Bioactive flavonoids in medicinal plants: Structure, activity and biological fate

Asian Journal of Pharmaceutical Sciences

Volumn 13, Issue 1, 2018, Pages 12-23

  Wang, Tian yang ^a   Li, Qing ^a   Bi, Kai shun ^a  

^a SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Activity; Bioavailability; Flavonoid; Pharmacokinetics; Structure

Indexed keywords

AGLYCONE; CARBONYL DERIVATIVE; DRUG METABOLITE; FLAVONOID; HYDROXYL GROUP;

ANTIBACTERIAL ACTIVITY; ANTIDIABETIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIVIRAL ACTIVITY; BIOLOGICAL ACTIVITY; CHEMICAL STRUCTURE; COVALENT BOND; DRUG ABSORPTION; DRUG MECHANISM; DRUG METABOLISM; GLYCOSYLATION; HEART PROTECTION; HUMAN; MEDICINAL PLANT; METHYLATION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PHARMACODYNAMICS; PHARMACOKINETIC PARAMETERS; REVIEW; STRUCTURE ACTIVITY RELATION;

EID: 85028833365     PISSN: 18180876     EISSN: 2221285X     Source Type: Journal    
DOI: 10.1016/j.ajps.2017.08.004     Document Type: Review

References (79)

1. Krych, J., Gebicka, L., Catalase is inhibited by flavonoids. Int J Biol Macromol 58 (2013), 148–153.
2. Ragab, F.A., Yahya, T.A.A., El-Naa, M.M., et al. Design, synthesis and structure–activity relationship of novel semi-synthetic flavonoids as antiproliferative agents. Eur J Med Chem 82:23 (2014), 506–520.
3. Tian, S.S., Jiang, F.S., Zhang, K., et al. Flavonoids from the leaves of Carya cathayensis Sarg. inhibit vascular endothelial growth factor-induced angiogenesis. Fitoterapia 92 (2014), 34–40.
4. Zhang, X., Huang, H., Zhao, X., et al. Effects of flavonoids-rich Chinese bayberry (Myrica rubra Sieb. et Zucc.) pulp extracts on glucose consumption in human HepG2 cells. J Funct Foods 14 (2015), 144–153.
5. Wang, Y., Chen, S., Yu, O., Metabolic engineering of flavonoids in plants and microorganisms. Appl Microbiol Biotechnol 91:4 (2011), 949–956.
6. Rakers, C., Schwerdtfeger, S.M., Mortier, J., et al. Inhibitory potency of flavonoid derivatives on influenza virus neuraminidase. Bioorg Med Chem Lett 24:17 (2014), 4312–4317.
7. Giuliani, C., Bucci, I., Di Santo, S., et al. The flavonoid quercetin inhibits thyroid-restricted genes expression and thyroid function. Food Chem Toxicol 66 (2014), 23–29.
8. Isoda, H., Motojima, H., Onaga, S., et al. Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells. Chem Biol Interact 220 (2014), 269–277.
9. Shibata, C., Ohno, M., Otsuka, M., et al. The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels. Virology 462–463 (2014), 42–48.
10. Gao, L., Li, C., Yang, R.-Y., et al. Ameliorative effects of baicalein in MPTP-induced mouse model of Parkinson's disease A microarray study. Pharmacol Biochem Behav 133 (2015), 155–163.
11. Balasuriya, N., Rupasinghe, H.P., Antihypertensive properties of flavonoid-rich apple peel extract. Food Chem 135:4 (2012), 2320–2325.
12. Carvalho, O.V., Botelho, C.V., Ferreira, C.G., et al. In vitro inhibition of canine distemper virus by flavonoids and phenolic acids: implications of structural differences for antiviral design. Res Vet Sci 95:2 (2013), 717–724.
13. Nguyen, T.T., Moon, Y.H., Ryu, Y.B., et al. The influence of flavonoid compounds on the in vitro inhibition study of a human fibroblast collagenase catalytic domain expressed in E. coli. Enzyme Microb Technol 52:1 (2013), 26–31.
14. Kim, Y.S., Ryu, Y.B., Curtis-Long, M.J., et al. Flavanones and rotenoids from the roots of Amorpha fruticosa L. that inhibit bacterial neuraminidase. Food Chem Toxicol 49:8 (2011), 1849–1856.
15. Sithisarn, P., Michaelis, M., Schubert-Zsilavecz, M., et al. Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells. Antiviral Res 97:1 (2013), 41–48.
16. Wu, T., He, M., Zang, X., et al. A structure-activity relationship study of flavonoids as inhibitors of E. coli by membrane interaction effect. Biochim Biophys Acta 1828:11 (2013), 2751–2756.
17. Amrutha, K., Nanjan, P., Shaji, S.K., et al. Discovery of lesser known flavones as inhibitors of NF-kappaB signaling in MDA-MB-231 breast cancer cells – a SAR study. Bioorg Med Chem Lett 24:19 (2014), 4735–4742.
