BioVin® French Red Grapes Extract

Common Name

Grape Pomace Extract


Top Benefits of BioVin®

Supports healthy aging *

Supports exercise performance *

Supports metabolic health and healthy weight maintenance*

Supports mitochondrial health *

Supports cellular responses and antioxidant defenses *

Supports maintenance of healthy cardiovascular function *

Supports maintenance of healthy brain function *

Supports healthy gut microbiota *


What is BioVin®?

BioVin® is made from the juice, seeds, and skins of French red grapes. It provides a full spectrum of grape’s health-promoting compounds (grapes contain thousands of compounds). Grape skins and seeds contain small amounts of trans-resveratrol. This compound has been the subject of hundreds of pre-clinical and clinical research studies. While trans-resveratrol has received a great deal of research attention, grapes are more than one compound: They contain resveratrol derivatives (e.g., viniferins, polydatin) and polyphenol compounds (e.g., oligomeric proanthocyanidins, quercetin, gallic acids, catechins). These compounds have complementarity with trans-resveratrol. We think it makes sense to use a full spectrum extract to capture these complementary activities.*


Qualia BioVin® Sourcing

BioVin® is a full spectrum French red grape extract. Made from grape juice, seeds, and skins of Vitis vinifera, whole red grapes.

Standardized to contain 5% trans-resveratrol and not less than 40% grape oligomeric proanthocyanidins.

BioVin® is from grapes responsibly grown and harvested in the Rhone Valley region of France.

BioVin® is non-GMO and vegan.

BioVin® Advanced is a registered trademark of Cyvex Nutrition, Inc dba Bioriginal.


BioVin® Dosing Principles and Rationale

When thinking about the dose of BioVin® there’s a few things to keep in mind. This grape extract has been standardized to contain 5% trans-resveratrol and not less than 40% oligomeric proanthocyanidins. The extract also has other compounds that naturally occur in grape juice, seeds, and skin. While trans-resveratrol may be part of the reason we use this extract, it’s the complementarity of all of grape’s phytonutrients that is the story. Focusing only on resveratrol misses the big picture. That said, we don’t view resveratrol as a more is better compound—some studies have used resveratrol alone in doses as low as 10 mg [1–4]. So, resveratrol might be better thought of as a hormetic substance; something that in low to moderate amounts supports an adaptive response to stress (see Neurohacker Dosing Principles).* Our goal with BioVin®, as with all ingredient choices, is to select an appropriate dose in the context of other ingredient complementarities. Depending on the product, the amount of Biovin® included will supply 2.5-10 mg of resveratrol and 20-80 mg of grape oligomeric proanthocyanidins. To get this amount of resveratrol would require drinking somewhere between 1-30 liters of red wine (red wine can vary quite a bit in resveratrol content).


BioVin® Key Mechanisms 

Grape extract and proanthocyanidins

Supports mitochondrial biogenesis*

Supports peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) [5–9]

Supports nuclear transcription factors of mitochondrial biogenesis (nuclear respiratory factor-1 [NRF1], NRF2, mitochondrial transcription factor A [TFAM] [6,7,10–12] 


Supports mitochondrial structure and function*

Supports healthy mitochondrial DNA (mtDNA) [7]

Supports mitochondrial structure [8]

Supports complex I-V function [13–18]

Supports the activities of TCA cycle enzymes [17]

Supports β-oxidation [15]

Supports the NAD+ pool [19]


Supports antioxidant defenses*

Counters reactive oxygen species (ROS) levels and oxidative stress [8,13,14,16,18,20]

Supports antioxidant defenses [6–9,11,13,20]


Promotes healthy metabolic function*

Supports maintenance of healthy insulin sensitivity [20–23]

Supports maintenance of the insulin signaling pathway [20]

Supports the glucose transporter GLUT4 [20,24]

Supports brown adipose tissue levels [5]

Supports maintenance of healthy body fat levels [13,14,20]

Supports maintenance of healthy liver lipid levels [15]


Promotes exercise performance*

Supports endurance performance [25]

Supports muscle mass [26]


Supports brain function and cognition*

Supports attention [27] 

Supports memory function [27]

Supports working memory function [27]

Supports learning and memory (in animals) [28–35]

Supports healthy sleep [26]

Supports brain metabolism [26]

Supports BDNF levels [29,30,33,36–38]

Supports long-term potentiation [28,31]

Supports synaptic plasticity [33,39]

Influences acetylcholinesterase (AChE) activity [33]

Supports choline acetyltransferase (ChAT) activity [33]

Supports neuroprotective functions [31,34,35,40]

Supports neuronal mitochondrial function [6,32]

Supports brain Nrf2 signaling [37]

Counters brain oxidative stress [28,30,32,34,41] 

Supports healthy brain cytokine signaling [34]


Supports a healthy mood and stress response*

Supports positive affect [26,27,29,38]

Supports a calm mood [26–30,32,41,42]

Influences stress hormone levels [29,32,41]


Supports healthy cardiovascular function*

Supports maintenance of healthy blood pressure [26,43]

Supports healthy vasodilation [43]

Supports endothelial progenitor cells [44]

Supports maintenance of healthy blood lipid levels [14,20]


Supports skin health* 

Supports uniform skin pigmentation [45–47]

Supports healthy skin structure [48]

Supports healthy dermal ECM structure [48,49] 

Supports skin Nrf2 signaling and phase II detox enzymes [48]  

Supports healthy immune/cytokine signaling [50] 

Supports skin in adapting to environmental stress [48,50]


Supports a healthy gut microbiota*

Supports healthy gut microbiota [22,51–55]

Supports gut barrier function [55–57]

Counters gut oxidative stress [57,58]


Supports healthy cellular signaling*

Supports AMPK signaling [7–9,11,15,20,21,59]

Supports healthy immune/cytokine signaling 

Supports SIRT1 levels [6–9,19]

Counters mTOR signaling [59]

Supports UCP1 [5]


