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Nutraceuticals and Botanicals: Bioactive Molecules and Therapeutic Properties for Human Health

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 March 2017) | Viewed by 69003

Special Issue Editor


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Guest Editor
1. Department of Agriculture, Forestry and Food Science, University of Torino, Largo Braccini 2, 10095 Grugliasco, Italy
2. Chestnut R&D Center—Piemonte, Regione Gambarello 23, 12013 Chiusa di Pesio, Italy
Interests: tree crops; chestnut cultivation; secondary metabolites; quality assessment; nutraceutical properties; sustainability
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nutraceuticals and botanicals are biologically active phytochemicals that possess health benefits. These may be delivered to the consumer as natural medicines, herbal preparations, and functional foods. These products are likely to play a vital role in human health and longevity. The consumption of these products by the most of the people is usually without a medical prescription and/or supervision: increasing use of these products has also led to concerns about their actual safety. Not only do consumers increasingly take charge of their health, but the scientific information and understanding of the beneficial health effects of bioactive substances have improved. In recent years, the industry has suffered a setback in its growth, due to certain instances of quality failures and/or adverse health effects. This situation has created an urgency for increased regulatory oversight and for monitoring the products at different stages of manufacturing for quality, safety, and integrity. Recent improvements in the identification, characterization, and standardization of raw materials, coupled with screening by human cell line and gene expression-directed fractionation, are expected to improve the development of new nutraceuticals and drugs. These will afford an important benefit to the rapidly emerging alternative, complementary, and integrated healthcare practices. It is also hoped that the nutraceutical/herbal industries and regulatory agencies will work together to prevent the ultimate cost of new drug development from becoming prohibitive.

The proposed topics include, but are not limited to:

  • biomarkers and medical properties;
  • nutraceuticals and new functional foods;
  • herbal preparations and natural medicines;
  • botanicals and medicinal plants;
  • antioxidants and healthy-properties;
  • benefits, adverse effects and drug interactions of herbal medicines;
  • quality control and regulatory guidelines;
  • marketing and economic evaluation;
  • bioactive substances and phytocomplexes;
  • analytical strategies for bioactive compound identification and quantification;
  • in vivo and in vitro bioactivity of botanicals.

Dr. Dario Donno
Guest Editor

Manuscript Submission Information

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Published Papers (5 papers)

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Research

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933 KiB  
Article
Green Extraction from Pomegranate Marcs for the Production of Functional Foods and Cosmetics
by Raffaella Boggia, Federica Turrini, Carla Villa, Chiara Lacapra, Paola Zunin and Brunella Parodi
Pharmaceuticals 2016, 9(4), 63; https://doi.org/10.3390/ph9040063 - 18 Oct 2016
Cited by 49 | Viewed by 7981
Abstract
The aim of this study was to investigate the potential of retrieving polyphenolic antioxidants directly from wet pomegranate marcs: the fresh by-products obtained after pomegranate juice processing. These by-products mainly consist of internal membranes (endocarp) and aril residues. Even if they are still [...] Read more.
The aim of this study was to investigate the potential of retrieving polyphenolic antioxidants directly from wet pomegranate marcs: the fresh by-products obtained after pomegranate juice processing. These by-products mainly consist of internal membranes (endocarp) and aril residues. Even if they are still edible, they are usually discharged during juice production and, thus, they represent a great challenge in an eco-sustainable industrial context. Green technologies, such as ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), have been employed to convert these organic residues into recycled products with high added value. UAE and MAE were used both in parallel and in series in order to make a comparison and to ensure exhaustive extractions, respectively. Water, as an environmentally friendly extraction solvent, has been employed. The results were compared with those ones coming from a conventional extraction. The most promising extract, in terms of total polyphenol yield and radical scavenging activity, has been tested both as a potential natural additive and as a functional ingredient after its incorporation in a real food model and in a real cosmetic matrix, respectively. This study represents a proposal to the agro-alimentary sector given the general need of environmental “responsible care”. Full article
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Graphical abstract

