Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Bioactive Flavonoids: A Comparative Overview of the Biogenetic and Chemical Synthesis Approach

Author(s): Mukta Gupta* and Awanish Mishra*

Volume 23, Issue 18, 2023

Published on: 16 March, 2023

Page: [1818 - 1837] Pages: 20

DOI: 10.2174/1389557523666230214101821

Price: $65

Abstract

Flavonoids are natural polyphenolic compounds and constitute a major class of plant secondary metabolites. To date, structures of more than 10,000 different flavonoids have been elucidated, and most of them are present in cells and tissues of plant parts. Flavonoids have been reported to exert multiple physiological activities and are also consumed as dietary supplements. Flavonoids have been extensively explored as anticancer, anti-inflammatory, antidiabetic, antirheumatic, antioxidant, antimalarial, neuroprotective, cardioprotective, anti-angiogenic, and antiproliferative agents. Most of the flavonoids are biosynthesized in plants via the phenylpropanoid pathway. However, they are associated with some limitations. Chemical synthesis is an alternative strategy to improve the yield and obtain purified products but is hampered by drawbacks, such as intolerance to stressful lab conditions. Pharmacokinetics is the rate-limiting step defining the bioavailability and metabolism of flavonoids, though greatly influenced by their chemical structure. However, nanoformulation is an emerging technique to improve biopharmaceutical fate and achieve target drug delivery. Thus, much attention should be given to identifying other possible chemical approaches for synthesizing flavonoids and improving their pharmacokinetic profiling, hence potentiating their efficacy in clinic.

« Previous Next »
Graphical Abstract

[1]
Ahmad, J.; Albarqi, H.A.; Ahmad, M.Z.; Orabi, M.A.A.; Md, S.; Bandopadhyay, R.; Ahmed, F.; Khan, M.A.; Ahamad, J.; Mishra, A. Utilization of nanotechnology to improve bone health in osteoporosis exploiting Nigella sativa and its active constituent thymoquinone. Bioengineering, 2022, 9(11), 631.
[http://dx.doi.org/10.3390/bioengineering9110631] [PMID: 36354542]
[2]
Taslimi, P. Kandemir, F.M.; Demir, Y.; İleritürk, M.; Temel, Y.; Caglayan, C.; Gulçin, İ. The antidiabetic and anticholinergic effects of chrysin on cyclophosphamide‐induced multiple organ toxicity in rats: Pharmacological evaluation of some metabolic enzyme activities. J. Biochem. Mol. Toxicol., 2019, 33(6), e22313.
[http://dx.doi.org/10.1002/jbt.22313] [PMID: 30801880]
[3]
Demir, Y.; Özaslan, M.S.; Duran, H.E. Küfrevioğlu, Ö.İ.; Beydemir, Ş. Inhibition effects of quinones on aldose reductase: Antidiabetic properties. Environ. Toxicol. Pharmacol., 2019, 70, 103195.
[http://dx.doi.org/10.1016/j.etap.2019.103195] [PMID: 31125830]
[4]
Maan, G.; Sikdar, B.; Kumar, A.; Shukla, R.; Mishra, A. Role of flavonoids in neurodegenerative diseases: Limitations and future perspectives. Curr. Top. Med. Chem., 2020, 20(13), 1169-1194.
[http://dx.doi.org/10.2174/1568026620666200416085330] [PMID: 32297582]
[5]
Mishra, A.; Oliinyk, P.; Lysiuk, R.; Lenchyk, L.; Rathod, S.S.S.; Antonyak, H.; Darmohray, R.; Dub, N.; Antoniv, O.; Tsal, O.; Upyr, T. Flavonoids and stilbenoids as a promising arsenal for the management of chronic arsenic toxicity. Environ. Toxicol. Pharmacol., 2022, 95, 103970.
[http://dx.doi.org/10.1016/j.etap.2022.103970] [PMID: 36067934]
[6]
Jaiswal, P.; Mandal, M.; Mishra, A. Effect of hesperidin on fluoride‐induced neurobehavioral and biochemical changes in rats. J. Biochem. Mol. Toxicol., 2020, 34(11), e22575.
[http://dx.doi.org/10.1002/jbt.22575] [PMID: 32627286]
[7]
Mishra, A.; Mishra, P.S.; Bandopadhyay, R.; Khurana, N.; Angelopoulou, E.; Paudel, Y.N.; Piperi, C. Neuroprotective potential of chrysin: mechanistic insights and therapeutic potential for neurological disorders. Molecules, 2021, 26(21), 6456.
[http://dx.doi.org/10.3390/molecules26216456]
[8]
Demir, Y.; Durmaz, L.; Taslimi, P. Gulçin, İ. Antidiabetic properties of dietary phenolic compounds: Inhibition effects on α‐amylase, aldose reductase, and α‐glycosidase. Biotechnol. Appl. Biochem., 2019, 66(5), 781-786.
[http://dx.doi.org/10.1002/bab.1781] [PMID: 31135076]
[9]
Aslan, H.E.; Demir, Y.; Özaslan, M.S.; Türkan, F. Beydemir, Ş.; Küfrevioğlu, Ö.I. The behavior of some chalcones on acetylcholinesterase and carbonic anhydrase activity. Drug Chem. Toxicol., 2019, 42(6), 634-640.
[http://dx.doi.org/10.1080/01480545.2018.1463242] [PMID: 29860891]
[10]
Pichersky, E.; Gang, D.R. Genetics and biochemistry of secondary metabolites in plants: An evolutionary perspective. Trends Plant Sci., 2000, 5(10), 439-445.
[http://dx.doi.org/10.1016/S1360-1385(00)01741-6] [PMID: 11044721]
[11]
Özaslan, M.S. Sağlamtaş R.; Demir, Y.; Genç, Y.; Saraçoğlu, İ.; Gülçin, İ. Isolation of some phenolic compounds from Plantago subulata L. and determination of their antidiabetic, anticholinesterase, antiepileptic and antioxidant activity. Chem. Biodivers., 2022, 19(8), e202200280.
