KiB  
Article
Protective Effects of Flavone from Tamarix aphylla against CCl4-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis
by Bishoy El-Aarag, Asmaa Khairy, Shaden A. M. Khalifa and Hesham R. El-Seedi
Int. J. Mol. Sci. 2019, 20(20), 5215; https://doi.org/10.3390/ijms20205215 - 21 Oct 2019
Cited by 26 | Viewed by 3990
Abstract
The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) at a dose of [...] Read more.
The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl4 caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl4 model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human. Full article
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17 pages, 2872 KiB  
Article
Poria cocus Wolf Extract Ameliorates Hepatic Steatosis through Regulation of Lipid Metabolism, Inhibition of ER Stress, and Activation of Autophagy via AMPK Activation
by Ji-Hyun Kim, Hyun A Sim, Dae Young Jung, Eun Yeong Lim, Yun Tai Kim, Byung Joo Kim and Myeong Ho Jung
Int. J. Mol. Sci. 2019, 20(19), 4801; https://doi.org/10.3390/ijms20194801 - 27 Sep 2019
Cited by 71 | Viewed by 6760
Abstract
Poria cocos Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and [...] Read more.
Poria cocos Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)—palmitic and oleic acid—and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis. Full article
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17 pages, 2459 KiB  
Article
Zerumbone Suppresses Enterotoxigenic Bacteroides fragilis Infection-Induced Colonic Inflammation through Inhibition of NF-κΒ
by Soonjae Hwang, Minjeong Jo, Ju Eun Hong, Chan Oh Park, Chang Gun Lee, Miyong Yun and Ki-Jong Rhee
Int. J. Mol. Sci. 2019, 20(18), 4560; https://doi.org/10.3390/ijms20184560 - 14 Sep 2019
Cited by 19 | Viewed by 4645
Abstract
Enterotoxigenic Bacteroides fragilis (ETBF) is human intestinal commensal bacterium and a potent initiator of colitis through secretion of the metalloprotease Bacteroides fragilis toxin (BFT). BFT induces cleavage of E-cadherin in colon cells, which subsequently leads to NF-κB activation. Zerumbone is a key component [...] Read more.
Enterotoxigenic Bacteroides fragilis (ETBF) is human intestinal commensal bacterium and a potent initiator of colitis through secretion of the metalloprotease Bacteroides fragilis toxin (BFT). BFT induces cleavage of E-cadherin in colon cells, which subsequently leads to NF-κB activation. Zerumbone is a key component of the Zingiber zerumbet (L.) Smith plant and can exhibit anti-bacterial and anti-inflammatory effects. However, whether zerumbone has anti-inflammatory effects in ETBF-induced colitis remains unknown. The aim of this study was to determine the anti-inflammatory effect of orally administered zerumbone in a murine model of ETBF infection. Wild-type C57BL/6 mice were infected with ETBF and orally administered zerumbone (30 or 60 mg/kg) once a day for 7 days. Treatment of ETBF-infected mice with zerumbone prevented weight loss and splenomegaly and reduced colonic inflammation with decreased macrophage infiltration. Zerumbone treatment significantly decreased expression of IL-17A, TNF-α, KC, and inducible nitric oxide synthase (iNOS) in colonic tissues of ETBF-infected mice. In addition, serum levels of KC and nitrite was also diminished. Zerumbone-treated ETBF-infected mice also showed decreased NF-κB signaling in the colon. HT29/C1 colonic epithelial cells treated with zerumbone suppressed BFT-induced NF-κB signaling and IL-8 secretion. However, BFT-mediated E-cadherin cleavage was unaffected. Furthermore, zerumbone did not affect ETBF colonization in mice. In conclusion, zerumbone decreased ETBF-induced colitis through inhibition of NF-κB signaling. Full article
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21 pages, 4081 KiB  
Article
Inhibition of Tyrosine-Phosphorylated STAT3 in Human Breast and Lung Cancer Cells by Manuka Honey is Mediated by Selective Antagonism of the IL-6 Receptor
by Priyanka Aryappalli, Khadija Shabbiri, Razan J. Masad, Roadha H. Al-Marri, Shoja M. Haneefa, Yassir A. Mohamed, Kholoud Arafat, Samir Attoub, Otavio Cabral-Marques, Khalil B. Ramadi, Maria J. Fernandez-Cabezudo and Basel K. al-Ramadi
Int. J. Mol. Sci. 2019, 20(18), 4340; https://doi.org/10.3390/ijms20184340 - 5 Sep 2019
Cited by 37 | Viewed by 6376
Abstract
Aberrantly high levels of tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) are found constitutively in ~50% of human lung and breast cancers, acting as an oncogenic transcription factor. We previously demonstrated that Manuka honey (MH) inhibits p-STAT3 in breast cancer cells, [...] Read more.