Promotes general health and longevity* 

Supports healthy liver structure and function [17]

Supports healthy circadian rhythms [60,61]

Supports lifespan extension (Drosophila melanogaster) [18]


Complementary ingredients*

Gynostemma pentaphyllum (in supporting healthy insulin sensitivity) [23]

Pomegranate fruit extract in supporting skin health [62]


Resveratrol

Supports mitochondrial biogenesis*

Supports peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) [63–70]

Supports nuclear transcriptional factors of mitochondrial biogenesis (nuclear respiratory factor-1 [NRF1], NRF2, mitochondrial transcription factor A [TFAM]) [64,67,69,71]


Supports mitochondrial structure and function*

Supports mitochondrial size and number [64,66]

Supports inner mitochondrial membrane folding (cristae) [64]

Supports mitochondrial DNA (mtDNA) [64,67,68]

Supports mitochondrial membrane potential [67]

Supports citrate synthase activity [63,64]

Supports ATP production [67,69]

Supports NAD+ pool [67,68,72]

Supports components of the electron transport chain - complex I-V [67]

Supports β-oxidation [64,70,72,73]


Supports signaling pathways*

Supports AMPK signaling [2,63,66–70,72,74]

Supports liver kinase B1 (LKB1) signaling [67,69]

Supports peroxisome proliferator-activated receptor alpha (PPARα) [64]

Influences peroxisome proliferator-activated receptor gamma (PPARγ) [70]

Supports normal estrogen receptor signaling [64,68,75,76]

Supports forkhead transcription factor O 1 (FOXO1) [70]

Supports cAMP levels (via phosphodiesterase [PDE] 1 and 4  and adenylate cyclase) [72,77]


Supports antioxidant defenses*

Counters reactive oxygen species (ROS) levels and oxidative stress [68,70–72,78–81]

Supports antioxidant defenses [82,83]

Influences NADPH oxidase [82,83]


Promotes healthy metabolic function*

Supports maintenance of healthy insulin sensitivity [63,64,66,68,74,78,84]

Supports maintenance of healthy body fat levels [64]

Supports maintenance of healthy liver lipid levels [63,70]

Supports thermogenesis [64]

Supports adiponectin levels [70]


Promotes exercise performance*

Supports endurance performance  [64]

Supports muscle structure and function [67,85]

Supports glucose uptake in muscles [86]


Supports healthy cardiovascular function*

Supports maintenance of healthy vascular function [82–84,87]

Supports maintenance of healthy cardiac function [86]

Supports maintenance of healthy blood lipid levels [63]


Supports brain function and cognition*

Supports maintenance of healthy executive function [88,89]

Supports learning and memory (animals) [90–93]

Supports cerebral blood flow [88,94–96]

Supports neuroprotective functions [79,80,97–101]

Supports maintenance of neural stem cells [102,103]

Supports neurogenesis [102–104]

Supports BDNF levels [91–93,98,101,104–110]

Supports healthy brain immune/cytokine signaling [101,105,108]

Supports HPA axis signaling [98,109]


Supports a healthy gut microbiota*

Supports healthy gut microbiota [111–117]

Supports healthy gut microbial metabolism [114]

Supports gut microbial gene expression [114]

Supports gut barrier function [114]

Supports healthy gut immune signaling [117]


Supports skin health*

Supports uniform skin pigmentation [118–120]

Supports healthy dermal ECM structure (collagen, elastin) [48,121,122]  

Supports healthy skin structure [48] 

Supports skin antioxidant defenses [121–124] 

Counters ROS production and oxidative stress [125] 

Supports skin Nrf2 signaling and phase II defenses [48,123,126]  

Supports healthy immune/cytokine signaling [121,122,127]

Supports skin in adapting to environmental stress [125,128–134]

Supports SIRT1 expression in the skin [121,122] 

Influences aging biomarkers S100 A8 and S100 A9 in the skin [121,122] 

Influences skin autophagy [135]


Promotes healthy aging and longevity*

Supports healthy stem cell functions [136–148]

Supports telomerase activity [136–138,149,150]

Counters cell senescence [124,137,138,143,150]

Supports SIRT1 levels [2,63,65,67,70,71,151,152] [121,122] 

Supports mitochondrial uncoupling proteins UCP1, UCP2, and UCP3 [64,68]

Supports Klotho levels [71,152]

Counters mTOR signaling [66]

Supports lifespan extension (mice on high-calorie diet, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae) [66,87,151,153,154] 


Supports circadian rhythms*

Supports healthy circadian rhythms [155–158]

Influences clock gene expression [155,158]


Complementary ingredients*

Apigenin - resveratrol is an apigenin bioenhancer [159]

Piperine as a bioenhancer [160–164] and for maintenance of cognitive function [165]

Hawthorn for cardiovascular function support [166]

Inositol for metabolic health [167]


*These statements have not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, cure, or prevent any disease.


REFERENCES 

[1]K. Magyar, R. Halmosi, A. Palfi, G. Feher, L. Czopf, A. Fulop, I. Battyany, B. Sumegi, K. Toth, E. Szabados, Clin. Hemorheol. Microcirc. 50 (2012) 179–187.

[2]K.P. Goh, H.Y. Lee, D.P. Lau, W. Supaat, Y.H. Chan, A.F.Y. Koh, Int. J. Sport Nutr. Exerc. Metab. 24 (2014) 2–13.

[3]C.W. Zhu, H. Grossman, J. Neugroschl, S. Parker, A. Burden, X. Luo, M. Sano, Alzheimer’s & Dementia: Translational Research & Clinical Interventions 4 (2018) 609–616.

[4]W. Zhu, W. Qin, K. Zhang, G.E. Rottinghaus, Y.-C. Chen, B. Kliethermes, E.R. Sauter, Nutrition and Cancer 64 (2012) 393–400.