[http://dx.doi.org/10.1002/cbdv.202200280] [PMID: 35796520]
[12]
Özaslan, M.S.; Demir, Y.; Aslan, H.E. Beydemir, Ş.; Küfrevioğlu, Ö.İ. Evaluation of chalcones as inhibitors of glutathione S-transferase. J. Biochem. Mol. Toxicol., 2018, 32(5), e22047.
[http://dx.doi.org/10.1002/jbt.22047] [PMID: 29473699]
[13]
Çağlayan, C.; Taslimi, P.; Demir, Y.; Küçükler, S.; Kandemir, F.M.; Gulçin, İ. The effects of zingerone against vancomycin‐induced lung, liver, kidney and testis toxicity in rats: The behavior of some metabolic enzymes. J. Biochem. Mol. Toxicol., 2019, 33(10), e22381.
[http://dx.doi.org/10.1002/jbt.22381] [PMID: 31454121]
[14]
Ceylan, H.; Demir, Y. Beydemir, Ş. Inhibitory effects of usnic and carnosic acid on some metabolic enzymes: An in vitro study. Protein Pept. Lett., 2019, 26(5), 364-370.
[http://dx.doi.org/10.2174/0929866526666190301115122] [PMID: 30827223]
[15]
Bayrak, S.; Öztürk, C.; Demir, Y. Alım, Z; Küfrevioglu, Öİ Purification of polyphenol oxidase from potato and investigation of the inhibitory effects of phenolic acids on enzyme activity. Protein Pept. Lett., 2020, 27(3), 187-192.
[http://dx.doi.org/10.2174/0929866526666191002142301]
[16]
Demir, Y. Naphthoquinones, benzoquinones, and anthraquinones: Molecular docking, ADME and inhibition studies on human serum paraoxonase‐1 associated with cardiovascular diseases. Drug Dev. Res., 2020, 81(5), 628-636.
[http://dx.doi.org/10.1002/ddr.21667] [PMID: 32232985]
[17]
Kumar, S; Pandey, AK Chemistry and biological activities of flavonoids: An overview. The Sci. World J., 2013, 2013
[http://dx.doi.org/10.1155/2013/162750]
[18]
Waheed Janabi, A.H.; Kamboh, A.A.; Saeed, M.; Xiaoyu, L. BiBi, J.; Majeed, F.; Naveed, M.; Mughal, M.J.; Korejo, N.A.; Kamboh, R.; Alagawany, M.; Lv, H. Flavonoid-rich foods (FRF): A promising nutraceutical approach against lifespan-shortening diseases. Iran. J. Basic Med. Sci., 2020, 23(2), 140-153.
[PMID: 32405356]
[19]
Kopustinskiene, D.M.; Jakstas, V.; Savickas, A.; Bernatoniene, J. Flavonoids as anticancer agents. Nutrients, 2020, 12(2), 457.
[http://dx.doi.org/10.3390/nu12020457] [PMID: 32059369]
[20]
Zhang, Z.; Shi, J.; Nice, E.C.; Huang, C.; Shi, Z. The multifaceted role of flavonoids in cancer therapy: leveraging autophagy with a double-edged sword. Antioxidants, 2021, 10(7), 1138.
[http://dx.doi.org/10.3390/antiox10071138] [PMID: 34356371]
[21]
Grynkiewicz, G.; Demchuk, O.M. New Perspectives for Fisetin. Front Chem., 2019, 7, 697.
[http://dx.doi.org/10.3389/fchem.2019.00697] [PMID: 31750288]
[22]
Xia, M.; Fang, Y.; Cao, W.; Liang, F.; Pan, S.; Xu, X. Quantitative structure–activity relationships for the flavonoid-mediated inhibition of P-glycoprotein in KB/MDR1 cells. Molecules, 2019, 24(9), 1661.
[http://dx.doi.org/10.3390/molecules24091661] [PMID: 31035631]
[23]
Srinivasan, R.; Natarajan, D.; Subramaniam Shivakumar, M.; Nagamurugan, N. Isolation of fisetin from elaeagnus indica Serv. Bull. (Elaeagnaceae) with antioxidant and antiproliferative activity. Free Radic. Antioxid., 2016, 6(2), 145-150.
[http://dx.doi.org/10.5530/fra.2016.2.3]
[24]
Batiha, G.E.S.; Beshbishy, A.M.; Ikram, M.; Mulla, Z.S.; El-Hack, M.E.A.; Taha, A.E.; Algammal, A.M.; Elewa, Y.H.A. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: Quercetin. Foods, 2020, 9(3), 374.
[http://dx.doi.org/10.3390/foods9030374] [PMID: 32210182]
[25]
Song, X.; Wang, Y.; Gao, L. Mechanism of antioxidant properties of quercetin and quercetin-DNA complex. J. Mol. Model., 2020, 26(6), 133.
[http://dx.doi.org/10.1007/s00894-020-04356-x] [PMID: 32399900]
[26]
Salehi, B.; Machin, L.; Monzote, L.; Sharifi-Rad, J.; Ezzat, S.M.; Salem, M.A.; Merghany, R.M.; El Mahdy, N.M. Kılıç, C.S.; Sytar, O.; Sharifi-Rad, M.; Sharopov, F.; Martins, N.; Martorell, M.; Cho, W.C. Therapeutic potential of quercetin: New insights and perspectives for human health. ACS Omega, 2020, 5(20), 11849-11872.
[http://dx.doi.org/10.1021/acsomega.0c01818] [PMID: 32478277]
[27]
Parasuraman, S.; Anand David, A.V.; Arulmoli, R. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn. Rev., 2016, 10(20), 84-89.
[http://dx.doi.org/10.4103/0973-7847.194044] [PMID: 28082789]
[28]
Alam, W.; Khan, H.; Shah, M.A.; Cauli, O.; Saso, L. Kaempferol as a dietary anti-inflammatory agent: Current therapeutic standing. Molecules, 2020, 25(18), 4073.