Aberrantly high levels of tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) are found constitutively in ~50% of human lung and breast cancers, acting as an oncogenic transcription factor. We previously demonstrated that Manuka honey (MH) inhibits p-STAT3 in breast cancer cells, but the exact mechanism remained unknown. Herein, we show that MH-mediated inhibition of p-STAT3 in breast (MDA-MB-231) and lung (A549) cancer cell lines is accompanied by decreased levels of gp130 and p-JAK2, two upstream components of the IL-6 receptor (IL-6R) signaling pathway. Using an ELISA-based assay, we demonstrate that MH binds directly to IL-6Rα, significantly inhibiting (~60%) its binding to the IL-6 ligand. Importantly, no evidence of MH binding to two other cytokine receptors, IL-11Rα and IL-8R, was found. Moreover, MH did not alter the levels of tyrosine-phosphorylated or total Src family kinases, which are also constitutively activated in cancer cells, suggesting that signaling via other growth factor receptors is unaffected by MH. Binding of five major MH flavonoids (luteolin, quercetin, galangin, pinocembrin, and chrysin) was also tested, and all but pinocembrin could demonstrably bind IL-6Rα, partially (30–35%) blocking IL-6 binding at the highest concentration (50 μM) used. In agreement, each flavonoid inhibited p-STAT3 in a dose-dependent manner, with estimated IC50 values in the 3.5–70 μM range. Finally, docking analysis confirmed the capacity of each flavonoid to bind in an energetically favorable configuration to IL-6Rα at a site predicted to interfere with ligand binding. Taken together, our findings identify IL-6Rα as a direct target of MH and its flavonoids, highlighting IL-6R blockade as a mechanism for the anti-tumor activity of MH, as well as a viable therapeutic target in IL-6-dependent cancers. Full article
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14 pages, 2008 KiB  
Article
Pachypodol, a Methoxyflavonoid Isolated from Pogostemon cablin Bentham Exerts Antioxidant and Cytoprotective Effects in HepG2 Cells: Possible Role of ERK-Dependent Nrf2 Activation
by Eun Kyung Kim, Ji Hoon Kim, Soyeon Jeong, Yong Won Choi, Hyun Jung Choi, Chul Young Kim and Young-Mi Kim
Int. J. Mol. Sci. 2019, 20(17), 4082; https://doi.org/10.3390/ijms20174082 - 21 Aug 2019
Cited by 23 | Viewed by 4582
Abstract
Oxidative stress has been implicated in the pathogenesis of many diseases including chronic liver diseases. Nrf2 is a master transcriptional factor regulating the induction of cellular antioxidant defense systems. Here, the Nrf2-activating effect of the crude methanol extract of dried leaves of Pogostemon [...] Read more.
Oxidative stress has been implicated in the pathogenesis of many diseases including chronic liver diseases. Nrf2 is a master transcriptional factor regulating the induction of cellular antioxidant defense systems. Here, the Nrf2-activating effect of the crude methanol extract of dried leaves of Pogostemon cablin Bentham was demonstrated by measuring the antioxidant response element (ARE)-driven luciferase activity and pachypodol, 4′,5-dihydroxy-3,3′,7-trimethoxyflavone, was isolated by bioactivity-guided fractionation and further separation using chromatographic techniques. To our knowledge, this is the first study to evaluate the antioxidant and cytoprotective effects of pachypodol in HepG2 cells as well as the underlying molecular mechanisms. Indeed, pachypodol protected HepG2 cells from cell death caused by tert-butylhydroperoxide-induced oxidative stress and also attenuated ROS production. The ability of pachypodol to activate Nrf2/ARE pathway was further confirmed by observing Nrf2 expression in nuclear fraction, mRNA levels of Nrf2 target antioxidants, and cellular glutathione content in HepG2 cells. Extracellular signal-regulated kinase (ERK) is one of the important kinases involved in Nrf2 activation. Pachypodol increased ERK phosphorylation and ERK inhibition by PD98059 totally abrogated the increase in ARE luciferase activity, nuclear Nrf2 accumulation and mRNA levels of antioxidant enzymes by pachypodol. In conclusion, pachypodol isolated from P. cablin can protect hepatocytes from oxidative injury, possibly mediated by enhancing endogenous antioxidant defense system through ERK-dependent Nrf2 activation. Full article
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14 pages, 2624 KiB  
Article
Ginseng Berry Prevents Alcohol-Induced Liver Damage by Improving the Anti-Inflammatory System Damage in Mice and Quality Control of Active Compounds
by Dae Young Lee, Min-Jee Kim, Dahye Yoon, Young-Seob Lee, Geum-Soog Kim and Yung Choon Yoo
Int. J. Mol. Sci. 2019, 20(14), 3522; https://doi.org/10.3390/ijms20143522 - 18 Jul 2019
Cited by 16 | Viewed by 4046
Abstract
The ginseng berry contains a variety of biologically active compounds and has a higher ginsenoside content than its roots. This study focused on the hepatoprotective activity of ginseng berry extract prepared by enzyme treatment (EGB) compared to the non-enzyme-treated ginseng berry extract (GB) [...] Read more.
The ginseng berry contains a variety of biologically active compounds and has a higher ginsenoside content than its roots. This study focused on the hepatoprotective activity of ginseng berry extract prepared by enzyme treatment (EGB) compared to the non-enzyme-treated ginseng berry extract (GB) and quality control of EGB. The feeding effect of EGB on alcohol-induced liver damage (AILD) was investigated by measuring the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with those of EtOH-fed mice. Furthermore, cytokine levels in the culture supernatants of EGB- or GB-treated RAW 264.7 cells were determined by enzyme-linked immunosorbent assay. The developed method was applied to the simultaneous quantification of four major ginsenosides in EGB using UPLC-QTOF/MS. Treatment with EGB at a dose of 0.5 or 1 mg/mouse significantly suppressed the AST and ALT levels in mice with AILD. Enzyme-treated ginseng berry was also found to suppress the production of inflammatory mediators like nitric oxide (NO), tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, showing higher activity than that of GB. The amount of ginsenoside Re, F5, F3, and Rd in the EGB obtained using UPLC-QTOF/MS was 45.9, 3.3, 4.0, and 6.2 mg/g, respectively. These results suggest that EGB has a potential effect on AILD, and its hepatoprotective effect provides beneficial insights into developing new candidates for the prevention and cure of AILD. Also, this study demonstrated the utility of UPLC-QTOF/MS-based major compounds for quality control (QC) of EGB. Full article
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14 pages, 2004 KiB  
Article
Bioavailability and In Vivo Antioxidant Activity of a Standardized Polyphenol Mixture Extracted from Brown Propolis
by Valeria Curti, Vincenzo Zaccaria, Arold Jorel Tsetegho Sokeng, Marco Dacrema, Irene Masiello, Anna Mascaro, Giuseppe D’Antona and Maria Daglia
Int. J. Mol. Sci. 2019, 20(5), 1250; https://doi.org/10.3390/ijms20051250 - 12 Mar 2019
Cited by 47 | Viewed by 6799
Abstract
Several lines of evidence demonstrate the antioxidant, anti-inflammatory and antimicrobial activities of propolis, mostly ascribed to its polyphenol content. However, little is known regarding the bioavailability of propolis in acute and prolonged settings of oral administration. In this study, we first determined the [...] Read more.
