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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

The Advances and Challenges in Enzymatic C-glycosylation of Flavonoids in Plants

Author(s): Hui-Yao Gao, Yan Liu, Fei-Fan Tan, Li-Wen Zhu, Kai-Zhi Jia* and Ya-Jie Tang

Volume 28, Issue 18, 2022

Published on: 24 June, 2022

Page: [1466 - 1479] Pages: 14

DOI: 10.2174/1381612828666220422085128

Price: $65

Abstract

Flavonoid glycosides play determinant roles in plants and have considerable potential for applications in medicine and biotechnology. Glycosyltransferases transfer a sugar moiety from uridine diphosphateactivated sugar molecules to an acceptor flavonoid via C-O and C-C linkages. Compared with O-glycosyl flavonoids, C-glycosyl flavonoids are more stable, resistant to glycosidase or acid hydrolysis, exhibit better pharmacological properties, and have received more attention. In this study, we discuss the mining of C-glycosyl flavones and the corresponding C-glycosyltransferases and evaluate the differences in structure and catalytic mechanisms between C-glycosyltransferase and O-glycosyltransferase. We conclude that promiscuity and specificity are key determinants for general flavonoid C-glycosyltransferase engineering and summarize the C-glycosyltransferase engineering strategy. A thorough understanding of the properties, catalytic mechanisms, and engineering of C-glycosyltransferases will be critical for future biotechnological applications in areas such as the production of desired C-glycosyl flavonoids for nutritional or medicinal use.

Keywords: Flavonoid glycosyltransferase, O-glycosyltransferase, catalytic mechanism, promiscuity, specificity engineering, c-glycosylation.