[http://dx.doi.org/10.3390/molecules25184073] [PMID: 32906577]
[29]
Imran, M.; Salehi, B.; Sharifi-Rad, J.; Aslam Gondal, T.; Saeed, F.; Imran, A.; Shahbaz, M.; Tsouh Fokou, P.V.; Umair Arshad, M.; Khan, H.; Guerreiro, S.G.; Martins, N.; Estevinho, L.M. Kaempferol: A key emphasis to its anticancer potential. Molecules, 2019, 24(12), 2277.
[http://dx.doi.org/10.3390/molecules24122277] [PMID: 31248102]
[30]
Kashyap, D.; Sharma, A.; Tuli, H.S.; Sak, K.; Punia, S.; Mukherjee, T.K. Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements. J. Funct. Foods, 2017, 30, 203-219.
[http://dx.doi.org/10.1016/j.jff.2017.01.022] [PMID: 32288791]
[31]
Devi, K.P.; Malar, D.S.; Nabavi, S.F.; Sureda, A.; Xiao, J.; Nabavi, S.M.; Daglia, M. Kaempferol and inflammation: From chemistry to medicine. Pharmacol. Res., 2015, 99, 1-10.
[http://dx.doi.org/10.1016/j.phrs.2015.05.002] [PMID: 25982933]
[32]
Sulaiman, G.M.; Waheeb, H.M.; Jabir, M.S.; Khazaal, S.H.; Dewir, Y.H.; Naidoo, Y. Hesperidin loaded on gold nanoparticles as a drug delivery system for a successful biocompatible, anticancer, anti-inflammatory and phagocytosis inducer model. Sci. Rep., 2020, 10(1), 9362.
[http://dx.doi.org/10.1038/s41598-020-66419-6] [PMID: 32518242]
[33]
Binkowska, I. Hesperidin: synthesis and characterization of bioflavonoid complex. SN Appl. Sci., 2020, 2(3), 445.
[http://dx.doi.org/10.1007/s42452-020-2256-8]
[34]
Xiong, H.; Wang, J.; Ran, Q.; Lou, G.; Peng, C.; Gan, Q.; Hu, J.; Sun, J.; Yao, R.; Huang, Q. Hesperidin: A therapeutic agent for obesity. Drug Des. Devel. Ther., 2019, 13, 3855-3866.
[http://dx.doi.org/10.2147/DDDT.S227499] [PMID: 32009777]
[35]
Man, MQ; Yang, B; Elias, PM Benefits of Hesperidin for Cutaneous Functions. Evid. Based Complement. Alternat. Med., 2019, 2676307.
[http://dx.doi.org/10.1155/2019/2676307] [PMID: 31061668] [PMCID: PMC6466919.10.1155/2019/2676307]
[36]
Hajialyani, M.; Hosein Farzaei, M.; Echeverría, J.; Nabavi, S.; Uriarte, E.; Sobarzo-Sánchez, E. Hesperidin as a neuroprotective agent: A review of animal and clinical evidence. Molecules, 2019, 24(3), 648.
[http://dx.doi.org/10.3390/molecules24030648] [PMID: 30759833]
[37]
Karim, N.; Shishir, M.R.I.; Gowd, V.; Chen, W. Hesperidin-an emerging bioactive compound against metabolic diseases and its potential biosynthesis pathway in microorganism. Food Rev. Int., 2021, 1-23.
[http://dx.doi.org/10.1080/87559129.2020.1858312]
[38]
Aggarwal, V.; Tuli, H.S.; Thakral, F.; Singhal, P.; Aggarwal, D.; Srivastava, S.; Pandey, A.; Sak, K.; Varol, M.; Khan, M.A.; Sethi, G. Molecular mechanisms of action of hesperidin in cancer: Recent trends and advancements. Exp. Biol. Med., 2020, 245(5), 486-497.
[http://dx.doi.org/10.1177/1535370220903671] [PMID: 32050794]
[39]
Salehi, B.; Venditti, A.; Sharifi-Rad, M. Kręgiel, D.; Sharifi-Rad, J.; Durazzo, A.; Lucarini, M.; Santini, A.; Souto, E.; Novellino, E.; Antolak, H.; Azzini, E.; Setzer, W.; Martins, N. The therapeutic potential of apigenin. Int. J. Mol. Sci., 2019, 20(6), 1305.
[http://dx.doi.org/10.3390/ijms20061305] [PMID: 30875872]
[40]
DeRango-Adem, E.F.; Blay, J. Does oral apigenin have real potential for a therapeutic effect in the context of human gastrointestinal and other cancers? Front. Pharmacol., 2021, 12, 681477.
[http://dx.doi.org/10.3389/fphar.2021.681477] [PMID: 34084146]
[41]
Ali, F. Rahul; Naz, F.; Jyoti, S.; Siddique, Y.H. Health functionality of apigenin: A review. Int. J. Food Prop., 2017, 20(6), 1197-1238.
[http://dx.doi.org/10.1080/10942912.2016.1207188]
[42]
Wang, M; Firrman, J; Liu, L; Yam, K. K. A review on flavonoid apigenin: Dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. Biomed. Res. Int., 2019, 7010467.
[http://dx.doi.org/10.1155/2019/7010467] [PMID: 31737673] [PMCID: PMC6817918]
[43]
Xie, Y.; Liang, D.; Wu, Q.; Chen, X.; Buabeid, M.A.; Wang, Y. A system-level investigation into the mechanisms of apigenin against inflammation. Nat. Prod. Commun., 2019, 14(19)
[http://dx.doi.org/10.1177/1934578X19878600]
[44]
Lee, J.H.; Zhou, H.Y.; Cho, S.Y.; Kim, Y.S.; Lee, Y.S.; Jeong, C.S. Anti-inflammatory mechanisms of apigenin: Inhibition of cyclooxygenase-2 expression, adhesion of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules. Arch. Pharm. Res., 2007, 30(10), 1318-1327.