Several lines of evidence demonstrate the antioxidant, anti-inflammatory and antimicrobial activities of propolis, mostly ascribed to its polyphenol content. However, little is known regarding the bioavailability of propolis in acute and prolonged settings of oral administration. In this study, we first determined the content of the main polyphenols in a brown propolis extract obtained using a patented extraction method (Multi Dinamic Extraction—M.E.D.) by RP-HPLC-UV-PDA-MSn analysis, followed by the bioavailability of galangin and chrysin, the most abundant polyphenols in the mixture (7.8% and 7.5% respectively), following acute (single bolus of 500 mg/kg containing about 3.65 mg of the polyphenol mixture) and prolonged (100, 250 and 500 mg/kg body for 30 days) oral administration in 30 male 8 weeks old C57BL/6 wild-type mice. In the acute setting, blood was taken at 30 s and 5, 10, 15, 20, 25, 30, 45, 60 and 120 min following the oral bolus. In the prolonged setting, blood samples were obtained after 10, 20 or 30 days of administration. At the end of treatment, expression of antioxidant enzymes (superoxyde dismutase, SOD-1; catalase, CAT; glutathione peroxidase, GSS) was evaluated in liver tissue. Following both acute and prolonged administration, neither galangin nor chrysin were detectable in the plasma of mice, whereas the glucuronide metabolite of galangine was detectable 5 min after acute administration. At the end of the prolonged treatment SOD-1 was found to have increased significantly, unlike CAT and GSS. Overall, these data suggest that oral administration of whole brown propolis extract is followed by rapid absorption and metabolization of galangin followed by adaptations of the antioxidant first line defense system. Full article
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11 pages, 2872 KiB  
Article
Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC
by Moon Joon Kim, Deok Yong Sim, Hye Min Lee, Hyo-Jung Lee and Sung-Hoon Kim
Int. J. Mol. Sci. 2019, 20(3), 582; https://doi.org/10.3390/ijms20030582 - 29 Jan 2019
Cited by 29 | Viewed by 6924
Abstract
Although shikimic acid from Illicium verum has antioxidant, antibacterial, anti-inflammatory, and analgesic effects, the effect of shikimic acid on lipogenesis has not yet been explored. Thus, in the present study, hypolipogenic mechanism of shikimic acid was examined in HepG2, Huh7 and 3T3-L1 adipocyte [...] Read more.
Although shikimic acid from Illicium verum has antioxidant, antibacterial, anti-inflammatory, and analgesic effects, the effect of shikimic acid on lipogenesis has not yet been explored. Thus, in the present study, hypolipogenic mechanism of shikimic acid was examined in HepG2, Huh7 and 3T3-L1 adipocyte cells. Shikimic acid showed weak cytotoxicity in HepG2, Huh7 and 3T3-L1 cells, but suppressed lipid accumulation in HepG2, Huh7 and 3T3-L1 cells by Oil Red O staining. Also, shikimic acid attenuated the mRNA expression of de novo lipogenesis related genes such as FAS, SREBP-1c, and LXR-α in HepG2 cells by RT-PCR analysis and suppressed the protein expression of SREBP-1c and LXR-α in HepG2 and 3T3-L1 cells. It should be noted that shikimic acid activated phosphorylation of AMP-activated protein kinase (AMPK)/Aacetyl-coenzyme A carboxylase (ACC) and reduced the expression of MID1 Interacting Protein 1 (MID1IP1) in HepG2, Huh7 and 3T3-L1 cells. Conversely, depletion of MID1IP1 activated phosphorylation of AMPK, while overexpression of MID1IP1 suppressed phosphorylation of AMPK in HepG2 cells. However, AMPK inhibitor compound c did not affect the expression of MID1IP1, indicating MID1IP1 as an upstream of AMPK. Taken together, our findings suggest that shikimic acid has hypolipogenic effect in HepG2 and 3T3-L1 cells via phosphorylation of AMPK/ACC and inhibition of MID1IP1 as a potent candidate for prevention or treatment of fatty liver and hyperlipidemia. Full article
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16 pages, 3346 KiB  
Article
Anthocyanin-Rich Extract from Red Chinese Cabbage Alleviates Vascular Inflammation in Endothelial Cells and Apo E−/− Mice
by Hee Kyoung Joo, Sunga Choi, Yu Ran Lee, Eun Ok Lee, Myoung Soo Park, Kyu Been Park, Cuk-Seong Kim, Yong Pyo Lim, Jong-Tae Park and Byeong Hwa Jeon
Int. J. Mol. Sci. 2018, 19(3), 816; https://doi.org/10.3390/ijms19030816 - 12 Mar 2018
Cited by 30 | Viewed by 6279
Abstract
Anthocyanins, the most prevalent flavonoids in red/purple fruits and vegetables, are known to improve immune responses and reduce chronic disease risks. In this study, the anti-inflammatory activities of an anthocyanin-rich extract from red Chinese cabbage (ArCC) were shown based on its inhibitory effects [...] Read more.