Graphical abstract
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<p>Total color difference (ΔE) to evaluate the anti-browning potential of the solutions. * Solution with the same concentration in terms of GAE.</p>
Full article ">Scheme 1
<p>The different extraction techniques used in parallel, the process conditions, the corresponding extracts’ names, and properties are reported, respectively.</p>
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<p>UAE and MAE used in series, the process conditions, the corresponding extracts’ names, and properties are reported, respectively.</p>
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1693 KiB  
Article
Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study
by Carla Gonzales-Arimborgo, Irma Yupanqui, Elsa Montero, Dulce E. Alarcón-Yaquetto, Alisson Zevallos-Concha, Lidia Caballero, Manuel Gasco, Jianping Zhao, Ikhlas A. Khan and Gustavo F. Gonzales
Pharmaceuticals 2016, 9(3), 49; https://doi.org/10.3390/ph9030049 - 18 Aug 2016
Cited by 46 | Viewed by 20137
Abstract
The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration [...] Read more.
The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration of spray-dried extracts of black or red maca (Lepidium meyenii) in adult human subjects living at low (LA) and high altitude (HA). A total of 175 participants were given 3 g of either placebo, black, or red maca extract daily for 12 weeks. Primary outcomes were changes in sexual desire, mood, energy, health-related quality of life score (HRQL), and chronic mountain sickness (CMS) score, or in glycaemia, blood pressure, and hemoglobin levels. Secondary outcomes were acceptability and safety, assessed using the Likert test and side effect self-recording, respectively, and the effect of altitude. At low altitude, 32, 30, and 32 participants started the study receiving placebo, red maca, or black maca, respectively. At high altitudes, 33, 35, and 31 participants started the study receiving placebo, red maca, and black maca, respectively. Consumption of spray-dried extracts of red and black maca resulted in improvement in mood, energy, and health status, and reduced CMS score. Fatty acids and macamides were higher in spray-dried extracts of black maca than in red maca. GABA predominated in spray-dried extracts of red maca. Effects on mood, energy, and CMS score were better with red maca. Black maca and, in smaller proportions, red maca reduced hemoglobin levels only in highlanders with abnormally high hemoglobin levels; neither variety of maca reduced hemoglobin levels in lowlanders. Black maca reduced blood glucose levels. Both varieties produced similar responses in mood, and HRQL score. Maca extracts consumed at LA or HA had good acceptability and did not show serious adverse effects. In conclusion, maca extract consumption relative to the placebo improved quality of life parameters. Differences in the level of improvement between red and black maca are probably due to differences in the composition of these two plant varieties. Both maca extracts were well tolerated and safe. Full article
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Figure 1

