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Plant Derived Natural Products and Age Related Diseases

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 January 2018) | Viewed by 79085

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Prof. Dr. Hermann Stuppner

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Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
Interests: natural products; pharmacognosy; phytochemistry; analytics; molecular modeling

Prof. Dr. Alexios Leandros Skaltsounis

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Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli, Zografou, GR-15771 Athens, Greece
Interests: green chemistry and large-scale extraction of high added-value natural products; isolation of natural products leads; identification and structural elucidation of natural products; semi- and total synthesis of natural products; characterization of natural extracts; design and synthesis of new molecules with pharmacological interest; structure–activity relationships
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Dear Colleagues,

In the absence of overt disease, changes in nutrition and lifestyle are by far the most cost-efficient ways to promote healthy ageing at the population level. Ageing is a complex molecular process driven by diverse molecular pathways that are promoted by both environmental and genetic factors. Numerous studies show that natural compounds represent an amazing inventory of high diversity structural scaffolds that can offer promising candidates in the major healthcare challenge of increasing healthspan and delaying ageing. Especially plant derived compounds (either pure forms or extracts) are involved in several physiological processes and have been shown to possess significant beneficial (chemo-preventive/ delaying cellular senescence or in vivo ageing) effects on human health and to support healthy aging. Plants offer not only products of their primary metabolism, e.g., carbohydrates, proteins or lipids, but also a variety of biologically active secondary natural products (NPs) like polyphenols, essential oils, alkaloids, and many others which exhibit pleiotropic and, likely, therapeutic effects in humans. Today, it is assumed that the generation of NPs has been subjected to natural selection during evolution since the presence of particular secondary metabolite improves the capacity for survival and reproduction of the producing organism. Up to now, approximately 200,000 metabolites have been elucidated in plants and it is expected that the final number will exceed 500,000.

This Special Issue on “Natural Products and Age Related Diseases” will cover several aspects, such as:

Medicinal plants used as diet with anti aging effects
Plant collection, ethnopharmacology, benefit sharing
Pharmacological aspects of aging
Key modulators of ageing and age-associated related diseases
Mechanism(s) of natural products in prevention of age-related disease
Natural products affecting cellular aging signaling
Advanced analytical approaches and techniques (microfractionation, microprobe-NMR, LC-SPE-NMR, LC-HR-MSⁿ) and dereplication strategies
In vitro and in vivo assays to identify bioactive extracts and NPs with health-span and longevity promoting effects
Pharmacokinetics of NPs
Gastrointestinal metabolisation of plant derived compounds
Aging—computational tools and medicinal chemistry concepts in anti-aging research

Prof. Dr. Hermann Stuppner
Prof. Dr. Leandros A. Skaltsounis
Guest Editors

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Keywords

aging
natural products
pharmacology
phytochemistry
biological effects
pharmakinetics
plants

Published Papers (12 papers)

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16 pages, 1681 KiB

Open AccessFeature PaperArticle

Phytochemical Composition of the Decoctions of Greek Edible Greens (Chórta) and Evaluation of Antioxidant and Cytotoxic Properties

by Eleni V. Mikropoulou, Konstantina Vougogiannopoulou, Eleftherios Kalpoutzakis, Aimilia D. Sklirou, Zoi Skaperda, Joëlle Houriet, Jean-Luc Wolfender, Ioannis P. Trougakos, Dimitrios Kouretas, Maria Halabalaki and Sofia Mitakou

Molecules 2018, 23(7), 1541; https://doi.org/10.3390/molecules23071541 - 26 Jun 2018

Cited by 24 | Viewed by 4908

Abstract

Wild or semi-wild edible greens (chórta) are an integral part of the traditional Greek Mediterranean diet due to their nutritional value, containing various phytonutrients beneficial to human health. Water-based decoctions of chórta are widely consumed in Greek alternative medicine as health promoting agents. This study examined the chemical profile of the decoctions of eight edible plants, Cichorium intybus, C. endivia, C. spinosum, Crepis sancta, Sonchus asper, Carthamus lanatus, Centaurea raphanina, and Amaranthus blitum, by UPLC-ESI-HRMS and HRMS/MS analysis, to determine possibly bioactive constituents. The profiles of the plants from the Asteraceae family are dominated by the presence of phenolic acids and flavonoid derivatives, whereas the A. blitum decoction is rich in triterpene saponins. Interestingly, the Centaurea raphanina decoction was found to be extremely rich in flavanones, particularly in the aglycone pinocembrin. Further phytochemical investigation and fractionation of this extract resulted in the isolation and identification of five compounds: phlorin (1), syringin (2), pinocembrin (3), pinocembroside (4), and pinocembrin-7-O-neohesperidoside (5). The extracts were also tested for their antioxidant and differential cytotoxic activity against tumor cells. C. raphanina was found to be differentially toxic against metastatic tumor cells. In conclusion, we found that Greek edible greens are a rich source of bioactive secondary metabolites and their consumption could contribute to the maintenance of overall health. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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12 pages, 22395 KiB