Anthocyanins, the most prevalent flavonoids in red/purple fruits and vegetables, are known to improve immune responses and reduce chronic disease risks. In this study, the anti-inflammatory activities of an anthocyanin-rich extract from red Chinese cabbage (ArCC) were shown based on its inhibitory effects in cultured endothelial cells and hyperlipidemic apolipoprotein E-deficient mice. ArCC treatment suppressed monocyte adhesion to tumor necrosis factor-α-stimulated endothelial cells. This was validated by ArCC’s ability to downregulate the expression and transcription of endothelial adhesion molecules, determined by immunoblot and luciferase promoter assays, respectively. The regulation of adhesion molecules was accompanied by transcriptional inhibition of nuclear factor-κB, which restricted cytoplasmic localization as shown by immunocytochemistry. Administration of ArCC (150 or 300 mg/kg/day) inhibited aortic inflammation in hyperlipidemic apolipoprotein E-deficient mice, as shown by in vivo imaging. Immunohistochemistry and plasma analysis showed that the aortas from these mice exhibited markedly lower leukocyte infiltration, reduced plaque formation, and lower concentrations of blood inflammatory cytokines than those observed in the control mice. The results suggest that the consumption of anthocyanin-rich red Chinese cabbage is closely correlated with lowering the risk of vascular inflammatory diseases. Full article
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13 pages, 3059 KiB  
Article
Scandoside Exerts Anti-Inflammatory Effect Via Suppressing NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages
by Jingyu He, Jiafeng Li, Han Liu, Zichao Yang, Fenghua Zhou, Ting Wei, Yaqian Dong, Hongjiao Xue, Lan Tang and Menghua Liu
Int. J. Mol. Sci. 2018, 19(2), 457; https://doi.org/10.3390/ijms19020457 - 3 Feb 2018
Cited by 43 | Viewed by 6764
Abstract
The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory [...] Read more.
The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 messenger RNA (mRNA) expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development. Full article
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19 pages, 2609 KiB  
Article
B Type and Complex A/B Type Epicatechin Trimers Isolated from Litchi pericarp Aqueous Extract Show High Antioxidant and Anticancer Activity
by Yihui Gong, Fang Fang, Xin Zhang, Bin Liu, Honghui Luo, Zhen Li, Xuelian Zhang, Zhaoqi Zhang and Xuequn Pang
Int. J. Mol. Sci. 2018, 19(1), 301; https://doi.org/10.3390/ijms19010301 - 19 Jan 2018
Cited by 35 | Viewed by 6151
Abstract
Litchi (Litchi chinensis Sonn.) fruit is known for its rich source of phenolics. Litchi pericarp contains high levels of epicatechin that may form oligomers of various lengths. Except for several A or B type epicatechin dimers, other soluble oligomers have rarely been [...] Read more.
Litchi (Litchi chinensis Sonn.) fruit is known for its rich source of phenolics. Litchi pericarp contains high levels of epicatechin that may form oligomers of various lengths. Except for several A or B type epicatechin dimers, other soluble oligomers have rarely been identified in the pericarp. Here, bioassay-guided column fractionation was applied to isolate bioactive phenolics from aqueous pericarp extract. A fraction (S3) was obtained by two rounds of Sephadex LH-20 column chromatography, and showed higher antioxidant activity and inhibition on the proliferation of human lung cancer cells (A549) than Litchi anthocyanins. S3 was further separated to isolate fractions P1–P4, which all showed higher antioxidant activity than vitamin C. P3 showed 32.9% inhibition on A549 cells at 30 μg/mL, higher than other fractions and cis-Dichlorodiamineplatinum (DDP, 0.5 μg/mL), but not as high as the combination of the four fractions. Using HPLC-Q-TOF-MS/MS, one B-type and complex A/B type epicatechin trimers were identified in P3; another B-type and two A/B-type trimers were identified in P4. P1 and P2, containing epicatechin and proanthocyanidin B2, respectively, showed no cell inhibition at 30 μg/mL. It is the first time that the two B type trimers of epicatechins (Litchitannin B1 and B2), have been found in Litchi species. The identified proanthocyanidins were detected in the pericarp of the young fruit, and the levels of the compounds decreased as the fruit developed, correlating to the decreasing patterns of the expression of LcLAR and LcANR, two key genes in the catechin biosynthesis pathway. Full article
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12 pages, 2319 KiB  
Article
Aeginetia indica Decoction Inhibits Hepatitis C Virus Life Cycle
by Cheng-Wei Lin, Chieh-Wen Lo, Chia-Ni Tsai, Ting-Chun Pan, Pin-Yin Chen and Ming-Jiun Yu
Int. J. Mol. Sci. 2018, 19(1), 208; https://doi.org/10.3390/ijms19010208 - 9 Jan 2018
Cited by 9 | Viewed by 5853
Abstract
Chronic hepatitis C virus (HCV) infection is still a global epidemic despite the introduction of several highly effective direct-acting antivirals that are tagged with sky-high prices. The present study aimed to identify an herbal decoction that ameliorates HCV infection. Among six herbal decoctions [...] Read more.
Chronic hepatitis C virus (HCV) infection is still a global epidemic despite the introduction of several highly effective direct-acting antivirals that are tagged with sky-high prices. The present study aimed to identify an herbal decoction that ameliorates HCV infection. Among six herbal decoctions tested, the Aeginetia indica decoction had the most profound effect on the HCV reporter activity in infected Huh7.5.1 liver cells in a dose- and time-dependent manner. The Aeginetia indica decoction exerted multiple inhibitory effects on the HCV life cycle. Pretreatment of the cells with the Aeginetia indica decoction prior to HCV infection reduced the HCV RNA and non-structural protein 3 (NS3) protein levels in the infected cells. The Aeginetia indica decoction reduced HCV internal ribosome entry site-mediated protein translation activity. It also reduced the HCV RNA level in the infected cells in association with reduced NS5A phosphorylation at serine 235, a predominant phosphorylation event indispensable to HCV replication. Thus, the Aeginetia indica decoction inhibits HCV infection, translation, and replication. Mechanistically, the Aeginetia indica decoction probably reduced HCV replication via reducing NS5A phosphorylation at serine 235. Full article
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14 pages, 2081 KiB  
Article
Skin Protective Effect of Epigallocatechin Gallate
by Eunji Kim, Kyeonghwan Hwang, Jongsung Lee, Sang Yun Han, Eun-Mi Kim, Junseong Park and Jae Youl Cho
Int. J. Mol. Sci. 2018, 19(1), 173; https://doi.org/10.3390/ijms19010173 - 6 Jan 2018
Cited by 118 | Viewed by 19282
Abstract
Epigallocatechin gallate (EGCG) is a catechin and an abundant polyphenol in green tea. Although several papers have evaluated EGCG as a cosmetic constituent, the skin hydration effect of EGCG is poorly understood. We aimed to investigate the mechanism by which EGCG promotes skin [...] Read more.
Epigallocatechin gallate (EGCG) is a catechin and an abundant polyphenol in green tea. Although several papers have evaluated EGCG as a cosmetic constituent, the skin hydration effect of EGCG is poorly understood. We aimed to investigate the mechanism by which EGCG promotes skin hydration by measuring hyaluronic acid synthase (HAS) and hyaluronidase (HYAL) gene expression and antioxidant and anti-pigmentation properties using cell proliferation assay, Western blotting analysis, luciferase assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and reverse transcription polymerase chain reaction (RT-PCR) analysis. RT-PCR showed that EGCG increased the expression of natural moisturizing factor-related genes filaggrin (FLG), transglutaminase-1, HAS-1, and HAS-2. Under UVB irradiation conditions, the expression level of HYAL was decreased in HaCaT cells. Furthermore, we confirmed the antioxidant activity of EGCG and also showed a preventive effect against radical-evoked apoptosis by downregulation of caspase-8 and -3 in HaCaT cells. EGCG reduced melanin secretion and production in melanoma cells. Together, these results suggest that EGCG might be used as a cosmetic ingredient with positive effects on skin hydration, moisture retention, and wrinkle formation, in addition to radical scavenging activity and reduction of melanin generation. Full article
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13 pages, 6161 KiB  
Article
Allyl Isothiocyanate Exhibits No Anticancer Activity in MDA-MB-231 Breast Cancer Cells
by Md. Abu Sayeed, Massimo Bracci, Veronica Ciarapica, Marco Malavolta, Mauro Provinciali, Ernesta Pieragostini, Simona Gaetani, Federica Monaco, Guendalina Lucarini, Venerando Rapisarda, Roberto Di Primio and Lory Santarelli
Int. J. Mol. Sci. 2018, 19(1), 145; https://doi.org/10.3390/ijms19010145 - 4 Jan 2018
Cited by 12 | Viewed by 5662
Abstract
It was reported recently that allyl isothiocyanate (AITC) could inhibit various types of cancer cell growth. In the present study, we further investigated whether AITC could inhibit the growth of human breast cancer cells. Unexpectedly, we found that AITC did not inhibit, rather [...] Read more.
It was reported recently that allyl isothiocyanate (AITC) could inhibit various types of cancer cell growth. In the present study, we further investigated whether AITC could inhibit the growth of human breast cancer cells. Unexpectedly, we found that AITC did not inhibit, rather slightly promoted, the proliferation of MDA-MB-231 breast cancer cells, although it did have inhibitory effect on MCF-7 breast cancer cells. Cytofluorimetric analysis revealed that AITC (10 µM) did not induce apoptosis and cell cycle arrest in MDA-MB-231 cells. In addition, AITC significantly (p < 0.05) increased the expression of BCL-2 and mTOR genes and Beclin-1 protein in MDA-MB-231 cells. No significant changes in expression of PRKAA1 and PER2 genes, Caspase-8, Caspase-9, PARP, p-mTOR, and NF-κB p65 proteins were observed in these AITC-treated cells. Importantly, AITC displayed cytotoxic effect on MCF-10A human breast epithelial cell line. These observations suggest that AITC may not have inhibitory activity in MDA-MB-231 breast cancer cells. This in vitro study warrants more preclinical and clinical studies on the beneficial and harmful effects of AITC in healthy and cancer cells. Full article
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943 KiB  
Article
Influence of Botanical Origin and Chemical Composition on the Protective Effect against Oxidative Damage and the Capacity to Reduce In Vitro Bacterial Biofilms of Monofloral Honeys from the Andean Region of Ecuador
by Marilyn García-Tenesaca, Eillen S. Navarrete, Gabriel A. Iturralde, Irina M. Villacrés Granda, Eduardo Tejera, Pablo Beltrán-Ayala, Francesca Giampieri, Maurizio Battino and José M. Alvarez-Suarez
Int. J. Mol. Sci. 2018, 19(1), 45; https://doi.org/10.3390/ijms19010045 - 23 Dec 2017
Cited by 31 | Viewed by 6033
Abstract
Three types of monofloral honey from the Andean regions of Ecuador (Avocado, Eucalyptus, and Rapeseed honey) were analyzed to determine their floral origin, physicochemical parameters, chemical composition, antioxidant capacity, and their capacity to reduce in vitro bacterial biofilms. The chemical composition varied considerably [...] Read more.