Figure 1
<p>Percentage of subjects perceiving an increase in sexual desire following a 12-week treatment with the placebo or a spray-dried extract of red or black maca at low (<b>Upper</b>) and high altitudes (<b>Bottom</b>). Bars are standard error. At LA, consumption of spray-dried extract of red maca increases the percentage of subjects with increased sexual desire over time (<span class="html-italic">p</span> = 0.0055). <span class="html-italic">p</span> &gt; 0.05 between placebo and maca-treated groups. HA: <span class="html-italic">p</span> = 0.0027, <span class="html-italic">p</span> = 0.0000, and <span class="html-italic">p</span> = 0.0019 over time for treatments with placebo, red maca, and black maca, respectively. <span class="html-italic">p</span> = 0.03 (chi square = 6.96) at week 12 between treatment with spray-dried extract of red maca and placebo or spray-dried extract of black maca.</p>
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<p>Percentage of subjects perceiving an increase in mood after treatment for 12 weeks with a placebo, spray-dried extract of red maca, and spray-dried extract of black maca. Percentage of subjects with a score for mood of 4–5 (in agreement or completely in agreement that consumption of the product increased their mood) at (<b>Upper</b>) low and (<b>Bottom</b>) high altitude. LA: <span class="html-italic">p</span> = 0.01; 0.01; 0.029; 0.0026 using chi square test at weeks 3, 4, 8, and 12 comparing treatment with placebo, spray-dried extract of red maca, and spray-dried extract of black maca. Placebo: <span class="html-italic">p</span> &gt; 0.05 over time (weeks 1 to 12); red maca <span class="html-italic">p</span> = 0.0001 over time; black maca <span class="html-italic">p</span> &gt; 0.05 over time (weeks 1 to 12). HA: <span class="html-italic">p</span> = 0.019; 0.04; and 0.05 using chi square test at weeks 1,2, and 12 comparing treatment with placebo, spray-dried extract of red maca and spray-dried extract of black maca. Placebo: <span class="html-italic">p</span> = 0.0001; red maca: <span class="html-italic">p</span> = 0.003; black maca: <span class="html-italic">p</span> = 0.0002 over time.</p>
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<p>Percentage of subjects perceiving an increase in energy after treatment for 12 weeks with a placebo, red maca, or black maca at low (<b>Upper</b>) and high (<b>Bottom</b>) altitude. LA: <span class="html-italic">p</span> = 0.07; 0.02; 0.01; 0.003; 0.001 and &lt;0.00001 using chi square test at weeks 1, 2, 3, 4, 8, and 12 comparing treatment with placebo, red maca, or black maca. Placebo group: <span class="html-italic">p</span> &gt; 0.05 over time (weeks 1 to 12); red maca group: <span class="html-italic">p</span> = 0.0001 over time (weeks 1 to 12); black maca group: <span class="html-italic">p</span> &gt; 0.05 over time (weeks 1 to 12). HA: <span class="html-italic">p</span> &gt; 0.05 between placebo group and groups with red or black maca (chi square test at weeks 1, 2, 3, 4, 8 and 12). Placebo: <span class="html-italic">p</span> = 0.0001; red maca: <span class="html-italic">p</span> = 0.0001; black maca: <span class="html-italic">p</span> = 0.0001 over time (weeks 1 to 12).</p>
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<p>Heath-Related Quality of Life Score (HRQL) in subjects receiving a 12-week treatment of a placebo, spray-dried extract of red maca, or spray-dried extract of black maca at low (<b>Upper</b>) or high altitude (<b>Bottom</b>). Data are mean ± standard error of the mean. <b>Upper</b>: LA: Placebo group: <span class="html-italic">p</span> &gt; 0.05 with respect to time 0. Red maca group: <span class="html-italic">p</span> &lt; 0.05 at week 8 and <span class="html-italic">p</span> &lt; 0.01 at week 12 with respect to time 0 (one tail). Black maca group: <span class="html-italic">p</span> &lt; 0.05 at week 4 with respect to time 0 and <span class="html-italic">p</span> &lt; 0.01 at weeks 8 and 12 (one tail). <span class="html-italic">p</span> &lt; 0.05 comparing red maca group with placebo group at eight and 12 weeks of treatment and <span class="html-italic">p</span> &lt; 0.05 at week 4, and <span class="html-italic">p</span> &lt; 0.01 at weeks 8 and 12, comparing the group treated with black maca with the group treated with a placebo; <b>Bottom</b>: HA: placebo group: <span class="html-italic">p</span> &gt; 0.05 with respect to time 0. Red Maca group: <span class="html-italic">p</span> &lt; 0.05 at week 8 and <span class="html-italic">p</span> &lt; 0.01 at week 12 with respect to time 0. Black maca group: <span class="html-italic">p</span> &lt; 0.01 at weeks 8 and 12 with respect to time 0. <span class="html-italic">p</span> &lt; 0.05 black and red maca groups at weeks 8 and 12 with respect to the placebo group.</p>