[http://dx.doi.org/10.1007/BF02980273] [PMID: 18038911]
[45]
Shukla, S.; Gupta, S. Apigenin: A promising molecule for cancer prevention. Pharm. Res., 2010, 27(6), 962-978.
[http://dx.doi.org/10.1007/s11095-010-0089-7] [PMID: 20306120]
[46]
Swaminathan, A.; Basu, M.; Bekri, A.; Drapeau, P.; Kundu, T.K. The dietary flavonoid, luteolin, negatively affects neuronal differentiation. Front. Mol. Neurosci., 2019, 12, 41.
[http://dx.doi.org/10.3389/fnmol.2019.00041]
[47]
Taheri, Y.; Sharifi-Rad, J.; Antika, G. Yılmaz, Y.B.; Tumer, T.B.; Abuhamdah, S.; Chandra, S.; Saklani, S.; Kılıç, C.S.; Sestito, S.; Daştan, S.D.; Kumar, M.; Alshehri, M.M.; Rapposelli, S.; Cruz-Martins, N.; Cho, W.C. Paving luteolin therapeutic potentialities and agro-food-pharma applications: Emphasis on in vivo pharmacological effects and bioavailability traits. Oxid. Med. Cell. Longev., 2021, 2021, 1-20.
[http://dx.doi.org/10.1155/2021/1987588] [PMID: 34594472]
[48]
Aziz, N.; Kim, M.Y.; Cho, J.Y. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J. Ethnopharmacol., 2018, 225, 342-358.
[http://dx.doi.org/10.1016/j.jep.2018.05.019] [PMID: 29801717]
[49]
Nabavi, S.F.; Braidy, N.; Gortzi, O.; Sobarzo-Sanchez, E.; Daglia, M. Skalicka-Woźniak, K.; Nabavi, S.M. Luteolin as an antiinflammatory and neuroprotective agent: A brief review. Brain Res. Bull., 2015, 119(Pt A), 1-11.
[http://dx.doi.org/10.1016/j.brainresbull.2015.09.002] [PMID: 26361743]
[50]
Lin, Y.; Shi, R.; Wang, X.; Shen, H.M. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr. Cancer Drug Targets, 2008, 8(7), 634-646.
[http://dx.doi.org/10.2174/156800908786241050] [PMID: 18991571]
[51]
Gendrisch, F.; Esser, P.R.; Schempp, C.M.; Wölfle, U. Luteolin as a modulator of skin aging and inflammation. Biofactors, 2021, 47(2), 170-180.
[http://dx.doi.org/10.1002/biof.1699] [PMID: 33368702]
[52]
Wu, T.; Shu, T.; Kang, L.; Wu, J.; Xing, J.; Lu, Z.; Chen, S.; Lv, J. Icaritin, a novel plant-derived osteoinductive agent, enhances the osteogenic differentiation of human bone marrow- and human adipose tissue-derived mesenchymal stem cells. Int. J. Mol. Med., 2017, 39(4), 984-992.
[http://dx.doi.org/10.3892/ijmm.2017.2906] [PMID: 28260001]
[53]
Li, H.; Li, Y.; Ao, H.; Fu, J.; Guo, Y.; Han, M.; Yan, X.; Chen, X.; Wang, X. A comparative study on the in vitro and in vivo antitumor efficacy of icaritin and hydrous icaritin nanorods. Drug Deliv., 2020, 27(1), 1176-1187.
[http://dx.doi.org/10.1080/10717544.2020.1801892] [PMID: 32762483]
[54]
Peng, H.; Li, J.; Xu, Y.; Lv, G. Icaritin enhancing bone formation initiated by sub-microstructured calcium phosphate ceramic for critical size defect repair. Front. Mater., 2020, 7, 598057.
[http://dx.doi.org/10.3389/fmats.2020.598057]
[55]
Li, Z-J.; Yao, C.; Liu, S-F.; Chen, L.; Xi, Y-M.; Zhang, W.; Zhang, GS. Cytotoxic effect of icaritin and its mechanisms in inducing apoptosis in human burkitt lymphoma cell line. Biomed. res. Int., 2014, 391512.
[http://dx.doi.org/10.1155/2014/391512]
[56]
Yang, XJ; Xi, YM; Li, ZJ Icaritin: A Novel Natural Candidate for Hematological Malignancies Therapy. Biomed. Res. Int., 2019, Mar 28, 2019, 4860268.
[http://dx.doi.org/10.1155/2019/4860268] [PMID: 31032347]
[57]
Li, S.; Priceman, S.J.; Xin, H.; Zhang, W.; Deng, J.; Liu, Y.; Huang, J.; Zhu, W.; Chen, M.; Hu, W.; Deng, X.; Zhang, J.; Yu, H.; He, G. Icaritin inhibits JAK/STAT3 signaling and growth of renal cell carcinoma. PLoS One, 2013, 8(12), e81657.
[http://dx.doi.org/10.1371/journal.pone.0081657] [PMID: 24324713]
[58]
Semwal, D.; Semwal, R.; Combrinck, S.; Viljoen, A. Myricetin: A dietary molecule with diverse biological activities. Nutrients, 2016, 8(2), 90.
[http://dx.doi.org/10.3390/nu8020090] [PMID: 26891321]
[59]
Taheri, Y.; Suleria, H.A.R.; Martins, N.; Sytar, O.; Beyatli, A.; Yeskaliyeva, B.; Seitimova, G.; Salehi, B.; Semwal, P.; Painuli, S.; Kumar, A.; Azzini, E.; Martorell, M.; Setzer, W.N.; Maroyi, A.; Sharifi-Rad, J. Myricetin bioactive effects: Moving from preclinical evidence to potential clinical applications. BMC Compl. Med. Therap., 2020, 20(1), 241.