[5]C. Rodriguez Lanzi, D.J. Perdicaro, M.S. Landa, A. Fontana, A. Antoniolli, R.M. Miatello, P.I. Oteiza, M.A. Vazquez Prieto, J. Nutr. Biochem. 56 (2018) 224–233.

[6]H. Asseburg, C. Schäfer, M. Müller, S. Hagl, M. Pohland, D. Berressem, M. Borchiellini, C. Plank, G.P. Eckert, Neuromolecular Med. 18 (2016) 378–395.

[7]L. Bao, X. Cai, X. Dai, Y. Ding, Y. Jiang, Y. Li, Z. Zhang, Y. Li, Food Funct. 5 (2014) 1872–1880.

[8]X. Cai, L. Bao, J. Ren, Y. Li, Z. Zhang, Food Funct. 7 (2016) 805–815.

[9]L. Bao, X. Cai, Z. Zhang, Y. Li, Br. J. Nutr. 113 (2015) 35–44.

[10]I. Pokkunuri, Q. Ali, M. Asghar, Oxid. Med. Cell. Longev. 2016 (2016) 6135319.

[11]J. Lu, H. Jiang, B. Liu, R. Baiyun, S. Li, Y. Lv, D. Li, S. Qiao, X. Tan, Z. Zhang, Food Chem. Toxicol. 116 (2018) 59–69.

[12]S.G. Li, Y.S. Ding, Q. Niu, S.Z. Xu, L.J. Pang, R.L. Ma, M.X. Jing, G.L. Feng, J.M. Liu, S.X. Guo, Biomed. Environ. Sci. 28 (2015) 272–280.

[13]M. El Ayed, S. Kadri, M. Mabrouk, E. Aouani, S. Elkahoui, Lipids Health Dis. 17 (2018) 109.

[14]D. Leonetti, R. Soleti, N. Clere, L. Vergori, C. Jacques, L. Duluc, C. Dourguia, M.C. Martínez, R. Andriantsitohaina, Front. Pharmacol. 9 (2018) 406.

[15]M. Yin, P. Zhang, F. Yu, Z. Zhang, Q. Cai, W. Lu, B. Li, W. Qin, M. Cheng, H. Wang, H. Gao, Mol. Med. Rep. 16 (2017) 2844–2850.

[16]N.F.F. de Sales, L. Silva da Costa, T.I.A. Carneiro, D.A. Minuzzo, F.L. Oliveira, L.M.C. Cabral, A.G. Torres, T. El-Bacha, Molecules 23 (2018).

[17]S. Miltonprabu, Nazimabashir, V. Manoharan, Toxicol Rep 3 (2016) 63–77.

[18]J. Long, H. Gao, L. Sun, J. Liu, X. Zhao-Wilson, Rejuvenation Res. 12 (2009) 321–331.

[19]G. Aragonès, M. Suárez, A. Ardid-Ruiz, M. Vinaixa, M.A. Rodríguez, X. Correig, L. Arola, C. Bladé, Sci. Rep. 6 (2016) 24977.

[20]G.F. da Costa, I.B. Santos, G.F. de Bem, V.S.C. Cordeiro, C.A. da Costa, L.C.R.M. de Carvalho, D.T. Ognibene, A.C. Resende, R.S. de Moura, Phytother. Res. 31 (2017) 1621–1632.

[21]E. Casanova, L. Baselga-Escudero, A. Ribas-Latre, L. Cedó, A. Arola-Arnal, M. Pinent, C. Bladé, L. Arola, M.J. Salvadó, J. Nutr. Biochem. 25 (2014) 1003–1010.

[22]W. Liu, S. Zhao, J. Wang, J. Shi, Y. Sun, W. Wang, G. Ning, J. Hong, R. Liu, Mol. Nutr. Food Res. 61 (2017).

[23]H.-J. Zhang, B.-P. Ji, G. Chen, F. Zhou, Y.-C. Luo, H.-Q. Yu, F.-Y. Gao, Z.-P. Zhang, H.-Y. Li, J. Food Sci. 74 (2009) H1–7.

[24]M. Aoun, F. Michel, G. Fouret, A. Schlernitzauer, V. Ollendorff, C. Wrutniak-Cabello, J.-P. Cristol, M.-A. Carbonneau, C. Coudray, C. Feillet-Coudray, Br. J. Nutr. 106 (2011) 491–501.

[25]L.T. Toscano, R.L. Tavares, L.T. Toscano, C.S.O. da Silva, A.E.M. de Almeida, A.C.T. Biasoto, M. da C.R. Gonçalves, A.S. Silva, Appl. Physiol. Nutr. Metab. 40 (2015) 899–906.

[26]M. Terauchi, N. Horiguchi, A. Kajiyama, M. Akiyoshi, Y. Owa, K. Kato, T. Kubota, Menopause 21 (2014) 990–996.

[27]G. Calapai, F. Bonina, A. Bonina, L. Rizza, C. Mannucci, V. Arcoraci, G. Laganà, A. Alibrandi, C. Pollicino, S. Inferrera, U. Alecci, Front. Pharmacol. 8 (2017) 776.

[28]G. Patki, F.H. Allam, F. Atrooz, A.T. Dao, N. Solanki, G. Chugh, M. Asghar, F. Jafri, R. Bohat, K.A. Alkadhi, S. Salim, PLoS One 8 (2013) e74522.

[29]N. Solanki, I. Alkadhi, F. Atrooz, G. Patki, S. Salim, Nutr. Res. 35 (2015) 65–75.

[30]F. Allam, A.T. Dao, G. Chugh, R. Bohat, F. Jafri, G. Patki, C. Mowrey, M. Asghar, K.A. Alkadhi, S. Salim, J. Nutr. 143 (2013) 835–842.

[31]A. Sarkaki, M. Rafieirad, S.E. Hossini, Y. Farbood, F. Motamedi, S.M.T. Mansouri, B. Naghizadeh, Iran. J. Basic Med. Sci. 16 (2013) 1004–1010.

[32]N. Solanki, A. Salvi, G. Patki, S. Salim, Int. J. Neuropsychopharmacol. 20 (2017) 550–561.

