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Resveratrol: From the Farm to the Clinic
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Resveratrol: From the Farm to the Clinic

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

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 28993

Special Issue Editors

Dr. Thomas Netticadan

E-Mail Website
Guest Editor
Canadian Centre for Agri-Food Research in Health and Medicine and Agriculture and Agri-Food Canada, Winnipeg, MB, Canada
Interests: cardiovascular disease; bioactive compounds; functional foods
Special Issues, Collections and Topics in MDPI journals
Dr. Jeffrey Wigle

E-Mail Website
Guest Editor
1. Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
2. Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
Interests: vascular development; transcription factors; fibroblasts/myofibroblasts and fibrosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Resveratrol is a polyphenol found in both edible plant sources such as grapes, peanuts and berries, and in medicinal plants such as polygonum cuspidatum and veratrum album. Resveratrol protects the plant against infections and environmental stresses. Research over the past two decades has also revealed that resveratrol can provide health benefits for animals and humans. In this Special Issue we would like to invite articles in areas such as the application of resveratrol in plant metabolic engineering for the nutritional improvement of food, and as a biopesticide. In addition, articles are invited on new findings on the impact of resveratrol and its analogues in animal and human health, and the underlying mechanisms of action of resveratrol.

Dr. Thomas Netticadan
Dr. Jeffrey Wigle
Guest Editors

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Keywords

  • Resveratrol
  • Resveratrol analogues
  • Health
  • Disease

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Published Papers (5 papers)