[http://dx.doi.org/10.1186/s12906-020-03033-z] [PMID: 32738903]
[60]
Imran, M.; Saeed, F.; Hussain, G.; Imran, A.; Mehmood, Z.; Gondal, T.A.; El-Ghorab, A.; Ahmad, I.; Pezzani, R.; Arshad, M.U.; Bacha, U.; Shariarti, M.A.; Rauf, A.; Muhammad, N.; Shah, Z.A.; Zengin, G.; Islam, S. Myricetin: A comprehensive review on its biological potentials. Food Sci. Nutr., 2021, 9(10), 5854-5868.
[http://dx.doi.org/10.1002/fsn3.2513] [PMID: 34646551]
[61]
Park, K.S.; Chong, Y.; Kim, M.K. Myricetin: Biological activity related to human health. Appl. Biol. Chem., 2016, 59(2), 259-269.
[http://dx.doi.org/10.1007/s13765-016-0150-2]
[62]
Stahlhut, S.G.; Siedler, S.; Malla, S.; Harrison, S.J.; Maury, J.; Neves, A.R.; Forster, J. Assembly of a novel biosynthetic pathway for production of the plant flavonoid fisetin in Escherichia coli. Metab. Eng., 2015, 31, 84-93.
[http://dx.doi.org/10.1016/j.ymben.2015.07.002] [PMID: 26192693]
[63]
Singh, P.; Arif, Y.; Bajguz, A.; Hayat, S. The role of quercetin in plants. Plant Physiol. Biochem., 2021, 166, 10-19.
[http://dx.doi.org/10.1016/j.plaphy.2021.05.023] [PMID: 34087741]
[64]
Marín, L.; Gutiérrez-del-Río, I.; Entrialgo-Cadierno, R.; Villar, C.J.; Lombó, F. De novo biosynthesis of myricetin, kaempferol and quercetin in Streptomyces albus and Streptomyces coelicolor. PLoS One, 2018, 13(11), e0207278.
[http://dx.doi.org/10.1371/journal.pone.0207278] [PMID: 30440014]
[65]
Zhao, C.; Wang, F.; Lian, Y.; Xiao, H.; Zheng, J. Biosynthesis of citrus flavonoids and their health effects. Crit. Rev. Food Sci. Nutr., 2020, 60(4), 566-583.
[http://dx.doi.org/10.1080/10408398.2018.1544885] [PMID: 30580548]
[66]
Lee, H.; Kim, B.G.; Kim, M.; Ahn, J.H. Biosynthesis of two flavones, apigenin and genkwanin, in Escherichia coli. J. Microbiol. Biotechnol., 2015, 25(9), 1442-1448.
[http://dx.doi.org/10.4014/jmb.1503.03011] [PMID: 25975614]
[67]
Marín, L.; Gutiérrez-del-Río, I.; Yagüe, P.; Manteca, Á.; Villar, C.J.; Lombó, F. De Novo Biosynthesis of Apigenin, Luteolin, and Eriodictyol in the Actinomycete Streptomyces albus and production improvement by feeding and spore conditioning. Front. Microbiol., 2017, 8, 921.
[http://dx.doi.org/10.3389/fmicb.2017.00921] [PMID: 28611737]
[68]
Wang, P.; Li, C.; Li, X.; Huang, W.; Wang, Y.; Wang, J.; Zhang, Y.; Yang, X.; Yan, X.; Wang, Y.; Zhou, Z. Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli. Sci. Bull., 2021, 66(18), 1906-1916.
[http://dx.doi.org/10.1016/j.scib.2021.03.002]
[69]
Irmisch, S.; Ruebsam, H.; Jancsik, S.; Man Saint Yuen, M.; Madilao, L.L.; Bohlmann, J. Flavonol biosynthesis genes and their use in engineering the plant antidiabetic metabolite montbretin A. Plant Physiol., 2019, 180(3), 1277-1290.
[http://dx.doi.org/10.1104/pp.19.00254] [PMID: 31004005]
[70]
Looker, J.H.; McMechan, J.H.; Mader, J.W. An amine solvent modification of the Kostanecki-Robinson reaction. Application to the synthesis of flavonols. J. Org. Chem., 1978, 43(12), 2344-2347.
[http://dx.doi.org/10.1021/jo00406a008]
[71]
Allan, J.; Robinson, R. CCCIX.—A new synthesis of fisetin and of quercetin. J. Chem. Soc., 1926, 129(0), 2334-2336.
[http://dx.doi.org/10.1039/JR9262902334]
[72]
Kostanecki, S.; Lampe, V. Tambor, J. Synthese des quercetins. Euro. J. Inorg. Chem., 1957, 37, 1402.
[73]
Booth, A.N.; DeEds, F. Isolation of quercitrin and quercetin from lemon flavine. J. Am. Pharm. Assoc., 1951, 40(8), 384-385.
[http://dx.doi.org/10.1002/jps.3030400809] [PMID: 14861094]
[74]
Wang, Q.; Cui, W.; Liu, M.; Zhang, J.; Liao, R.; Liao, X.; Yang, J. An improved synthesis of apigenin. J. Chem. Res., 2015, 39(2), 67-69.
[http://dx.doi.org/10.3184/174751915X14204548288464]
[75]
Zhang, J.; Liu, M.; Cui, W.; Yang, J.; Yang, B. Total synthesis of luteolin. J. Chem. Res., 2014, 38(1), 60-61.
[http://dx.doi.org/10.3184/174751914X13867643876192]
[76]
Mei, Q.; Wang, C.; Zhao, Z.; Yuan, W.; Zhang, G. Synthesis of icariin from kaempferol through regioselective methylation and para -Claisen–Cope rearrangement. Beilstein J. Org. Chem., 2015, 11, 1220-1225.
[http://dx.doi.org/10.3762/bjoc.11.135] [PMID: 26425179]
[77]
Tong, J.; Liu, C.; Wang, B. Improved synthesis of icaritin and total synthesis of β- anhydroicaritin. Chem. Res. Chin. Univ., 2019, 35(4), 616-620.