[33]L. Ma, H. Xiao, J. Wen, Z. Liu, Y. He, F. Yuan, Lipids Health Dis. 17 (2018) 152.

[34]I.H. Borai, M.K. Ezz, M.Z. Rizk, H.F. Aly, M. El-Sherbiny, A.A. Matloub, G.I. Fouad, Biomed. Pharmacother. 93 (2017) 837–851.

[35]D. Rapaka, V.R. Bitra, T.C. Vishala, A. Akula, J. Ayurveda Integr. Med. 10 (2019) 241–247.

[36]C. Dani, A.C. Andreazza, C.A. Gonçalves, F. Kapizinski, J.A.P. Henriques, M. Salvador, An. Acad. Bras. Cienc. 89 (2017) 155–161.

[37]H. Liao, L.-M. Chou, Y.-W. Chien, C.-H. Wu, J.-S. Chang, C.-I. Lin, S.-H. Lin, J. Nutr. Biochem. 43 (2017) 132–140.

[38]C. Jiang, E. Sakakibara, W.-J. Lin, J. Wang, G.M. Pasinetti, S.R. Salton, Ann. N. Y. Acad. Sci. 1455 (2019) 196–205.

[39]J. Wang, C. Tang, M.G. Ferruzzi, B. Gong, B.J. Song, E.M. Janle, T.-Y. Chen, B. Cooper, M. Varghese, A. Cheng, D. Freire, A. Bilski, J. Roman, T. Nguyen, L. Ho, S.T. Talcott, J.E. Simon, Q. Wu, G.M. Pasinetti, Mol. Nutr. Food Res. 57 (2013) 2091–2102.

[40]K. Narita, M. Hisamoto, T. Okuda, S. Takeda, PLoS One 6 (2011) e14575.

[41]G. Patki, Q. Ali, I. Pokkunuri, M. Asghar, S. Salim, Nutr. Res. 35 (2015) 504–511.

[42]Z. Alrefaie, Int. J. Vitam. Nutr. Res. 85 (2015) 282–291.

[43]J.-K. Kim, K.-A. Kim, H.-M. Choi, S.-K. Park, C.L. Stebbins, J. Med. Food 21 (2018) 445–453.

[44]F. Felice, Y. Zambito, G. Di Colo, C. D’Onofrio, C. Fausto, A. Balbarini, R. Di Stefano, Eur. J. Pharm. Biopharm. 80 (2012) 176–184.

[45]J. Yamakoshi, A. Sano, S. Tokutake, M. Saito, M. Kikuchi, Y. Kubota, Y. Kawachi, F. Otsuka, Phytother. Res. 18 (2004) 895–899.

[46]J. Yamakoshi, F. Otsuka, A. Sano, S. Tokutake, M. Saito, M. Kikuchi, Y. Kubota, Pigment Cell Res. 16 (2003) 629–638.

[47]Y.-S. Lin, H.-J. Chen, J.-P. Huang, P.-C. Lee, C.-R. Tsai, T.-F. Hsu, W.-Y. Huang, Biomed Res. Int. 2017 (2017) 5232680.

[48]J. Kim, J. Oh, J.N. Averilla, H.J. Kim, J.-S. Kim, J.-S. Kim, J. Food Sci. 84 (2019) 1600–1608.

[49]J. Wittenauer, S. Mäckle, D. Sußmann, U. Schweiggert-Weisz, R. Carle, Fitoterapia 101 (2015) 179–187.

[50]H.P. Decean, I.C. Brie, C.B. Tatomir, M. Perde-Schrepler, E. Fischer-Fodor, P. Virag, J. Environ. Pathol. Toxicol. Oncol. 37 (2018) 261–272.

[51]V. Nash, C.S. Ranadheera, E.N. Georgousopoulou, D.D. Mellor, D.B. Panagiotakos, A.J. McKune, J. Kellett, N. Naumovski, Food Res. Int. 113 (2018) 277–287.

[52]S. Chacar, M. Tarighi, N. Fares, J.-F. Faivre, N. Louka, R.G. Maroun, Antioxidants (Basel) 7 (2018).

[53]À. Casanova-Martí, J. Serrano, K.J. Portune, Y. Sanz, M.T. Blay, X. Terra, A. Ardévol, M. Pinent, Food Funct. 9 (2018) 1672–1682.

[54]S. Chacar, T. Itani, J. Hajal, Y. Saliba, N. Louka, J.-F. Faivre, R. Maroun, N. Fares, J. Food Sci. 83 (2018) 246–251.

[55]M. Van Hul, L. Geurts, H. Plovier, C. Druart, A. Everard, M. Ståhlman, M. Rhimi, K. Chira, P.-L. Teissedre, N.M. Delzenne, E. Maguin, A. Guilbot, A. Brochot, P. Gérard, F. Bäckhed, P.D. Cani, Am. J. Physiol. Endocrinol. Metab. 314 (2018) E334–E352.

[56]K. Gil-Cardoso, I. Ginés, M. Pinent, A. Ardévol, M. Blay, X. Terra, J. Nutr. Biochem. 62 (2018) 35–42.

[57]K. Gil-Cardoso, I. Ginés, M. Pinent, A. Ardévol, L. Arola, M. Blay, X. Terra, Mol. Nutr. Food Res. 61 (2017).

[58]P. Kuhn, H.M. Kalariya, A. Poulev, D.M. Ribnicky, A. Jaja-Chimedza, D.E. Roopchand, I. Raskin, PLoS One 13 (2018) e0198716.

[59]L. Castillo-Pichardo, S.F. Dharmawardhane, Nutr. Cancer 64 (2012) 1058–1069.

[60]A. Ribas-Latre, L. Baselga-Escudero, E. Casanova, A. Arola-Arnal, M.-J. Salvadó, C. Bladé, L. Arola, Sci. Rep. 5 (2015) 10954.