Full article ">Figure 5
<p>Delta of Qinghai score for Chronic Mountain Sickness (CMS) diagnosis in adult human subjects after a 12-week treatment with spray-dried extract of maca (red or black) or with a placebo at high altitude. Data are mean ± standard error of the mean. Placebo: <span class="html-italic">p</span> &gt; 0.05 over time. Red maca: <span class="html-italic">p</span> &lt; 0.05 at week 4 and <span class="html-italic">p</span> &lt; 0.01 at weeks 8 and 12 with respect to values at time 0. Black maca: <span class="html-italic">p</span> &lt; 0.05 at weeks 8 and 12 with respect to values at time 0. Red maca group: <span class="html-italic">p</span> &lt; 0.05 at weeks 4 and 8 with respect to the placebo and <span class="html-italic">p</span> &lt; 0.01 with respect to the placebo at week 12.</p>
Full article ">Figure 6
<p>Flow diagram following the recruitment, enrollment, and number of subjects that finished treatment of the clinical trial at low altitude (<b>A</b>) and high altitude (<b>B</b>). Low altitude: Chi square: 0.11; <span class="html-italic">p</span> = 0.99 with respect to subjects who failed to complete the follow-up among different groups of treatment. High altitude: Chi square: 0.6; <span class="html-italic">p</span> = 0.99 with respect to subjects who failed to complete the follow-up among different treatment groups.</p>
Full article ">Figure 6 Cont.
<p>Flow diagram following the recruitment, enrollment, and number of subjects that finished treatment of the clinical trial at low altitude (<b>A</b>) and high altitude (<b>B</b>). Low altitude: Chi square: 0.11; <span class="html-italic">p</span> = 0.99 with respect to subjects who failed to complete the follow-up among different groups of treatment. High altitude: Chi square: 0.6; <span class="html-italic">p</span> = 0.99 with respect to subjects who failed to complete the follow-up among different treatment groups.</p>
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2209 KiB  
Article
Nutraceutical Improvement Increases the Protective Activity of Broccoli Sprout Juice in a Human Intestinal Cell Model of Gut Inflammation
by Simonetta Ferruzza, Fausta Natella, Giulia Ranaldi, Chiara Murgia, Carlotta Rossi, Kajetan Trošt, Fulvio Mattivi, Mirella Nardini, Mariateresa Maldini, Anna Maria Giusti, Elisabetta Moneta, Cristina Scaccini, Yula Sambuy, Giorgio Morelli and Simona Baima
Pharmaceuticals 2016, 9(3), 48; https://doi.org/10.3390/ph9030048 - 12 Aug 2016
Cited by 23 | Viewed by 9154
Abstract
Benefits to health from a high consumption of fruits and vegetables are well established and have been attributed to bioactive secondary metabolites present in edible plants. However, the effects of specific health-related phytochemicals within a complex food matrix are difficult to assess. In [...] Read more.
Benefits to health from a high consumption of fruits and vegetables are well established and have been attributed to bioactive secondary metabolites present in edible plants. However, the effects of specific health-related phytochemicals within a complex food matrix are difficult to assess. In an attempt to address this problem, we have used elicitation to improve the nutraceutical content of seedlings of Brassica oleracea grown under controlled conditions. Analysis, by LC-MS, of the glucosinolate, isothiocyanate and phenolic compound content of juices obtained from sprouts indicated that elicitation induces an enrichment of several phenolics, particularly of the anthocyanin fraction. To test the biological activity of basal and enriched juices we took advantage of a recently developed in vitro model of inflamed human intestinal epithelium. Both sprouts’ juices protected intestinal barrier integrity in Caco-2 cells exposed to tumor necrosis factor α under marginal zinc deprivation, with the enriched juice showing higher protection. Multivariate regression analysis indicated that the extent of rescue from stress-induced epithelial dysfunction correlated with the composition in bioactive molecules of the juices and, in particular, with a group of phenolic compounds, including several anthocyanins, quercetin-3-Glc, cryptochlorogenic, neochlorogenic and cinnamic acids. Full article
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Graphical abstract

