Exploration of natural flavones’ bioactivity and bioavailability in chronic inflammation induced-type-2 diabetes mellitus

References

• Ahad, A., A. A. Ganai, M. Mujeeb, and W. A. Siddiqui. 2014. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats. Toxicology and Applied Pharmacology 279 (1):1–7. doi: 10.1016/j.taap.2014.05.007.
   PubMed Web of Science ®Google Scholar
• Ahad, A., M. Mujeeb, H. Ahsan, and W. A. Siddiqui. 2014. Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats. Biochimie 106:101–10. doi: 10.1016/j.biochi.2014.08.006.
   PubMed Web of Science ®Google Scholar
• Alam, W., C. Rocca, H. Khan, Y. Hussain, M. Aschner, A. De Bartolo, N. Amodio, T. Angelone, and W. S. Cheang. 2021. Current status and future perspectives on therapeutic potential of apigenin: Focus on metabolic-syndrome-dependent organ dysfunction. Antioxidants (Basel) 10 (10):1643. doi: 10.3390/antiox10101643.
   PubMedGoogle Scholar
• Al-Ishaq, R. K., M. Abotaleb, P. Kubatka, K Kajo, and D. Büsselberg. 2019. Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels. Biomolecules 9 (9):430 doi:10.3390/biom9090430.
   PubMed Web of Science ®Google Scholar
• Amélia, P. R., A. Martins, C. Borges, H. Mota-Filipe, R. Pinto, B. Sepodes, and J. Justino. 2010. Antihyperglycaemic and protective effects of flavonoids on streptozotocin-induced diabetic rats. Phytotherapy Research 24 (S2):S133–S138.
   PubMedGoogle Scholar
• American Diabetes Association. (2019). American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes — 2019. Diabetes Care 42 (Suppl. 1):S165–S172.
   PubMedGoogle Scholar
• Amidon, G. L., H. Lennernas, V. P. Shah, and J. R. Crison. 1995. A theoretical basis for a biopharmaceutic drug classification - the correlation of in-vitro drug product dissolution and in-vivo bioavailability. Pharmaceutical Research 12 (3):413–20. doi: 10.1023/A:1016212804288.
   PubMed Web of Science ®Google Scholar
• Arai, Y., S. Watanabe, M. Kimira, K. Shimoi, R. Mochizuki, and N. Kinae. 2000. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. The Journal of Nutrition 130 (9):2243–50. doi: 10.1093/jn/130.9.2243.
   PubMed Web of Science ®Google Scholar
• Arkan, M. C., A. L. Hevener, F. R. Greten, S. Maeda, Z.-W. Li, J. M. Long, A. Wynshaw-Boris, G. Poli, J. Olefsky, and M. Karin. 2005. IKK-β links inflammation to obesity-induced insulin resistance. Nature Medicine 11 (2):191–8. doi: 10.1038/nm1185.
   PubMed Web of Science ®Google Scholar
• Asadi, A., F. Shidfar, M. Safari, A. F. Hosseini, H. Fallah Huseini, I. Heidari, and A. Rajab. 2019. Efficacy of Melissa officinalis L. (lemon balm) extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes: A randomized, double-blind, clinical trial. Phytotherapy Research: PTR 33 (3):651–9. doi: 10.1002/ptr.6254.
   PubMed Web of Science ®Google Scholar
• Asadi, A., F. Shidfar, M. Safari, A. F. Hosseini, H. Fallah Huseini, I. Heidari, and A. Rajab. 2019. Efficacy of Melissa officinalis L. (lemon balm) extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes: A randomized, double-blind, clinical trial. Phytotherapy Research 33 (3):651–9.
   PubMed Web of Science ®Google Scholar
• Azimi, A., A. Eidi, P. Mortazavi, and A. H. Rohani. 2021. Protective effect of apigenin on ethylene glycol-induced urolithiasis via attenuating oxidative stress and inflammatory parameters in adult male Wistar rats. Life Sciences 279:119641. doi: 10.1016/j.lfs.2021.119641.
   PubMed Web of Science ®Google Scholar
• Azizi, G., S. S. Navabi, A. Al-Shukaili, M. H. Seyedzadeh, R. Yazdani, and A. Mirshafiey. 2015. The role of inflammatory mediators in the pathogenesis of Alzheimer’s disease. Sultan Qaboos University Medical Journal 15 (3):e305–e316. doi: 10.18295/squmj.2015.15.03.002.
   PubMedGoogle Scholar
• Babu, P. V. A., D. Liu, and E. R. Gilbert. 2013. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. The Journal of Nutritional Biochemistry 24 (11):1777–89. doi: 10.1016/j.jnutbio.2013.06.003.
   PubMed Web of Science ®Google Scholar
• Bai, L., X. Li, L. He, Y. Zheng, H. Lu, J. Li, L. Zhong, R. Tong, Z. Jiang, J. Shi, et al. 2019. Antidiabetic potential of flavonoids from traditional Chinese Medicine: A review. The American Journal of Chinese Medicine 47 (5):933–57. doi: 10.1142/S0192415X19500496.
   PubMed Web of Science ®Google Scholar
• Baradaran Rahimi, V., V. R. Askari, and H. Hosseinzadeh. 2021. Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against metabolic syndrome: A review. Phytotherapy Research: PTR 35 (7):3558–74. doi: 10.1002/ptr.7046.
   PubMed Web of Science ®Google Scholar
• Bartholomé, R., G. Haenen, C. H. Hollman, A. Bast, P. C. Dagnelie, D. Roos, J. Keijer, P. A. Kroon, P. W. Needs, and I. C. W. Arts. 2010. Deconjugation kinetics of glucuronidated phase II flavonoid metabolites by beta-glucuronidase from neutrophils. Drug Metabolism and Pharmacokinetics 25 (4):379–87. doi: 10.2133/dmpk.dmpk-10-rg-002.
   PubMed Web of Science ®Google Scholar
• Baskaran, K., K. V. Pugalendi, and R. Saravanan. 2015. Antidiabetic and antihyperlipidemic activity of chrysoeriol in diabetic rats, role of HMG CoA reductase, LCAT and LPL: In vivo and in silico approaches. Journal of Pharmacy Research 9 (9):597–605.
   Google Scholar
• Bastard, J.-P., M. Maachi, J. T. van Nhieu, C. Jardel, E. Bruckert, A. Grimaldi, J.-J. Robert, J. Capeau, and B. Hainque. 2002. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. The Journal of Clinical Endocrinology & Metabolism 87 (5):2084–9. doi: 10.1210/jcem.87.5.8450.
   PubMed Web of Science ®Google Scholar
• Beecher G. R. (2003). Overview of dietary flavonoids: Nomenclature, occurrence and intake. The Journal of Nutrition, 133(10), 3248S–3254S. doi: 10.1093/jn/133.10.3248S.
   PubMed Web of Science ®Google Scholar
• Benavente-García, O., and J. Castillo. 2008. Update on uses and properties of citrus flavonoids: New findings in anticancer, cardiovascular, and anti-inflammatory activity. Journal of Agricultural and Food Chemistry 56 (15):6185–205. doi: 10.1021/jf8006568.
   PubMed Web of Science ®Google Scholar
• Bommer, C., V. Sagalova, E. Heesemann, J. Manne-Goehler, R. Atun, T. Bärnighausen, J. Davies, and S. Vollmer. 2018. Global economic burden of diabetes in adults: Projections from 2015 to 2030. Diabetes Care 41 (5):963–70. ; doi: 10.2337/dc17-1962.
   PubMed Web of Science ®Google Scholar
• Böni-Schnetzler, M., and M. Y. Donath. 2011. Increased IL-1β activation, the culprit not only for defective insulin secretion but also for insulin resistance? Cell Research 21 (7):995–7. doi: 10.1038/cr.2011.85.
   PubMed Web of Science ®Google Scholar
• Boulaiz, H., P. J. Alvarez, A. Ramirez, J. A. Marchal, J. Prados, F. Rodriguez-Serrano, M. Peran, C. Melguizo, and A. Aranega. 2011. Nanomedicine: Application areas and development prospects. International Journal of Molecular Sciences 12 (5):3303–21. doi: 10.3390/ijms12053303.
   PubMed Web of Science ®Google Scholar
• Boura-Halfon, S., and Y. Zick. 2009. Phosphorylation of IRS proteins, insulin action, and insulin resistance. American Journal of Physiology. Endocrinology and Metabolism 296 (4):E581–E591. doi: 10.1152/ajpendo.90437.2008.
   PubMed Web of Science ®Google Scholar
• Brownlee, M. 2005. The pathobiology of diabetic complications. Diabetes 54 (6):1615–25. doi: 10.2337/diabetes.54.6.1615.
   PubMed Web of Science ®Google Scholar
• Bruschi, M. L., S. L. Franco, and M. P. D. Gremião. 2003. Application of an HPLC method for analysis of propolis extract. Journal of Liquid Chromatography & Related Technologies 26 (14):2399–409. doi: 10.1081/JLC-120023254.
   Web of Science ®Google Scholar
• Burda, S., and W. Oleszek. 2001. Antioxidant and antiradical activities of flavonoids. Journal of Agricultural and Food Chemistry 49 (6):2774–9. doi: 10.1021/jf001413m.