[http://dx.doi.org/10.1007/s40242-019-9012-x]
[78]
Kalff, J.; Robinson, R. XXVIII.—A synthesis of myricetin and of a galangin monomethyl ether occurring in galanga root. J. Chem. Soc. Trans., 1925, 127(0), 181-184.
[http://dx.doi.org/10.1039/CT9252700181]
[79]
Ramachandra Row, L.; Seshadri, T.R.; Thiruvengadam, T.R. (1949)Nuclear oxidation in flavones and related compounds. Part XIX. A new synthesis of Robinetin and Kanugin Proceedings of the Indian Academy of Sciences, Section A, 1949, 29(3), pp. 168-170. ISSN 0370-0089.
[http://dx.doi.org/10.1007/BF03171364]
[80]
Kaur, H; Kaur, G. A critical appraisal of solubility enhancement techniques of polyphenols. J. Pharm., 2014, 2014
[http://dx.doi.org/10.1155/2014/180845]
[81]
Hanske, L.; Loh, G.; Sczesny, S.; Blaut, M.; Braune, A. The bioavailability of apigenin-7-glucoside is influenced by human intestinal microbiota in rats. J. Nutr., 2009, 139(6), 1095-1102.
[http://dx.doi.org/10.3945/jn.108.102814] [PMID: 19403720]
[82]
Zhang, J.; Liu, D.; Huang, Y.; Gao, Y.; Qian, S. Biopharmaceutics classification and intestinal absorption study of apigenin. Int. J. Pharm., 2012, 436(1-2), 311-317.
[http://dx.doi.org/10.1016/j.ijpharm.2012.07.002] [PMID: 22796171]
[83]
Liu, Y.; Hu, M. Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model. Drug Metab. Dispos., 2002, 30(4), 370-377.
[http://dx.doi.org/10.1124/dmd.30.4.370] [PMID: 11901089]
[84]
Griffiths, L.A.; Smith, G.E. Metabolism of apigenin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. Biochem. J., 1972, 128(4), 901-911.
[http://dx.doi.org/10.1042/bj1280901] [PMID: 4638796]
[85]
Tang, D.; Chen, K.; Huang, L.; Li, J. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert Opin. Drug Metab. Toxicol., 2017, 13(3), 323-330.
[http://dx.doi.org/10.1080/17425255.2017.1251903] [PMID: 27766890]
[86]
Gradolatto, A.; Basly, J.P.; Berges, R.; Teyssier, C.; Chagnon, M.C.; Siess, M.H.; Canivenc-Lavier, M.C. Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metab. Dispos., 2005, 33(1), 49-54.
[http://dx.doi.org/10.1124/dmd.104.000893] [PMID: 15466493]
[87]
Kadari, A.; Gudem, S.; Kulhari, H.; Bhandi, M.M.; Borkar, R.M.; Kolapalli, V.R.M.; Sistla, R. Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles. Drug Deliv., 2017, 24(1), 224-232.
[http://dx.doi.org/10.1080/10717544.2016.1245366] [PMID: 28156161]
[88]
Syed, D.N.; Adhami, V.M.; Khan, N.; Khan, M.I.; Mukhtar, H. Exploring the molecular targets of dietary flavonoid fisetin in cancer. Semin. Cancer Biol., 2016, 40-41, 130-140.
[http://dx.doi.org/10.1016/j.semcancer.2016.04.003] [PMID: 27163728]
[89]
Touil, Y.S.; Auzeil, N.; Boulinguez, F.; Saighi, H.; Regazzetti, A.; Scherman, D.; Chabot, G.G. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. Biochem. Pharmacol., 2011, 82(11), 1731-1739.
[http://dx.doi.org/10.1016/j.bcp.2011.07.097] [PMID: 21840301]
[90]
Huang, M.C.; Hsueh, T.Y.; Cheng, Y.Y.; Lin, L.C.; Tsai, T.H. Pharmacokinetics and biliary excretion of fisetin in rats. J. Agric. Food Chem., 2018, 66(25), 6300-6307.
[http://dx.doi.org/10.1021/acs.jafc.8b00917] [PMID: 29862816]
[91]
Fang, G.; Cheng, C.; Zhang, M.; Ma, X.; Yang, S.; Hou, X.; Deng, J.; Hou, Y.; Bai, G. The glucuronide metabolites of kaempferol and quercetin, targeting to the AKT PH domain, activate AKT/GSK3β signaling pathway and improve glucose metabolism. J. Funct. Foods, 2021, 82, 104501.
[http://dx.doi.org/10.1016/j.jff.2021.104501]
[92]
Ren, J.; Lu, Y.; Qian, Y.; Chen, B.; Wu, T.; Ji, G. Recent progress regarding kaempferol for the treatment of various diseases. (Review). Exp. Ther. Med., 2019, 18(4), 2759-2776.
[http://dx.doi.org/10.3892/etm.2019.7886] [PMID: 31572524]
[93]
Dabeek, W.M.; Marra, M.V. Dietary quercetin and kaempferol: Bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients, 2019, 11(10), 2288.
[http://dx.doi.org/10.3390/nu11102288] [PMID: 31557798]
[94]
de Vries, J.H.; Hollman, P.C.; Meyboom, S.; Buysman, M.N.; Zock, P.L.; van Staveren, W.A.; Katan, M.B. Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake. Am. J. Clin. Nutr., 1998, 68(1), 60-65.
[http://dx.doi.org/10.1093/ajcn/68.1.60] [PMID: 9665097]
[95]
Bonetti, A.; Marotti, I.; Dinelli, G. Urinary excretion of kaempferol from common beans (Phaseolus vulgaris L.) in humans. Int. J. Food Sci. Nutr., 2007, 58(4), 261-269.