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Research

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13 pages, 9150 KiB  
Article
Production of Prenylated Stilbenoids in Hairy Root Cultures of Peanut (Arachis hypogaea) and Its Wild Relatives A. ipaensis and A. duranensis via an Optimized Elicitation Procedure
by Lingling Fang, Tianhong Yang and Fabricio Medina-Bolivar
Molecules 2020, 25(3), 509; https://doi.org/10.3390/molecules25030509 - 24 Jan 2020
Cited by 21 | Viewed by 4206
Abstract
Prenylated stilbenoids are phenolic compounds produced in a small number of plants such as peanut (Arachis hypogaea) to counteract biotic and abiotic stresses. In addition to their role in plant defense, they exhibit biological activities with potential application in human health. [...] Read more.
Prenylated stilbenoids are phenolic compounds produced in a small number of plants such as peanut (Arachis hypogaea) to counteract biotic and abiotic stresses. In addition to their role in plant defense, they exhibit biological activities with potential application in human health. Whereas non-prenylated stilbenoids such as resveratrol are commercially available, the availability of prenylated stilbenoids is limited. To this end, hairy root cultures of peanut were developed as an elicitor-controlled bioproduction platform for prenylated stilbenoids. An orthogonal array design approach led to the elucidation of an optimized elicitation procedure consisting of co-treatment of the hairy root cultures with 18 g/L methyl-β-cyclodextrin, 125 µM methyl jasmonate, 3 mM hydrogen peroxide (H2O2) and medium supplementation with additional 1 mM magnesium chloride. After 168-h of elicitor treatment, the combined yield of the prenylated stilbenoids arachidin-1, arachidin-2, arachidin-3 and arachidin-5 reached approximately 750 mg/L (equivalent to 107 mg/g DW). Moreover, hairy root cultures from the wild Arachis species A. duranensis and A. ipaensis were developed and shown to produce prenylated stilbenoids upon elicitor treatment. These wild Arachis hairy root lines may provide a platform to elucidate the biosynthetic origin of prenylated stilbenoids in peanut. Full article
(This article belongs to the Special Issue Resveratrol: From the Farm to the Clinic)
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11 pages, 2280 KiB  
Article
Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes
by Xavier Lieben Louis, Zach Meikle, Laura Chan, Garret DeGagne, Rebecca Cummer, Shannon Meikle, Sampath Krishnan, Liping Yu, Thomas Netticadan and Jeffrey T. Wigle
Molecules 2019, 24(14), 2604; https://doi.org/10.3390/molecules24142604 - 17 Jul 2019
Cited by 6 | Viewed by 3302
Abstract
In this study, we tested the potential cardioprotective effects of the phytoalexin resveratrol (Rsv) on primary adult rat cardiac fibroblasts (CF), myofibroblasts (MF) and cardiomyocytes. Adult rat CF and cardiomyocytes were isolated from male 10-week old Sprague–Dawley rats, cultured for either 24 h [...] Read more.
In this study, we tested the potential cardioprotective effects of the phytoalexin resveratrol (Rsv) on primary adult rat cardiac fibroblasts (CF), myofibroblasts (MF) and cardiomyocytes. Adult rat CF and cardiomyocytes were isolated from male 10-week old Sprague–Dawley rats, cultured for either 24 h (cardiomyocytes) or 48 h (CF) before treatments. To isolate MF, CF were trypsinized after 48 h in culture, seeded in fresh plates and cultured for 24 h prior to treatment. All three cells were then treated for a further 24 h with a range of Rsv doses. In CF and MF, cell proliferation, viability, apoptosis assays were performed with or without Rsv treatment for 24 h. In cardiomyocytes, cell viability and apoptosis assay were performed 24 h after treatment. In separate experiments, CF was pre-incubated with estrogen, tamoxifen and fulvestrant for 30 min prior to Rsv treatment. Rsv treatment decreased proliferation of both fibroblasts and myofibroblasts. Rsv treatment also increased the proportion of dead CF and MF in a dose dependent manner. However, treatment with Rsv did not induce cell death in adult cardiomyocytes. There was an increase in the percentage of cells with condensed nuclei with Rsv treatment in both CF and MF, but not in cardiomyocytes. Treatment with estrogen, tamoxifen and fulvestrant alone or in combination with Rsv did not have any additional effects on CF survival. Our results demonstrate that treatment with Rsv can inhibit cell proliferation and induce cell death in rat CF and MF, while not affecting cardiomyocyte survival. We also demonstrated that the induction of cell death in CF with Rsv treatment was independent of estrogen receptor alpha (ERα) signaling. Full article
(This article belongs to the Special Issue Resveratrol: From the Farm to the Clinic)
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13 pages, 6502 KiB  
Article
Regulation of Noise-Induced Loss of Serotonin Transporters with Resveratrol in a Rat Model Using 4-[18F]-ADAM/Small-Animal Positron Emission Tomography
by I-Hsun Li, Jui-Hu Shih, Yun-Tin Jhao, Hsin-Chien Chen, Chuang-Hsin Chiu, Chien-Fu F. Chen, Yuahn-Sieh Huang, Chyng-Yann Shiue and Kuo-Hsing Ma
Molecules 2019, 24(7), 1344; https://doi.org/10.3390/molecules24071344 - 5 Apr 2019
Cited by 19 | Viewed by 3392
Abstract
Serotonin (5-HT) plays a crucial role in modulating the afferent fiber discharge rate in the inferior colliculus, auditory cortex, and other nuclei of the ascending auditory system. Resveratrol, a natural polyphenol phytoalexin, can inhibit serotonin transporters (SERT) to increase synaptic 5-HT levels. In [...] Read more.
Serotonin (5-HT) plays a crucial role in modulating the afferent fiber discharge rate in the inferior colliculus, auditory cortex, and other nuclei of the ascending auditory system. Resveratrol, a natural polyphenol phytoalexin, can inhibit serotonin transporters (SERT) to increase synaptic 5-HT levels. In this study, we investigated the effects of resveratrol on noise-induced damage in the serotonergic system. Male Sprague-Dawley rats were anaesthetized and exposed to an 8-kHz tone at 116 dB for 3.5 h. Resveratrol (30 mg/kg, intraperitoneal injection [IP]) and citalopram (20 mg/kg, IP), a specific SERT inhibitor used as a positive control, were administered once a day for four consecutive days, with the first treatment occurring 2 days before noise exposure. Auditory brainstem response testing and positron emission tomography (PET) with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM, a specific radioligand for SERT) were used to evaluate functionality of the auditory system and integrity of the serotonergic system, respectively, before and after noise exposure. Finally, immunohistochemistry was performed 1 day after the last PET scan. Our results indicate that noise-induced serotonergic fiber loss occurred in multiple brain regions including the midbrain, thalamus, hypothalamus, striatum, auditory cortex, and frontal cortex. This noise-induced damage to the serotonergic system was ameliorated in response to treatment with resveratrol and citalopram. However, noise exposure increased the hearing threshold in the rats regardless of drug treatment status. We conclude that resveratrol has protective effects against noise-induced loss of SERT. Full article
(This article belongs to the Special Issue Resveratrol: From the Farm to the Clinic)
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Review