« Previous Next »
[1]
Yang M, Fehl C, Lees KV, et al. Functional and informatics analysis enables glycosyltransferase activity prediction. Nat Chem Biol 2018; 14(12): 1109-17.
[http://dx.doi.org/10.1038/s41589-018-0154-9] [PMID: 30420693]
[2]
Liang DM, Liu JH, Wu H, Wang BB, Zhu HJ, Qiao JJ. Glycosyltransferases: Mechanisms and applications in natural product develop-ment. Chem Soc Rev 2015; 44(22): 8350-74.
[http://dx.doi.org/10.1039/C5CS00600G] [PMID: 26330279]
[3]
Thibodeaux CJ, Melançon CE III, Liu HW. Natural-product sugar biosynthesis and enzymatic glycodiversification. Angew Chem Int Ed Engl 2008; 47(51): 9814-59.
[http://dx.doi.org/10.1002/anie.200801204] [PMID: 19058170]
[4]
Elshahawi SI, Shaaban KA, Kharel MK, Thorson JS. A comprehensive review of glycosylated bacterial natural products. Chem Soc Rev 2015; 44(21): 7591-697.
[http://dx.doi.org/10.1039/C4CS00426D] [PMID: 25735878]
[5]
De Bruyn F, Maertens J, Beauprez J, Soetaert W, De Mey M. Biotechnological advances in UDP-sugar based glycosylation of small mol-ecules. Biotechnol Adv 2015; 33(2): 288-302.
[http://dx.doi.org/10.1016/j.biotechadv.2015.02.005] [PMID: 25698505]
[6]
Ahmed OM. Natural flavonoids: Chemistry, therapeutic potentials, therapeutic targets and mechanisms of actions. Curr Pharm Des 2021; 27(4): 455.
[http://dx.doi.org/10.2174/138161282704210210113537] [PMID: 33685386]
[7]
Mutha RE, Tatiya AU, Surana SJ. Flavonoids as natural phenolic compounds and their role in therapeutics: An overview. Futur J Pharm Sci 2021; 7(1): 25.
[http://dx.doi.org/10.1186/s43094-020-00161-8] [PMID: 33495733]
[8]
Xiao J, Muzashvili TS, Georgiev MI. Advances in the biotechnological glycosylation of valuable flavonoids. Biotechnol Adv 2014; 32(6): 1145-56.
[http://dx.doi.org/10.1016/j.biotechadv.2014.04.006] [PMID: 24780153]
[9]
Naeem A, Ming Y, Pengyi H, et al. The fate of flavonoids after oral administration: A comprehensive overview of its bioavailability. Crit Rev Food Sci Nutr 2021; 1-18.
[http://dx.doi.org/10.1080/10408398.2021.1898333] [PMID: 33847202]
[10]
Musumeci L, Maugeri A, Cirmi S, et al. Citrus fruits and their flavonoids in inflammatory bowel disease: An overview. Nat Prod Res 2020; 34(1): 122-36.
[http://dx.doi.org/10.1080/14786419.2019.1601196] [PMID: 30990326]
[11]
Alkhalidy H, Wang Y, Liu D. Dietary flavonoids in the prevention of T2D: An overview. Nutrients 2018; 10(4): 438.
[http://dx.doi.org/10.3390/nu10040438] [PMID: 29614722]
[12]
Zhao J, Yang J, Xie Y. Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview. Int J Pharm 2019; 570: 118642.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118642] [PMID: 31446024]
[13]
Su HX, Yao S, Zhao WF, et al. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol Sin 2020; 41(9): 1167-77.
[http://dx.doi.org/10.1038/s41401-020-0483-6] [PMID: 32737471]
[14]
Shadrack DM, Deogratias G, Kiruri LW, Swai HS, Vianney JM, Nyandoro SS. Ensemble-based screening of natural products and FDA-approved drugs identified potent inhibitors of SARS-CoV-2 that work with two distinct mechanisms. J Mol Graph Model 2021; 105: 107871.
[http://dx.doi.org/10.1016/j.jmgm.2021.107871] [PMID: 33684603]
[15]
Kempuraj D, Thangavel R, Kempuraj DD, et al. Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma. Biofactors 2021; 47(2): 190-7.
[http://dx.doi.org/10.1002/biof.1687] [PMID: 33098588]
[16]
McIntosh CA, Owens DK. Advances in flavonoid glycosyltransferase research: Integrating recent findings with long-term citrus studies. Phytochem Rev 2016; 15(6): 1075-91.
[http://dx.doi.org/10.1007/s11101-016-9460-6]
[17]
Bililign T, Griffith BR, Thorson JS. Structure, activity, synthesis and biosynthesis of aryl-C-glycosides. Nat Prod Rep 2005; 22(6): 742-60.