   PubMed Web of Science ®Google Scholar
• Burke, S. J., K. Stadler, D. Lu, E. Gleason, A. Han, D. R. Donohoe, R. C. Rogers, G. E. Hermann, M. D. Karlstad, and J. J. Collier. 2015. IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB. American Journal of Physiology. Endocrinology and Metabolism 309 (8):E715–E726. doi: 10.1152/ajpendo.00153.2015.
   PubMed Web of Science ®Google Scholar
• Cao, H., et al. 2022. Stability of quercetin in DMEM and cell culture with A549 cells. eFood 3:e13.
   Google Scholar
• Castellino, G., D. Nikolic, A. Magán-Fernández, G. A. Malfa, R. Chianetta, A. M. Patti, A. Amato, G. Montalto, P. P. Toth, M. Banach, et al. 2019. Altilix(®) supplement containing chlorogenic acid and luteolin improved hepatic and cardiometabolic parameters in subjects with metabolic syndrome: A 6 month randomized, double-blind, placebo-controlled study. Nutrients 11 (11):2580. doi: 10.3390/nu11112580.
   PubMed Web of Science ®Google Scholar
• Catalkaya, G., K. Venema, L. Lucini, G. Rocchetti, D. Delmas, M. Daglia, A. De Filippis, H. Xiao, J. L. Quiles, J. Xiao, et al. 2020. Interaction of dietary polyphenols and gut microbiota: Microbial metabolism of polyphenols, influence on the gut microbiota, and implications on host health. Food Frontiers 1 (2):109–33. doi: 10.1002/fft2.25.
   Google Scholar
• Cha, B.-Y., W. L. Shi, T. Yonezawa, T. Teruya, K. Nagai, and J.-T. Woo. 2009. An inhibitory effect of chrysoeriol on platelet-derived growth factor (PDGF)-induced proliferation and PDGF receptor signaling in human aortic smooth muscle cells. Journal of Pharmacological Sciences 110 (1):105–10. doi: 10.1254/jphs.08282fp.
   PubMed Web of Science ®Google Scholar
• Charalabopoulos, A., S. Davakis, M. Lambropoulou, A. Papalois, C. Simopoulos, and A. Tsaroucha. 2019. Apigenin exerts anti-inflammatory effects in an experimental model of acute pancreatitis by down-regulating TNF-α. In Vivo 33 (4):1133–41. doi: 10.21873/invivo.11583.
   PubMed Web of Science ®Google Scholar
• Charbonnel, B. 2009. PPAR-alpha and PPAR-gamma agonists for type 2 diabetes. Lancet (London, England) 374 (9684):96–8. doi: 10.1016/S0140-6736(09)61040-0.
   PubMed Web of Science ®Google Scholar
• Chen, L.-Y., H.-L. Cheng, Y.-H. Kuan, T.-J. Liang, Y.-Y. Chao, and H.-C. Lin. 2021. Therapeutic potential of luteolin on impaired wound healing in streptozotocin-induced rats. Biomedicines 9 (7):761. doi: 10.3390/biomedicines9070761.
   PubMed Web of Science ®Google Scholar
• Chen, L., H. Deng, H. Cui, J. Fang, Z. Zuo, J. Deng, Y. Li, X. Wang, and L. Zhao. 2018. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9 (6):7204–18. doi: 10.18632/oncotarget.23208.
   PubMedGoogle Scholar
• Chen, L., X. Fan, X. Lin, L. Qian, G. Zengin, D. Delmas, P. Paoli, H. Teng, and J. Xiao. 2020. Phenolic extract from Sonchus oleraceus L. protects diabetes-related liver injury in rats through TLR4/NF-κB Signaling Pathway. eFood 1 (1):77–84. doi: 10.2991/efood.k.191018.002.
   Google Scholar
• Chen, X., R. Han, P. Hao, L. Wang, M. Liu, M. Jin, D. Kong, and X. Li. 2018. Nepetin inhibits IL-1 beta induced inflammation via NF-kappa B and MAPKs signaling pathways in ARPE-19 cells. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 101:87–93. doi: 10.1016/j.biopha.2018.02.054.
   PubMed Web of Science ®Google Scholar
• Chen, P., X. Huo, W. Liu, K. Li, Z. Sun, and J. Tian. 2020. Apigenin exhibits anti-inflammatory effects in LPS-stimulated BV2 microglia through activating GSK3β/Nrf2 signaling pathway. Immunopharmacology and Immunotoxicology 42 (1):9–16. doi: 10.1080/08923973.2019.1688345.
   PubMed Web of Science ®Google Scholar
• Chen, C.-C., M.-W. Lin, C.-J. Liang, and S.-H. Wang. 2016. The anti-inflammatory effects and mechanisms of eupafolin in lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages. PloS One 11 (7):e0158662. doi: 10.1371/journal.pone.0158662.
   PubMed Web of Science ®Google Scholar
• Chen, L., H. Teng, Z. Xie, H. Cao, W. S. Cheang, K. Skalicka-Woniak, M. I. Georgiev, and J. Xiao. 2018. Modifications of dietary flavonoids towards improved bioactivity: An update on structure-activity relationship. Critical Reviews in Food Science and Nutrition 58 (4):513–27. doi: 10.1080/10408398.2016.1196334.
   PubMed Web of Science ®Google Scholar
• Chen, X., Z. Yao, X. Peng, L. Wu, H. Wu, Y. Ou, and J. Lai. 2020. Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF-kappa B signaling pathway. Molecular Medicine Reports 22 (6):5135–44. doi: 10.3892/mmr.2020.11637.
   PubMed Web of Science ®Google Scholar
• Choi, D.-Y., J. Y. Lee, M.-R. Kim, E.-R. Woo, Y. G. Kim, and K. W. Kang. 2005. Chrysoeriol potently inhibits the induction of nitric oxide synthase by blocking AP-1 activation. Journal of Biomedical Science 12 (6):949–59. doi: 10.1007/s11373-005-9028-8.
   PubMed Web of Science ®Google Scholar
• Choy, K. W., D. Murugan, X.-F. Leong, R. Abas, A. Alias, and M. R. Mustafa. 2019. Flavonoids as natural anti-inflammatory agents targeting nuclear factor-Kappa B (NFkappaB) signaling in cardiovascular diseases: A mini review. Frontiers in Pharmacology 10:1295. doi: 10.3389/fphar.2019.01295.
   PubMed Web of Science ®Google Scholar
• Cnop, M., J. Vidal, R. L. Hull, K. M. Utzschneider, D. B. Carr, T. Schraw, P. E. Scherer, E. J. Boyko, W. Y. Fujimoto, and S. E. Kahn. 2007. Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. Diabetes Care 30 (3):677–82. doi: 10.2337/dc06-1834.
   PubMed Web of Science ®Google Scholar
• Comalada, M., I. Ballester, E. Bailón, S. Sierra, J. Xaus, J. Gálvez, F. S. d. Medina, and A. Zarzuelo. 2006. Inhibition of pro-inflammatory markers in primary bone marrowderived mouse macrophages by naturally occurring flavonoids: Analysis of the structure–activity relationship. Biochemical Pharmacology 72 (8):1010–21. doi: 10.1016/j.bcp.2006.07.016.
   PubMed Web of Science ®Google Scholar
• Dang, H., M. H. W. Meng, H. W. Zhao, J. Iqbal, R. J. Dai, Y. L. Deng, and F. Lv. 2014. Luteolin-loaded solid lipid nanoparticles synthesis, characterization, & improvement of bioavailability, pharmacokinetics in vitro and vivo studies. Journal of Nanoparticle Research 16 (4): 2347. doi: 10.1007/s11051-014-2347-9.
   Web of Science ®Google Scholar
• de Heredia, F. P., S. Gómez-Martínez, and A. Marcos. 2012. Obesity, inflammation and the immune system. The Proceedings of the Nutrition Society 71 (2):332–8. doi: 10.1017/S0029665112000092.
   PubMed Web of Science ®Google Scholar
• De Luca, C., and J. M. Olefsky. 2008. Inflammation and insulin resistance. FEBS Letters 582 (1):97–105. doi: 10.1016/j.febslet.2007.11.057.
   PubMed Web of Science ®Google Scholar
• Delneste, Y., C. Beauvillain, and P. Jeannin. 2007. Innate immunity: Structure and function of TLRs. Medicine Science 23:67–73.
   Google Scholar
• DeRango-Adem, E. F., and J. Blay. 2021. Does oral apigenin have real potential for a therapeutic effect in the context of human gastrointestinal and other cancers? Frontiers in Pharmacology 12: 681477.
   PubMedGoogle Scholar
• Devaraj, S., I. Jialal, J.-M. Yun, and A. Bremer. 2011. Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. Metabolism 60 (2):256–9. doi:10.1016/j.metabol.2010.01.005.
   PubMed Web of Science ®Google Scholar
• Dewanjee, S., P. Chakraborty, B. Mukherjee, and V. De Feo. 2020. Plant-based antidiabetic nanoformulations: The emerging paradigm for effective therapy. International Journal of Molecular Sciences 21 (6): 2217.
   PubMed Web of Science ®Google Scholar
• Dinda, B., S. Dinda, S. DasSharma, R. Banik, A. Chakraborty, and M. Dinda. 2017. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. European Journal of Medicinal Chemistry 131:68–80. doi: 10.1016/j.ejmech.2017.03.004.
   PubMed Web of Science ®Google Scholar
• Ding, L., D. Jin, and X. Chen. 2010. Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes. The Journal of Nutritional Biochemistry 21 (10):941–7. doi: 10.1016/j.jnutbio.2009.07.009.
   PubMed Web of Science ®Google Scholar
• Ding, S-m., Z.-h. Zhang, J. Song, X.-d. Cheng, J. Jiang, and X.-b. Jia. 2014. Enhanced bioavailability of apigenin via preparation of a carbon nanopowder solid dispersion. International Journal of Nanomedicine 9:2327–33. doi: 10.2147/IJN.S60938.
   PubMed Web of Science ®Google Scholar
• Dirscherl, K., M. Karlstetter, S. Ebert, D. Kraus, J. Hlawatsch, Y. Walczak, C. Moehle, R. Fuchshofer, and T. Langmann. 2010. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype. Journal of Neuroinflammation 7 (1):3. doi: 10.1186/1742-2094-7-3.
   PubMedGoogle Scholar
• Duthie, G. G., P. T. Gardner, and J. A. Kyle. 2003. Plant polyphenols: Are they the new magic bullet? The Proceedings of the Nutrition Society 62 (3):599–603. doi: 10.1079/PNS2003275.
   PubMed Web of Science ®Google Scholar
• Eizirik, D.L., Pasquali, L., and Cnop, M. (2020). Pancreatic β-cells in type 1 and type 2 diabetes mellitus: Different pathways to failure. Nature Reviews. Endocrinology 16(7):349–362. doi: 10.1038/s41574-020-0355-7.
   PubMed Web of Science ®Google Scholar
• El-Hussien, D., G. M. El-Zaafarany, M. Nasr, and O. Sammour. 2021. Chrysin nanocapsules with dual anti-glycemic and anti-hyperlipidemic effects: Chemometric optimization, physicochemical characterization and pharmacodynamic assessment. International Journal of Pharmaceutics 592:120044. doi: 10.1016/j.ijpharm.2020.120044.
   PubMed Web of Science ®Google Scholar
• Esser, N., S. Legrand-Poels, J. Piette, A. J. Scheen, and N. Paquot. 2014. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Research and Clinical Practice 105 (2):141–50. doi: 10.1016/j.diabres.2014.04.006.
   PubMed Web of Science ®Google Scholar
• Fardoun, M. M., D. Maaliki, N. Halabi, R. Iratni, A. Bitto, E. Baydoun, and A. H. Eid. 2020. Flavonoids in adipose tissue inflammation and atherosclerosis: One arrow, two targets. Clinical Science (London, England: 1979) 134 (12):1403–32. doi: 10.1042/CS20200356.
   PubMed Web of Science ®Google Scholar
• Feng, X., H. Qin, Q. Shi, Y. Zhang, F. Zhou, H. Wu, S. Ding, Z. Niu, Y. Lu, and P. Shen. 2014. Chrysin attenuates inflammation by regulating M1/M2 status via activating PPARγ. Biochemical Pharmacology 89 (4):503–14. doi: 10.1016/j.bcp.2014.03.016.
   PubMed Web of Science ®Google Scholar
• Fenyvesi, F., T. L. P. Nguyen, Á. Haimhoffer, Á. Rusznyák, G. Vasvári, I. Bácskay, M. Vecsernyés, S.-R. Ignat, S. Dinescu, M. Costache, et al. 2020. Cyclodextrin complexation improves the solubility and Caco-2 permeability of chrysin. Materials 13 (16):3618. doi: 10.3390/ma13163618.
   PubMed Web of Science ®Google Scholar
• Flamment, M., E. Hajduch, P. Ferré, and F. Foufelle. 2012. New insights into ER stress-induced insulin resistance. Trends in Endocrinology and Metabolism: TEM 23 (8):381–90. doi: 10.1016/j.tem.2012.06.003.
   PubMed Web of Science ®Google Scholar
• Fu, Y., J. Luo, Z. Jia, W. Zhen, K. Zhou, E. Gilbert, and D. Liu. 2014. Baicalein protects against Type 2 diabetes via promoting islet beta-cell function in obese diabetic mice. International Journal of Endocrinology 2014:846742. doi: 10.1155/2014/846742.
   PubMed Web of Science ®Google Scholar
• Galati, G., and P. J. O’Brien. 2004. Potential toxicity of flavonoids and other dietary phenolics: Significance for their chemopreventive and anticancer properties. Free Radical Biology & Medicine 37 (3):287–303. doi: 10.1016/j.freeradbiomed.2004.04.034.
   PubMed Web of Science ®Google Scholar
• Gao, W., X. Du, L. Lei, H. Wang, M. Zhang, Z. Wang, X. Li, G. Liu, and X. Li. 2018. NEFA‐induced ROS impaired insulin signalling through the JNK and p38MAPK pathways in non‐alcoholic steatohepatitis. Journal of Cellular and Molecular Medicine 22 (7):3408–22. doi: 10.1111/jcmm.13617.
   PubMed Web of Science ®Google Scholar
• García-Lafuente, A., E. Guillamón, A. Villares, M. A. Rostagno, and J. A. Martínez. 2009. Flavonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease. Inflammation Research: Official Journal of the European Histamine Research Society. [et al.] 58 (9):537–52. doi: 10.1007/s00011-009-0037-3.
   PubMed Web of Science ®Google Scholar
• Giglio, R. V., A. M. Patti, A. F. G. Cicero, G. Lippi, M. Rizzo, P. P. Toth, and M. Banach. 2018. Polyphenols: Potential use in the prevention and treatment of cardiovascular diseases. Current Pharmaceutical Design 24 (2):239–58. doi: 10.2174/1381612824666180130112652.
   PubMed Web of Science ®Google Scholar
• Ginwala, R., R. Bhavsar, D. I. Chigbu, P. Jain, and Z. K. Khan. 2019. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants 8 (2):35. doi: 10.3390/antiox8020035.
   Web of Science ®Google Scholar
• Grosso, G., U. Stepaniak, A. Micek, M. Kozela, D. Stefler, M. Bobak, and A. Pajak. 2017. Dietary polyphenol intake and risk of type 2 diabetes in the Polish arm of the health, alcohol and psychosocial factors in Eastern Europe (HAPIEE) study. The British Journal of Nutrition 118 (1):60–8. doi: 10.1017/S0007114517001805.
   PubMed Web of Science ®Google Scholar
• Guo, X. F., Y. Ruan, Z. H. Li, and D. Li. 2019. Flavonoid subclasses and type 2 diabetes mellitus risk: A meta-analysis of prospective cohort studies. Critical Reviews in Food Science and Nutrition 59 (17):2850–62. doi: 10.1080/10408398.2018.1476964.
   PubMed Web of Science ®Google Scholar
• de Haan, B. J. 2011. Nrf2 activators as attractive therapeutics for diabetic nephropathy. Diabetes 60 (11):2683.
   PubMed Web of Science ®Google Scholar
• Hai, Y., Y. Zhang, Y. Liang, X. Ma, X. Qi, J. Xiao, W. Xue, Y. Luo, and T. Yue. 2020. Advance on the absorption, metabolism, and efficacy exertion of quercetin and its important derivatives. Food Frontiers 1 (4):420–34. doi: 10.1002/fft2.50.
   Google Scholar
• He, X., Z. Wei, E. Zhou, L. Chen, J. Kou, J. Wang, and Z. Yang. 2015. Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-kappa B and MAPK signaling pathways in LPS-induced mastitis in mice. International Immunopharmacology 28 (1):470–6. doi: 10.1016/j.intimp.2015.07.012.
   PubMed Web of Science ®Google Scholar
• Hensel, A., M. Maas, J. Sendker, M. Lechtenberg, F. Petereit, A. Deters, T. Schmidt, and T. Stark. 2011. Eupatorium perfoliatum L.: Phytochemistry, traditional use and current applications. Journal of Ethnopharmacology 138 (3):641–51. doi: 10.1016/j.jep.2011.10.002.
   PubMed Web of Science ®Google Scholar
• Hostetler, G. L., R. A. Ralston, and S. J. Schwartz. 2017. Flavones: Food sources, bioavailability, metabolism, and bioactivity. Advances in Nutrition (Bethesda, MD) 8 (3):423–35. doi: 10.3945/an.116.012948.
   PubMed Web of Science ®Google Scholar
• Hu, M., J. Chen, and H. Lin. 2003. Metabolism of flavonoids via enteric recycling: Mechanistic studies of disposition of apigenin in the Caco-2 cell culture model. Journal of Pharmacology and Experimental Therapeutics 307 (1):314–21. doi: 10.1124/jpet.103.053496.
   PubMed Web of Science ®Google Scholar
• Huang, F., K. Liu, H. Du, J. Kou, and B. Liu. 2012. Puerarin attenuates endothelial insulin resistance through inhibition of inflammatory response in an IKKβ/IRS-1-dependent manner. Biochimie 94 (5):1143–50. doi: 10.1016/j.biochi.2012.01.018.
   PubMed Web of Science ®Google Scholar
• Hu, B., X. Liu, C. Zhang, and X. Zeng. 2017. Food macromolecule based nanodelivery systems for enhancing the bioavailability of polyphenols. Journal of Food and Drug Analysis 25 (1):3–15. doi: 10.1016/j.jfda.2016.11.004.
   PubMed Web of Science ®Google Scholar
• Hussain, T., B. Tan, G. Murtaza, G. Liu, N. Rahu, M. Saleem Kalhoro, D. Hussain Kalhoro, T. O. Adebowale, M. Usman Mazhar, Z. U. Rehman, et al. 2020. Flavonoids and type 2 diabetes: Evidence of efficacy in clinical and animal studies and delivery strategies to enhance their therapeutic efficacy. Pharmacological Research 152:104629. doi: 10.1016/j.phrs.2020.104629.
   PubMed Web of Science ®Google Scholar
• Hwang, S.-L., P.-H. Shih, and G.-C. Yen. 2012. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. Journal of Agricultural and Food Chemistry 60 (4):877–85. doi: 10.1021/jf204452y.
   PubMed Web of Science ®Google Scholar
• Jeon, I. H., H. S. Kim, H. J. Kang, H.-S. Lee, S. I. Jeong, S. J. Kim, and S. I. Jang. 2014. Anti-inflammatory and antipruritic effects of luteolin from perilla (P. frutescens L.) leaves. Molecules (Basel, Switzerland) 19 (6):6941–51. doi: 10.3390/molecules19066941.
   PubMed Web of Science ®Google Scholar
• Ji, N., S.-G. Kim, H.-H. Park, E. Lee, Y. J. Lee, M. Jin, and E. Lee. 2020. Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells. Archives of Pharmacal Research 43 (2):224–32. doi: 10.1007/s12272-020-01212-7.
   PubMed Web of Science ®Google Scholar
• Kahn, B. B., and J. S. Flier. 2000. Obesity and insulin resistance. The Journal of Clinical Investigation 106 (4):473–81. doi: 10.1172/JCI10842.
   PubMed Web of Science ®Google Scholar
• Kamiloglu, S., M. Tomas, T. Ozdal, and E. Capanoglu. 2021. Effect of food matrix on the content and bioavailability of flavonoids. Trends in Food Science & Technology 117:15–33. doi: 10.1016/j.tifs.2020.10.030.
   Web of Science ®Google Scholar
• Keane, K. N., V. F. Cruzat, R. Carlessi, P. I. H. de Bittencourt, and P. Newsholme. 2015. Molecular events linking oxidative stress and inflammation to insulin resistance and β cell dysfunction. Oxidative Medicine and Cellular Longevity 2015:181643. doi: 10.1155/2015/181643.
   PubMed Web of Science ®Google Scholar
• Khan, J., S. Saraf, and S. Saraf. 2016. Preparation and evaluation of luteolin-phospholipid complex as an effective drug delivery tool against GalN/LPS induced liver damage. Pharmaceutical Development and Technology 21 (4):475–86. doi: 10.3109/10837450.2015.1022786.
   PubMed Web of Science ®Google Scholar
• Kim, S. M., and J. Y. Imm. 2020. The effect of chrysin-loaded phytosomes on insulin resistance and blood sugar control in type 2 diabetic db/db mice. Molecules 25 (23):5503. doi: 10.3390/molecules25235503.
   PubMed Web of Science ®Google Scholar
• Kim, M. H., S. Y. Kwon, S.-Y. Woo, W. D. Seo, and D. Y. Kim. 2021. Antioxidative effects of chrysoeriol via activation of the Nrf2 signaling pathway and modulation of mitochondrial function. Molecules 26 (2):313. doi: 10.3390/molecules26020313.
   PubMed Web of Science ®Google Scholar
• Kim, H. P., K. H. Son, H. W. Chang, and S. S. Kang. 2004. Anti-inflammatory plant flavonoids and cellular action mechanisms. Journal of Pharmacological Sciences 96 (3):229–45. doi: 10.1254/jphs.crj04003x.
   PubMed Web of Science ®Google Scholar
• Koirala, N., N. H. Thuan, G. P. Ghimire, D. V. Thang, and J. K. Sohng. 2016. Methylation of flavonoids: Chemical structures, bioactivities, progress and perspectives for biotechnological production. Enzyme and Microbial Technology 86:103–16. doi: 10.1016/j.enzmictec.2016.02.003.
   PubMed Web of Science ®Google Scholar
• Krishnan, B., K. V. Pugalendi, and R. Saravanan. 2019. Ameliorative potential of Chrysoeriol, a bioactive flavonoid on oxidative stress and hepatic marker enzymes in Streptozotocin induced diabetic rats. Asian Journal of Pharmacy and Pharmacology 5 (3):614–24. doi: 10.31024/ajpp.2019.5.3.25.
   Google Scholar
• Krishnan, B., A. Ramu Ganesan, R. Balasubramani, D. D. Nguyen, S. W. Chang, S. Wang, J. Xiao, and B. Balasubramanian. 2020. Chrysoeriol ameliorates hyperglycemia by regulating the carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats. Food Science and Human Wellness 9 (4):346–54. doi: 10.1016/j.fshw.2020.05.014.
   Google Scholar
• Kumar, R., et al. 2012. Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease. The Indian Journal of Medical Research 136 (2):229.
   PubMed Web of Science ®Google Scholar
• Kumar, K. S., V. Sabu, G. Sindhu, A. A. Rauf, and A. Helen. 2018. Isolation, identification and characterization of apigenin from Justicia gendarussa and its anti-inflammatory activity. International Immunopharmacology 59:157–67. doi: 10.1016/j.intimp.2018.04.004.
   PubMed Web of Science ®Google Scholar
• Lai, Z.-R., Y.-L. Ho, S.-C. Huang, T.-H. Huang, S.-C. Lai, J.-C. Tsai, C.-Y. Wang, G.-J. Huang, and Y.-S. Chang. 2011. Antioxidant, anti-inflammatory and antiproliferative activities of kalanchoe gracilis (L.) DC stem. The American Journal of Chinese Medicine 39 (6):1275–90. doi: 10.1142/S0192415X1100955X.
   PubMed Web of Science ®Google Scholar
• Landete, J. M. 2012. Updated knowledge about polyphenols: Functions, bioavailability, metabolism, and health. Critical Reviews in Food Science and Nutrition 52 (10):936–48. doi: 10.1080/10408398.2010.513779.
   PubMed Web of Science ®Google Scholar
• Larsen, N., F. K. Vogensen, F. W. J. van den Berg, D. S. Nielsen, A. S. Andreasen, B. K. Pedersen, W. A. Al-Soud, S. J. Sørensen, L. H. Hansen, and M. Jakobsen. 2010. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PloS One 5 (2):e9085. doi: 10.1371/journal.pone.0009085.
   PubMed Web of Science ®Google Scholar
• Lee, E.-J., M.-K. Kang, Y.-H. Kim, D. Y. Kim, H. Oh, S.-I. Kim, S. Y. Oh, and Y.-H. Kang. 2019. Dietary chrysin suppresses formation of actin cytoskeleton and focal adhesion in AGE-exposed mesangial cells and diabetic kidney: Role of autophagy. Nutrients 11 (1):127. doi: 10.3390/nu11010127.
   PubMed Web of Science ®Google Scholar
• Lee, H., Y. O. Kim, H. Kim, S. Y. Kim, H. S. Noh, S. S. Kang, G. J. Cho, W. S. Choi, and K. Suk. 2003. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 17 (13):1943–4. doi: 10.1096/fj.03-0057fje.
   PubMedGoogle Scholar
• Lee, C.-W., Z.-C. Lin, L.-F. Hsu, J.-Y. Fang, Y.-C. Chiang, M.-H. Tsai, M.-H. Lee, S.-Y. Li, S. C.-S. Hu, I.-T. Lee, et al. 2016. Eupafolin ameliorates COX-2 expression and PGE2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways. Journal of Ethnopharmacology 189:300–9. doi: 10.1016/j.jep.2016.05.002.
   PubMed Web of Science ®Google Scholar
• Lee, Y.-s., W.-K. Yang, S.-M. Yee, S.-M. Kim, Y.-C. Park, H. J. Shin, C. K. Han, Y. C. Lee, H.-S. Kang, and S.-H. Kim. 2019. KGC3P attenuates ovalbumin-induced airway inflammation through downregulation of p-PTEN in asthmatic mice. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 62:152942. doi: 10.1016/j.phymed.2019.152942.
   PubMed Web of Science ®Google Scholar
• Leguisamo, N. M., A. M. Lehnen, U. F. Machado, M. M. Okamoto, M. M. Markoski, G. H. Pinto, and B. D. Schaan. 2012. GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome. Cardiovascular Diabetology 11 (1):1–10. doi: 10.1186/1475-2840-11-100.
   PubMedGoogle Scholar
• Liao, Z.-Y., I.-C. Liang, H.-J. Li, C.-C. Wu, H.-M. Lo, D.-C. Chang, and C.-F. Hung. 2020. Chrysin inhibits high glucose-induced migration on chorioretinal endothelial cells via VEGF and VEGFR down-regulation. International Journal of Molecular Sciences 21 (15):5541. doi: 10.3390/ijms21155541.
   PubMed Web of Science ®Google Scholar
• Liu, W., R. Tian, W. Hu, Y. Jia, H. Jiang, J. Zhang, and L. Zhang. 2012. Preparation and evaluation of self-microemulsifying drug delivery system of baicalein. Fitoterapia 83 (8):1532–9. doi: 10.1016/j.fitote.2012.08.021.
   PubMed Web of Science ®Google Scholar
• Liu, Y., C. Liang, X. Liu, B. Liao, X. Pan, Y. Ren, M. Fan, M. Li, Z. He, J. Wu, et al. 2010. AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-κB pathways. Atherosclerosis 208 (1):34–42. doi: 10.1016/j.atherosclerosis.2009.06.007.
   PubMed Web of Science ®Google Scholar
• Liu, X., Y. Fu, Q. Ma, J. Yi, and S. Cai. 2021. Anti-diabetic effects of different phenolic-rich fractions from Rhus Chinensis Mill. fruits in vitro. eFood 2 (1):37–46. doi: 10.2991/efood.k.210222.002.
   Google Scholar
• Liu, J., L. Y. Qiu, J. Q. Gao, and Y. Jin. 2006. Preparation, characterization and in vivo evaluation of formulation of baicalein with hydroxypropyl-beta-cyclodextrin. International Journal of Pharmaceutics 312 (1–2):137–43. doi: 10.1016/j.ijpharm.2006.01.011.
   PubMed Web of Science ®Google Scholar
• Liu, Y.-J., J. Zhan, X.-L. Liu, Y. Wang, J. Ji, and Q.-Q. He. 2014. Dietary flavonoids intake and risk of type 2 diabetes: A meta-analysis of prospective cohort studies. Clinical Nutrition (Edinburgh, Scotland) 33 (1):59–63. doi: 10.1016/j.clnu.2013.03.011.
   PubMed Web of Science ®Google Scholar
• Li, K., Z. He, X. Wang, M. Pineda, R. Chen, H. Liu, K. Ma, H. Shen, C. Wu, N. Huang, et al. 2018. Apigenin C-glycosides of Microcos paniculata protects lipopolysaccharide induced apoptosis and inflammation in acute lung injury through TLR4 signaling pathway. Free Radical Biology & Medicine 124:163–75. doi: 10.1016/j.freeradbiomed.2018.06.009.
   PubMed Web of Science ®Google Scholar
• Li, M., Q. Li, Q. Zhao, J. Zhang, and J. Lin. 2015. Luteolin improves the impaired nerve functions in diabetic neuropathy: Behavioral and biochemical evidences. International Journal of Clinical and Experimental Pathology 8 (9):10112–20.
   PubMed Web of Science ®Google Scholar
• Li, W., J. X. Pi, Y. Zhang, X. T. Ma, B. Zhang, S. Y. Wang, D. L. Qi, N. Li, P. Guo, and Z. D. Liu. 2018. A strategy to improve the oral availability of baicalein: The baicalein-theophylline cocrystal. Fitoterapia 129:85–93. doi: 10.1016/j.fitote.2018.06.018.
   PubMed Web of Science ®Google Scholar
• Lim, M., L. Park, G. Shin, H. Hong, I. Kang, and Y. Park. 2008. Induction of apoptosis of β cells of the pancreas by advanced glycation end‐products, important mediators of chronic complications of diabetes mellitus. Annals of the New York Academy of Sciences 1150 (1):311–5. doi: 10.1196/annals.1447.011.
   PubMedGoogle Scholar
• Lin, Y., R. Shi, X. Wang, and H.-M. Shen. 2008. Luteolin, a flavonoid with potential for cancer prevention and therapy. Current Cancer Drug Targets 8 (7):634–46. doi: 10.2174/156800908786241050.
   PubMed Web of Science ®Google Scholar
• Lingohr, M. K., R. Buettner, and C. J. Rhodes. 2002. Pancreatic β-cell growth and survival–a role in obesity-linked type 2 diabetes? Trends in Molecular Medicine 8 (8):375–84. doi: 10.1016/s1471-4914(02)02377-8.
   PubMed Web of Science ®Google Scholar
• Lyssenko, V., P. Almgren, D. Anevski, R. Perfekt, K. Lahti, M. Nissén, B. Isomaa, B. Forsen, N. Homström, C. Saloranta, for the Botnia Study Group, et al. 2005. Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes 54 (1):166–74. doi: 10.2337/diabetes.54.1.166.
   PubMed Web of Science ®Google Scholar
• Maas, M., A. M. Deters, and A. Hensel. 2011. Anti-inflammatory activity of Eupatorium perfoliatum L. extracts, eupafolin, and dimeric guaianolide via iNOS inhibitory activity and modulation of inflammation-related cytokines and chemokines. Journal of Ethnopharmacology 137 (1):371–81. doi: 10.1016/j.jep.2011.05.040.
   PubMed Web of Science ®Google Scholar
• Madhavi, Y. V., N. Gaikwad, V. G. Yerra, A. K. Kalvala, S. Nanduri, and A. Kumar. 2019. Targeting AMPK in diabetes and diabetic complications: Energy homeostasis, autophagy and mitochondrial health. Current Medicinal Chemistry 26 (27):5207–29. doi: 10.2174/0929867325666180406120051.
   PubMed Web of Science ®Google Scholar
• Manach, C., et al. (2004). Polyphenols: Food sources and bioavailability. The American Journal of Clinical Nutrition 79(5):727–747. doi: 10.1093/ajcn/79.5.727.
   PubMed Web of Science ®Google Scholar
• Mani, R., and V. Natesan. 2018. Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry 145:187–96. doi: 10.1016/j.phytochem.2017.09.016.
   PubMed Web of Science ®Google Scholar
• Medzhitov, R. (2010). Inflammation 2010: New adventures of an old flame. Cell 140(6): 771–776. doi: 10.1016/j.cell.2010.03.006.
   PubMed Web of Science ®Google Scholar
• Meng, X., S. Fang, Z. Zhang, Y. Wang, C. You, J. Zhang, and H. Yan. 2017. Preventive effect of chrysin on experimental autoimmune uveitis triggered by injection of human IRBP peptide 1–20 in mice. Cellular & Molecular Immunology 14 (8):702–11. doi: 10.1038/cmi.2015.107.
   PubMed Web of Science ®Google Scholar
• Miao, L., H. Tao, Y. Peng, S. Wang, Z. Zhong, H. El-Seedi, S. Dragan, G. Zengin, W. S. Cheang, Y. Wang, et al. 2019. The anti-inflammatory potential of Portulaca oleracea L. (purslane) extract by partial suppression on NF-kappa B and MAPK activation. Food Chemistry 290:239–45. doi: 10.1016/j.foodchem.2019.04.005.
   PubMed Web of Science ®Google Scholar
• NCD Risk Factor Collaboration. (2016). Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 387:1513–1530.
   PubMed Web of Science ®Google Scholar
• Nickavar, B., and L. Abolhasani. 2013. Bioactivity-Guided Separation of an α-Amylase Inhibitor Flavonoid from Salvia virgata. Iranian Journal of Pharmaceutical Research: IJPR 12 (1):57–61.
   PubMed Web of Science ®Google Scholar
• Oyadomari, S., E. Araki, and M. Mori. 2002. Endoplasmic reticulum stress-mediated apoptosis in pancreatic β-cells. Apoptosis: An International Journal on Programmed Cell Death 7 (4):335–45. doi: 10.1023/a:1016175429877.
   PubMed Web of Science ®Google Scholar
• Pan, M.-H., C.-S. Lai, and C.-T. Ho. 2010. Anti-inflammatory activity of natural dietary flavonoids. Food & Function 1 (1):15–31. doi: 10.1039/c0fo00103a.
   PubMed Web of Science ®Google Scholar
• Panche, A., A. Diwan, and S. Chandra. 2016. Flavonoids: An overview. Journal of Nutritional Science 5:E47e47. doi: 10.1017/jns.2016.41.
   Google Scholar
• Park, C.-H., S.-Y. Min, H.-W. Yu, K. Kim, S. Kim, H.-J. Lee, J.-H. Kim, and Y.-J. Park. 2020. Effects of apigenin on RBL-2H3, RAW264.7, and HaCaT cells: Anti-allergic, anti-inflammatory, and skin-protective activities. International Journal of Molecular Sciences 21 (13):4620. doi: 10.3390/ijms21134620.
   PubMed Web of Science ®Google Scholar
• Patel, S., and D. Santani. 2009. Role of NF-kappa B in the pathogenesis of diabetes and its associated complications. Pharmacological Reports: PR 61 (4):595–603. doi: 10.1016/S1734-1140(09)70111-2.
   PubMed Web of Science ®Google Scholar
• Patel, D., and K. K. Sawant. 2009. Self micro-emulsifying drug delivery system: Formulation development and biopharmaceutical evaluation of lipophilic drugs. Current Drug Delivery 6 (4):419–24. doi: 10.2174/156720109789000519.
   PubMedGoogle Scholar
• Pichichero, E., R. Cicconi, M. Mattei, M. G. Muzi, and A. Canini. 2010. Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression. International Journal of Oncology 37 (4):973–81. doi: 10.3892/ijo_00000748.
   PubMed Web of Science ®Google Scholar
• Poulton, J. E., K. Hahlbrock, and H. Grisebach. 1977. O-Methylation of flavonoid substrates by a partially purified enzyme from soybean cell suspension cultures. Archives of Biochemistry and Biophysics 180 (2):543–9. doi: 10.1016/0003-9861(77)90071-6.
   PubMed Web of Science ®Google Scholar
• Prasain, J. K., and S. Barnes. 2020. Cranberry polyphenols-gut microbiota interactions and potential health benefits: An updated review. Food Frontiers 1 (4):459–64. doi: 10.1002/fft2.56.
   Google Scholar
• Rambaran, T. F., and A. Nordström. 2021. Medical and pharmacokinetic effects of nanopolyphenols: A systematic review of clinical trials. Food Frontiers 2 (2):140–52. doi: 10.1002/fft2.72.
   Google Scholar
• Ramirez, G., A. Zamilpa, M. Zavala, J. Perez, D. Morales, and J. Tortoriello. 2016. Chrysoeriol and other polyphenols from Tecoma stans with lipase inhibitory activity. Journal of Ethnopharmacology 185:1–8. doi: 10.1016/j.jep.2016.03.014.
   PubMed Web of Science ®Google Scholar
• Reaven, G., F. Abbasi, and T. McLaughlin. 2004. Obesity, insulin resistance, and cardiovascular disease. Recent Progress in Hormone Research 59:207–24. doi: 10.1210/rp.59.1.207.
   PubMedGoogle Scholar
• Ren, W., Z. Qiao, H. Wang, L. Zhu, and L. Zhang. 2003. Flavonoids: Promising anticancer agents. Medicinal Research Reviews 23 (4):519–34. doi: 10.1002/med.10033.
   PubMed Web of Science ®Google Scholar
• Renaud, S., and M. de Lorgeril. 1993. The French paradox: Dietary factors and cigarette smoking-related health risks. Annals of the New York Academy of Sciences 686:299–309. doi: 10.1111/j.1749-6632.1993.tb39191.x.
   PubMed Web of Science ®Google Scholar
• Rice-Evans, C. A., N. J. Miller, P. G. Bolwell, P. M. Bramley, and J. B. Pridham. 1995. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radical Research 22 (4):375–83. doi: 10.3109/10715769509145649.
   PubMed Web of Science ®Google Scholar
• Rithidech, K. N., M. Tungjai, P. Reungpatthanaphong, L. Honikel, and S. R. Simon. 2012. Attenuation of oxidative damage and inflammatory responses by apigenin given to mice after irradiation. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 749 (1–2):29–38. doi: 10.1016/j.mrgentox.2012.08.001.
   PubMed Web of Science ®Google Scholar
• Ross, J. A., and C. M. Kasum. 2002. Dietary flavonoids: Bioavailability, metabolic effects, and safety. Annual Review of Nutrition 22 (1):19–34. doi: 10.1146/annurev.nutr.22.111401.144957.
   PubMed Web of Science ®Google Scholar
• Robak, J., and R. J. Gryglewski. (1996). Bioactivity of flavonoids. Polish Journal of Pharmacology 48(6):555–564.
   PubMedGoogle Scholar
• Rothwell, J., et al. 2013. Phenol-Explorer 3.0: A major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content. Database (Oxford) 2013: bat070.
   Google Scholar
• Saba, E., Y.-S. Lee, W.-K. Yang, Y. Y. Lee, M. Kim, S.-M. Woo, K. Kim, Y.-S. Kwon, T.-H. Kim, D. Kwak, et al. 2020. Effects of a herbal formulation, KGC3P, and its individual component, nepetin, on coal fly dust-induced airway inflammation. Scientific Reports 10 (1):14036. doi: 10.1038/s41598-020-68965-5.
   PubMed Web of Science ®Google Scholar
• Sada, K., T. Nishikawa, D. Kukidome, T. Yoshinaga, N. Kajihara, K. Sonoda, T. Senokuchi, H. Motoshima, T. Matsumura, E. Araki, et al. 2016. Hyperglycemia induces cellular hypoxia through production of mitochondrial ROS followed by suppression of aquaporin-1. PloS One 11 (7):e0158619. doi: 10.1371/journal.pone.0158619.
   PubMed Web of Science ®Google Scholar
• Saeedi, P., I. Petersohn, P. Salpea, B. Malanda, S. Karuranga, N. Unwin, S. Colagiuri, L. Guariguata, A. A. Motala, K. Ogurtsova, et al. 2019. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Research and Clinical Practice 157:107843. doi: 10.1016/j.diabres.2019.107843.
   PubMed Web of Science ®Google Scholar
• Salehi, B., et al. 2019. The therapeutic potential of apigenin. International Journal of Molecular Sciences 20 (6): 1305.
   PubMed Web of Science ®Google Scholar
• Sangeetha, R. 2019. Luteolin in the management of type 2 diabetes mellitus. Current Research in Nutrition and Food Science Journal 7 (2):393–8. doi: 10.12944/CRNFSJ.7.2.09.
   Web of Science ®Google Scholar
• Scalbert, A., et al. (2002). Absorption and metabolism of polyphenols in the gut and impact on health. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 56(6):276–282. doi: 10.1016/s0753-3322(02)00205-6.
   PubMed Web of Science ®Google Scholar
• Seraglio, S. K. T., A. C. Valese, H. Daguer, G. Bergamo, M. S. Azevedo, P. Nehring, L. V. Gonzaga, R. Fett, and A. C. O. Costa. 2017. Effect of in vitro gastrointestinal digestion on the bioaccessibility of phenolic compounds, minerals, and antioxidant capacity of Mimosa scabrella Bentham honeydew honeys. Food Research International (Ottawa, ON) 99 (Pt 1):670–8. doi: 10.1016/j.foodres.2017.06.024.
   PubMedGoogle Scholar
• Shaw, J. E., R. A. Sicree, and P. Z. Zimmet. (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice 87(1):4–14.
   PubMed Web of Science ®Google Scholar
• Shen, Y.-C., W.-F. Chiou, Y.-C. Chou, and C.-F. Chen. 2003. Mechanisms in mediating the anti-inflammatory effects of baicalin and baicalein in human leukocytes. European Journal of Pharmacology 465 (1–2):171–81. doi: 10.1016/s0014-2999(03)01378-5.
   PubMed Web of Science ®Google Scholar
• Shen, Q., X. Li, W. Li, and X. Zhao. 2011. Enhanced intestinal absorption of daidzein by borneol/menthol eutectic mixture and microemulsion. AAPS PharmSciTech 12 (4):1044–9. doi: 10.1208/s12249-011-9672-4.
   PubMed Web of Science ®Google Scholar
• Shi, S., J. Li, X. Zhao, Q. Liu, and S.-J. Song. 2021. A comprehensive review: Biological activity, modification and synthetic methodologies of prenylated flavonoids. Phytochemistry 191:112895. doi: 10.1016/j.phytochem.2021.112895.
   PubMed Web of Science ®Google Scholar
• Shin, E. K., H.-S. Kwon, Y. H. Kim, H.-K. Shin, and J.-K. Kim. 2009. Chrysin, a natural flavone, improves murine inflammatory bowel diseases. Biochemical and Biophysical Research Communications 381 (4):502–7. doi: 10.1016/j.bbrc.2009.02.071.
   PubMed Web of Science ®Google Scholar
• Shoelson, S. E., L. Herrero, and A. Naaz. 2007. Obesity, inflammation, and insulin resistance. Gastroenterology 132 (6):2169–80. doi: 10.1053/j.gastro.2007.03.059.
   PubMed Web of Science ®Google Scholar
• Shoelson, S. E., J. Lee, and A. B. Goldfine. 2006. Inflammation and insulin resistance. The Journal of Clinical Investigation 116 (7):1793–801. doi: 10.1172/JCI29069.
   PubMed Web of Science ®Google Scholar
• Singh, J., B. P. Chaudhari, and P. Kakkar. 2017. Baicalin and chrysin mixture imparts cyto-protection against methylglyoxal induced cytotoxicity and diabetic tubular injury by modulating RAGE, oxidative stress and inflammation. Environmental Toxicology and Pharmacology 50:67–75. doi: 10.1016/j.etap.2017.01.013.
   PubMed Web of Science ®Google Scholar
• Sun, C., C. Zhao, E. C. Guven, P. Paoli, J. Simal-Gandara, K. M. m. Ramkumar, S. Wang, F. Buleu, A. Pah, V. Turi, et al. 2020. Dietary polyphenols as antidiabetic agents: Advances and opportunities. Food Frontiers 1 (1):18–44. doi: 10.1002/fft2.15.
   Google Scholar
• Sung, H.-C., C.-J. Liang, C.-W. Lee, F.-L. Yen, C.-Y. Hsiao, S.-H. Wang, Y.-F. Jiang-Shieh, J.-S. Tsai, and Y.-L. Chen. 2015. The protective effect of eupafolin against TNF-α-induced lung inflammation via the reduction of intercellular cell adhesion molecule-1 expression. Journal of Ethnopharmacology 170:136–47. doi: 10.1016/j.jep.2015.04.058.
   PubMed Web of Science ®Google Scholar
• Ta, N., and T. Walle. 2007. Aromatase inhibition by bioavailable methylated flavones. The Journal of Steroid Biochemistry and Molecular Biology 107 (1–2):127–9. doi: 10.1016/j.jsbmb.2007.01.006.
   PubMed Web of Science ®Google Scholar
• Taha, I. M., A. M. Abdu Allah, and E. M. Abd El Gayed. 2018. Expression of toll-like receptor 4 and its connection with type 2 diabetes mellitus. Cellular and Molecular Biology (Noisy-Le-Grand, France) 64 (13):15–20. PMID: 30403590
   PubMed Web of Science ®Google Scholar
• Taleb, R. E., et al. 2020. In vivo and in vitro anti-diabetic activity of ethanolic propolis extract. Journal of Food Biochemistry 44 (7): 458–470.
   Web of Science ®Google Scholar
• Tanti, J. F., and J. Jager. 2009. Cellular mechanisms of insulin resistance: Role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Current Opinion in Pharmacology 9 (6):753–62. doi: 10.1016/j.coph.2009.07.004.
   PubMed Web of Science ®Google Scholar
• Terao, J. 2017. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function. Biochemical Pharmacology 139:15–23. doi: 10.1016/j.bcp.2017.03.021.
   PubMed Web of Science ®Google Scholar
• Thilakarathna, S. H., and H. P. V. Rupasinghe. 2013. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients 5 (9):3367–87. doi: 10.3390/nu5093367.
   PubMed Web of Science ®Google Scholar
• Thitilertdecha, P., V. Tantithavorn, P. Poungpairoj, and N. Onlamoon. 2019. Determination of suppressive effect on human T-cell activation by hispidulin, nepetin, and vanillic acid. Immunopharmacology and Immunotoxicology 41 (6):591–8. doi: 10.1080/08923973.2019.1675165.
   PubMed Web of Science ®Google Scholar
• Tilg, H., and A. R. Moschen. 2008. Inflammatory mechanisms in the regulation of insulin resistance. Molecular Medicine 14 (3–4):222–31. doi: 10.2119/2007-00119.Tilg.
   PubMed Web of Science ®Google Scholar
• Torres-Piedra, M., R. Ortiz-Andrade, R. Villalobos-Molina, N. Singh, J. L. Medina-Franco, S. P. Webster, M. Binnie, G. Navarrete-Vázquez, and S. Estrada-Soto. 2010. A comparative study of flavonoid analogues on streptozotocin–nicotinamide induced diabetic rats: Quercetin as a potential antidiabetic agent acting via 11β-Hydroxysteroid dehydrogenase type 1 inhibition. European Journal of Medicinal Chemistry 45 (6):2606–12. doi: 10.1016/j.ejmech.2010.02.049.
   PubMed Web of Science ®Google Scholar
• Tsilioni, I., A. Taliou, K. Francis, and T. C. Theoharides. 2015. Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Translational Psychiatry 5:e647. doi: 10.1038/tp.2015.142.
   PubMed Web of Science ®Google Scholar
• Valavanidis, A., T. Vlachogianni, and C. Fiotakis. 2009. 8-Hydroxy-2’-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews 27 (2):120–39. doi: 10.1080/10590500902885684.
   PubMed Web of Science ®Google Scholar
• Van Greevenbroek, M. M., C. G. Schalkwijk, and C. D. Stehouwer. 2013. Obesity-associated low-grade inflammation in type 2 diabetes mellitus: Causes and consequences. The Netherlands Journal of Medicine 71 (4):174–87.
   PubMed Web of Science ®Google Scholar
• Vauzour, D., K. Vafeiadou, A. Rodriguez-Mateos, C. Rendeiro, and J. P. E. Spencer. 2008. The neuroprotective potential of flavonoids: a multiplicity of effects. Genes & Nutrition 3 (3–4):115–26. doi: 10.1007/s12263-008-0091-4.
   PubMed Web of Science ®Google Scholar
• Vitale, M., O. Vaccaro, M. Masulli, E. Bonora, S. Del Prato, C. B. Giorda, A. Nicolucci, S. Squatrito, S. Auciello, A. C. Babini, et al. 2017. Polyphenol intake and cardiovascular risk factors in a population with type 2 diabetes: The TOSCA.IT study. Clinical Nutrition 36 (6):1686–92. doi: 10.1016/j.clnu.2016.11.002.
   PubMed Web of Science ®Google Scholar
• Vuruskan, H., Z. Caliskan, Y. Kordan, C. Ozakin, I. Yavascaoglu, and B. Oktay. 2005. Elevated plasma concentrations of transforming growth factor-beta 1 in patients with unilateral ureteral obstruction. Urological Research 33 (6):465–9. doi: 10.1007/s00240-005-0509-z.
   PubMedGoogle Scholar
• Waisundara, V. Y., A. N. Hsu, B. K. H. Tan, and D. J. Huang. 2009. Baicalin improves antioxidant status of streptozotocin-induced diabetic wistar rats. Journal of Agricultural and Food Chemistry 57 (10):4096–102. doi: 10.1021/jf8028539.
   PubMed Web of Science ®Google Scholar
• Wang, G. G., X. H. Lu, W. Li, X. Zhao, and C. Zhang. 2011. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evidence-Based Complementary and Alternative Medicine: eCAM 2011:323171. doi: 10.1155/2011/323171.
   PubMed Web of Science ®Google Scholar
• Wang, J., M. Xiao, J. Wang, S. Wang, J. Zhang, Y. Guo, Y. Tang, and J. Gu. 2021. NRF2-related epigenetic modifications in cardiac and vascular complications of diabetes mellitus. Frontiers in Endocrinology 12:598005. doi: 10.3389/fendo.2021.598005.
   PubMed Web of Science ®Google Scholar
• Wang, C.-Z., C.-F. Zhang, Y. Luo, H. Yao, C. Yu, L. Chen, J. Yuan, W.-H. Huang, J.-Y. Wan, J. Zeng, et al. 2020. Baicalein, an enteric microbial metabolite, suppresses gut inflammation and cancer progression in ApcMin/+ mice. Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 22 (7):1013–22. doi: 10.1007/s12094-019-02225-5.
   PubMed Web of Science ®Google Scholar
• Wei, W., Q. Liu, Y. Tan, L. Liu, X. Li, and L. Cai. 2009. Oxidative stress, diabetes, and diabetic complications. Hemoglobin 33 (5):370–7. doi: 10.3109/03630260903212175.
   PubMed Web of Science ®Google Scholar
• Wen, X., and T. Walle. 2006. Methylated flavonoids have greatly improved intestinal absorption and metabolic stability. Drug Metabolism and Disposition: The Biological Fate of Chemicals 34 (10):1786–92. doi: 10.1124/dmd.106.011122.
   PubMed Web of Science ®Google Scholar
• Weyer, C., C. Bogardus, D. M. Mott, and R. E. Pratley. 1999. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. The Journal of Clinical Investigation 104 (6):787–94. doi: 10.1172/JCI7231.
   PubMed Web of Science ®Google Scholar
• Widjajakusuma, E. C., A. Jonosewojo, L. Hendriati, S. Wijaya, A. Surjadhana, W. Sastrowardoyo, N. Monita, N. M. Muna, R. P. Fajarwati, M. Ervina, et al. 2019. Phytochemical screening and preliminary clinical trials of the aqueous extract mixture of Andrographis paniculata (Burm. f.) Wall. ex Nees and Syzygium polyanthum (Wight.) Walp leaves in metformin treated patients with type 2 diabetes. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 55:137–47. doi: 10.1016/j.phymed.2018.07.002.
   PubMed Web of Science ®Google Scholar
• Wu, J.-Y., Y.-J. Chen, L. Bai, Y.-X. Liu, X.-Q. Fu, P.-L. Zhu, J.-K. Li, J.-Y. Chou, C.-L. Yin, Y.-P. Wang, et al. 2020. Chrysoeriol ameliorates TPA-induced acute skin inflammation in mice and inhibits NF-kappaB and STAT3 pathways. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 68:153173. doi: 10.1016/j.phymed.2020.153173.
   PubMed Web of Science ®Google Scholar
• Xiao, J. B., and P. Hogger. 2014. Influence of diabetes on the pharmacokinetic behavior of natural polyphenols. Current Drug Metabolism 15 (1):23–9. doi: 10.2174/1389200214666131210142614.
   PubMed Web of Science ®Google Scholar
• Xingjun, et al. 2018. The PI3K/AKT pathway in obesity and type 2 diabetes. International Journal of Biological Sciences. 14(11): 1483-1496.
   PubMed Web of Science ®Google Scholar
• Xiong, J., K. Wang, C. Yuan, R. Xing, J. Ni, G. Hu, F. Chen, and X. Wang. 2017. Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects. International Journal of Molecular Medicine 39 (1):113–25. doi: 10.3892/ijmm.2016.2809.
   PubMed Web of Science ®Google Scholar
• Xu, Z., Z.-H. Shen, B. Wu, S.-L. Gong, and B. Chen. 2021. Small molecule natural compound targets the NF-κB signaling and ameliorates the development of osteoarthritis. Journal of Cellular Physiology 236 (11):7298–307. doi: 10.1002/jcp.30392.
   PubMed Web of Science ®Google Scholar
• Xue, C., Z. Shi, Z. He, Z. Wang, F. Qin, J. Chen, and M. Zeng. 2020. Formation of three selected AGEs and their corresponding intermediates in aldose- and ketose-lysine systems. eFood 1 (3):270–8. doi: 10.2991/efood.k.200508.001.
   Google Scholar
• Yamamoto, M., S. Sato, H. Hemmi, K. Hoshino, T. Kaisho, H. Sanjo, O. Takeuchi, M. Sugiyama, M. Okabe, K. Takeda, et al. 2003. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science (New York, NY) 301 (5633):640–3. doi: 10.1126/science.1087262.
   Google Scholar
• Yang, Z., W. Huang, J. Zhang, M. Xie, and X. Wang. 2019. Baicalein improves glucose metabolism in insulin resistant HepG2 cells. European Journal of Pharmacology 854:187–93. doi: 10.1016/j.ejphar.2019.04.005.
   PubMed Web of Science ®Google Scholar
• Yang, X. M., Y. M. Jiang, J. L. Yang, J. R. He, J. Sun, F. Chen, M. W. Zhang, and B. Yang. 2015. Prenylated flavonoids, promising nutraceuticals with impressive biological activities. Trends in Food Science & Technology 44 (1):93–104. doi: 10.1016/j.tifs.2015.03.007.
   Web of Science ®Google Scholar
• Yoon, H., and H. Yoon. 2021. Chrysoeriol ameliorates COX-2 expression through NF-κB, AP-1 and MAPK regulation via the TLR4/MyD88 signaling pathway in LPS-stimulated murine macrophages. Experimental and Therapeutic Medicine 22 (1):718. doi: 10.3892/etm.2021.10150.
   PubMed Web of Science ®Google Scholar
• Zafar, A., N. K. Alruwaili, S. S. Imam, N. Hadal Alotaibi, K. S. Alharbi, M. Afzal, R. Ali, S. Alshehri, S. I. Alzarea, M. Elmowafy, et al. 2021. Bioactive Apigenin loaded oral nano bilosomes: Formulation optimization to preclinical assessment. Saudi Pharmaceutical Journal 29 (3):269–79. doi: 10.1016/j.jsps.2021.02.003.
   PubMed Web of Science ®Google Scholar
• Zang, Y., K. Igarashi, and Y. Li. 2016. Anti-diabetic effects of luteolin and luteolin-7-O-glucoside on KK-Ay mice. Bioscience, Biotechnology, and Biochemistry 80 (8):1580–6. doi: 10.1080/09168451.2015.1116928.
   PubMed Web of Science ®Google Scholar
• Zang, M., S. Xu, K. A. Maitland-Toolan, A. Zuccollo, X. Hou, B. Jiang, M. Wierzbicki, T. J. Verbeuren, and R. A. Cohen. 2006. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 55 (8):2180–91. doi: 10.2337/db05-1188.
   PubMed Web of Science ®Google Scholar
• Zhang, H. L., G. Caprioli, H. Hussain, N. P. Khoi Le, M. A. Farag, and J. B. Xiao. 2021. A multifaceted review on dihydromyricetin resources, extraction, bioavailability, biotransformation, bioactivities, and food applications with future perspectives to maximize its value. eFood 2 (4):164–84. doi: 10.53365/efood.k/143518.
   Google Scholar
• Zhang, Z., C. Cui, F. Wei, and H. Lv. 2017. Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system. Drug Development and Industrial Pharmacy 43 (8):1276–82. doi: 10.1080/03639045.2017.1313857.
   PubMed Web of Science ®Google Scholar
• Zhang, B.-W., X. Li, W.-L. Sun, Y. Xing, Z.-L. Xiu, C.-L. Zhuang, and Y.-S. Dong. 2017. Dietary flavonoids and acarbose synergistically inhibit α-glucosidase and lower postprandial blood glucose. Journal of Agricultural and Food Chemistry 65 (38):8319–30. doi: 10.1021/acs.jafc.7b02531.
   PubMed Web of Science ®Google Scholar
• Zhang, B., W. Sun, N. Yu, J. Sun, X. Yu, X. Li, Y. Xing, D. Yan, Q. Ding, Z. Xiu, et al. 2018. Anti-diabetic effect of baicalein is associated with the modulation of gut microbiota in streptozotocin and high-fat-diet induced diabetic rats. Journal of Functional Foods 46:256–67. doi: 10.1016/j.jff.2018.04.070.
   Web of Science ®Google Scholar
• Zhang, Y., Q. Xie, L. You, P C. ‐K. Cheung, and Z. Zhao. 2021. Behavior of non-digestible polysaccharides in gastrointestinal tract: a mechanistic review of its anti-obesity effect. eFood 2 (2):59–72. doi: 10.2991/efood.k.210310.001.
   Google Scholar
• Zhao, C., X. Wan, S. Zhou, and H. Cao. 2020. Natural polyphenols: A potential therapeutic approach to hypoglycemia. eFood 1 (2):107–18. doi: 10.2991/efood.k.200302.001.
   Google Scholar
• Zhao, L., Y. Wei, Y. Huang, B. He, Y. Zhou, and J. Fu. 2013. Nanoemulsion improves the oral bioavailability of baicalin in rats: In vitro and in vivo evaluation. International Journal of Nanomedicine 8:3769–79. doi: 10.2147/IJN.S51578.
   PubMed Web of Science ®Google Scholar
• Zhao, C., C. Yang, S. T. C. Wai, Y. Zhang, M. P Portillo, P. Paoli, Y. Wu, W. San Cheang, B. Liu, C. Carpéné, et al. 2019. Regulation of glucose metabolism by bioactive phytochemicals for the management of type 2 diabetes mellitus. Critical Reviews in Food Science and Nutrition 59 (6):830–47. doi: 10.1080/10408398.2018.1501658.
   PubMed Web of Science ®Google Scholar
• Zheng, Z., W. Zhu, B. Yang, R. Chai, T. Liu, F. Li, G. Ren, S. Ji, S. Liu, G. Li, et al. 2018. The co-treatment of metformin with flavone synergistically induces apoptosis through inhibition of PI3K/AKT pathway in breast cancer cells. Oncology Letters 15 (4):5952–8. doi: 10.3892/ol.2018.7999.
   PubMed Web of Science ®Google Scholar
• Zheng, Y., S. H. Ley, and F. B. Hu. 2018. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Reviews. Endocrinology 14(2):88–98.
   PubMed Web of Science ®Google Scholar
• Zheng, W., Z. Tao, L. Cai, C. Chen, C. Zhang, Q. Wang, X. Ying, W. Hu, and H. Chen. 2017. Chrysin attenuates IL-1β-induced expression of inflammatory mediators by suppressing NF-κB in human osteoarthritis chondrocytes. Inflammation 40 (4):1143–54. doi: 10.1007/s10753-017-0558-9.
   PubMed Web of Science ®Google Scholar
• Zheng, X.-K., L. Zhang, W.-W. Wang, Y.-Y. Wu, Q.-B. Zhang, and W.-S. Feng. 2011. Anti-diabetic activity and potential mechanism of total flavonoids of Selaginella tamariscina (Beauv.) Spring in rats induced by high fat diet and low dose STZ. Journal of Ethnopharmacology 137 (1):662–8. doi: 10.1016/j.jep.2011.06.018.
   PubMed Web of Science ®Google Scholar
• Zhong, R., M. A. Farag, M. Chen, C. He, and J. Xiao. 2022. Recent advances in the biosynthesis, structure–activity relationships, formulations, pharmacology, and clinical trials of fisetin. eFood 3 (1-2):e3. doi: 10.1002/efd2.3.
   Google Scholar
• Zhou, X., L. Fu, P. L. Wang, L. Yang, X. S. Zhu, and C. G. Li. 2021. Drug-herb interactions between Scutellaria baicalensis and pharmaceutical drugs: Insights from experimental studies, mechanistic actions to clinical applications. Biomedicine & Pharmacotherapy 138:111445. doi: 10.1016/j.biopha.2021.111445.
   PubMed Web of Science ®Google Scholar
• Zhou, Y.-J., N. Xu, X.-C. Zhang, Y.-Y. Zhu, S.-W. Liu, and Y.-N. Chang. 2021. Chrysin improves glucose and lipid metabolism disorders by regulating the AMPK/PI3K/AKT signaling pathway in insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. Journal of Agricultural and Food Chemistry 69 (20):5618–27. doi: 10.1021/acs.jafc.1c01109.
   PubMed Web of Science ®Google Scholar
• Zhou, R.-J., H. Ye, F. Wang, J.-L. Wang, and M.-L. Xie. 2017. Apigenin inhibits D-galactosamine/LPS-induced liver injury through upregulation of hepatic Nrf-2 and PPARg expressions in mice. Biochemical and Biophysical Research Communications 493 (1):625–e30. doi: 10.1016/j.bbrc.2017.08.141.
   PubMed Web of Science ®Google Scholar
• Zhu, F. M., J. X. Li, Z. L. Ma, J. Li, and B. Du. 2021. Structural identification and in vitro antioxidant activities of anthocyanins in black chokeberry (Aronia melanocarpa lliot). eFood 2 (4):201–8. doi: 10.53365/efood.k/143829.
   Google Scholar
• Ziyan, L., Z. Yongmei, Z. Nan, T. Ning, and L. Baolin. 2007. Evaluation of the anti-inflammatory activity of luteolin in experimental animal models. Planta Medica 73 (3):221–6. doi: 10.1055/s-2007-967122.
   PubMed Web of Science ®Google Scholar
• Żyżyńska-Granica, B., B. Gierlikowska, A. Parzonko, A. K. Kiss, and S. Granica. 2020. The bioactivity of flavonoid glucuronides and free aglycones in the context of their absorption, II phase metabolism and deconjugation at the inflammation site. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 135:110929. doi: 10.1016/j.fct.2019.110929.
   PubMed Web of Science ®Google Scholar