Graphical abstract
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<p>Assessment of growth conditions on composition and biological activity of broccoli sprouts. Schematic representation of the experimental workflow used to evaluate and compare the composition and the biological activity of juices prepared from broccoli sprouts grown under two different conditions.</p>
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<p>Box plot of LC-MS untargeted metabolomic fingerprinting. Distribution of LC-MS normalized (Z-scores) data from three biological replicates of juice from sprouts grown under two experimental conditions (basal, BJ; enriching, EJ). (<b>A</b>) Negative ion mode (mean values of <span class="html-italic">n</span> = 598 peaks); (<b>B</b>) Positive ion mode (mean values of <span class="html-italic">n</span> = 855 peaks). Center line shows the median; box limits indicate the 25th and 75th percentiles; whiskers extend to the most extreme data point within 1.5 times the interquartile range. *** <span class="html-italic">p</span> &lt; 0.0001 EJ vs. BJ.</p>
Full article ">Figure 3
<p>Broccoli sprout juices protect epithelial barrier integrity of zinc-depleted Caco-2 cells exposed to TNFα. Caco-2 cells differentiated on filters for 21 days were pre-incubated for 14 h with experimental medium containing the indicated amount of broccoli juice in the AP compartment (red bars: EJ; blue bars: BJ; green bar: experimental medium without juice addition, noJ). Cells were then zinc deprived by TPEN incubation and exposed to TNFα for 5 h. As control, a set of filters was pre-incubated with the addition of 250 μL/mL of BJ or EJ for 14 h and then maintained in experimental medium for the whole experiment. TEER values, measured at the end of the experiment, are expressed as means ± SD from three experiments performed in triplicate. Statistical analysis was performed by one-way ANOVA followed by Fischer post hoc test. Different letters above bars indicate significant differences vs. TPEN/TNFα-treated cells without juice pre-treatement (green bar). a: <span class="html-italic">p</span> &lt; 0.0001; b: <span class="html-italic">p</span> &lt; 0.01; c: <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 4
<p>Time course of the protective effects of broccoli sprout juices in TPEN/TNFα treated Caco-2 cells. Caco-2 cells differentiated on filters for 21 days were pre-incubated for 14 h in experimental medium with BJ (green triangles), EJ (purple circles) or without juice (red squares) addition in the AP compartment. Cells were zinc deprived by TPEN incubation and exposed to TNFα except untreated control cells (blue diamonds) that were maintained in experimental medium throughout the experiment. TEER was monitored in the last 5 h of the experiment during TNFα treatment. Data are the mean ± SD from three experiments performed in triplicate. One-way ANOVA was performed on mean-centered data followed by Fischer post hoc test. Different letters above bars indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) among treatments.</p>
Full article ">Figure 5
<p>Juices from independendent sprouts growths show similar effects in TPEN/TNFα treated Caco-2 cells. Caco-2 cells differentiated on filters for 21 days were pre-incubated for 14 h in experimental medium with BJ (full bars) or EJ (striped bars) obtained from three indipendent sprouts growths (green, blue and orange bars) or without juice (red bar) addition in the AP compartment. Cells were then zinc deprived by TPEN incubation and exposed to TNFα. TEER values were measured after 5 h of TNFα treatment. Statistical analysis was performed by one-way ANOVA followed by Fischer post hoc test. Different letters above bars indicate significant differences (<span class="html-italic">p</span> &lt; 0.01) among treatments.</p>
Full article ">Figure 6
<p>TPEN/TNFα-treated Caco-2 cell protection is correlated to phytochemical enrichment of broccoli sprout juice. Partial least square (PLS) regression analysis was used to predict the biological effect exerted on Caco-2 intestinal cells exposed to TPEN/TNFα from composition data (see <a href="#pharmaceuticals-09-00048-t001" class="html-table">Table 1</a>) of six juice samples corresponding to three independent replicates of sprouts grown under two different conditions. (<b>A</b>) Scores plot showing the distribution of juice samples: BJ-1 to 3, juices from sprouts grown in basal conditions; EJ-1 to 3, juices from sprouts grown in enriching conditions; (<b>B</b>) Loadings plot showing the correlation between phytochemical descriptors (X-variables) and biological effect (Y-variable). The secondary metabolites that significantly affect response prediction are circled.</p>
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Review

