The Role of Flavonoids in Inhibiting IL-6 and Inflammatory Arthritis

Ayman   M.   Mahmoud; Ahmed   M.   Sayed; Osama   S.   Ahmed; Mohamed   M.   Abdel-Daim; Emad   H.M.   Hassanein
doi:10.2174/1568026622666220107105233
Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the synovial joints. RA has well-known clinical manifestations and can cause progressive disability and premature death along with socioeconomic burdens. Interleukin-6 (IL-6) has been implicated in the pathology of RA where it can stimulate pannus formation, osteoclastogenesis, and oxidative stress. Flavonoids are plant metabolites with beneficial pharmacological effects, including anti-inflammatory, antioxidant, antidiabetic, anticancer, etc. Flavonoids are polyphenolic compounds found in a variety of plants, vegetables, and fruits. Many flavonoids have demonstrated anti-arthritic activity mediated mainly through the suppression of pro-inflammatory cytokines. This review thoroughly discusses the accumulated data on the role of flavonoids on IL-6 in RA.
Keywords: Rheumatoid arthritis, Inflammation, Flavonoids, Cytokines, IL-6, Polyphenols.
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[1] 
Johnson, V.L.; Hunter, D.J. The epidemiology of osteoarthritis. Best Pract. Res. Clin. Rheumatol.,  2014, 28(1), 5-15.
[http://dx.doi.org/10.1016/j.berh.2014.01.004] [PMID:  24792942] 
[2] 
Goldring, S.R. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology (Oxford),  2003, 42(Suppl. 2), ii11-ii16.
[http://dx.doi.org/10.1093/rheumatology/keg327] [PMID:  12817090] 
[3] 
Sharif, K.; Sharif, A.; Jumah, F.; Oskouian, R.; Tubbs, R.S. Rheumatoid arthritis in review: Clinical, anatomical, cellular and molecular points of view. Clin. Anat.,  2018, 31(2), 216-223.
[http://dx.doi.org/10.1002/ca.22980] [PMID:  28833647] 
[4] 
Smolen, J.S.; Aletaha, D.; McInnes, I.B. Rheumatoid arthritis. Lancet,  2016, 388(10055), 2023-2038.
[http://dx.doi.org/10.1016/S0140-6736(16)30173-8] [PMID:  27156434] 
[5] 
Charles, J.; Britt, H.; Pan, Y. Rheumatoid arthritis. Aust. Fam. Physician,  2013, 42(11), 765.
[PMID:  24217093] 
[6] 
Karlson, E.W.; Deane, K. Environmental and gene-environment interactions and risk of rheumatoid arthritis. Rheum. Dis. Clin. North Am.,  2012, 38(2), 405-426.
[http://dx.doi.org/10.1016/j.rdc.2012.04.002] [PMID:  22819092] 
[7] 
Pradeepkiran, J.A. Insights of rheumatoid arthritis risk factors and associations. J. Transl. Autoimmun.,  2019, 2, 100012.
[http://dx.doi.org/10.1016/j.jtauto.2019.100012] [PMID:  32743500] 
[8] 
Bullock, J.; Rizvi, S.A.A.; Saleh, A.M.; Ahmed, S.S.; Do, D.P.; Ansari, R.A.; Ahmed, J. Rheumatoid arthritis: A brief overview of the treatment. Med. Princ. Pract.,  2018, 27(6), 501-507.
[9] 
Havsteen, B.H. The biochemistry and medical significance of the flavonoids. Pharmacol. Ther.,  2002, 96(2-3), 67-202.
[http://dx.doi.org/10.1016/S0163-7258(02)00298-X] [PMID:  12453566] 
[10] 
Althunibat, O.Y.; Al Hroob, A.M.; Abukhalil, M.H.; Germoush, M.O.; Bin-Jumah, M.; Mahmoud, A.M. Fisetin ameliorates oxidative stress, inflammation and apoptosis in diabetic cardiomyopathy. Life Sci.,  2019, 221, 83-92.