Three types of monofloral honey from the Andean regions of Ecuador (Avocado, Eucalyptus, and Rapeseed honey) were analyzed to determine their floral origin, physicochemical parameters, chemical composition, antioxidant capacity, and their capacity to reduce in vitro bacterial biofilms. The chemical composition varied considerably depending on floral origin. The highest values of bioactive compounds were found in Avocado honey, classified as dark amber in color, while the lowest values were found in Eucalyptus honey followed by Rapeseed honey, both classified as extra light amber. When compared to Eucalyptus and Rapeseed honey, Avocado honey showed a more effective superoxide scavenging activity, chelating metal ions capacity, and a higher ability to protect human erythrocyte membranes against lipid peroxidation. For antimicrobial activity, the hydrogen peroxide content and the capacity to inhibit the biofilm formation, and to remove preformed biofilm from Staphylococcus aureus and Klebsiella pneumoniae was determined. Avocado honey showed the highest values of hydrogen peroxide content, as well as the highest capacity to reduce in vitro bacterial biofilms. A correlation between color vs. phenolics content vs. superoxide scavenging activity vs. chelating metal ions capacity, and the capacity to protect human erythrocyte membranes against lipid peroxidation was found. Full article
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3525 KiB  
Article
Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2, and Cytokine Production of Mouse and Human Macrophages Are Suppressed by Pheophytin-b
by Chun-Yu Lin, Wen-Hung Wang, Shin-Huei Chen, Yu-Wei Chang, Ling-Chien Hung, Chung-Yi Chen and Yen-Hsu Chen
Int. J. Mol. Sci. 2017, 18(12), 2637; https://doi.org/10.3390/ijms18122637 - 6 Dec 2017
Cited by 42 | Viewed by 11536
Abstract
Sepsis is an overwhelming systemic response to infection that frequently results in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine overproduction are thought to be associated with the immunostimulatory cascade in sepsis. In the present study, [...] Read more.
Sepsis is an overwhelming systemic response to infection that frequently results in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine overproduction are thought to be associated with the immunostimulatory cascade in sepsis. In the present study, we analyzed the anti-inflammatory efficacy of the pheophytin-b on both RAW 264.7 murine macrophage and purified human CD14+ monocytes stimulated with lipopolysaccharide (LPS) and elucidated the mechanisms by analyzing the cell signaling pathways known to be activated in sepsis. Pheophytin-b suppressed the overexpression of NO, PGE2, and cytokines in LPS-stimulated macrophages without inducing cytotoxicity. It also reduced NOS2 and COX-2 mRNA and protein levels. The inhibitory effects on NO, PGE2, and cytokine overproduction arose from the suppression of STAT-1 and PI3K/Akt pathways; no changes in NF-κB, MAPK, and AP-1 signaling were detected. Thus, pheophytin-b may represent a potential candidate to beneficially modulate the inflammatory response in sepsis. Full article
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Article
Coumestrol Epigenetically Suppresses Cancer Cell Proliferation: Coumestrol Is a Natural Haspin Kinase Inhibitor
by Jong-Eun Kim, Sung-Young Lee, Mi Jang, Hyo-Kyung Choi, Jong Hun Kim, Hanyong Chen, Tae-Gyu Lim, Zigang Dong and Ki Won Lee
Int. J. Mol. Sci. 2017, 18(10), 2228; https://doi.org/10.3390/ijms18102228 - 24 Oct 2017
Cited by 30 | Viewed by 6242
Abstract
Targeting epigenetic changes in gene expression in cancer cells may offer new strategies for the development of selective cancer therapies. In the present study, we investigated coumestrol, a natural compound exhibiting broad anti-cancer effects against skin melanoma, lung cancer and colon cancer cell [...] Read more.
Targeting epigenetic changes in gene expression in cancer cells may offer new strategies for the development of selective cancer therapies. In the present study, we investigated coumestrol, a natural compound exhibiting broad anti-cancer effects against skin melanoma, lung cancer and colon cancer cell growth. Haspin kinase was identified as a direct target protein of coumestrol using kinase profiling analysis. Histone H3 is a direct substrate of haspin kinase. We observed haspin kinase overexpression as well as greater phosphorylation of histone H3 at threonine 3 (Thr-3) in the cancer cells compared to normal cells. Computer modeling using the Schrödinger Suite program identified the binding interface within the ATP binding site. These findings suggest that the anti-cancer effect of coumestrol is due to the direct targeting of haspin kinase. Coumestrol has considerable potential for further development as a novel anti-cancer agent. Full article
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1993 KiB  
Article
DNA Protecting Activities of Nymphaea nouchali (Burm. f) Flower Extract Attenuate t-BHP-Induced Oxidative Stress Cell Death through Nrf2-Mediated Induction of Heme Oxygenase-1 Expression by Activating MAP-Kinases
by Md Badrul Alam, Mi-Kyoung Ju and Sang-Han Lee
Int. J. Mol. Sci. 2017, 18(10), 2069; https://doi.org/10.3390/ijms18102069 - 28 Sep 2017
Cited by 35 | Viewed by 6460
Abstract
This study was performed to investigate the antioxidant activities of Nymphaea nouchali flower (NNF) extract and the underlying mechanism using RAW 264.7 cells. The presence of gallic acid, catechin, epicatechin, epigallocatechin, epicatechin gallate, caffeic acid, quercetin, and apigenin in the NNF was confirmed [...] Read more.