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12 pages, 797 KiB  
Review
The Potential Use of Resveratrol for Cancer Prevention
by Dominique Vervandier-Fasseur and Norbert Latruffe
Molecules 2019, 24(24), 4506; https://doi.org/10.3390/molecules24244506 - 9 Dec 2019
Cited by 97 | Viewed by 9075
Abstract
In addition to the traditional treatments of cancer and cancer prevention, the use of natural compounds, especially those found in food, should be considered. To clarify if resveratrol has the potential for cancer prevention and the possibility of use in therapy, the following [...] Read more.
In addition to the traditional treatments of cancer and cancer prevention, the use of natural compounds, especially those found in food, should be considered. To clarify if resveratrol has the potential for cancer prevention and the possibility of use in therapy, the following must be taken into account: data from epidemiology, clinical protocol (case and control), preclinical studies (lab animals), use of established cell lines as models of cancer cells, test tube assays (enzymes activities), and requirements of nanotechnologies in order to discover new drugs to fight cancer. From this perspective and future expected advances, more information is needed such as improved efficacy, methods of application, and the synergistic sensitization of resveratrol as an adjuvant. In addition, resveratrol nanoformulation is considered to overcome its weak bioavailability. Full article
(This article belongs to the Special Issue Resveratrol: From the Farm to the Clinic)
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21 pages, 1207 KiB  
Review
Biotechnological Advances in Resveratrol Production and its Chemical Diversity
by Samir Bahadur Thapa, Ramesh Prasad Pandey, Yong Il Park and Jae Kyung Sohng
Molecules 2019, 24(14), 2571; https://doi.org/10.3390/molecules24142571 - 15 Jul 2019
Cited by 64 | Viewed by 8539
Abstract
The very well-known bioactive natural product, resveratrol (3,5,4′-trihydroxystilbene), is a highly studied secondary metabolite produced by several plants, particularly grapes, passion fruit, white tea, and berries. It is in high demand not only because of its wide range of biological activities against various [...] Read more.
The very well-known bioactive natural product, resveratrol (3,5,4′-trihydroxystilbene), is a highly studied secondary metabolite produced by several plants, particularly grapes, passion fruit, white tea, and berries. It is in high demand not only because of its wide range of biological activities against various kinds of cardiovascular and nerve-related diseases, but also as important ingredients in pharmaceuticals and nutritional supplements. Due to its very low content in plants, multi-step isolation and purification processes, and environmental and chemical hazards issues, resveratrol extraction from plants is difficult, time consuming, impracticable, and unsustainable. Therefore, microbial hosts, such as Escherichia coli, Saccharomyces cerevisiae, and Corynebacterium glutamicum, are commonly used as an alternative production source by improvising resveratrol biosynthetic genes in them. The biosynthesis genes are rewired applying combinatorial biosynthetic systems, including metabolic engineering and synthetic biology, while optimizing the various production processes. The native biosynthesis of resveratrol is not present in microbes, which are easy to manipulate genetically, so the use of microbial hosts is increasing these days. This review will mainly focus on the recent biotechnological advances for the production of resveratrol, including the various strategies used to produce its chemically diverse derivatives. Full article
(This article belongs to the Special Issue Resveratrol: From the Farm to the Clinic)
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