[http://dx.doi.org/10.1016/j.lfs.2019.02.017] [PMID:  30742869] 
[11] 
Mahmoud, A.M.; Ashour, M.B.; Abdel-Moneim, A.; Ahmed, O.M. Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats. J. Diabetes Complications,  2012, 26(6), 483-490.
[http://dx.doi.org/10.1016/j.jdiacomp.2012.06.001] [PMID:  22809898] 
[12] 
Mahmoud, A.M.; Mohammed, H.M.; Khadrawy, S.M.; Galaly, S.R. Hesperidin protects against chemically induced hepatocarcinogenesis via modulation of Nrf2/ARE/HO-1, PPARγ and TGF-β1/Smad3 signaling, and amelioration of oxidative stress and inflammation. Chem. Biol. Interact.,  2017, 277, 146-158.
[http://dx.doi.org/10.1016/j.cbi.2017.09.015] [PMID:  28935427] 
[13] 
Mahmoud, A.M. Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation. Can. J. Physiol. Pharmacol.,  2014, 92(9), 717-724.
[http://dx.doi.org/10.1139/cjpp-2014-0204] [PMID:  25079140] 
[14] 
Mahmoud, A.M. Influence of rutin on biochemical alterations in hyperammonemia in rats. Exp. Toxicol. Pathol.,  2012, 64(7-8), 783-789.
[15] 
Pan, H-D.; Xiao, Y.; Wang, W-Y.; Ren, R-T.; Leung, E.L-H.; Liu, L. Traditional Chinese medicine as a treatment for rheumatoid arthritis: from empirical practice to evidence-based therapy. Engineering,  2019, 5(5), 895-906.
[http://dx.doi.org/10.1016/j.eng.2019.01.018] 
[16] 
Sung, S.; Kwon, D.; Um, E.; Kim, B. Could polyphenols help in the control of rheumatoid arthritis? Molecules,  2019, 24(8), 1589.
[http://dx.doi.org/10.3390/molecules24081589] [PMID:  31013659] 
[17] 
Bungau, S.; Behl, T.; Mehta, K.; Sehgal, A.; Singh, S.; Sharma, N.; Ahmadi, A.; Arora, S. Exploring the role of polyphenols in rheumatoid arthritis; Critic. Rev. Food Sci. Nutrit, 2021, pp. 1-22.
[18] 
Oliviero, F.; Scanu, A.; Zamudio-Cuevas, Y.; Punzi, L.; Spinella, P. Anti-inflammatory effects of polyphenols in arthritis. J. Sci. Food Agric.,  2018, 98(5), 1653-1659.
[http://dx.doi.org/10.1002/jsfa.8664] [PMID:  28886220] 
[19] 
McInnes, I.B.; Schett, G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med.,  2011, 365(23), 2205-2219.
[http://dx.doi.org/10.1056/NEJMra1004965] 
[20] 
Ballanti, E.; Perricone, C.; Di Muzio, G.; Kroegler, B.; Chimenti, M.S.; Graceffa, D.; Perricone, R. Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationship with anti-TNF inhibitors. Autoimmun. Rev.,  2011, 10(10), 617-623.
[http://dx.doi.org/10.1016/j.autrev.2011.04.012] 
[21] 
Kuwabara, T.; Ishikawa, F.; Kondo, M.; Kakiuchi, T. The role of IL-17 and related cytokines in inflammatory autoimmune diseases. Mediators Inflamm.,  2017, 2017, 3908061.
[22] 
Firestein, G.S.; McInnes, I.B. Immunopathogenesis of rheumatoid arthritis. Immunity,  2017, 46(2), 183-196.
[http://dx.doi.org/10.1016/j.immuni.2017.02.006] 
[23] 
Srirangan, S.; Choy, E.H. The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther. Adv. Musculoskelet. Dis.,  2010, 2(5), 247-256.