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203 KiB  
Review
Herbal Products in Italy: The Thin Line between Phytotherapy, Nutrition and Parapharmaceuticals; A Normative Overview of the Fastest Growing Market in Europe
by Marco Biagi, Rita Pecorari, Giovanni Appendino, Elisabetta Miraldi, Anna Rosa Magnano, Paolo Governa, Giulia Cettolin and Daniela Giachetti
Pharmaceuticals 2016, 9(4), 65; https://doi.org/10.3390/ph9040065 - 29 Oct 2016
Cited by 28 | Viewed by 12332
Abstract
The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause [...] Read more.
The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause and consequence of this peculiar situation. In fact, the legislation on botanical food supplements in Italy is very permissive and at the same time the market shows an overall satisfaction of users and strong feedback in terms of consumption, which brings a widening use of medicinal plants, formerly the prerogative of pharmaceuticals, to other fields such as nutrition. This review summarizes the market and normative panorama of herbal products in Italy, highlighting the blurred boundaries of health indications, marketing authorizations and quality controls between herbal medicines and non pharmaceutical products, such as food supplements, cosmetics and other herbal-based “parapharmaceuticals”. Full article
704 KiB  
Review
Lactoferrin from Milk: Nutraceutical and Pharmacological Properties
by Francesco Giansanti, Gloria Panella, Loris Leboffe and Giovanni Antonini
Pharmaceuticals 2016, 9(4), 61; https://doi.org/10.3390/ph9040061 - 27 Sep 2016
Cited by 155 | Viewed by 17834
Abstract
Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin’s main function is non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i) [...] Read more.
Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin’s main function is non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i) antimicrobial activity, which has been presumed due to iron deprivation, but more recently attributed also to a specific interaction with the bacterial cell wall and extended to viruses and parasites; (ii) immunomodulatory activity, with a direct effect on the development of the immune system in the newborn, together with a specific antinflammatory effects; (iii) a more recently discovered anticancer activity. It is worth noting that most of the protective activities of lactoferrin have been found, sometimes to a greater extent, also in peptides derived from limited proteolysis of lactoferrin that could be generated after lactoferrin ingestion. Lactoferrin could therefore be considered an ideal nutraceutic product because of its relatively cheap production from bovine milk and of its widely recognized tolerance after ingestion, along with its well demonstrated protective activities. The most important protective activities shown by orally administered bovine lactoferrin are reviewed in this article. Full article
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Figure 1

Figure 1
<p>Three-dimensional structures of holo-bLf (PDB ID:1BLF), Lf(1–11), Lfcin (PDB ID: 1LFC), and Lfampin (PDB ID: 2MD1). N1, N2, C1, and C2 indicate the subdomains of each lobe. The iron atom is shown as a red sphere, while the interacting amino acid residues of Lf are highlighted. Lf(1–11) is shown with the conformation it has in the intact protein (i.e., bovine lactoferrin) and the missing residues have been added with MODELLER-9.15 [<a href="#B24-pharmaceuticals-09-00061" class="html-bibr">24</a>]. The colors of peptides indicate aminoacid properties: Green: hydrophobic; Blue: negatively charged; Red: positively charged; White: polar. For details, see text. The pictures were drawn by UCSF-Chimera package [<a href="#B25-pharmaceuticals-09-00061" class="html-bibr">25</a>].</p>
Full article ">
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