[http://dx.doi.org/10.1080/09637480601154228] [PMID: 17566888]
[96]
DuPont, M.S.; Day, A.J.; Bennett, R.N.; Mellon, F.A.; Kroon, P.A. Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans. Eur. J. Clin. Nutr., 2004, 58(6), 947-954.
[http://dx.doi.org/10.1038/sj.ejcn.1601916] [PMID: 15164116]
[97]
Barve, A.; Chen, C.; Hebbar, V.; Desiderio, J.; Saw, C.L.L.; Kong, A.N. Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats. Biopharm. Drug Dispos., 2009, 30(7), 356-365.
[http://dx.doi.org/10.1002/bdd.677] [PMID: 19722166]
[98]
Zabela, V.; Sampath, C.; Oufir, M.; Moradi-Afrapoli, F.; Butterweck, V.; Hamburger, M. Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats. Fitoterapia, 2016, 115, 189-197.
[http://dx.doi.org/10.1016/j.fitote.2016.10.008] [PMID: 27810397]
[99]
Nielsen, I.L.F.; Chee, W.S.S.; Poulsen, L.; Offord-Cavin, E.; Rasmussen, S.E.; Frederiksen, H.; Enslen, M.; Barron, D.; Horcajada, M.N.; Williamson, G. Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial. J. Nutr., 2006, 136(2), 404-408.
[http://dx.doi.org/10.1093/jn/136.2.404] [PMID: 16424119]
[100]
Manach, C.; Morand, C.; Gil-Izquierdo, A.; Bouteloup-Demange, C.; Rémésy, C. Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice. Eur. J. Clin. Nutr., 2003, 57(2), 235-242.
[http://dx.doi.org/10.1038/sj.ejcn.1601547] [PMID: 12571654]
[101]
Guo, X.; Li, K.; Guo, A.; Li, E. Intestinal absorption and distribution of naringin, hesperidin, and their metabolites in mice. J. Funct. Foods, 2020, 74, 104158.
[http://dx.doi.org/10.1016/j.jff.2020.104158]
[102]
Hering, A.; Ochocka, J.R.; Baranska, H.; Cal, K.; Stefanowicz-Hajduk, J. Mangiferin and hesperidin transdermal distribution and permeability through the skin from solutions and honeybush extracts (Cyclopia sp.)—A comparison ex vivo study. Molecules, 2021, 26(21), 6547.
[http://dx.doi.org/10.3390/molecules26216547] [PMID: 34770957]
[103]
Nectoux, A.M.; Abe, C.; Huang, S.W.; Ohno, N.; Tabata, J.; Miyata, Y.; Tanaka, K.; Tanaka, T.; Yamamura, H.; Matsui, T. Absorption and metabolic behavior of hesperidin (Rutinosylated Hesperetin) after single oral administration to sprague-dawley rats. J. Agric. Food Chem., 2019, 67(35), 9812-9819.
[http://dx.doi.org/10.1021/acs.jafc.9b03594] [PMID: 31392887]
[104]
Boonpawa, R.; Spenkelink, A.; Punt, A.; Rietjens, I.M.C.M. Physiologically based kinetic modeling of hesperidin metabolism and its use to predict in vivo effective doses in humans. Mol. Nutr. Food Res., 2017, 61(8), 1600894.
[http://dx.doi.org/10.1002/mnfr.201600894] [PMID: 28218440]
[105]
Jiao, Q.; Xu, L.; Jiang, L.; Jiang, Y.; Zhang, J.; Liu, B. Metabolism study of hesperetin and hesperidin in rats by UHPLC-LTQ-Orbitrap MSn. Xenobiotica, 2020, 50(11), 1311-1322.
[http://dx.doi.org/10.1080/00498254.2019.1567956] [PMID: 30654682]
[106]
Hollman, P.C.; de Vries, J.H.; van Leeuwen, S.D.; Mengelers, M.J.; Katan, M.B. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am. J. Clin. Nutr., 1995, 62(6), 1276-1282.
[http://dx.doi.org/10.1093/ajcn/62.6.1276] [PMID: 7491892]
[107]
Yang, L.L.; Xiao, N.; Li, X.W.; Fan, Y.; Alolga, R.N.; Sun, X.Y.; Wang, S.L.; Li, P.; Qi, L.W. Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS. Sci. Rep., 2016, 6(1), 35460.
[http://dx.doi.org/10.1038/srep35460] [PMID: 27775094]
[108]
Sharma, A.; Kashyap, D.; Sak, K.; Tuli, H.S.; Sharma, A.K. Therapeutic charm of quercetin and its derivatives: A review of research and patents. Pharm. Pat. Anal., 2018, 7(1), 15-32.
[http://dx.doi.org/10.4155/ppa-2017-0030] [PMID: 29227203]
[109]
Lee, J.; Mitchell, A.E. Pharmacokinetics of quercetin absorption from apples and onions in healthy humans. J. Agric. Food Chem., 2012, 60(15), 3874-3881.
[http://dx.doi.org/10.1021/jf3001857] [PMID: 22439822]
[110]
Ou-yang, Z.; Cao, X.; Wei, Y.; Zhang, W.W.Q.; Zhao, M.; Duan, J. Pharmacokinetic study of rutin and quercetin in rats after oral administration of total flavones of mulberry leaf extract. Rev. Bras. Farmacogn., 2013, 23(5), 776-782.
[http://dx.doi.org/10.1590/S0102-695X2013000500009]
[111]
Young, J.F.; Nielsen, S.E.; Haraldsdóttir, J.; Daneshvar, B.; Lauridsen, S.T.; Knuthsen, P.; Crozier, A.; Sandström, B.; Dragsted, L.O. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status. Am. J. Clin. Nutr., 1999, 69(1), 87-94.
[http://dx.doi.org/10.1093/ajcn/69.1.87] [PMID: 9925128]
[112]
Hai, Y.; Zhang, Y.; Liang, Y.; Ma, X.; Qi, X.; Xiao, J.; Xue, W.; Luo, Y.; Yue, T. Advance on the absorption, metabolism, and efficacy exertion of quercetin and its important derivatives. Food Front., 2020, 1(4), 420-434.