[http://dx.doi.org/10.1177/1759720X10378372] 
[24] 
Dayer, J-M.; Choy, E.J.R. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford),  2010, 49(1), 15-24.
[http://dx.doi.org/10.1093/rheumatology/kep329] 
[25] 
Kimura, A. Kishimoto, T. IL-6: regulator of Treg/Th17 balance. Eur. J. Immunol.,  2010, 40(7), 1830-1835.
[26] 
Kotake, S.; Sato, K.; Kim, K.J.; Takahashi, N.; Udagawa, N.; Nakamura, I.; Yamaguchi, A.; Kishimoto, T.; Suda, T.; Kashiwazaki, S. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J. Bone Miner. Res.,  1996, 11(1), 88-95.
[27] 
Pandolfi, F.; Altamura, S.; Frosali, S.; Conti, P. Key role of DAMP in inflammation, cancer, and tissue repair. Clin. Ther.,  2016, 38(5), 1017-1028.
[http://dx.doi.org/10.1016/j.clinthera.2016.02.028] [PMID:  27021609] 
[28] 
Hunter, C.A.; Jones, S.A. IL-6 as a keystone cytokine in health and disease. Nat. Immunol.,  2015, 16(5), 448-457.
[http://dx.doi.org/10.1038/ni.3153] [PMID:  25898198] 
[29] 
Tanaka, T.; Narazaki, M.; Kishimoto, T. Interleukin (IL-6) immunotherapy. Cold Spring Harb. Perspect. Biol.,  2018, 10(8), a028456.
[http://dx.doi.org/10.1101/cshperspect.a028456] [PMID:  28778870] 
[30] 
Madhok, R.; Crilly, A.; Watson, J.; Capell, H.A. Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann. Rheum. Dis.,  1993, 52(3), 232-234.
[http://dx.doi.org/10.1136/ard.52.3.232] 
[31] 
Sack, U.; Kinne, R.; Marx, T.; Heppt, P.; Bender, S.; Emmrich, F. Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. Rheumatol. Int.,  1993, 13(2), 45-51.
[32] 
Muraguchi, A.; Hirano, T.; Tang, B.; Matsuda, T.; Horii, Y.; Nakajima, K.; Kishimoto, T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. Blood,  1988, 167(2), 332-344.
[33] 
Jego, G.; Bataille, R.; Pellat-Deceunynck, C.J. Interleukin-6 is a growth factor for nonmalignant human plasmablasts. Immunobiology,  2001, 97(6), 1817-1822.
[34] 
Dienz, O.; Eaton, S.M.; Bond, J.P.; Neveu, W.; Moquin, D.; Noubade, R.; Briso, E.M.; Charland, C.; Leonard, W.J.; Ciliberto, G.; Teuscher, C.; Haynes, L.; Rincon, M. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells. J. Exp. Med.,  2009, 206(1), 69-78.
[35] 
Chizzolini, C.; Chicheportiche, R.; Alvarez, M.; De Rham, C.; Roux-Lombard, P.; Ferrari-Lacraz, S.; Dayer, J-M. Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion. Blood,  2008, 112(9), 3696-3703.
[36] 
Lally, F.; Smith, E.; Filer, A.; Stone, M.A.; Shaw, J.S.; Nash, G.B.; Buckley, C.D.; Ed Rainger, G. A novel mechanism of neutrophil recruitment in a coculture model of the rheumatoid synovium. Arthritis Rheum.,  2005, 52(11), 3460-3469.
[37] 
Maruotti, N.; Cantatore, F.P.; Crivellato, E.; Vacca, A.; Ribatti, D.J.H. Angiogenesis in rheumatoid arthritis. Histol. Histopathol.,  2006, 21, 557-566.