Open AccessArticle

Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice

by Yue-Qin Zeng, Yin-Bo Cui, Juan-Hua Gu, Chen Liang and Xin-Fu Zhou

Molecules 2018, 23(4), 869; https://doi.org/10.3390/molecules23040869 - 10 Apr 2018

Cited by 24 | Viewed by 5567

Abstract

Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aβ amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aβ42, efficiently inhibits oligomerization as well as fibril formation and reduces Aβ oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aβ levels in the brain and plasma, decreases Aβ plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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11 pages, 3018 KiB

Open AccessArticle

Antioxidant Activity of Coconut (Cocos nucifera L.) Protein Fractions

by Yan Li, Yajun Zheng, Yufeng Zhang, Jianguo Xu and Gang Gao

Molecules 2018, 23(3), 707; https://doi.org/10.3390/molecules23030707 - 20 Mar 2018

Cited by 37 | Viewed by 7022

Abstract

Coconut cake is an abundant and good potential edible protein source. However, until now it has not been extensively used in the food industry. To promote its usage, the characterization, nutrition value and antioxidant activity of coconut cake protein fractions (albumin, globulin, prolamine, glutelin-1 and glutelin-2) were studied. Results revealed that all the albumin, globulin, glutelin-1 and glutelin-2 fractions showed a high nutrition value. The prolamine, glutelin-1 and glutelin-2 all exhibited good radical scavenging activity and reducing power, and the globulin and prolamine showed high ion chelating ability (89.14–80.38%). Moreover, all the fractions except glutelin-2 could effectively protect DNA against oxidative damage. Several peptides containing five to eight amino acids with antioxidant activity were also identified by LC-MS/MS from the globulin and glutelin-2 fractions. The results demonstrated that the coconut cake protein fractions have potential usages in functional foods. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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12 pages, 1627 KiB

Open AccessArticle

Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus

by Silvia Revoltella, Giorgia Baraldo, Birgit Waltenberger, Stefan Schwaiger, Philipp Kofler, Julia Moesslacher, Astrid Huber-Seidel, Konrad Pagitz, Roland Kohl, Pidder Jansen-Duerr and Hermann Stuppner

Molecules 2018, 23(3), 653; https://doi.org/10.3390/molecules23030653 - 14 Mar 2018

Cited by 11 | Viewed by 4338

Abstract

NADPH oxidase 4 (Nox4) has recently been implicated as driving force in cellular senescence. Thus, there is growing interest to develop Nox4 inhibitors, which might be valuable agents for cosmeceutical applications. Alpine plants represent a valuable source for the identification of novel bioactive natural products with anti-ageing effects, especially substances that protect plants against UV radiation, which is also known to contribute to the ageing of human skin. Therefore, the aim of this study was to identify novel Nox4 inhibitors from alpine plants. Within an initial screening of extracts of alpine plants on their ability to inhibit Nox4 activity in HEK cells, the methanolic extract of the subaerial parts of Lycopus europaeus showed a strong inhibition of Nox4 (81% chemiluminescence quenching) and a simultaneously high cell viability (91% vitality). Rosmarinic acid was isolated and identified as the major compound in this bioactive extract. It showed a dose dependent inhibitory activity on Nox4 with an IC₅₀ of 1 µM. Moreover, it also showed a significant inhibitory activity on Nox2 in the low micromolar range, whereas no inhibition of Nox5 was detected. Further investigations confirmed that the observed effects of rosmarinic acid on Nox2 and Nox4 are real inhibitory activities, and not due to ROS scavenging effects. Therefore, L. europaeus, which we demonstrated to be a good source of rosmarinic acid, has great potential for usage in cosmeceutical products with anti-ageing activity. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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12 pages, 2443 KiB

Open AccessArticle

Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum

by Aymeric Monteillier, Pierre-Marie Allard, Katia Gindro, Jean-Luc Wolfender and Muriel Cuendet

Molecules 2018, 23(3), 636; https://doi.org/10.3390/molecules23030636 - 12 Mar 2018