[http://dx.doi.org/10.1039/b407364a] [PMID: 16311633]
[18]
Hultin PG. Bioactive C-glycosides from bacterial secondary metabolism. Curr Top Med Chem 2005; 5(14): 1299-331.
[http://dx.doi.org/10.2174/156802605774643015] [PMID: 16305533]
[19]
Jesus AR, Vila-Viçosa D, Machuqueiro M, Marques AP, Dore TM, Rauter AP. Targeting type 2 diabetes with C-glucosyl dihydrochal-cones as selective sodium glucose co-transporter 2 (SGLT2) Inhibitors: Synthesis and biological evaluation. J Med Chem 2017; 60(2): 568-79.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01134] [PMID: 28098449]
[20]
Yang Y, Yu B. Recent Advances in the chemical synthesis of C-glycosides. Chem Rev 2017; 117(19): 12281-356.
[http://dx.doi.org/10.1021/acs.chemrev.7b00234] [PMID: 28915018]
[21]
Satoh H, Manabe S. Design of chemical glycosyl donors: Does changing ring conformation influence selectivity/reactivity? Chem Soc Rev 2013; 42(10): 4297-309.
[http://dx.doi.org/10.1039/c3cs35457a] [PMID: 23364773]
[22]
Lemaire S, Houpis IN, Xiao T, et al. Stereoselective C-glycosylation reactions with arylzinc reagents. Org Lett 2012; 14(6): 1480-3.
[http://dx.doi.org/10.1021/ol300220p] [PMID: 22385274]
[23]
Chen D, Chen R, Wang R, et al. Probing the catalytic promiscuity of a regio- and stereospecific C-glycosyltransferase from Mangifera indica. Angew Chem Int Ed Engl 2015; 54(43): 12678-82.
[http://dx.doi.org/10.1002/anie.201506505] [PMID: 26331569]
[24]
Hoffmeister D, Dräger G, Ichinose K, Rohr J, Bechthold A. The C-Glycosyltransferase UrdGT2 is unselective toward d- and l-configured nucleotide-bound rhodinoses. J Am Chem Soc 2003; 125(16): 4678-9.
[http://dx.doi.org/10.1021/ja029645k] [PMID: 12696864]
[25]
He JB, Zhao P, Hu ZM, et al. Molecular characterization and structural basis of a prosmiscuous C-glycosyltransferase from Trollius chinensis. Angew Chem Int Ed Engl 2019; 58(33): 11513-20.
[http://dx.doi.org/10.1002/anie.201905505] [PMID: 31163097]
[26]
Zhang M, Li FD, Li K, et al. Functional characterization and structural basis of an efficient di-C-glycosyltransferase from Glycyrrhiza glabra. J Am Chem Soc 2020; 142(7): 3506-12.
[http://dx.doi.org/10.1021/jacs.9b12211] [PMID: 31986016]
[27]
Liu M, Wang D, Li Y, et al. Crystal structures of the C-glycosyltransferase UGT708C1 from buckwheat provide insights into the mecha-nism of C-glycosylation. Plant Cell 2020; 32(9): 2917-31.
[http://dx.doi.org/10.1105/tpc.20.00002] [PMID: 32699169]
[28]
Fang R, Veitch NC, Kite GC, Porter EA, Simmonds MS. Enhanced profiling of flavonol glycosides in the fruits of sea buckthorn (Hip-pophae rhamnoides). J Agric Food Chem 2013; 61(16): 3868-75.
[http://dx.doi.org/10.1021/jf304604v] [PMID: 23517173]
[29]
Pugliese AG, Tomas-Barberan FA, Truchado P, Genovese MI. Flavonoids, proanthocyanidins, vitamin C, and antioxidant activity of Theobroma grandiflorum (Cupuassu) pulp and seeds. J Agric Food Chem 2013; 61(11): 2720-8.
[http://dx.doi.org/10.1021/jf304349u] [PMID: 23431956]
[30]
Taheri R, Connolly BA, Brand MH, Bolling BW. Underutilized chokeberry (Aronia melanocarpa, Aronia arbutifolia, Aronia prunifolia) accessions are rich sources of anthocyanins, flavonoids, hydroxycinnamic acids, and proanthocyanidins. J Agric Food Chem 2013; 61(36): 8581-8.
[http://dx.doi.org/10.1021/jf402449q] [PMID: 23941506]
[31]
Mathesius U. Flavonoid functions in plants and their interactions with other organisms. Plants 2018; 7(2): 30.
[http://dx.doi.org/10.3390/plants7020030] [PMID: 29614017]
[32]
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci 2016; 5: e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[33]