This study was performed to investigate the antioxidant activities of Nymphaea nouchali flower (NNF) extract and the underlying mechanism using RAW 264.7 cells. The presence of gallic acid, catechin, epicatechin, epigallocatechin, epicatechin gallate, caffeic acid, quercetin, and apigenin in the NNF was confirmed by high-performance liquid chromatography (HPLC). The extract had a very potent capacity to scavenge numerous free radicals. NNF extract was also able to prevent DNA damage and quench cellular reactive oxygen species (ROS) generation induced by tert-Butyl hydroperoxide (t-BHP) with no signs of toxicity. The NNF extract was able to augment the expression of both primary and phase II detoxifying enzyme, resulting in combat the oxidative stress. This is accomplished by phosphorylation of mitogen-activated protein kinase (MAP kinase) (p38 kinase and extracellular signal-regulated kinase (ERK)) followed by enhancing the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2). This attenuates cellular ROS generation and confers protection from cell death. Altogether, the results of current study revealed that Nymphaea nouchali flower could be a source of natural phytochemicals that could lead to the development of new therapeutic agents for preventing oxidative stress associated diseases and attenuating disease progression. Full article
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1951 KiB  
Article
Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin
by Seung-Hyun Choi, Sun-Il Choi, Tae-Dong Jung, Bong-Yeon Cho, Jin-Ha Lee, Seung-Hyung Kim, Seon-A Yoon, Young-Min Ham, Weon-Jong Yoon, Ju-Hyun Cho and Ok-Hawn Lee
Int. J. Mol. Sci. 2017, 18(10), 2052; https://doi.org/10.3390/ijms18102052 - 25 Sep 2017
Cited by 26 | Viewed by 9568
Abstract
Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs [...] Read more.
Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased β-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging. Full article
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Article
Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway
by Cheng-Chen Zhang, Chen-Yu Cao, Miwa Kubo, Kenichi Harada, Xi-Tao Yan, Yoshiyasu Fukuyama and Jin-Ming Gao
Int. J. Mol. Sci. 2017, 18(8), 1659; https://doi.org/10.3390/ijms18081659 - 30 Jul 2017
Cited by 54 | Viewed by 11005
Abstract
Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms [...] Read more.
Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6) and one new natural product (2) together with five known compounds (1,35,7) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1) and a cyathane diterpenoid, erincine A (3), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells. Full article
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Article
Dose-Dependent Responses of I3C and DIM on T-Cell Activation in the Human T Lymphocyte Jurkat Cell Line
by Man Liu, Rumana Yasmeen, Naomi K. Fukagawa, Liangli Yu, Young S. Kim and Thomas T. Y. Wang
Int. J. Mol. Sci. 2017, 18(7), 1409; https://doi.org/10.3390/ijms18071409 - 1 Jul 2017
Cited by 7 | Viewed by 9141
Abstract
Indole-3-carbinol (I3C) and its dimer diindolylmethane (DIM) are bioactive metabolites of a glucosinolate, glucobrassicin, found in cruciferous vegetables. Both I3C and DIM have been reported to possess pro-apoptotic, anti-proliferative and anti-carcinogenic properties via modulation of immune pathways. However, results from these studies remain [...] Read more.
Indole-3-carbinol (I3C) and its dimer diindolylmethane (DIM) are bioactive metabolites of a glucosinolate, glucobrassicin, found in cruciferous vegetables. Both I3C and DIM have been reported to possess pro-apoptotic, anti-proliferative and anti-carcinogenic properties via modulation of immune pathways. However, results from these studies remain inconclusive since they lack thorough evaluation of these bioactives’ physiological versus pharmacological effects. In the present study, we investigated I3C and DIM’s dose-dependent effects on cytokines production in human T lymphocytes Jurkat cell line (Clone E6-1). The results showed that I3C and DIM pretreatment, at higher concentrations of 50 and 10 μM, respectively, significantly increased PMA/ionomycin-induced interleukin-2 (IL-2), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) production, measured by real time polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). As a plausible mechanism underlying such pronounced cytokine release, we found robust increase in downstream nuclear factor κB (NF-κB) and nuclear factor of activated T-cells 1 (NFAT1) signaling with I3C pretreatment, whereas DIM pretreatment only significantly induced NF-κB activation, but not NFAT1. We hypothesize that I3C/DIM pretreatment primes the T cells to become hyperresponsive upon PMA/ionomycin stimulation which in turn differentially induces two major downstream Ca2+-dependent inflammatory pathways, NF-κB and NFAT1. Our data show novel insights into the mechanisms underlying induction of pro-inflammatory cytokine release by pharmacological concentrations of I3C and DIM, an effect negligible under physiological conditions. Full article
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1933 KiB  
Article
5-(3′,4′-Dihydroxyphenyl-γ-valerolactone), a Major Microbial Metabolite of Proanthocyanidin, Attenuates THP-1 Monocyte-Endothelial Adhesion
by Charles C. Lee, Jong Hun Kim, Ji Seung Kim, Yun Sil Oh, Seung Min Han, Jung Han Yoon Park, Ki Won Lee and Chang Yong Lee
Int. J. Mol. Sci. 2017, 18(7), 1363; https://doi.org/10.3390/ijms18071363 - 26 Jun 2017
Cited by 61 | Viewed by 7877
Abstract
Several metabolomics of polymeric flavan-3-ols have reported that proanthocyanidins are extensively metabolized by gut microbiota. 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (DHPV) has been reported to be the major microbial metabolite of proanthocyanidins. We demonstrated that DHPV has stronger prevention effect on tumor necrosis factor (TNF)-α-stimulated adhesion of [...] Read more.