Cited by 11 | Viewed by 4473

Abstract

Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB) pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after for both cancer chemoprevention and therapy, and fungi represent an interesting unexplored reservoir for such molecules. The aim of the present work was to find naturally occurring lung cancer chemopreventive compounds by investigating the metabolites of Penicillium vulpinum, a fungus that grows naturally on dung. Penicillium vulpinum was cultivated in Potato Dextrose Broth and extracted with ethyl acetate. Bioassay-guided fractionation of this extract was performed by measuring NF-κB activity using a HEK293 cell line transfected with an NF-κB-driven luciferase reporter gene. The mycotoxin patulin was identified as a nanomolar inhibitor of TNF-α-induced NF-κB activity. Immunocytochemistry and Western blot analyses revealed that its mechanism of action involved an inhibition of p65 nuclear translocation and was independent from the NF-κB inhibitor α (IκBα) degradation process. Enhancing its interest in lung cancer chemoprevention, patulin also exhibited antiproliferative, proapoptotic, and antimigration effects on human lung adenocarcinoma cells through inhibition of the Wnt pathway. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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15 pages, 2333 KiB

Open AccessArticle

Calycophyllum spruceanum (Benth.), the Amazonian “Tree of Youth” Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans

by Herbenya Peixoto, Mariana Roxo, Hector Koolen, Felipe Da Silva, Emerson Silva, Markus Santhosh Braun, Xiaojuan Wang and Michael Wink

Molecules 2018, 23(3), 534; https://doi.org/10.3390/molecules23030534 - 27 Feb 2018

Cited by 19 | Viewed by 6279

Abstract

The tree popularly known in Brazil as mulateiro or pau-mulato (Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum. To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry)/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans. The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the “tree of youth”, however more studies are needed to clarify its putative benefits to human health. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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14 pages, 2265 KiB

Open AccessArticle

Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G

by Andreas Koeberle, Arne Henkel, Moritz Verhoff, Lars Tausch, Stefanie König, Dagmar Fischer, Nicole Kather, Stefanie Seitz, Michael Paul, Johann Jauch and Oliver Werz

Molecules 2018, 23(2), 506; https://doi.org/10.3390/molecules23020506 - 24 Feb 2018

Cited by 17 | Viewed by 6798

Abstract

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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12 pages, 4069 KiB

Open AccessArticle

Dietary Total Prenylflavonoids from the Fruits of Psoralea corylifolia L. Prevents Age-Related Cognitive Deficits and Down-Regulates Alzheimer’s Markers in SAMP8 Mice

by Zhi-Jing Chen, Yan-Fang Yang, Ying-Tao Zhang and Dong-Hui Yang

Molecules 2018, 23(1), 196; https://doi.org/10.3390/molecules23010196 - 18 Jan 2018

Cited by 25 | Viewed by 4953

Abstract

Alzheimer’s disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1. TPFB significantly reduced the level of amyloid β-peptide 42 (Aβ42), inhibited hyperphosphorylation of the microtubule-associated protein Tau, induced phosphorylation of Ser9 of the glycogen synthase kinase 3β (GSK-3β), and decreased the expression of the proinflammatory cytokines TNFα, IL-6, and IL-1β. Finally, TPFB also markedly reduced the level of serum derivatives of reactive oxygen metabolites (d-ROMs), a biomarker of oxidative stress in vivo. These results showed that dietary TPFB could effectively prevent age-related cognitive deficits and AD-like neurobiochemical changes, and may have a potential role in the prevention of Alzheimer’s disease. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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5529 KiB

Open AccessArticle

Steppogenin Isolated from Cudrania tricuspidata Shows Antineuroinflammatory Effects via NF-κB and MAPK Pathways in LPS-Stimulated BV2 and Primary Rat Microglial Cells

by Dong-Cheol Kim, Tran Hong Quang, Hyuncheol Oh and Youn-Chul Kim

Molecules 2017, 22(12), 2130; https://doi.org/10.3390/molecules22122130 - 2 Dec 2017