[38] 
Lacey, D.; Timms, E.; Tan, H-L.; Kelley, M.; Dunstan, C.; Burgess, T.; Elliott, R.; Colombero, A.; Elliott, G.; Scully, S.; Hsu, H.; Sullivan, J.; Hawkins, N.; Davy, E.; Capparelli, C.; Eli, A.; Qian, Y.X.; Kaufman, S.; Sarosi, I.; Shalhoub, V.; Senaldi, G.; Guo, J.; Delaney, J.; Boyle, W.J. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell,  1998, 93(2), 165-176.
[http://dx.doi.org/10.1016/S0092-8674(00)81569-X] 
[39] 
Ohta, S.; Imai, K.; Yamashita, K.; Matsumoto, T.; Azumano, I.; Okada, Y. Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage. Lab. Invest.,  1998, 78(1), 79-87.
[40] 
Ganz, T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood,  2003, 102(3), 783-788.
[http://dx.doi.org/10.1182/blood-2003-03-0672] 
[41] 
Kim, G.W.; Lee, N.R.; Pi, R.H.; Lim, Y.S.; Lee, Y.M.; Lee, J.M.; Jeong, H.S.; Chung, S.H. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch. Pharm. Res.,  2015, 38(5), 575-584.
[http://dx.doi.org/10.1007/s12272-015-0569-8] [PMID:  25648633] 
[42] 
Weinblatt, M.E.; Mease, P.; Mysler, E.; Takeuchi, T.; Drescher, E.; Berman, A.; Xing, J.; Zilberstein, M.; Banerjee, S.; Emery, P. The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging study. Arthritis Rheumatol.,  2015, 67(10), 2591-2600.
[http://dx.doi.org/10.1002/art.39249] [PMID:  26138593] 
[43] 
Marcu, K.B.; Otero, M.; Olivotto, E.; Borzi, R.M.; Goldring, M.B. NF-kappaB signaling: multiple angles to target OA. Curr. Drug Targets,  2010, 11(5), 599-613.
[http://dx.doi.org/10.2174/138945010791011938] [PMID:  20199390] 
[44] 
Suokas, A.K.; Sagar, D.R.; Mapp, P.I.; Chapman, V.; Walsh, D.A. Design, study quality and evidence of analgesic efficacy in studies of drugs in models of OA pain: a systematic review and a meta-analysis. Osteoarthritis Cartilage,  2014, 22(9), 1207-1223.
[http://dx.doi.org/10.1016/j.joca.2014.06.015] [PMID:  25008207] 
[45] 
Schnitzer, T.J. Update on guidelines for the treatment of chronic musculoskeletal pain. Clin. Rheumatol.,  2006, 25(Suppl. 1), S22-S29.
[http://dx.doi.org/10.1007/s10067-006-0203-8] [PMID:  16741783] 
[46] 
Chu, C.; Deng, J.; Man, Y.; Qu, Y. Green tea extracts epigallocatechin-3-gallate for different treatments. BioMed Res. Int.,  2017, 2017, 5615647.
[http://dx.doi.org/10.1155/2017/5615647] [PMID:  28884125] 
[47] 
Xicota, L.; Rodriguez-Morato, J.; Dierssen, M.; de la Torre, R. Potential role of (-)-epigallocatechin-3-gallate (EGCG) in the secondary prevention of Alzheimer disease. Curr. Drug Targets,  2017, 18(2), 174-195.
[http://dx.doi.org/10.2174/1389450116666150825113655] [PMID:  26302801] 
[48] 
Steinmann, J.; Buer, J.; Pietschmann, T.; Steinmann, E. Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea. Br. J. Pharmacol.,  2013, 168(5), 1059-1073.
[http://dx.doi.org/10.1111/bph.12009] [PMID:  23072320] 
[49] 
Hsu, S. Compounds derived from epigallocatechin-3-gallate (EGCG) as a novel approach to the prevention of viral infections. Inflamm. Allergy Drug Targets,  2015, 14(1), 13-18.