[61]A. Ribas-Latre, J.M. Del Bas, L. Baselga-Escudero, E. Casanova, A. Arola-Arnal, M.-J. Salvadó, L. Arola, C. Bladé, Mol. Nutr. Food Res. 59 (2015) 865–878.

[62]D. Buonocore, A. Lazzeretti, P. Tocabens, V. Nobile, E. Cestone, G. Santin, M.G. Bottone, F. Marzatico, Clin. Cosmet. Investig. Dermatol. 5 (2012) 159–165.

[63]S. Timmers, E. Konings, L. Bilet, R.H. Houtkooper, T. van de Weijer, G.H. Goossens, J. Hoeks, S. van der Krieken, D. Ryu, S. Kersten, E. Moonen-Kornips, M.K.C. Hesselink, I. Kunz, V.B. Schrauwen-Hinderling, E. Blaak, J. Auwerx, P. Schrauwen, Cell Metab. 14 (2011) 612–622.

[64]M. Lagouge, C. Argmann, Z. Gerhart-Hines, H. Meziane, C. Lerin, F. Daussin, N. Messadeq, J. Milne, P. Lambert, P. Elliott, B. Geny, M. Laakso, P. Puigserver, J. Auwerx, Cell 127 (2006) 1109–1122.

[65]T.D. Scribbans, J.K. Ma, B.A. Edgett, K.A. Vorobej, A.S. Mitchell, J.G.E. Zelt, C.A. Simpson, J. Quadrilatero, B.J. Gurd, Appl. Physiol. Nutr. Metab. 39 (2014) 1305–1313.

[66]J.A. Baur, K.J. Pearson, N.L. Price, H.A. Jamieson, C. Lerin, A. Kalra, V.V. Prabhu, J.S. Allard, G. Lopez-Lluch, K. Lewis, P.J. Pistell, S. Poosala, K.G. Becker, O. Boss, D. Gwinn, M. Wang, S. Ramaswamy, K.W. Fishbein, R.G. Spencer, E.G. Lakatta, D. Le Couteur, R.J. Shaw, P. Navas, P. Puigserver, D.K. Ingram, R. de Cabo, D.A. Sinclair, Nature 444 (2006) 337–342.

[67]N.L. Price, A.P. Gomes, A.J.Y. Ling, F.V. Duarte, A. Martin-Montalvo, B.J. North, B. Agarwal, L. Ye, G. Ramadori, J.S. Teodoro, B.P. Hubbard, A.T. Varela, J.G. Davis, B. Varamini, A. Hafner, R. Moaddel, A.P. Rolo, R. Coppari, C.M. Palmeira, R. de Cabo, J.A. Baur, D.A. Sinclair, Cell Metab. 15 (2012) 675–690.

[68]J.-H. Um, S.-J. Park, H. Kang, S. Yang, M. Foretz, M.W. McBurney, M.K. Kim, B. Viollet, J.H. Chung, Diabetes 59 (2010) 554–563.

[69]B. Dasgupta, J. Milbrandt, Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 7217–7222.

[70]J.M. Ajmo, X. Liang, C.Q. Rogers, B. Pennock, M. You, Am. J. Physiol. Gastrointest. Liver Physiol. 295 (2008) G833–42.

[71]P. Zhang, Y. Li, Y. Du, G. Li, L. Wang, F. Zhou, Transplant. Proc. 48 (2016) 3378–3386.

[72]S.-J. Park, F. Ahmad, A. Philp, K. Baar, T. Williams, H. Luo, H. Ke, H. Rehmann, R. Taussig, A.L. Brown, M.K. Kim, M.A. Beaven, A.B. Burgin, V. Manganiello, J.H. Chung, Cell 148 (2012) 421–433.

[73]J. Most, S. Timmers, I. Warnke, J.W. Jocken, M. van Boekschoten, P. de Groot, I. Bendik, P. Schrauwen, G.H. Goossens, E.E. Blaak, Am. J. Clin. Nutr. 104 (2016) 215–227.

[74]C.E. Park, M.-J. Kim, J.H. Lee, B.-I. Min, H. Bae, W. Choe, S.-S. Kim, J. Ha, Exp. Mol. Med. 39 (2007) 222–229.

[75]B.D. Gehm, J.M. McAndrews, P.Y. Chien, J.L. Jameson, Proc. Natl. Acad. Sci. U. S. A. 94 (1997) 14138–14143.

[76]J.L. Bowers, V.V. Tyulmenkov, S.C. Jernigan, C.M. Klinge, Endocrinology 141 (2000) 3657–3667.

[77]A.M. El-Mowafy, M. Alkhalaf, Carcinogenesis 24 (2003) 869–873.

[78]P. Brasnyó, G.A. Molnár, M. Mohás, L. Markó, B. Laczy, J. Cseh, E. Mikolás, I.A. Szijártó, A. Mérei, R. Halmai, L.G. Mészáros, B. Sümegi, I. Wittmann, Br. J. Nutr. 106 (2011) 383–389.

[79]R. Moldzio, K. Radad, C. Krewenka, B. Kranner, J.C. Duvigneau, W.-D. Rausch, J. Neural Transm. 120 (2013) 1271–1280.

[80]Y.K. Gupta, S. Briyal, G. Chaudhary, Pharmacol. Biochem. Behav. 71 (2002) 245–249.

[81]S.S. Leonard, C. Xia, B.-H. Jiang, B. Stinefelt, H. Klandorf, G.K. Harris, X. Shi, Biochem. Biophys. Res. Commun. 309 (2003) 1017–1026.

[82]G. Spanier, H. Xu, N. Xia, S. Tobias, S. Deng, L. Wojnowski, U. Forstermann, H. Li, J. Physiol. Pharmacol. 60 Suppl 4 (2009) 111–116.

[83]N. Xia, A. Daiber, A. Habermeier, E.I. Closs, T. Thum, G. Spanier, Q. Lu, M. Oelze, M. Torzewski, K.J. Lackner, T. Münzel, U. Förstermann, H. Li, J. Pharmacol. Exp. Ther. 335 (2010) 149–154.

[84]J.P. Crandall, V. Oram, G. Trandafirescu, M. Reid, P. Kishore, M. Hawkins, H.W. Cohen, N. Barzilai, J. Gerontol. A Biol. Sci. Med. Sci. 67 (2012) 1307–1312.

[85]J.-P.K. Hyatt, L. Nguyen, A.E. Hall, A.M. Huber, J.C. Kocan, J.A. Mattison, R. de Cabo, J.R. LaRocque, R.J. Talmadge, Front. Physiol. 7 (2016) 77.

[86]J.L. Barger, T. Kayo, J.M. Vann, E.B. Arias, J. Wang, T.A. Hacker, Y. Wang, D. Raederstorff, J.D. Morrow, C. Leeuwenburgh, D.B. Allison, K.W. Saupe, G.D. Cartee, R. Weindruch, T.A. Prolla, PLoS One 3 (2008) e2264.

[87]K.J. Pearson, J.A. Baur, K.N. Lewis, L. Peshkin, N.L. Price, N. Labinskyy, W.R. Swindell, D. Kamara, R.K. Minor, E. Perez, H.A. Jamieson, Y. Zhang, S.R. Dunn, K. Sharma, N. Pleshko, L.A. Woollett, A. Csiszar, Y. Ikeno, D. Le Couteur, P.J. Elliott, K.G. Becker, P. Navas, D.K. Ingram, N.S. Wolf, Z. Ungvari, D.A. Sinclair, R. de Cabo, Cell Metab. 8 (2008) 157–168.

[88]R.H.X. Wong, D. Raederstorff, P.R.C. Howe, Nutrients 8 (2016).

[89]S.D. Anton, N. Ebner, J.M. Dzierzewski, Z.Z. Zlatar, M.J. Gurka, V.M. Dotson, J. Kirton, R.T. Mankowski, M. Marsiske, T.M. Manini, J. Altern. Complement. Med. 24 (2018) 725–732.

[90]Y. Yazir, T. Utkan, N. Gacar, F. Aricioglu, Physiol. Behav. 138 (2015) 297–304.

[91]J.-F. Ge, Y.-Y. Xu, N. Li, Y. Zhang, G.-L. Qiu, C.-H. Chu, C.-Y. Wang, G. Qin, F.-H. Chen, Endocrine Journal 62 (2015) 927–938.

[92]Y.-N. Zhao, W.-F. Li, F. Li, Z. Zhang, Y.-D. Dai, A.-L. Xu, C. Qi, J.-M. Gao, J. Gao, Biochem. Biophys. Res. Commun. 435 (2013) 597–602.

[93]J. Shen, L. Xu, C. Qu, H. Sun, J. Zhang, Behav. Brain Res. 349 (2018) 1–7.

[94]D.O. Kennedy, E.L. Wightman, J.L. Reay, G. Lietz, E.J. Okello, A. Wilde, C.F. Haskell, Am. J. Clin. Nutr. 91 (2010) 1590–1597.

[95]E.L. Wightman, C.F. Haskell-Ramsay, J.L. Reay, G. Williamson, T. Dew, W. Zhang, D.O. Kennedy, Br. J. Nutr. 114 (2015) 1427–1437.

[96]H.M. Evans, P.R.C. Howe, R.H.X. Wong, Nutrients 9 (2017).

[97]Q. Wang, S. Yu, A. Simonyi, G. Rottinghaus, G.Y. Sun, A.Y. Sun, Neurochem. Res. 29 (2004) 2105–2112.

[98]C. Pang, L. Cao, F. Wu, L. Wang, G. Wang, Y. Yu, M. Zhang, L. Chen, W. Wang, W. Lv, L. Chen, J. Zhu, J. Pan, H. Zhang, Y. Xu, L. Ding, Neuropharmacology 97 (2015) 447–456.

[99]G. Wang, L. Chen, X. Pan, J. Chen, L. Wang, W. Wang, R. Cheng, F. Wu, X. Feng, Y. Yu, H.-T. Zhang, J.M. O’Donnell, Y. Xu, Oncotarget 7 (2016).

[100]Q. Zhang, X. Wang, X. Bai, Y. Xie, T. Zhang, S. Bo, X. Chen, Mol. Med. Rep. 16 (2017) 2095–2100.

[101]L. Ge, L. Liu, H. Liu, S. Liu, H. Xue, X. Wang, L. Yuan, Z. Wang, D. Liu, Eur. J. Pharmacol. 768 (2015) 49–57.

[102]L. Xu, Y. Yang, L. Gao, J. Zhao, Y. Cai, J. Huang, S. Jing, X. Bao, Y. Wang, J. Gao, H. Xu, X. Fan, Biochim. Biophys. Acta 1852 (2015) 1298–1310.

[103]N.B. Bottari, M.R.C. Schetinger, M.M. Pillat, T.V. Palma, H. Ulrich, M.S. Alves, V.M. Morsch, C. Melazzo, L.D. de Barros, J.L. Garcia, A.S. Da Silva, Mol. Neurobiol. 56 (2019) 2328–2338.

[104]S. Madhyastha, S. Sekhar, G. Rao, Int. J. Dev. Neurosci. 31 (2013) 580–585.

[105]M. Wiciński, M. Socha, M. Walczak, E. Wódkiewicz, B. Malinowski, S. Rewerski, K. Górski, K. Pawlak-Osińska, Nutrients 10 (2018).

[106]M. Rahvar, M. Nikseresht, S.M. Shafiee, F. Naghibalhossaini, M. Rasti, M.R. Panjehshahin, A.A. Owji, Neurochem. Res. 36 (2011) 761–765.

[107]G. Li, G. Wang, J. Shi, X. Xie, N. Fei, L. Chen, N. Liu, M. Yang, J. Pan, W. Huang, Y. Xu, Neuropharmacology 133 (2018) 181–188.

[108]X.-H. Yang, S.-Q. Song, Y. Xu, Neuropsychiatr. Dis. Treat. 13 (2017) 2727–2736.

[109]S.H. Ali, R.M. Madhana, A. K V., E.R. Kasala, L.N. Bodduluru, S. Pitta, J.R. Mahareddy, M. Lahkar, Steroids 101 (2015) 37–42.

[110]J. Song, S.Y. Cheon, W. Jung, W.T. Lee, J.E. Lee, Int. J. Mol. Sci. 15 (2014) 15512–15529.

[111]Y.-L. Tain, W.-C. Lee, K.L.H. Wu, S. Leu, J.Y.H. Chan, Mol. Nutr. Food Res. (2018) e1800066.

[112]Y. Zheng, W. Wu, G. Hu, L. Qiu, S. Meng, C. Song, L. Fan, Z. Zhao, X. Bing, J. Chen, Fish Shellfish Immunol. 77 (2018) 200–207.

[113]L. Zhao, Q. Zhang, W. Ma, F. Tian, H. Shen, M. Zhou, Food Funct. 8 (2017) 4644–4656.

[114]J.K. Bird, D. Raederstorff, P. Weber, R.E. Steinert, Adv. Nutr. 8 (2017) 839–849.

[115]A.S. Korsholm, T.N. Kjær, M.J. Ornstrup, S.B. Pedersen, Int. J. Mol. Sci. 18 (2017).

[116]M.M. Sung, T.T. Kim, E. Denou, C.-L.M. Soltys, S.M. Hamza, N.J. Byrne, G. Masson, H. Park, D.S. Wishart, K.L. Madsen, J.D. Schertzer, J.R.B. Dyck, Diabetes 66 (2017) 418–425.

[117]M. Larrosa, M.J. Yañéz-Gascón, M.V. Selma, A. González-Sarrías, S. Toti, J.J. Cerón, F. Tomás-Barberán, P. Dolara, J.C. Espín, J. Agric. Food Chem. 57 (2009) 2211–2220.

[118]T.H. Lee, J.O. Seo, S.-H. Baek, S.Y. Kim, Biomol. Ther. 22 (2014) 35–40.

[119]Q. Liu, C. Kim, Y.H. Jo, S.B. Kim, B.Y. Hwang, M.K. Lee, Molecules 20 (2015) 16933–16945.

[120]R.A. Newton, A.L. Cook, D.W. Roberts, J.H. Leonard, R.A. Sturm, J. Invest. Dermatol. 127 (2007) 2216–2227.

[121]E.D. Lephart, M.B. Andrus, Exp. Biol. Med. 242 (2017) 1482–1489.

[122]E.D. Lephart, J.M. Sommerfeldt, M.B. Andrus, J. Funct. Foods 10 (2014) 377–384.

[123]J. Soeur, J. Eilstein, G. Léreaux, C. Jones, L. Marrot, Free Radic. Biol. Med. 78 (2015) 213–223.

[124]Y. Ido, A. Duranton, F. Lan, K.A. Weikel, L. Breton, N.B. Ruderman, PLoS One 10 (2015) e0115341.

[125]K. Park, J.-H. Lee, Oncol. Rep. 19 (2008) 413–417.

[126]Y. Liu, F. Chan, H. Sun, J. Yan, D. Fan, D. Zhao, J. An, D. Zhou, Eur. J. Pharmacol. 650 (2011) 130–137.

[127]X. Zhu, Q. Liu, M. Wang, M. Liang, X. Yang, X. Xu, H. Zou, J. Qiu, PLoS One 6 (2011) e27081.

[128]F. Zhou, X. Huang, Y. Pan, D. Cao, C. Liu, Y. Liu, A. Chen, Biochem. Biophys. Res. Commun. 499 (2018) 662–668.

[129]S. Reagan-Shaw, F. Afaq, M.H. Aziz, N. Ahmad, Oncogene 23 (2004) 5151–5160.

[130]M.A. Choi, J.K. Seok, J.W. Lee, S.Y. Lee, Y.M. Kim, Y.C. Boo, J. Soc. Cosmet. Sci. Korea 44 (2018) 249–258.

[131]M.-H. Tsai, L.-F. Hsu, C.-W. Lee, Y.-C. Chiang, M.-H. Lee, J.-M. How, C.-M. Wu, C.-L. Huang, I.-T. Lee, Int. J. Biochem. Cell Biol. 88 (2017) 113–123.

[132]J.-W. Shin, H.-S. Lee, J.-I. Na, C.-H. Huh, K.-C. Park, H.-R. Choi, Int. J. Mol. Sci. 21 (2020).

[133]C. Sticozzi, G. Belmonte, F. Cervellati, X.M. Muresan, F. Pessina, Y. Lim, H.J. Forman, G. Valacchi, Free Radic. Biol. Med. 69 (2014) 50–57.

[134]C. Sticozzi, F. Cervellati, X.M. Muresan, C. Cervellati, G. Valacchi, Food Funct. 5 (2014) 2348–2356.

[135]D.K. Mostafa, S.I. Omar, A.A. Abdellatif, O.A. Sorour, O.A. Nayel, M.R.A. Al Obaidi, Curr. Mol. Pharmacol. (2020).

[136]V.P. Pearce, J. Sherrell, Z. Lou, L. Kopelovich, W.E. Wright, J.W. Shay, Oncogene 27 (2008) 2365–2374.

[137]L. Xia, X.X. Wang, X.S. Hu, X.G. Guo, Y.P. Shang, H.J. Chen, C.L. Zeng, F.R. Zhang, J.Z. Chen, Br. J. Pharmacol. 155 (2008) 387–394.

[138]X.-B. Wang, L. Zhu, J. Huang, Y.-G. Yin, X.-Q. Kong, Q.-F. Rong, A.-W. Shi, K.-J. Cao, Chin. Med. J. 124 (2011) 4310–4315.

[139]M.L. Balestrieri, C. Schiano, F. Felice, A. Casamassimi, A. Balestrieri, L. Milone, L. Servillo, C. Napoli, J. Biochem. 143 (2008) 179–186.

[140]L. Ling, S. Gu, Y. Cheng, Mol. Med. Rep. 15 (2017) 1188–1194.

[141]X.-H. Chen, Z.-G. Shi, H.-B. Lin, F. Wu, F. Zheng, C.-F. Wu, M.-W. Huang, Eur. Rev. Med. Pharmacol. Sci. 23 (2019) 6352–6359.

[142]H. Zhang, Z. Zhai, Y. Wang, J. Zhang, H. Wu, Y. Wang, C. Li, D. Li, L. Lu, X. Wang, J. Chang, Q. Hou, Z. Ju, D. Zhou, A. Meng, Free Radic. Biol. Med. 54 (2013) 40–50.

[143]Y.-J. Lv, Y. Yang, B.-D. Sui, C.-H. Hu, P. Zhao, L. Liao, J. Chen, L.-Q. Zhang, T.-T. Yang, S.-F. Zhang, Y. Jin, Theranostics 8 (2018) 2387–2406.

[144]H. Liu, S. Zhang, L. Zhao, Y. Zhang, Q. Li, X. Chai, Y. Zhang, Stem Cells Int. 2016 (2016) 2524092.

[145]I.I. Suvorova, A.R. Knyazeva, A.V. Petukhov, N.D. Aksenov, V.A. Pospelov, Cell Death Discov 5 (2019) 61.

[146]Y.-J. Wang, P. Zhao, B.-D. Sui, N. Liu, C.-H. Hu, J. Chen, C.-X. Zheng, A.-Q. Liu, K. Xuan, Y.-P. Pan, Y. Jin, Exp. Mol. Med. 50 (2018) 1–15.

[147]T.-S. Chen, C.-H. Kuo, C.H. Day, L.-F. Pan, R.-J. Chen, B.-C. Chen, V.V. Padma, Y.-M. Lin, C.-Y. Huang, J. Cell. Physiol. 234 (2019) 20443–20452.

[148]Z. Safaeinejad, M. Nabiuni, M. Peymani, K. Ghaedi, M.H. Nasr-Esfahani, H. Baharvand, Eur. J. Cell Biol. 96 (2017) 665–672.

[149]F. Uchiumi, T. Watanabe, S. Hasegawa, T. Hoshi, Y. Higami, S.-I. Tanuma, Curr. Aging Sci. 4 (2011) 1–7.

[150]J. Li, C.-X. Zhang, Y.-M. Liu, K.-L. Chen, G. Chen, Oncotarget 8 (2017) 65717–65729.

[151]K.T. Howitz, K.J. Bitterman, H.Y. Cohen, D.W. Lamming, S. Lavu, J.G. Wood, R.E. Zipkin, P. Chung, A. Kisielewski, L.-L. Zhang, B. Scherer, D.A. Sinclair, Nature 425 (2003) 191–196.

[152]S.-C. Hsu, S.-M. Huang, A. Chen, C.-Y. Sun, S.-H. Lin, J.-S. Chen, S.-T. Liu, Y.-J. Hsu, Int. J. Biochem. Cell Biol. 53 (2014) 361–371.

[153]T.M. Bass, D. Weinkove, K. Houthoofd, D. Gems, L. Partridge, Mech. Ageing Dev. 128 (2007) 546–552.

[154]J.G. Wood, B. Rogina, S. Lavu, K. Howitz, S.L. Helfand, M. Tatar, D. Sinclair, Nature 430 (2004) 686–689.

[155]J. Miranda, M.P. Portillo, J.A. Madrid, N. Arias, M.T. Macarulla, M. Garaulet, Br. J. Nutr. 110 (2013) 1421–1428.

[156]F. Pifferi, A. Dal-Pan, S. Languille, F. Aujard, Oxid. Med. Cell. Longev. 2013 (2013) 187301.

[157]J.R. Leheste, G. Torres, Front. Mol. Neurosci. 8 (2015) 61.

[158]L. Sun, Y. Wang, Y. Song, X.-R. Cheng, S. Xia, M.R.T. Rahman, Y. Shi, G. Le, Biochem. Biophys. Res. Commun. 458 (2015) 86–91.

[159]J.-A. Lee, S.K. Ha, E. Cho, I. Choi, Nutrients 7 (2015) 9650–9661.

[160]J.J. Johnson, M. Nihal, I.A. Siddiqui, C.O. Scarlett, H.H. Bailey, H. Mukhtar, N. Ahmad, Mol. Nutr. Food Res. 55 (2011) 1169–1176.

[161]N. Pannu, A. Bhatnagar, Inflammopharmacology 28 (2020) 719–735.

[162]K.R. Polley, N. Jenkins, P. O’Connor, K. McCully, Appl. Physiol. Nutr. Metab. 41 (2016) 26–32.

[163]W. Huang, Z. Chen, Q. Wang, M. Lin, S. Wu, Q. Yan, F. Wu, X. Yu, X. Xie, G. Li, Y. Xu, J. Pan, Metab. Brain Dis. 28 (2013) 585–595.

[164]Y. Xu, C. Zhang, F. Wu, X. Xu, G. Wang, M. Lin, Y. Yu, Y. An, J. Pan, Metab. Brain Dis. 31 (2016) 837–848.

[165]E.L. Wightman, J.L. Reay, C.F. Haskell, G. Williamson, T.P. Dew, D.O. Kennedy, Br. J. Nutr. 112 (2014) 203–213.

[166]Y. Zhu, B. Feng, S. He, Z. Su, G. Zheng, Phytomedicine 40 (2018) 20–26.

[167]A. Malvasi, I. Kosmas, O.A. Mynbaev, R. Sparic, S. Gustapane, M. Guido, A. Tinelli, Clin. Ter. 168 (2017) e240–e247.