Cited by 41 | Viewed by 6651 | Correction

Abstract

Excessive microglial stimulation has been recognized in several neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple sclerosis (MS), and stroke. When microglia are stimulated, they produce proinflammatory mediators and cytokines, including nitric oxide (NO) derived from inducible NO synthase (iNOS), prostaglandin E2 (PGE₂) derived from cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12 (IL-12), and interleukin-6 (IL-6). These inflammatory reactions are related to the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, the modulation of NF-κB and MAPK is vital to prevent microglial activation and confer resistance against neuronal injury. In this study, steppogenin (1) isolated from Cudrania tricuspidata suppressed the neuroinflammatory responses to lipopolysaccharide (LPS). Steppogenin (1) inhibited the production of proinflammatory mediators and cytokines in LPS-challenged BV2 and rat primary microglial cells. Moreover, western blot analysis and immunofluorescence revealed that the nuclear translocation of NF-κB was inhibited in LPS-induced BV2 and rat primary microglial cells. The LPS-stimulated activation of BV2 and rat primary microglial cells was inhibited by steppogenin (1) through the suppression of c-Jun NH2-terminal kinase (JNK) and p38 MAPK signaling. These results suggested that steppogenin (1) exerted antineuroinflammatory effects against acute neuroinflammation in BV2 and rat primary microglial cells by suppressing the activation of NF-κB and MAPK signaling and the production of proinflammatory mediators and cytokines. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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25 pages, 2024 KiB

Open AccessFeature PaperReview

Targeting Protein Quality Control Mechanisms by Natural Products to Promote Healthy Ageing

by Sophia Wedel, Maria Manola, Maria Cavinato, Ioannis P. Trougakos and Pidder Jansen-Dürr

Molecules 2018, 23(5), 1219; https://doi.org/10.3390/molecules23051219 - 19 May 2018

Cited by 31 | Viewed by 7441

Abstract

Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due to the time-dependent decline of stress resistance and functional capacity, which eventually compromise cellular homeodynamics. As protein machines carry out the majority of cellular functions, proteome quality control is critical for cellular functionality and is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the two main degradation machineries, namely the ubiquitin-proteasome and autophagy-lysosome pathways along with several stress-responsive pathways, such as that of nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises cytoprotective genomic responses against oxidative and/or xenobiotic damage. Reportedly, genetic or dietary interventions that activate components of the PN delay ageing in evolutionarily diverse organisms. Natural products (extracts or pure compounds) represent an extraordinary inventory of highly diverse structural scaffolds that offer promising activities towards meeting the challenge of increasing healthspan and/or delaying ageing (e.g., spermidine, quercetin or sulforaphane). Herein, we review those natural compounds that have been found to activate proteostatic and/or anti-stress cellular responses and hence have the potential to delay cellular senescence and/or in vivo ageing. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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14 pages, 2179 KiB

Open AccessReview

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

by Sathish Sundar Dhilip Kumar, Nicolette Nadene Houreld and Heidi Abrahamse

Molecules 2018, 23(4), 835; https://doi.org/10.3390/molecules23040835 - 5 Apr 2018

Cited by 81 | Viewed by 13651

Abstract

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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16 pages, 675 KiB

Open AccessFeature PaperConcept Paper

Novel Natural Products for Healthy Ageing from the Mediterranean Diet and Food Plants of Other Global Sources—The MediHealth Project

by Birgit Waltenberger, Maria Halabalaki, Stefan Schwaiger, Nicolas Adamopoulos, Noureddine Allouche, Bernd L. Fiebich, Nina Hermans, Pidder Jansen-Dürr, Victor Kesternich, Luc Pieters, Stefan Schönbichler, Alexios-Leandros Skaltsounis, Hung Tran, Ioannis P. Trougakos, Alvaro Viljoen, Jean-Luc Wolfender, Christian Wolfrum, Nikos Xynos and Hermann Stuppner

Molecules 2018, 23(5), 1097; https://doi.org/10.3390/molecules23051097 - 6 May 2018

Cited by 16 | Viewed by 6053

Abstract

There is a rapid increase in the percentage of elderly people in Europe. Consequently, the prevalence of age-related diseases will also significantly increase. Therefore, the main goal of MediHealth, an international research project, is to introduce a novel approach for the discovery of active agents of food plants from the Mediterranean diet and other global sources that promote healthy ageing. To achieve this goal, a series of plants from the Mediterranean diet and food plants from other origins are carefully selected and subjected to in silico, cell-based, in vivo (fly and mouse models), and metabolism analyses. Advanced analytical techniques complement the bio-evaluation process for the efficient isolation and identification of the bioactive plant constituents. Furthermore, pharmacological profiling of bioactive natural products, as well as the identification and synthesis of their metabolites, is carried out. Finally, optimization studies are performed in order to proceed to the development of innovative nutraceuticals, dietary supplements or herbal medicinal products. The project is based on an exchange of researchers between nine universities and four companies from European and non-European countries, exploiting the existing complementary multidisciplinary expertise. Herein, the unique and novel approach of this interdisciplinary project is presented. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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