[http://dx.doi.org/10.2174/1871528114666151022150122] [PMID:  26490660] 
[50] 
Kwon, O.S.; Han, J.H.; Yoo, H.G.; Chung, J.H.; Cho, K.H.; Eun, H.C.; Kim, K.H. Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine,  2007, 14(7-8), 551-555.
[51] 
Mereles, D.; Hunstein, W. Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises? Int. J. Mol. Sci.,  2011, 12(9), 5592-5603.
[http://dx.doi.org/10.3390/ijms12095592] [PMID:  22016611] 
[52] 
Shankar, S.; Chen, Q.; Srivastava, R.K. Inhibition of PI3K/AKT and MEK/ERK pathways act synergistically to enhance antiangiogenic effects of EGCG through activation of FOXO transcription factor. J. Mol. Signal.,  2008, 3, 7.
[http://dx.doi.org/10.1186/1750-2187-3-7] [PMID:  18355401] 
[53] 
Zhu, C.; Xu, Y.; Liu, Z.H.; Wan, X.C.; Li, D.X.; Tai, L.L. The anti-hyperuricemic effect of epigallocatechin-3-gallate (EGCG) on hyperuricemic mice. Biomed. Pharmacother.,  2018, 97, 168-173.
[54] 
Riegsecker, S.; Wiczynski, D.; Kaplan, M.J.; Ahmed, S. Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis. Life Sci.,  2013, 93(8), 307-312.
[http://dx.doi.org/10.1016/j.lfs.2013.07.006] [PMID:  23871988] 
[55] 
Karatas, A.; Dagli, A.F.; Orhan, C.; Gencoglu, H.; Ozgen, M.; Sahin, N.; Sahin, K.; Koca, S.S. Epigallocatechin 3-gallate attenuates arthritis by regulating Nrf2, HO-1, and cytokine levels in an experimental arthritis model. Biotechnol. Appl. Biochem.,  2020, 67(3), 317-322.
[PMID:  31746064] 
[56] 
Lee, S.Y.; Jung, Y.O.; Ryu, J.G.; Oh, H.J.; Son, H.J.; Lee, S.H.; Kwon, J.E.; Kim, E.K.; Park, M.K.; Park, S.H.; Kim, H.Y.; Cho, M.L. Epigallocatechin-3-gallate ameliorates autoimmune arthritis by reciprocal regulation of T helper-17 regulatory T cells and inhibition of osteoclastogenesis by inhibiting STAT3 signaling. J. Leukoc. Biol.,  2016, 100(3), 559-568.
[http://dx.doi.org/10.1189/jlb.3A0514-261RR] [PMID:  26957211] 
[57] 
Yun, H.J.; Yoo, W.H.; Han, M.K.; Lee, Y.R.; Kim, J.S.; Lee, S.I. Epigallocatechin-3-gallate suppresses TNF-alpha -induced production of MMP-1 and -3 in rheumatoid arthritis synovial fibroblasts. Rheumatol. Int.,  2008, 29(1), 23-29.
[http://dx.doi.org/10.1007/s00296-008-0597-5] [PMID:  18496696] 
[58] 
Morinobu, A.; Biao, W.; Tanaka, S.; Horiuchi, M.; Jun, L.; Tsuji, G.; Sakai, Y.; Kurosaka, M.; Kumagai, S. (-)-Epigallocatechin-3-gallate suppresses osteoclast differentiation and ameliorates experimental arthritis in mice. Arthritis Rheum.,  2008, 58(7), 2012-2018.
[http://dx.doi.org/10.1002/art.23594] [PMID:  18576345] 
[59] 
Min, S.Y.; Yan, M.; Kim, S.B.; Ravikumar, S.; Kwon, S.R.; Vanarsa, K.; Kim, H.Y.; Davis, L.S.; Mohan, C. Green Tea epigallocatechin-3-gallate suppresses autoimmune arthritis through indoleamine-2,3-dioxygenase expressing dendritic cells and the nuclear factor, erythroid 2-like 2 antioxidant pathway. J. Inflamm. (Lond.),  2015, 12, 53.