Song W, Qiao X, Chen K, et al. Biosynthesis-based quantitative analysis of 151 secondary metabolites of licorice to differentiate medici-nal Glycyrrhiza species and their hybrids. Anal Chem 2017; 89(5): 3146-53.
[http://dx.doi.org/10.1021/acs.analchem.6b04919] [PMID: 28192986]
[34]
Wang ZL, Gao HM, Wang S, et al. Dissection of the general two-step di-C-glycosylation pathway for the biosynthesis of (iso)schaftosides in higher plants. Proc Natl Acad Sci USA 2020; 117(48): 30816-23.
[http://dx.doi.org/10.1073/pnas.2012745117] [PMID: 33199630]
[35]
Galland M, Boutet-Mercey S, Lounifi I, et al. Compartmentation and dynamics of flavone metabolism in dry and germinated rice seeds. Plant Cell Physiol 2014; 55(9): 1646-59.
[http://dx.doi.org/10.1093/pcp/pcu095] [PMID: 25008975]
[36]
Hao PY, Feng YL, Zhou YS, et al. Schaftoside interacts with NICDK1 protein: A mechanism of rice resistance to brown planthopper, Nilaparvata lugens. Front Plant Sci 2018; 9: 710.
[http://dx.doi.org/10.3389/fpls.2018.00710] [PMID: 29896209]
[37]
Khan ZR, Midega CAO, Bruce TJA, Hooper AM, Pickett JA. Exploiting phytochemicals for developing a ‘push-pull’ crop protection strategy for cereal farmers in Africa. J Exp Bot 2010; 61(15): 4185-96.
[http://dx.doi.org/10.1093/jxb/erq229] [PMID: 20670998]
[38]
Uawisetwathana U, Chevallier OP, Xu Y, et al. Global metabolite profiles of rice brown planthopper-resistant traits reveal potential sec-ondary metabolites for both constitutive and inducible defenses. Metabolomics 2019; 15(12): 151.
[http://dx.doi.org/10.1007/s11306-019-1616-0] [PMID: 31741127]
[39]
Wei SY, Chen Y, Xu XY. Progress on the pharmacological research of puerarin: A review. Chin J Nat Med 2014; 12(6): 407-14.
[http://dx.doi.org/10.1016/S1875-5364(14)60064-9] [PMID: 24969520]
[40]
Ho TC, Kamimura H, Ohmori K, Suzuki K. Total synthesis of (+)-vicenin-2. Org Lett 2016; 18(18): 4488-90.
[http://dx.doi.org/10.1021/acs.orglett.6b02203] [PMID: 27569251]
[41]
Ku SK, Bae JS. Vicenin-2 and scolymoside inhibit high-glucose-induced vascular inflammation in vitro and in vivo. Can J Physiol Pharmacol 2016; 94(3): 287-95.
[http://dx.doi.org/10.1139/cjpp-2015-0215] [PMID: 26766560]
[42]
Ito T, Fujimoto S, Suito F, Shimosaka M, Taguchi G. C-Glycosyltransferases catalyzing the formation of di-C-glucosyl flavonoids in citrus plants. Plant J 2017; 91(2): 187-98.
[http://dx.doi.org/10.1111/tpj.13555] [PMID: 28370711]
[43]
Putkaradze N, Teze D, Fredslund F, Welner DH. Natural product C-glycosyltransferases - a scarcely characterised enzymatic activity with biotechnological potential. Nat Prod Rep 2021; 38(3): 432-43.
[http://dx.doi.org/10.1039/D0NP00040J] [PMID: 33005913]
[44]
Xiao J, Capanoglu E, Jassbi AR, Miron A. Advance on the flavonoid C-glycosides and health benefits Crit Rev Food Sci Nutr 2016; 56((sup1)(Suppl. 1)): S29-45.
[http://dx.doi.org/10.1080/10408398.2015.1067595] [PMID: 26462718]
[45]
Xie K, Zhang X, Sui S, Ye F, Dai J. Exploring and applying the substrate promiscuity of a C-glycosyltransferase in the chemo-enzymatic synthesis of bioactive C-glycosides. Nat Commun 2020; 11(1): 5162.
[http://dx.doi.org/10.1038/s41467-020-18990-9] [PMID: 33056984]
[46]
Han S, Hagan DL, Taylor JR, et al. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 2008; 57(6): 1723-9.
[http://dx.doi.org/10.2337/db07-1472] [PMID: 18356408]
[47]
Brazier-Hicks M, Evans KM, Gershater MC, Puschmann H, Steel PG, Edwards R. The C-glycosylation of flavonoids in cereals. J Biol Chem 2009; 284(27): 17926-34.
[http://dx.doi.org/10.1074/jbc.M109.009258] [PMID: 19411659]
[48]
Falcone Ferreyra ML, Rodriguez E, Casas MI, Labadie G, Grotewold E, Casati P. Identification of a bifunctional maize C- and O-glucosyltransferase. J Biol Chem 2013; 288(44): 31678-88.
[http://dx.doi.org/10.1074/jbc.M113.510040] [PMID: 24045947]