Several metabolomics of polymeric flavan-3-ols have reported that proanthocyanidins are extensively metabolized by gut microbiota. 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (DHPV) has been reported to be the major microbial metabolite of proanthocyanidins. We demonstrated that DHPV has stronger prevention effect on tumor necrosis factor (TNF)-α-stimulated adhesion of THP-1 human monocytic cells to human umbilical vein endothelial cells compared to its potential precursors such as procyanidin A1, A2, B1 and B2, (+)catechin, (−)epicatechin and its microbial metabolites such as 3-(3,4-dihydroxyphenyl)propionic acid and 2-(3,4-dihydroxyphenyl)acetic acid. Mechanism study showed that DHPV prevents THP-1 monocyte-endothelial cell adhesion by downregulating TNF-α-stimulated expressions of the two biomarkers of atherosclerosis such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1, activation of nuclear factor kappa B transcription and phosphorylation of I kappa-B kinase and IκBα. We suggested that DHPV has higher potentiality in prevention of atherosclerosis among the proanthocyanidin metabolites. Full article
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1898 KiB  
Article
Effect of Light- and Dark-Germination on the Phenolic Biosynthesis, Phytochemical Profiles, and Antioxidant Activities in Sweet Corn (Zea mays L.) Sprouts
by Nan Xiang, Xinbo Guo, Fengyuan Liu, Quan Li, Jianguang Hu and Charles Stephen Brennan
Int. J. Mol. Sci. 2017, 18(6), 1246; https://doi.org/10.3390/ijms18061246 - 10 Jun 2017
Cited by 48 | Viewed by 6941
Abstract
Sweet corn is one of the most widely planted crops in China. Sprouting of grains is a new processes to increase the nutritional value of grain products. The present study explores the effects of light on the nutritional quality of sweet corn sprouts. [...] Read more.
Sweet corn is one of the most widely planted crops in China. Sprouting of grains is a new processes to increase the nutritional value of grain products. The present study explores the effects of light on the nutritional quality of sweet corn sprouts. Gene expression of phenolic biosynthesis, phytochemical profiles and antioxidant activity were studied. Two treatments (light and dark) were selected and the morphological structure of sweet corn sprouts, as well as their biochemical composition were investigated to determine the effects of light on the regulation of genes responsible for nutritional compounds. Transcription analyses for three key-encoding genes in the biosynthesis of the precursors of phenolic were studied. Results revealed a negative regulation in the expression of ZmPAL with total phenolic content (TPC) in the light group. TPC and total flavonoid content (TFC) increased during germination and this was correlated with an increase in antioxidant activity (r = 0.95 and 1.0). The findings illustrate that the nutritional value of sweet corn for the consumer can be improved through germination to the euphylla stage. Full article
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5062 KiB  
Article
Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades
by Hanwool Lee, Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seok-Geun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Woong Mo Yang, Jae-Young Um, Gautam Sethi and Kwang Seok Ahn
Int. J. Mol. Sci. 2017, 18(5), 1095; https://doi.org/10.3390/ijms18051095 - 19 May 2017
Cited by 46 | Viewed by 6949
Abstract
Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of [...] Read more.
Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells. Full article
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7771 KiB  
Article
Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression
by Mustafa S. Atta, Essam A. Almadaly, Ali H. El-Far, Rasha M. Saleh, Doaa H. Assar, Soad K. Al Jaouni and Shaker A. Mousa
Int. J. Mol. Sci. 2017, 18(5), 919; https://doi.org/10.3390/ijms18050919 - 27 Apr 2017
Cited by 90 | Viewed by 8236
Abstract
Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60) [...] Read more.
Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats. Full article
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Review

Jump to: Editorial, Research

26 pages, 7511 KiB  
Review
Physiologically Active Molecules and Functional Properties of Soybeans in Human Health—A Current Perspective
by Il-Sup Kim, Cheorl-Ho Kim and Woong-Suk Yang
Int. J. Mol. Sci. 2021, 22(8), 4054; https://doi.org/10.3390/ijms22084054 - 14 Apr 2021
Cited by 68 | Viewed by 10589
Abstract
In addition to providing nutrients, food can help prevent and treat certain diseases. In particular, research on soy products has increased dramatically following their emergence as functional foods capable of improving blood circulation and intestinal regulation. In addition to their nutritional value, soybeans [...] Read more.
In addition to providing nutrients, food can help prevent and treat certain diseases. In particular, research on soy products has increased dramatically following their emergence as functional foods capable of improving blood circulation and intestinal regulation. In addition to their nutritional value, soybeans contain specific phytochemical substances that promote health and are a source of dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, and phytic acid, while serving as a trypsin inhibitor. These individual substances have demonstrated effectiveness in preventing chronic diseases, such as arteriosclerosis, cardiac diseases, diabetes, and senile dementia, as well as in treating cancer and suppressing osteoporosis. Furthermore, soybean can affect fibrinolytic activity, control blood pressure, and improve lipid metabolism, while eliciting antimutagenic, anticarcinogenic, and antibacterial effects. In this review, rather than to improve on the established studies on the reported nutritional qualities of soybeans, we intend to examine the physiological activities of soybeans that have recently been studied and confirm their potential as a high-functional, well-being food. Full article
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11 pages, 218 KiB  
Review
Could Aspirin and Diets High in Fiber Act Synergistically to Reduce the Risk of Colon Cancer in Humans?
by Pan Pan, Yi-Wen Huang, Kiyoko Oshima, Martha Yearsley, Jianying Zhang, Jianhua Yu, Mark Arnold and Li-Shu Wang
Int. J. Mol. Sci. 2018, 19(1), 166; https://doi.org/10.3390/ijms19010166 - 6 Jan 2018
Cited by 19 | Viewed by 6785
Abstract
Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The [...] Read more.
Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin’s principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose–response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on ‘more is better’. Solutions include: (1) using special delivery systems (e.g., nanoparticles) to retain phytochemicals; (2) developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3) selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals. Full article
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