18. Huang, Z., Fang, F., Wang, J., et al. Structural activity relationship of flavonoids with estrogen-related receptor gamma. FEBS Lett 584:1 (2010), 22–26.
19. Zhang, J., Wu, Y., Zhao, X., et al. Chemopreventive effect of flavonoids from Ougan (Citrus reticulata cv. Suavissima) fruit against cancer cell proliferation and migration. J Funct Foods 10 (2014), 511–519.
20. Chidambara Murthy, K.N., Kim, J., Vikram, A., et al. Differential inhibition of human colon cancer cells by structurally similar flavonoids of citrus. Food Chem 132:1 (2012), 27–34.
21. Kothandan, G., Gadhe, C.G., Madhavan, T., et al. Docking and 3D-QSAR (quantitative structure activity relationship) studies of flavones, the potent inhibitors of p-glycoprotein targeting the nucleotide binding domain. Eur J Med Chem 46:9 (2011), 4078–4088.
22. Gopinath, K., Sudhandiran, G., Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway. Neuroscience 227 (2012), 134–143.
23. Orhan, I.E., Senol, F.S., Ercetin, T., et al. Assessment of anticholinesterase and antioxidant properties of selected sage (Salvia) species with their total phenol and flavonoid contents. Ind Crops Prod 41 (2013), 21–30.
24. Eghorn, L.F., Hoestgaard-Jensen, K., Kongstad, K.T., et al. Positive allosteric modulation of the GHB high-affinity binding site by the GABAA receptor modulator monastrol and the flavonoid catechin. Eur J Pharmacol 740:5 (2014), 570–577.
25. Sandhir, R., Mehrotra, A., Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: implications in Huntington's disease. Biochim Biophys Acta 1832:3 (2013), 421–430.
26. Lou, H., Jing, X., Wei, X., et al. Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2/ARE signaling pathway. Neuropharmacology 79 (2014), 380–388.
27. Lei, Y., Chen, J., Zhang, W., et al. In vivo investigation on the potential of galangin, kaempferol and myricetin for protection of D-galactose-induced cognitive impairment. Food Chem 135:4 (2012), 2702–2707.
28. Cho, N., Choi, J.H., Yang, H., et al. Neuroprotective and anti-inflammatory effects of flavonoids isolated from Rhus verniciflua in neuronal HT22 and microglial BV2 cell lines. Food Chem Toxicol 50:6 (2012), 1940–1945.
29. Spencer, J.P., Vafeiadou, K., Williams, R.J., et al. Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol Aspects Med 33:1 (2012), 83–97.
30. Katalinic, M., Rusak, G., Barovic, J.D., et al. Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase. Eur J Med Chem 45:1 (2010), 186–192.
31. Li, G., Zhu, Y., Zhang, Y., et al. Estimated daily flavonoid and stilbene intake from fruits, vegetables, and nuts and associations with lipid profiles in Chinese adults. J Acad Nutr Diet 113:6 (2013), 786–794.
32. Hamauzu, Y., Nosaka, T., Ito, F., et al. Physicochemical characteristics of rapidly dried onion powder and its anti-atherogenic effect on rats fed high-fat diet. Food Chem 129:3 (2011), 810–815.
33. Martinez-Fernandez, L., Pons, Z., Margalef, M., et al. Regulation of vascular endothelial genes by dietary flavonoids: structure-expression relationship studies and the role of the transcription factor KLF-2. J Nutr Biochem 26:3 (2015), 277–284.
34. Atrahimovich, D., Vaya, J., Khatib, S., The effects and mechanism of flavonoid–rePON1 interactions. Structure–activity relationship study. Bioorg Med Chem 21:11 (2013), 3348–3355.
35. Abdallah, H.M., Almowallad, F.M., Esmat, A., et al. Anti-inflammatory activity of flavonoids from Chrozophora tinctoria. Phytochem Lett 13 (2015), 74–80.
36. Medzhitov, R., Inflammation 2010: new adventures of an old flame. Cell 140:6 (2010), 771–776.
37. Grivennikov, S.I., Greten, F.R., Karin, M., Immunity, inflammation, and cancer. Cell 140:6 (2010), 883–899.
38. Chen, M., Wang, T., Jiang, Z.-Z., et al. Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts. Chin J Nat Med 12:8 (2014), 590–598.