[49]
Gutmann A, Nidetzky B. Switching between O- and C-glycosyltransferase through exchange of active-site motifs. Angew Chem Int Ed Engl 2012; 51(51): 12879-83.
[http://dx.doi.org/10.1002/anie.201206141] [PMID: 23154910]
[50]
Sasaki N, Nishizaki Y, Yamada E, et al. Identification of the glucosyltransferase that mediates direct flavone C-glucosylation in Gentiana triflora. FEBS Lett 2015; 589(1): 182-7.
[http://dx.doi.org/10.1016/j.febslet.2014.11.045] [PMID: 25479084]
[51]
Nomura Y, Seki H, Suzuki T, et al. Functional specialization of UDP-glycosyltransferase 73P12 in licorice to produce a sweet triterpe-noid saponin, glycyrrhizin. Plant J 2019; 99(6): 1127-43.
[http://dx.doi.org/10.1111/tpj.14409] [PMID: 31095780]
[52]
Ren Z, Ji X, Jiao Z, et al. Functional analysis of a novel C-glycosyltransferase in the orchid Dendrobium catenatum. Hortic Res 2020; 7(1): 111.
[http://dx.doi.org/10.1038/s41438-020-0330-4] [PMID: 32637139]
[53]
Kubo A, Arai Y, Nagashima S, Yoshikawa T. Alteration of sugar donor specificities of plant glycosyltransferases by a single point muta-tion. Arch Biochem Biophys 2004; 429(2): 198-203.
[http://dx.doi.org/10.1016/j.abb.2004.06.021] [PMID: 15313223]
[54]
Cheng J, Wei G, Zhou H, et al. Unraveling the mechanism underlying the glycosylation and methylation of anthocyanins in peach. Plant Physiol 2014; 166(2): 1044-58.
[http://dx.doi.org/10.1104/pp.114.246876] [PMID: 25106821]
[55]
Jánváry L, Hoffmann T, Pfeiffer J, et al. A double mutation in the anthocyanin 5-O-glucosyltransferase gene disrupts enzymatic activity in Vitis vinifera L. J Agric Food Chem 2009; 57(9): 3512-8.
[http://dx.doi.org/10.1021/jf900146a] [PMID: 19338353]
[56]
Song C, Hong X, Zhao S, et al. Glucosylation of 4-hydroxy-2,5-dimethyl-3(2H)-furanone, the key strawberry flavor compound in strawberry fruit. Plant Physiol 2016; 171(1): 139-51.
[http://dx.doi.org/10.1104/pp.16.00226] [PMID: 26993618]
[57]
Jia KZ, Zhu LW, Qu X, et al. Enzymatic O-glycosylation of etoposide aglycone by exploration of the substrate promiscuity for glycosyl-transferases. ACS Synth Biol 2019; 8(12): 2718-25.
[http://dx.doi.org/10.1021/acssynbio.9b00318] [PMID: 31774653]
[58]
Albesa-Jové D, Guerin ME. The conformational plasticity of glycosyltransferases. Curr Opin Struct Biol 2016; 40: 23-32.
[http://dx.doi.org/10.1016/j.sbi.2016.07.007] [PMID: 27450114]
[59]
Mittler M, Bechthold A, Schulz GE. Structure and action of the C-C bond-forming glycosyltransferase UrdGT2 involved in the biosyn-thesis of the antibiotic urdamycin. J Mol Biol 2007; 372(1): 67-76.
[http://dx.doi.org/10.1016/j.jmb.2007.06.005] [PMID: 17640665]
[60]
Bililign T, Hyun CG, Williams JS, Czisny AM, Thorson JS. The hedamycin locus implicates a novel aromatic PKS priming mechanism. Chem Biol 2004; 11(7): 959-69.
[http://dx.doi.org/10.1016/j.chembiol.2004.04.016] [PMID: 15271354]
[61]
Dürr C, Hoffmeister D, Wohlert SE, et al. The glycosyltransferase UrdGT2 catalyzes both C- and O-glycosidic sugar transfers. Angew Chem Int Ed 2004; 43(22): 2962-5.
[http://dx.doi.org/10.1002/anie.200453758] [PMID: 15170316]
[62]
Copley SD. Shining a light on enzyme promiscuity. Curr Opin Struct Biol 2017; 47: 167-75.
[http://dx.doi.org/10.1016/j.sbi.2017.11.001] [PMID: 29169066]
[63]
Sun Y, Chen Z, Yang J, et al. Pathway-specific enzymes from bamboo and crop leaves biosynthesize anti-nociceptive C-glycosylated flavones. Commun Biol 2020; 3(1): 110.
[http://dx.doi.org/10.1038/s42003-020-0834-3] [PMID: 32144397]
[64]
Wang X, Li C, Zhou C, Li J, Zhang Y. Molecular characterization of the C-glucosylation for puerarin biosynthesis in Pueraria lobata. Plant J 2017; 90(3): 535-46.
[http://dx.doi.org/10.1111/tpj.13510] [PMID: 28207970]
[65]
Chen DW, Fan S, Chen RD, et al. Probing and engineering key residues for bis-C-glycosylation and promiscuity of a C-glycosyltransferase. ACS Catal 2018; 8(6): 4917-27.
[http://dx.doi.org/10.1021/acscatal.8b00376]
[66]
Saiki W, Ma C, Okajima T, Takeuchi H. Current views on the roles of O-glycosylation in controlling notch-ligand interactions. Biomolecules 2021; 11(2): 309.
[http://dx.doi.org/10.3390/biom11020309] [PMID: 33670724]
[67]
Mashima K, Hatano M, Suzuki H, Shimosaka M, Taguchi G. Identification and characterization of apigenin 6-C-glucosyltransferase in-volved in biosynthesis of isosaponarin in wasabi (Eutrema japonicum). Plant Cell Physiol 2019; 60(12): 2733-43.
[http://dx.doi.org/10.1093/pcp/pcz164] [PMID: 31418788]
[68]
Tam HK, Härle J, Gerhardt S, et al. Structural characterization of O- and C-glycosylating variants of the landomycin glycosyltransferase LanGT2. Angew Chem Int Ed Engl 2015; 54(9): 2811-5.
[http://dx.doi.org/10.1002/anie.201409792] [PMID: 25581707]
[69]
Nagatomo Y, Usui S, Ito T, Kato A, Shimosaka M, Taguchi G. Purification, molecular cloning and functional characterization of flavo-noid C-glucosyltransferases from Fagopyrum esculentum M. (buckwheat) cotyledon. Plant J 2014; 80(3): 437-48.
[http://dx.doi.org/10.1111/tpj.12645] [PMID: 25142187]
[70]
Hirade Y, Kotoku N, Terasaka K, Saijo-Hamano Y, Fukumoto A, Mizukami H. Identification and functional analysis of 2-hydroxyflavanone C-glucosyltransferase in soybean (Glycine max). FEBS Lett 2015; 589(15): 1778-86.
[http://dx.doi.org/10.1016/j.febslet.2015.05.010] [PMID: 25979175]
[71]
Meech R, Hu DG, McKinnon RA, et al. The UDP-Glycosyltransferase (UGT) superfamily: New members, new functions, and novel paradigms. Physiol Rev 2019; 99(2): 1153-222.
[http://dx.doi.org/10.1152/physrev.00058.2017] [PMID: 30724669]
[72]
Aziz N, Kim MY, Cho JY. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J Ethnopharmacol 2018; 225: 342-58.
[http://dx.doi.org/10.1016/j.jep.2018.05.019] [PMID: 29801717]
[73]
Imran M, Rauf A, Abu-Izneid T, et al. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacother 2019; 112: 108612.
[http://dx.doi.org/10.1016/j.biopha.2019.108612] [PMID: 30798142]
[74]
Huang S, Li Z, Jiang S, Xu M. Metabolomic study on the protective effect of isoorientin against myocardial infarction. Biochem Biophys Res Commun 2022; 598: 81-8.
[http://dx.doi.org/10.1016/j.bbrc.2022.02.008] [PMID: 35151208]
[75]
Bai YL, Han LL, Qian JH, Wang HZ. Molecular mechanism of puerarin against diabetes and its complications. Front Pharmacol 2022; 12: 780419.
[http://dx.doi.org/10.3389/fphar.2021.780419] [PMID: 35058775]
[76]
Deng T, Zhang N, Liu Y, Li J. Daidzein ameliorates experimental acute reflux esophagitis in rats via regulation of cytokines. Pharmazie 2021; 76(2): 84-91.
[PMID: 33714284]
[77]
Laddha AP, Kulkarni YA. Daidzein mitigates myocardial injury in streptozotocin-induced diabetes in rats. Life Sci 2021; 284: 119664.
[http://dx.doi.org/10.1016/j.lfs.2021.119664] [PMID: 34090859]
[78]
Yu Z, Yang L, Deng S, Liang M. Daidzein ameliorates LPS-induced hepatocyte injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol 2020; 885: 173399.
[http://dx.doi.org/10.1016/j.ejphar.2020.173399] [PMID: 32712091]
[79]
Wu M, Li P, An Y, et al. Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. Pharmacol Res 2019; 150: 104489.
[http://dx.doi.org/10.1016/j.phrs.2019.104489] [PMID: 31689519]
[80]
Anunciato Casarini TP, Frank LA, Pohlmann AR, Guterres SS. Dermatological applications of the flavonoid phloretin. Eur J Pharmacol 2020; 889: 173593.
[http://dx.doi.org/10.1016/j.ejphar.2020.173593] [PMID: 32971088]

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