[http://dx.doi.org/10.1002/fft2.50]
[113]
Konrad, M.; Nieman, D.C. Evaluation of quercetin as a countermeasure to exercise-induced physiological stress. Antioxid Sport Nutr, 2014, 10, 155-170.
[http://dx.doi.org/10.1201/b17442-10]
[114]
Walle, T.; Walle, U.K.; Halushka, P.V. Carbon dioxide is the major metabolite of quercetin in humans. J. Nutr., 2001, 131(10), 2648-2652.
[http://dx.doi.org/10.1093/jn/131.10.2648] [PMID: 11584085]
[115]
Graefe, E.U.; Wittig, J.; Mueller, S.; Riethling, A.K.; Uehleke, B.; Drewelow, B.; Pforte, H.; Jacobasch, G.; Derendorf, H.; Veit, M. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J. Clin. Pharmacol., 2001, 41(5), 492-499.
[http://dx.doi.org/10.1177/00912700122010366] [PMID: 11361045]
[116]
Shimoi, K.; Okada, H.; Furugori, M.; Goda, T.; Takase, S.; Suzuki, M.; Hara, Y.; Yamamoto, H.; Kinae, N. Intestinal absorption of luteolin and luteolin 7- O -β-glucoside in rats and humans. FEBS Lett., 1998, 438(3), 220-224.
[http://dx.doi.org/10.1016/S0014-5793(98)01304-0] [PMID: 9827549]
[117]
Zhou, P.; Li, L.P.; Luo, S.Q.; Jiang, H.D.; Zeng, S. Intestinal absorption of luteolin from peanut hull extract is more efficient than that from individual pure luteolin. J. Agric. Food Chem., 2008, 56(1), 296-300.
[http://dx.doi.org/10.1021/jf072612+] [PMID: 18052241]
[118]
Wang, L.; Chen, Q.; Zhu, L.; Li, Q.; Zeng, X.; Lu, L.; Hu, M.; Wang, X.; Liu, Z. Metabolic disposition of luteolin is mediated by the interplay of UDP-glucuronosyltransferases and catechol-O-methyltransferases in rats. Drug Metab. Dispos., 2017, 45(3), 306-315.
[http://dx.doi.org/10.1124/dmd.116.073619] [PMID: 28031430]
[119]
Boersma, M.G.; van der Woude, H.; Bogaards, J.; Boeren, S.; Vervoort, J.; Cnubben, N.H.P.; van Iersel, M.L.P.S.; van Bladeren, P.J.; Rietjens, I.M.C.M. Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases. Chem. Res. Toxicol., 2002, 15(5), 662-670.
[http://dx.doi.org/10.1021/tx0101705] [PMID: 12018987]
[120]
Deng, C.; Gao, C.; Tian, X.; Chao, B.; Wang, F.; Zhang, Y.; Zou, J.; Liu, D. Pharmacokinetics, tissue distribution and excretion of luteolin and its major metabolites in rats: Metabolites predominate in blood, tissues and are mainly excreted via bile. J. Funct. Foods, 2017, 35, 332-340.
[http://dx.doi.org/10.1016/j.jff.2017.05.056]
[121]
Tang, C.; Chen, X.; Yao, H.; Yin, H.; Ma, X.; Jin, M.; Lu, X.; Wang, Q.; Meng, K.; Yuan, Q. Enhanced Oral Absorption of Icaritin by Using Mixed Polymeric Micelles Prepared with a Creative Acid-Base Shift Method. Molecules, 2021, 26(11), 3450.
[http://dx.doi.org/10.3390/molecules26113450] [PMID: 34204150]
[122]
Zhang, S.Q.; Zhang, S.Z. Oral absorption, distribution, metabolism, and excretion of icaritin in rats by Q-TOF and UHPLC-MS/MS. Drug Test. Anal., 2017, 9(10), 1604-1610.
[http://dx.doi.org/10.1002/dta.2188] [PMID: 28303675]
[123]
Chang, Q.; Wang, G.N.; Li, Y.; Zhang, L.; You, C.; Zheng, Y. Oral absorption and excretion of icaritin, an aglycone and also active metabolite of prenylflavonoids from the Chinese medicine Herba Epimedii in rats. Phytomedicine, 2012, 19(11), 1024-1028.
[http://dx.doi.org/10.1016/j.phymed.2012.05.017] [PMID: 22762938]
[124]
Huang, Z.W.; Yang, Y.X.; Huang, L.H.; Zhang, S.Q. Pharmacokinetics and metabolism of icaritin in rats by UPLC‐MS/MS. Food Sci. Nutr., 2019, 7(12), 4001-4006.
[http://dx.doi.org/10.1002/fsn3.1263] [PMID: 31890179]
[125]
Soorya, C.; Balamurugan, S.; Ramya, S.; Neethirajan, K.; Kandeepan, C.; Jayakumararaj, R. Physicochemical, ADMET and druggable properties of myricetin: A Key Flavonoid in Syzygium cumini that regulates metabolic inflammations. J. Drug Deliv. Ther., 2021, 11(4), 66-73.
[http://dx.doi.org/10.22270/jddt.v11i4.4890]
[126]
Dang, Y.; Lin, G.; Xie, Y.; Duan, J.; Ma, P.; Li, G.; Ji, G. Quantitative determination of myricetin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its absolute bioavailability. Drug Res., 2014, 64(10), 516-522.
[PMID: 24357136]
[127]
Zhang, S.; Wang, R.; Zhao, Y.; Tareq, F.S.; Sang, S. Biotransformation of myricetin: A novel metabolic pathway to produce aminated products in mice. Mol. Nutr. Food Res., 2019, 63(14), 1900203.
[http://dx.doi.org/10.1002/mnfr.201900203] [PMID: 31087612]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy