Quercetin and Related Analogs as Therapeutics to Promote Tissue Repair
Abstract
:1. Introduction
2. Bioactivity
2.1. Wound Healing
2.2. Aging
3. Therapeutic Development
4. Future Outlooks
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Solecki, R.S. Shanidar IV, a Neanderthal Flower Burial in Northern Iraq. Science 1975, 190, 880–881. [Google Scholar] [CrossRef]
- Weyrich, L.S.; Duchene, S.; Soubrier, J.; Arriola, L.; Llamas, B.; Breen, J.; Morris, A.G.; Alt, K.W.; Caramelli, D.; Dresely, V.; et al. Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus. Nature 2017, 544, 357–361. [Google Scholar] [CrossRef] [PubMed]
- Hardy, K.; Buckley, S.; Collins, M.J.; Estalrrich, A.; Brothwell, D.; Copeland, L.; García-Tabernero, A.; García-Vargas, S.; de la Rasilla, M.; Lalueza-Fox, C.; et al. Neanderthal medics? Evidence for food, cooking, and medicinal plants entrapped in dental calculus. Naturwissenschaften 2012, 99, 617–626. [Google Scholar] [CrossRef] [PubMed]
- Patridge, E.; Gareiss, P.; Kinch, M.S.; Hoyer, D. An analysis of FDA-approved drugs: Natural products and their derivatives. Drug Discov. Today 2016, 21, 204–207. [Google Scholar] [CrossRef] [PubMed]
- Newman, D.J.; Cragg, G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J. Nat. Prod. 2020, 83, 770–803. [Google Scholar] [CrossRef] [PubMed]
- Andrews, E.A.; Lewis, C.T. A Latin Dictionary Founded on Andrews’ Edition of Freund’s Latin Dictionary; Clarendon Press: Oxford, UK, 1896. [Google Scholar]
- Bhagwat, S.; Haytowitz, D.B.; Holden, J.M. USDA Database for the Flavonoid Content of Selected Foods, Release 3; US Department of Agriculture: Beltsville, MD, USA, 2011; p. 159. [Google Scholar]
- Miean, K.H.; Mohamed, S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J. Agric. Food Chem. 2001, 49, 3106–3112. [Google Scholar] [CrossRef]
- Ojong, P.B.; Njiti, V.; Guo, Z.; Gao, M.; Besong, S.; Barnes, S.L. Variation of flavonoid content among sweetpotato accessions. J. Am. Soc. Hortic. Sci. 2008, 133, 819–824. [Google Scholar] [CrossRef]
- Koes, R.E.; Quattrocchio, F.; Mol, J.N. The flavonoid biosynthetic pathway in plants: Function and evolution. BioEssays 1994, 16, 123–132. [Google Scholar] [CrossRef]
- Shirley, B.W. Flavonoid biosynthesis:‘new’functions for an ‘old’pathway. Trends Plant Sci. 1996, 1, 377–382. [Google Scholar]
- Liu, W.; Feng, Y.; Yu, S.; Fan, Z.; Li, X.; Li, J.; Yin, H. The flavonoid biosynthesis network in plants. Int. J. Mol. Sci. 2021, 22, 12824. [Google Scholar] [CrossRef]
- Fraser, D.P.; Sharma, A.; Fletcher, T.; Budge, S.; Moncrieff, C.; Dodd, A.N.; Franklin, K.A. UV-B antagonises shade avoidance and increases levels of the flavonoid quercetin in coriander (Coriandrum sativum). Sci. Rep. 2017, 7, 17758. [Google Scholar] [CrossRef]
- Lois, R. Accumulation of UV-absorbing flavonoids induced by UV-B radiation in Arabidopsis thaliana L. Planta 1994, 194, 498–503. [Google Scholar] [CrossRef]
- Mattson, M.P. Hormesis defined. Ageing Res. Rev. 2008, 7, 1–7. [Google Scholar] [CrossRef]
- Lamming, D.W.; Wood, J.G.; Sinclair, D.A. Small molecules that regulate lifespan: Evidence for xenohormesis. Mol. Microbiol. 2004, 53, 1003–1009. [Google Scholar] [CrossRef] [PubMed]
- Cao, G.; Sofic, E.; Prior, R.L. Antioxidant and prooxidant behavior of flavonoids: Structure-activity relationships. Free Radic. Biol. Med. 1997, 22, 749–760. [Google Scholar] [CrossRef]
- Aherne, S.A.; O’Brien, N.M. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic. Biol. Med. 2000, 29, 507–514. [Google Scholar] [CrossRef]
- Zhang, M.; Lu, P.; Terada, T.; Sui, M.; Furuta, H.; Iida, K.; Katayama, Y.; Lu, Y.; Okamoto, K.; Suzuki, M. Quercetin 3, 5, 7, 3′, 4′-pentamethyl ether from Kaempferia parviflora directly and effectively activates human SIRT1. Commun. Biol. 2021, 4, 209. [Google Scholar] [CrossRef]
- Wei, X.; Jia, R.; Yang, Z.; Jiang, J.; Huang, J.; Yan, J.; Luo, X. NAD+/sirtuin metabolism is enhanced in response to cold-induced changes in lipid metabolism in mouse liver. FEBS Lett. 2020, 594, 1711–1725. [Google Scholar] [CrossRef] [PubMed]
- Chen, R.; Dioum, E.M.; Hogg, R.T.; Gerard, R.D.; Garcia, J.A. Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner. J. Biol. Chem. 2011, 286, 13869–13878. [Google Scholar] [PubMed]
- Crujeiras, A.; Parra, D.; Goyenechea, E.; Martínez, J. Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction. Eur. J. Clin. Investig. 2008, 38, 672–678. [Google Scholar]
- Lazo-Gomez, R.; Tapia, R. Quercetin prevents spinal motor neuron degeneration induced by chronic excitotoxic stimulus by a sirtuin 1-dependent mechanism. Transl. Neurodegener. 2017, 6, 31. [Google Scholar] [CrossRef] [PubMed]
- Howitz, K.T.; Bitterman, K.J.; Cohen, H.Y.; Lamming, D.W.; Lavu, S.; Wood, J.G.; Zipkin, R.E.; Chung, P.; Kisielewski, A.; Zhang, L.-L.; et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003, 425, 191–196. [Google Scholar] [CrossRef] [PubMed]
- van der Woude, H.; Ter Veld, M.G.; Jacobs, N.; van der Saag, P.T.; Murk, A.J.; Rietjens, I.M. The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol. Nutr. Food Res. 2005, 49, 763–771. [Google Scholar] [CrossRef] [PubMed]
- Khanam, U.K.S.; Oba, S.; Yanase, E.; Murakami, Y. Phenolic acids, flavonoids and total antioxidant capacity of selected leafy vegetables. J. Funct. Foods 2012, 4, 979–987. [Google Scholar] [CrossRef]
- Sultana, B.; Anwar, F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chem. 2008, 108, 879–884. [Google Scholar] [CrossRef]
- Barba, F.J.; Esteve, M.J.; Frígola, A. Bioactive components from leaf vegetable products. Stud. Nat. Prod. Chem. 2014, 41, 321–346. [Google Scholar]
- Poetschke, J.; Gauglitz, G.G. Onion extract. In Textbook on Scar Management: State of the Art Management and Emerging Technologies; Springer: Cham, Switzerland, 2020; pp. 209–213. [Google Scholar]
- Tziotzios, C.; Profyris, C.; Sterling, J. Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics: Part II. Strategies to reduce scar formation after dermatologic procedures. J. Am. Acad. Dermatol. 2012, 66, 13–24. [Google Scholar] [CrossRef]
- Burak, C.; Brüll, V.; Langguth, P.; Zimmermann, B.F.; Stoffel-Wagner, B.; Sausen, U.; Stehle, P.; Wolffram, S.; Egert, S. Higher plasma quercetin levels following oral administration of an onion skin extract compared with pure quercetin dihydrate in humans. Eur. J. Nutr. 2017, 56, 343–353. [Google Scholar] [CrossRef]
- Mullen, W.; Edwards, C.A.; Crozier, A. Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions. Br. J. Nutr. 2006, 96, 107–116. [Google Scholar] [CrossRef]
- DuPont, M.S.; Bennett, R.N.; Mellon, F.A.; Williamson, G. Polyphenols from Alcoholic Apple Cider Are Absorbed, Metabolized and Excreted by Humans. J. Nutr. 2002, 132, 172–175. [Google Scholar] [CrossRef] [PubMed]
- Harwood, M.; Danielewska-Nikiel, B.; Borzelleca, J.; Flamm, G.; Williams, G.; Lines, T. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem. Toxicol. 2007, 45, 2179–2205. [Google Scholar] [CrossRef]
- Platzer, M.; Kiese, S.; Tybussek, T.; Herfellner, T.; Schneider, F.; Schweiggert-Weisz, U.; Eisner, P. Radical Scavenging Mechanisms of Phenolic Compounds: A Quantitative Structure-Property Relationship (QSPR) Study. Front. Nutr. 2022, 9, 882458. [Google Scholar] [CrossRef]
- McKay, T.B.; Kivanany, P.B.; Nicholas, S.E.; Nag, O.K.; Elliott, M.H.; Petroll, W.M.; Karamichos, D. Quercetin Decreases Corneal Haze In Vivo and Influences Gene Expression of TGF-Beta Mediators In Vitro. Metabolites 2022, 12, 626. [Google Scholar] [CrossRef]
- Du, L.; Hao, M.; Li, C.; Wu, W.; Wang, W.; Ma, Z.; Yang, T.; Zhang, N.; Isaac, A.T.; Zhu, X.; et al. Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high-glucose-cultured lens, and SRA01/04 cells through transforming growth factor-β2/phosphoinositide 3-kinase/Akt pathway. Mol. Cell Endocrinol. 2017, 452, 44–56. [Google Scholar] [CrossRef]
- Lu, Q.; Hao, M.; Wu, W.; Zhang, N.; Isaac, A.T.; Yin, J.; Zhu, X.; Du, L.; Yin, X. Antidiabetic cataract effects of GbE, rutin and quercetin are mediated by the inhibition of oxidative stress and polyol pathway. Acta Biochim. Pol. 2018, 65, 35–41. [Google Scholar] [CrossRef]
- Oh, H.N.; Kim, C.E.; Lee, J.H.; Yang, J.W. Effects of quercetin in a mouse model of experimental dry eye. Cornea 2015, 34, 1130–1136. [Google Scholar] [CrossRef]
- Abengózar-Vela, A.; Schaumburg, C.S.; Stern, M.E.; Calonge, M.; Enríquez-de-Salamanca, A.; González-García, M.J. Topical quercetin and resveratrol protect the ocular surface in experimental dry eye disease. Ocul. Immunol. Inflamm. 2019, 27, 1023–1032. [Google Scholar] [CrossRef]
- Horton, J.A.; Li, F.; Chung, E.J.; Hudak, K.; White, A.; Krausz, K.; Gonzalez, F.; Citrin, D. Quercetin inhibits radiation-induced skin fibrosis. Radiat. Res. 2013, 180, 205–215. [Google Scholar] [CrossRef] [PubMed]
- Yang, N.; Shi, N.; Yao, Z.; Liu, H.; Guo, W. Gallium-modified gelatin nanoparticles loaded with quercetin promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization. Front. Bioeng. Biotechnol. 2023, 11, 1124944. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.J.; Cheng, H.W.; Yen, W.Y.; Tsai, J.H.; Yeh, C.Y.; Chen, C.J.; Liu, J.T.; Chen, S.Y.; Chang, S.J. The Treatment of Keloid Scars via Modulating Heterogeneous Gelatin-Structured Composite Microneedles to Control Transdermal Dual-Drug Release. Polymers 2022, 14, 4436. [Google Scholar] [CrossRef] [PubMed]
- Fu, J.; Huang, J.; Lin, M.; Xie, T.; You, T. Quercetin Promotes Diabetic Wound Healing via Switching Macrophages From M1 to M2 Polarization. J. Surg. Res. 2020, 246, 213–223. [Google Scholar] [CrossRef]
- Jee, J.-P.; Pangeni, R.; Jha, S.K.; Byun, Y.; Park, J.W. Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy. Int. J. Nanomed. 2019, 14, 5449–5475. [Google Scholar] [CrossRef]
- Shisheva, A.; Shechter, Y. Quercetin selectively inhibits insulin receptor function in vitro and the bioresponses of insulin and insulinomimetic agents in rat adipocytes. Biochemistry 1992, 31, 8059–8063. [Google Scholar] [CrossRef]
- Jung, C.H.; Cho, I.; Ahn, J.; Jeon, T.I.; Ha, T.Y. Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes. Phytother. Res. 2013, 27, 139–143. [Google Scholar] [CrossRef]
- Yang, D.K.; Kang, H.S. Anti-Diabetic Effect of Cotreatment with Quercetin and Resveratrol in Streptozotocin-Induced Diabetic Rats. Biomol. Ther. 2018, 26, 130–138. [Google Scholar] [CrossRef]
- Kottmann, R.M.; Kulkarni, A.A.; Smolnycki, K.A.; Lyda, E.; Dahanayake, T.; Salibi, R.; Honnons, S.; Jones, C.; Isern, N.G.; Hu, J.Z. Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-β. Am. J. Respir. Crit. Care Med. 2012, 186, 740–751. [Google Scholar] [CrossRef] [PubMed]
- Cui, H.; Xie, N.; Banerjee, S.; Ge, J.; Jiang, D.; Dey, T.; Matthews, Q.L.; Liu, R.-M.; Liu, G. Lung myofibroblasts promote macrophage profibrotic activity through lactate-induced histone lactylation. Am. J. Respir. Cell Mol. Biol. 2021, 64, 115–125. [Google Scholar] [CrossRef]
- Nakamura, T.; Matsushima, M.; Hayashi, Y.; Shibasaki, M.; Imaizumi, K.; Hashimoto, N.; Shimokata, K.; Hasegawa, Y.; Kawabe, T. Attenuation of transforming growth factor-β-stimulated collagen production in fibroblasts by quercetin-induced heme oxygenase-1. Am. J. Respir. Cell Mol. Biol. 2011, 44, 614–620. [Google Scholar] [CrossRef] [PubMed]
- Veith, C.; Drent, M.; Bast, A.; van Schooten, F.J.; Boots, A.W. The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin. Toxicol. Appl. Pharmacol. 2017, 336, 40–48. [Google Scholar] [CrossRef] [PubMed]
- McKay, T.B.; Lyon, D.; Sarker-Nag, A.; Priyadarsini, S.; Asara, J.M.; Karamichos, D. Quercetin attenuates lactate production and extracellular matrix secretion in keratoconus. Sci. Rep. 2015, 5, 9003. [Google Scholar] [CrossRef] [PubMed]
- Karamichos, D.; Hutcheon, A.E.; Rich, C.B.; Trinkaus-Randall, V.; Asara, J.M.; Zieske, J.D. In vitro model suggests oxidative stress involved in keratoconus disease. Sci. Rep. 2014, 4, 4608. [Google Scholar] [CrossRef]
- McKay, T.B.; Sarker-Nag, A.; Lyon, D.; Asara, J.M.; Karamichos, D. Quercetin modulates keratoconus metabolism in vitro. Cell Biochem. Funct. 2015, 33, 341–350. [Google Scholar] [CrossRef] [PubMed]
- Jia, L.; Huang, S.; Yin, X.; Zan, Y.; Guo, Y.; Han, L. Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction. Life Sci. 2018, 208, 123–130. [Google Scholar] [CrossRef]
- Pani, S.; Sahoo, A.; Patra, A.; Debata, P.R. Phytocompounds curcumin, quercetin, indole-3-carbinol, and resveratrol modulate lactate-pyruvate level along with cytotoxic activity in HeLa cervical cancer cells. Biotechnol. Appl. Biochem. 2021, 68, 1396–1402. [Google Scholar] [CrossRef]
- Vander Heiden, M.G.; Cantley, L.C.; Thompson, C.B. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009, 324, 1029–1033. [Google Scholar] [CrossRef] [PubMed]
- Mi, Y.; Zhong, L.; Lu, S.; Hu, P.; Pan, Y.; Ma, X.; Yan, B.; Wei, Z.; Yang, G. Quercetin promotes cutaneous wound healing in mice through Wnt/β-catenin signaling pathway. J. Ethnopharmacol. 2022, 290, 115066. [Google Scholar] [CrossRef]
- Jalali, M.; Bayat, A. Current use of steroids in management of abnormal raised skin scars. Surgeon 2007, 5, 175–180. [Google Scholar] [CrossRef] [PubMed]
- Beken, B.; Serttas, R.; Yazicioglu, M.; Turkekul, K.; Erdogan, S. Quercetin Improves Inflammation, Oxidative Stress, and Impaired Wound Healing in Atopic Dermatitis Model of Human Keratinocytes. Pediatr. Allergy Immunol. Pulmonol. 2020, 33, 69–79. [Google Scholar] [CrossRef] [PubMed]
- Li, F.; Bai, Y.; Zhao, M.; Huang, L.; Li, S.; Li, X.; Chen, Y. Quercetin inhibits vascular endothelial growth factor-induced choroidal and retinal angiogenesis in vitro. Ophthalmic Res. 2015, 53, 109–116. [Google Scholar] [CrossRef]
- Lupo, G.; Cambria, M.T.; Olivieri, M.; Rocco, C.; Caporarello, N.; Longo, A.; Zanghì, G.; Salmeri, M.; Foti, M.C.; Anfuso, C.D. Anti-angiogenic effect of quercetin and its 8-methyl pentamethyl ether derivative in human microvascular endothelial cells. J. Cell. Mol. Med. 2019, 23, 6565–6577. [Google Scholar] [CrossRef]
- López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. Hallmarks of aging: An expanding universe. Cell 2023, 186, 243–278. [Google Scholar] [CrossRef]
- Wood, J.G.; Rogina, B.; Lavu, S.; Howitz, K.; Helfand, S.L.; Tatar, M.; Sinclair, D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004, 430, 686–689. [Google Scholar] [CrossRef]
- Baur, J.A.; Pearson, K.J.; Price, N.L.; Jamieson, H.A.; Lerin, C.; Kalra, A.; Prabhu, V.V.; Allard, J.S.; Lopez-Lluch, G.; Lewis, K.; et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444, 337–342. [Google Scholar] [CrossRef]
- Sun, Y.; Yang, Y.M.; Hu, Y.Y.; Ouyang, L.; Sun, Z.H.; Yin, X.F.; Li, N.; He, Q.Y.; Wang, Y. Inhibition of nuclear deacetylase Sirtuin-1 induces mitochondrial acetylation and calcium overload leading to cell death. Redox Biol. 2022, 53, 102334. [Google Scholar] [CrossRef]
- Gurd, B.J. Deacetylation of PGC-1α by SIRT1: Importance for skeletal muscle function and exercise-induced mitochondrial biogenesis. Appl. Physiol. Nutr. Metab. 2011, 36, 589–597. [Google Scholar] [CrossRef] [PubMed]
- Belinha, I.; Amorim, M.A.; Rodrigues, P.; de Freitas, V.; Moradas-Ferreira, P.; Mateus, N.; Costa, V. Quercetin increases oxidative stress resistance and longevity in Saccharomyces cerevisiae. J. Agric. Food Chem. 2007, 55, 2446–2451. [Google Scholar] [CrossRef] [PubMed]
- Scambia, G.; Mancuso, S.; Panici, P.B.; De Vincenzo, R.; Ferrandina, G.; Bonanno, G.; Ranelletti, F.O.; Piantelli, M.; Capelli, A. Quercetin induces type-II estrogen-binding sites in estrogen-receptor-negative (MDA-MB231) and estrogen-receptor-positive (MCF-7) human breast-cancer cell lines. Int. J. Cancer 1993, 54, 462–466. [Google Scholar] [CrossRef]
- Redza-Dutordoir, M.; Averill-Bates, D.A. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim. Biophys. Acta 2016, 1863, 2977–2992. [Google Scholar] [CrossRef] [PubMed]
- Iside, C.; Scafuro, M.; Nebbioso, A.; Altucci, L. SIRT1 Activation by Natural Phytochemicals: An Overview. Front. Pharmacol. 2020, 11, 1225. [Google Scholar] [CrossRef] [PubMed]
- Moutsatsou, P. The spectrum of phytoestrogens in nature: Our knowledge is expanding. HORMONES-ATHENS- 2007, 6, 173. [Google Scholar]
- Björnström, L.; Sjöberg, M. Mechanisms of Estrogen Receptor Signaling: Convergence of Genomic and Nongenomic Actions on Target Genes. Mol. Endocrinol. 2005, 19, 833–842. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Chen, Y.; Liu, X.; Gao, Y.; Hu, J.; Chen, H. Discovery of novel negletein derivatives as potent anticancer agents for acute myeloid leukemia. Chem. Biol. Drug Des. 2018, 91, 924–932. [Google Scholar] [CrossRef]
- Yang, A.; Liu, C.; Zhang, H.; Wu, J.; Shen, R.; Kou, X. A multifunctional anti-AD approach: Design, synthesis, X-ray crystal structure, biological evaluation and molecular docking of chrysin derivatives. Eur. J. Med. Chem. 2022, 233, 114216. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.H.; Kim, H.J.; Yoo, H.; Jung, S.Y.; Kwon, B.J.; Kim, N.J.; Jin, C.; Lee, Y.S. Synthesis of (2-amino)ethyl derivatives of quercetin 3-O-methyl ether and their antioxidant and neuroprotective effects. Bioorg Med. Chem. 2015, 23, 4970–4979. [Google Scholar] [CrossRef] [PubMed]
- Sun, J.; Li, F.; Zhao, Y.; Zhao, L.; Qiao, C.; Li, Z.; Guo, Q.; Lu, N. LZ-207, a Newly Synthesized Flavonoid, Induces Apoptosis and Suppresses Inflammation-Related Colon Cancer by Inhibiting the NF-kappaB Signaling Pathway. PLoS ONE 2015, 10, e0127282. [Google Scholar] [CrossRef]
- Helgren, T.R.; Sciotti, R.J.; Lee, P.; Duffy, S.; Avery, V.M.; Igbinoba, O.; Akoto, M.; Hagen, T.J. The synthesis, antimalarial activity and CoMFA analysis of novel aminoalkylated quercetin analogs. Bioorg. Med. Chem. Lett. 2015, 25, 327–332. [Google Scholar] [CrossRef] [PubMed]
- Mukherjee, A.; Mishra, S.; Kotla, N.K.; Manna, K.; Roy, S.; Kundu, B.; Bhattacharya, D.; Das Saha, K.; Talukdar, A. Semisynthetic Quercetin Derivatives with Potent Antitumor Activity in Colon Carcinoma. ACS Omega 2019, 4, 7285–7298. [Google Scholar] [CrossRef]
- Chen, H.; Mrazek, A.A.; Wang, X.; Ding, C.; Ding, Y.; Porro, L.J.; Liu, H.; Chao, C.; Hellmich, M.R.; Zhou, J. Design, synthesis, and characterization of novel apigenin analogues that suppress pancreatic stellate cell proliferation in vitro and associated pancreatic fibrosis in vivo. Bioorg. Med. Chem. 2014, 22, 3393–3404. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Li, T.; Zhao, T.; Wu, T.; Liu, C.; Ding, H.; Li, Z.; Bian, J. Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity. Eur. J. Med. Chem. 2019, 178, 782–801. [Google Scholar] [CrossRef]
- Feng, S.; Zhou, H.; Wu, D.; Zheng, D.; Qu, B.; Liu, R.; Zhang, C.; Li, Z.; Xie, Y.; Luo, H.B. Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: Total synthesis and discovery of potent MDR reversal agents. Acta Pharm. Sin. B 2020, 10, 327–343. [Google Scholar] [CrossRef] [PubMed]
- Lombardo, E.; Sabellico, C.; Hajek, J.; Stankova, V.; Filipsky, T.; Balducci, V.; De Vito, P.; Leone, S.; Bavavea, E.I.; Silvestri, I.P.; et al. Protection of cells against oxidative stress by nanomolar levels of hydroxyflavones indicates a new type of intracellular antioxidant mechanism. PLoS ONE 2013, 8, e60796. [Google Scholar] [CrossRef] [PubMed]
- Zhu, S.; Yang, C.; Zhang, L.; Wang, S.; Ma, M.; Zhao, J.; Song, Z.; Wang, F.; Qu, X.; Li, F.; et al. Development of M10, myricetin-3-O-beta-d-lactose sodium salt, a derivative of myricetin as a potent agent of anti-chronic colonic inflammation. Eur. J. Med. Chem. 2019, 174, 9–15. [Google Scholar] [CrossRef] [PubMed]
- Li, F.; Yang, C.; Zhang, L.; Li, W. Synthesis of myricetin derivatives and evaluation of their hypoglycemic activities. Med. Chem. Res. 2023, 32, 76–84. [Google Scholar] [CrossRef]
- Li, M.; Li, Y.; Ludwik, K.A.; Sandusky, Z.M.; Lannigan, D.A.; O’Doherty, G.A. Stereoselective Synthesis and Evaluation of C6’’-Substituted 5a-Carbasugar Analogues of SL0101 as Inhibitors of RSK1/2. Org. Lett. 2017, 19, 2410–2413. [Google Scholar] [CrossRef]
- Seley-Radtke, K.L.; Yates, M.K. The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold. Antivir. Res. 2018, 154, 66–86. [Google Scholar] [CrossRef]
- Ludwik, K.A.; Campbell, J.P.; Li, M.; Li, Y.; Sandusky, Z.M.; Pasic, L.; Sowder, M.E.; Brenin, D.R.; Pietenpol, J.A.; O’Doherty, G.A.; et al. Development of a RSK Inhibitor as a Novel Therapy for Triple-Negative Breast Cancer. Mol Cancer Ther. 2016, 15, 2598–2608. [Google Scholar] [CrossRef]
- Xu, D.; Hu, M.J.; Wang, Y.Q.; Cui, Y.L. Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules 2019, 24, 1123. [Google Scholar] [CrossRef] [PubMed]
- Suganthy, N.; Devi, K.P.; Nabavi, S.F.; Braidy, N.; Nabavi, S.M. Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions. Biomed. Pharmacother. 2016, 84, 892–908. [Google Scholar] [CrossRef] [PubMed]
- Qi, Y.; Guo, L.; Jiang, Y.; Shi, Y.; Sui, H.; Zhao, L. Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles. Drug Deliv. 2020, 27, 745–755. [Google Scholar] [CrossRef]
- Wang, S.; Chen, Y.; Xia, C.; Yang, C.; Chen, J.; Hai, L.; Wu, Y.; Yang, Z. Synthesis and evaluation of glycosylated quercetin to enhance neuroprotective effects on cerebral ischemia-reperfusion. Bioorg. Med. Chem. 2022, 73, 117008. [Google Scholar] [CrossRef] [PubMed]
- Tron, G.C.; Pirali, T.; Billington, R.A.; Canonico, P.L.; Sorba, G.; Genazzani, A.A. Click chemistry reactions in medicinal chemistry: Applications of the 1,3-dipolar cycloaddition between azides and alkynes. Med. Res. Rev. 2008, 28, 278–308. [Google Scholar] [CrossRef] [PubMed]
- Matos, A.M.; Man, T.; Idrissi, I.; Souza, C.C.; Mead, E.; Dunbar, C.; Wolak, J.; Oliveira, M.C.; Evans, D.; Grayson, J.; et al. Discovery of N-methylpiperazinyl flavones as a novel class of compounds with therapeutic potential against Alzheimer’s disease: Synthesis, binding affinity towards amyloid β oligomers (Aβo) and ability to disrupt Aβo-PrPC interactions. Pure Appl. Chem. 2019, 91, 1107–1136. [Google Scholar] [CrossRef]
- Kandemir, K.; Tomas, M.; McClements, D.J.; Capanoglu, E. Recent advances on the improvement of quercetin bioavailability. Trends Food Sci. Technol. 2022, 119, 192–200. [Google Scholar] [CrossRef]
Biological Properties | Model System | Injury | Drug Treatment | Results | Ref. |
---|---|---|---|---|---|
Antifibrotic | C57BL/6J mice | Corneal epithelial and stromal debridement | Topical ocular application of 5 mM quercetin | Reduction in corneal opacity based on slit lamp | [36] |
New Zealand white rabbits | Corneal lamellar keratectomy | Topical ocular application of 5 mM quercetin | Reduction in corneal haze based on in vivo confocal microscopy | [36] | |
Antioxidative | Sprague- Dawley rats | STZ treatment to induce diabetes-associated complications | 30–120 mg/kg quercetin administered i.g. | Reduced lens opacity based on slit lamp and decreased AGEs | [37] |
Sprague-Dawley rats | STZ treatment to induce hyperglycemia | 90 mg/kg quercetin i.p. | Reduced lens opacity based on slit lamp and increased GSH production | [38] | |
Anti-inflammatory | NOD.B10.H2 mice | Injection of muscarinic receptor blocker followed by desiccation for 10 days to induce dry eye symptoms | Topical ocular application of 0.5% w/v quercetin | Increased tear production and reduced pro-inflammatory cytokine secretion | [39] |
WT C57BL/6 and T-cell-deficient C57BL/6 mice | Desiccation for 10 days and continuous injection of scopolamine hydrobromide to induce dry eye symptoms | Topical ocular application of 0.01% w/v quercetin | Improved ocular surface barrier function and decreased pro-inflammatory cytokine secretion | [40] |
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McKay, T.B.; Emmitte, K.A.; German, C.; Karamichos, D. Quercetin and Related Analogs as Therapeutics to Promote Tissue Repair. Bioengineering 2023, 10, 1127. https://doi.org/10.3390/bioengineering10101127
McKay TB, Emmitte KA, German C, Karamichos D. Quercetin and Related Analogs as Therapeutics to Promote Tissue Repair. Bioengineering. 2023; 10(10):1127. https://doi.org/10.3390/bioengineering10101127
Chicago/Turabian StyleMcKay, Tina B., Kyle A. Emmitte, Carrie German, and Dimitrios Karamichos. 2023. "Quercetin and Related Analogs as Therapeutics to Promote Tissue Repair" Bioengineering 10, no. 10: 1127. https://doi.org/10.3390/bioengineering10101127