The Physiologic Activity and Mechanism of Quercetin-Like Natural Plant Flavonoids

Author(s): Wujun Chen, Shuai Wang, Yudong Wu, Xin Shen, Shutan Xu, Zhu Guo*, Renshuai Zhang*, Dongming Xing*

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 8 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

The term “vitamin P” is an old but interesting concept. Most substances in this category belong to the family of flavonoids. “Vitamin P” has also been used to define the activity of some flavonoids, including quercetin, myricetin, and rutin. According to experimental studies, the “quercetin-like natural plant flavonoids” are beneficial to the body due to their various physiological and pharmacological activities in large doses (5 μM in vitro, 50 mg/kg in mice and 100 mg/kg in rats). The physiologically achievable concentration is 10 to 100 nM, which is quite high and hard to achieve from a normal diet. Thus, the physiologic activity and mechanism of "vitamin P" are still not clear. It should be noted that the quercetin-like natural plant flavonoids are physiological co-factors of cyclooxygenases (COXs), which are the rate-limiting key enzymes of prostaglandins. These quercetin-like natural plant flavonoids can strongly stimulate prostaglandin levels at lower doses (10 nM in vitro and in 0.1 mg/kg in vivo in rats). Although these "vitamin P" substances are not original substances in the body, their physiological functions affect the body. This review is focused on the most compelling evidence regarding the physiologic role and mechanism of quercetin-like natural plant flavonoids, which may be useful in understanding the physiological functions of "vitamin P", with the goal of focusing on the role of flavonoids in human physiological health.

Keywords: Physiologic activity, vitamin P, quercetin-like nature plant flavonoids, prostaglandin, COXs, co-factor.