39. Shalini, V., Bhaskar, S., Kumar, K.S., et al. Molecular mechanisms of anti-inflammatory action of the flavonoid, tricin from Njavara rice (Oryza sativa L.) in human peripheral blood mononuclear cells: possible role in the inflammatory signaling. Int Immunopharmacol 14:1 (2012), 32–38.
40. Mascaraque, C., Aranda, C., Ocon, B., et al. Rutin has intestinal antiinflammatory effects in the CD4+ CD62L+ T cell transfer model of colitis. Pharmacol Res 90 (2014), 48–57.
41. Mascaraque, C., López-Posadas, R., Monte, M.J., et al. The small intestinal mucosa acts as a rutin reservoir to extend flavonoid anti-inflammatory activity in experimental ileitis and colitis. J Funct Foods 13 (2015), 117–125.
42. Medda, R., Lyros, O., Schmidt, J.L., et al. Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells. Microvasc Res 97 (2015), 167–180.
43. Jung, H.A., Jin, S.E., Min, B.S., et al. Anti-inflammatory activity of Korean thistle Cirsium maackii and its major flavonoid, luteolin 5-O-glucoside. Food Chem Toxicol 50:6 (2012), 2171–2179.
44. Kang, S.R., Park, K.I., Park, H.S., et al. Anti-inflammatory effect of flavonoids isolated from Korea Citrus aurantium L. on lipopolysaccharide-induced mouse macrophage RAW 264.7 cells by blocking of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways. Food Chem 129:4 (2011), 1721–1728.
45. Fu, Y., Chen, J., Li, Y.-J., et al. Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice. Food Chem 141:2 (2013), 1063–1071.
46. Das, T., Mukherjee, S., Chaudhuri, K., Effect of quercetin on Vibrio cholerae induced nuclear factor-kappaB activation and interleukin-8 expression in intestinal epithelial cells. Microbes Infect 14:9 (2012), 690–695.
47. During, A., Larondelle, Y., The O-methylation of chrysin markedly improves its intestinal anti-inflammatory properties: structure-activity relationships of flavones. Biochem Pharmacol 86:12 (2013), 1739–1746.
48. Celik, H., Kosar, M., Inhibitory effects of dietary flavonoids on purified hepatic NADH-cytochrome b5 reductase: structure-activity relationships. Chem Biol Interact 197:2–3 (2012), 103–109.
49. Feng, R., Guo, Z.K., Yan, C.M., et al. Anti-inflammatory flavonoids from Cryptocarya chingii. Phytochemistry 76 (2012), 98–105.
50. Yeon, J.Y., Bae, Y.J., Kim, E.Y., et al. Association between flavonoid intake and diabetes risk among the Koreans. Clin Chim Acta 439 (2015), 225–230.
51. Hummel, C.S., Lu, C., Liu, J., et al. Structural selectivity of human SGLT inhibitors. Am J Physiol Cell Physiol 302 (2012), 373–382.
52. Matin, A., Doddareddy, M.R., Gavande, N., et al. The discovery of novel isoflavone pan peroxisome proliferator-activated receptor agonists. Bioorg Med Chem 21:3 (2013), 766–778.
53. Matsuda, H., Kogami, Y., Nakamura, S., et al. Structural requirements of flavonoids for the adipogenesis of 3T3-L1 cells. Bioorg Med Chem 19:9 (2011), 2835–2841.
54. Zhang, R., Yao, Y., Wang, Y., et al. Antidiabetic activity of isoquercetin in diabetic KK -Ay mice. Nutr Metab (Lond), 8, 2011, 85.
55. Verma, A.K., Singh, H., Satyanarayana, M., et al. Flavone-based novel antidiabetic and antidyslipidemic agents. J Med Chem 55:10 (2012), 4551–4567.
56. Xie, P.-J., Huang, L.-X., Zhang, C.-H., et al. Phenolic compositions, and antioxidant performance of olive leaf and fruit (Olea europaea L.) extracts and their structure–activity relationships. J Funct Foods 16 (2015), 460–471.
57. Chen, Y.H., Yang, Z.S., Wen, C.C., et al. Evaluation of the structure-activity relationship of flavonoids as antioxidants and toxicants of zebrafish larvae. Food Chem 134:2 (2012), 717–724.
58. Ribeiro, D., Freitas, M., Tome, S.M., et al. Inhibition of LOX by flavonoids: a structure-activity relationship study. Eur J Med Chem 72 (2014), 137–145.
59. Zielińska, D., Zieliński, H., Antioxidant activity of flavone C-glucosides determined by updated analytical strategies. Food Chem 124:2 (2011), 672–678.
60. Hidalgo, M., Sánchez-Moreno, C., de Pascual-Teresa, S., Flavonoid–flavonoid interaction and its effect on their antioxidant activity. Food Chem 121:3 (2010), 691–696.
61. Androutsopoulos, V.P., Tsatsakis, A.M., Benzo[a]pyrene sensitizes MCF7 breast cancer cells to induction of G1 arrest by the natural flavonoid eupatorin-5-methyl ether, via activation of cell signaling proteins and CYP1-mediated metabolism. Toxicol Lett 230:2 (2014), 304–313.
62. Albishi, T., John, J.A., Al-Khalifa, A.S., et al. Phenolic content and antioxidant activities of selected potato varieties and their processing by-products. J Funct Foods 5:2 (2013), 590–600.
63. Das, S., Mitra, I., Batuta, S., et al. Design, synthesis and exploring the quantitative structure–activity relationship of some antioxidant flavonoid analogues. Bioorg Med Chem Lett 24:21 (2014), 5050–5054.
64. Guo, Y., Bruno, R.S., Endogenous and exogenous mediators of quercetin bioavailability. J Nutr Biochem 26:3 (2015), 201–210.
65. Breiter, T., Laue, C., Kressel, G., et al. Bioavailability and antioxidant potential of rooibos flavonoids in humans following the consumption of different rooibos formulations. Food Chem 128:2 (2011), 338–347.
66. Buqui, G.A., Sy, S.K.B., Merino-Sanjuán, M., et al. Characterization of intestinal absorption of C-glycoside flavonoid vicenin-2 from Lychnophora ericoides leafs in rats by nonlinear mixed effects modeling. Rev Bras Farmacogn 25:3 (2015), 212–218.
67. Touil, Y.S., Auzeil, N., Boulinguez, F.O., et al. Fisetin disposition and metabolism in mice: identification of geraldol as an active metabolite. Biochem Pharmacol 82:11 (2011), 1731–1739.
68. Kim, H., Moon, J.Y., Mosaddik, A., et al. Induction of apoptosis in human cervical carcinoma HeLa cells by polymethoxylated flavone-rich Citrus grandis Osbeck (Dangyuja) leaf extract. Food Chem Toxicol 48:8–9 (2010), 2435–2442.
69. Androutsopoulos, V.P., Papakyriakou, A., Vourloumis, D., et al. Dietary flavonoids in cancer therapy and prevention Substrates and inhibitors of cytochrome P450 CYP1 enzymes. Pharmacol Ther 126:1 (2010), 9–20.
70. Surichan, S., Androutsopoulos, V.P., Sifakis, S., et al. Bioactivation of the citrus flavonoid nobiletin by CYP1 enzymes in MCF7 breast adenocarcinoma cells. Food Chem Toxicol 50:9 (2012), 3320–3328.
71. Wei, G.-J., Hwang, L.S., Tsai, C.-L., Absolute bioavailability, pharmacokinetics and excretion of 5,7,3′,4′-tetramethoxyflavone in rats. J Funct Foods 7 (2014), 136–141.
72. Chen, Z.P., Sun, J., Chen, H.X., et al. Comparative pharmacokinetics and bioavailability studies of quercetin, kaempferol and isorhamnetin after oral administration of Ginkgo biloba extracts, Ginkgo biloba extract phospholipid complexes and Ginkgo biloba extract solid dispersions in rats. Fitoterapia 81:8 (2010), 1045–1052.
73. Wittemer, S.M., Ploch, M., Windeck, T., et al. Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine 12:1–2 (2005), 28–38.
74. Lorendeau, D., Dury, L., Genoux-Bastide, E., et al. Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux. Biochem Pharmacol 90:3 (2014), 235–245.
75. Lotito, S.B., Zhang, W.-J., Yang, C.S., et al. Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radic Biol Med 51:2 (2011), 454–463.
76. Zhao, J., Tang, W., Wang, J., et al. Pharmacokinetic and pharmacodynamic studies of four major phytochemical components of Da-Cheng-Qi decoction to treat acute pancreatitis. J Pharmacol Sci 122:2 (2013), 118–127.
77. Boonpawa, R., Moradi, N., Spenkelink, A., et al. Use of physiologically based kinetic (PBK) modeling to study interindividual human variation and species differences in plasma concentrations of quercetin and its metabolites. Biochem Pharmacol 98:4 (2015), 690–702.
78. Berger, L.M., Wein, S., Blank, R., et al. Bioavailability of the flavonol quercetin in cows after intraruminal application of quercetin aglycone and rutin. J Dairy Sci 95:9 (2012), 5047–5055.
79. Maciej, J., Schaff, C.T., Kanitz, E., et al. Bioavailability of the flavonol quercetin in neonatal calves after oral administration of quercetin aglycone or rutin. J Dairy Sci 98:6 (2015), 3906–3917.