[1]
Uehara, M. [Vitamin P (flavonoid)]. Nihon Rinsho, 2004, 62(Suppl. 12), 181-184.
[PMID: 15658295]
[2]
Jucá, M.M.; Cysne Filho, F.M.S.; de Almeida, J.C.; Mesquita, D.D.S.; Barriga, J.R.M.; Dias, K.C.F.; Barbosa, T.M.; Vasconcelos, L.C.; Leal, L.K.A.M.; Ribeiro, J.E.; Vasconcelos, S.M.M. Flavonoids: biological activities and therapeutic potential. Nat. Prod. Res., 2020, 34(5), 692-705.
[http://dx.doi.org/10.1080/14786419.2018.1493588] [PMID: 30445839]
[3]
Musumeci, L.; Maugeri, A.; Cirmi, S.; Lombardo, G.E.; Russo, C.; Gangemi, S.; Calapai, G.; Navarra, M. Citrus fruits and their flavonoids in inflammatory bowel disease: an overview. Nat. Prod. Res., 2020, 34(1), 122-136.
[PMID: 30990326]
[4]
Terahara, N. Flavonoids in foods: a review. Nat. Prod. Commun., 2015, 10(3), 521-528.
[http://dx.doi.org/10.1177/1934578X1501000334] [PMID: 25924542]
[5]
Ganeshpurkar, A.; Saluja, A.K. The pharmacological potential of rutin. Saudi Pharm. J., 2017, 25(2), 149-164.
[http://dx.doi.org/10.1016/j.jsps.2016.04.025] [PMID: 28344465]
[6]
Ghiasi, M.; Heravi, M.M. Quantum mechanical study of antioxidative ability and antioxidative mechanism of rutin (vitamin P) in solution. Carbohydr. Res., 2011, 346(6), 739-744.
[http://dx.doi.org/10.1016/j.carres.2011.01.021] [PMID: 21397896]
[7]
Singh, H.; Kaur, P.; Kaur, P.; Muthuraman, A.; Singh, G.; Kaur, M. Investigation of therapeutic potential and molecular mechanism of vitamin P and digoxin in I/R-induced myocardial infarction in rat. Naunyn Schmiedebergs Arch. Pharmacol., 2015, 388(5), 565-574.
[http://dx.doi.org/10.1007/s00210-015-1103-8] [PMID: 25693978]
[8]
Muthuraman, A.; Kaur, P.; Kaur, P.; Singh, H.; Boparai, P.S. Ameliorative potential of vitamin P and digoxin in ischemic-reperfusion induced renal injury using the Langendorff apparatus. Life Sci., 2015, 124, 75-80.
[http://dx.doi.org/10.1016/j.lfs.2014.12.022] [PMID: 25592137]
[9]
Ren, K.; Jiang, T.; Zhao, G.J. Quercetin induces the selective uptake of HDL-cholesterol via promoting SR-BI expression and the activation of the PPARγ/LXRα pathway. Food Funct., 2018, 9(1), 624-635.
[http://dx.doi.org/10.1039/C7FO01107E] [PMID: 29292466]
[10]
Khan, S.; Andrews, K.L.; Chin-Dusting, J.P.F. Cyclo-Oxygenase (COX) inhibitors and cardiovascular risk: Are non-steroidal anti-inflammatory drugs really anti-inflammatory? Int. J. Mol. Sci., 2019, 20(17),E4262.
[http://dx.doi.org/10.3390/ijms20174262] [PMID: 31480335]
[11]
Bai, H.W.; Zhu, B.T. Strong activation of cyclooxygenase I and II catalytic activity by dietary bioflavonoids. J. Lipid Res., 2008, 49(12), 2557-2570.
[http://dx.doi.org/10.1194/jlr.M800358-JLR200] [PMID: 18660529]
[12]
Bai, H.W.; Zhu, B.T. Myricetin and quercetin are naturally occurring co-substrates of cyclooxygenases in vivo. Prostaglandins Leukot. Essent. Fatty Acids, 2010, 82(1), 45-50.
[http://dx.doi.org/10.1016/j.plefa.2009.10.006] [PMID: 19897347]
[13]
Wang, H.R.; Sui, H.C.; Ding, Y.Y.; Zhu, B.T. Stimulation of the production of prostaglandin E(2) by ethyl gallate, a natural phenolic compound richly contained in Longan. Biomolecules, 2018, 8(3),E91.
[http://dx.doi.org/10.3390/biom8030091]
[14]
Wang, H.R.; Sui, H.C.; Zhu, B.T. Ellagic acid, a plant phenolic compound, activates cyclooxygenase-mediated prostaglandin production. Exp. Ther. Med., 2019, 18(2), 987-996.
[http://dx.doi.org/10.3892/etm.2016.3431] [PMID: 31316596]
[15]
Wang, P.; Bai, H.W.; Zhu, B.T. Structural basis for certain naturally occurring bioflavonoids to function as reducing co-substrates of cyclooxygenase I and II. PLoS One, 2010, 5(8),e12316.
[http://dx.doi.org/10.1371/journal.pone.0012316] [PMID: 20808785]
[16]
Modulation of COX-1 and COX-2-mediated formation of various arachidonic acid metabolites in vitro and in vivo by dietary polyphenols. Doctoral thesis of the university of Kansas, USA,, 2009.
[17]
Chen, Y.C.; Shen, S.C.; Lee, W.R.; Hou, W.C.; Yang, L.L.; Lee, T.J. Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages. J. Cell. Biochem., 2001, 82(4), 537-548.
[http://dx.doi.org/10.1002/jcb.1184] [PMID: 11500931]
[18]
Niu, G.; Yin, S.; Xie, S.; Li, Y.; Nie, D.; Ma, L.; Wang, X.; Wu, Y. Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells. Acta Biochim. Biophys. Sin. (Shanghai), 2011, 43(1), 30-37.
[http://dx.doi.org/10.1093/abbs/gmq107] [PMID: 21173056]
[19]
Ramyaa, P.; Krishnaswamy, R.; Padma, V.V. Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells - up regulation of Nrf2 expression and down regulation of NF-κB and COX-2. Biochim. Biophys. Acta, 2014, 1840(1), 681-692.
[http://dx.doi.org/10.1016/j.bbagen.2013.10.024] [PMID: 24161694]
[20]
Xiao, X.; Shi, D.; Liu, L.; Wang, J.; Xie, X.; Kang, T.; Deng, W. Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. PLoS One, 2011, 6(8)e22934
[http://dx.doi.org/10.1371/journal.pone.0022934] [PMID: 21857970]
[21]
Paoletti, T.; Fallarini, S.; Gugliesi, F.; Minassi, A.; Appendino, G.; Lombardi, G. Anti-inflammatory and vascularprotective properties of 8-prenylapigenin. Eur. J. Pharmacol., 2009, 620(1-3), 120-130.
[http://dx.doi.org/10.1016/j.ejphar.2009.08.015] [PMID: 19686724]
[22]
de Pascual-Teresa, S.; Johnston, K.L.; DuPont, M.S.; O’Leary, K.A.; Needs, P.W.; Morgan, L.M.; Clifford, M.N.; Bao, Y.; Williamson, G. Quercetin metabolites downregulate cyclooxygenase-2 transcription in human lymphocytes ex vivo but not in vivo. J. Nutr., 2004, 134(3), 552-557.
[http://dx.doi.org/10.1093/jn/134.3.552] [PMID: 14988445]
[23]
Arias, N.; Macarulla, M.T.; Aguirre, L.; Martínez-Castaño, M.G.; Portillo, M.P. Quercetin can reduce insulin resistance without decreasing adipose tissue and skeletal muscle fat accumulation. Genes Nutr., 2014, 9(1), 361.
[http://dx.doi.org/10.1007/s12263-013-0361-7] [PMID: 24338341]
[24]
Nieman, D.C.; Henson, D.A.; Davis, J.M.; Angela Murphy, E.; Jenkins, D.P.; Gross, S.J.; Carmichael, M.D.; Quindry, J.C.; Dumke, C.L.; Utter, A.C.; McAnulty, S.R.; McAnulty, L.S.; Triplett, N.T.; Mayer, E.P. Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA. J. Appl. Physiol.(1985), 2007, 103, 1728-1735.
[25]
Choi, S.Y.; Park, J.H.; Kim, J.S.; Kim, M.K.; Aruoma, O.I.; Sung, M.K. Effects of quercetin and beta-carotene supplementation on azoxymethane-induced colon carcinogenesis and inflammatory responses in rats fed with high-fat diet rich in omega-6 fatty acids. Biofactors, 2006, 27(1-4), 137-146.
[http://dx.doi.org/10.1002/biof.5520270112] [PMID: 17012770]
[26]
Saad, J.; Pellegrini, M.V. Nonsteroidal Anti-Inflammatory Drugs (NSAID); Toxicity, StatPearls: Treasure Island, FL, 2019.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 8
Year: 2020
Published on: 07 July, 2020
Page: [654 - 658]
Pages: 5
DOI: 10.2174/1389201021666200212093130
Price: $65

Article Metrics

PDF: 26
HTML: 1