[http://dx.doi.org/10.1186/s12950-015-0097-9] [PMID:  26379475] 
[60] 
Leichsenring, A.; Bäcker, I.; Furtmüller, P.G.; Obinger, C.; Lange, F.; Flemmig, J. Long-term effects of (-)-epigallocatechin gallate (EGCG) on pristane-induced arthritis (PIA) in female dark agouti rats. PLoS One,  2016, 11(3), e0152518.
[http://dx.doi.org/10.1371/journal.pone.0152518] [PMID:  27023113] 
[61] 
Jhang, J.J.; Lu, C.C.; Yen, G.C. Epigallocatechin gallate inhibits urate crystals-induced peritoneal inflammation in C57BL/6 mice. Mol. Nutr. Food Res.,  2016, 60(10), 2297-2303.
[http://dx.doi.org/10.1002/mnfr.201600106] [PMID:  27234527] 
[62] 
Fechtner, S.; Singh, A.; Chourasia, M.; Ahmed, S. Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts. Toxicol. Appl. Pharmacol.,  2017, 329, 112-120.
[http://dx.doi.org/10.1016/j.taap.2017.05.016] [PMID:  28532672] 
[63] 
Singh, A.K.; Umar, S.; Riegsecker, S.; Chourasia, M.; Ahmed, S. Regulation of transforming growth factor β-activated kinase activation by epigallocatechin-3-gallate in rheumatoid arthritis synovial fibroblasts: suppression of K(63) -linked autoubiquitination of tumor necrosis factor receptor-associated factor 6. Arthritis Rheumatol.,  2016, 68(2), 347-358.
[http://dx.doi.org/10.1002/art.39447] [PMID:  26473505] 
[64] 
Ahmed, S.; Marotte, H.; Kwan, K.; Ruth, J.H.; Campbell, P.L.; Rabquer, B.J.; Pakozdi, A.; Koch, A.E. Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses transsignaling by enhancing soluble gp130 production. Proc. Natl. Acad. Sci. USA,  2008, 105(38), 14692-14697.
[http://dx.doi.org/10.1073/pnas.0802675105] [PMID:  18796608] 
[65] 
Ferreira, P.S.; Spolidorio, L.C.; Manthey, J.A.; Cesar, T.B. Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet. Food Funct.,  2016, 7(6), 2675-2681.
[http://dx.doi.org/10.1039/C5FO01541C] [PMID:  27182608] 
[66] 
Liu, D.; Zhang, X.; Jiang, L.; Guo, Y.; Zheng, C. Epigallocatechin-3-gallate (EGCG) attenuates concanavalin A-induced hepatic injury in mice. Acta Histochem.,  2014, 116(4), 654-662.
[http://dx.doi.org/10.1016/j.acthis.2013.12.002] [PMID:  24373695] 
[67] 
El-Missiry, M.A.; Othman, A.I.; El-Sawy, M.R.; Lebede, M.F. Neuroprotective effect of epigallocatechin-3-gallate (EGCG) on radiation-induced damage and apoptosis in the rat hippocampus. Int. J. Radiat. Biol.,  2018, 94(9), 798-808.
[http://dx.doi.org/10.1080/09553002.2018.1492755] [PMID:  29939076] 
[68] 
Tian, Y.; Bao, Z.; Ji, Y.; Mei, X.; Yang, H. Epigallocatechin-3-gallate protects H2O2-Induced nucleus pulposus cell apoptosis and inflammation by inhibiting CGAS/sting/NLRP3 activation. Drug Des. Devel. Ther.,  2020, 14, 2113-2122.
[http://dx.doi.org/10.2147/DDDT.S251623] [PMID:  32546974] 
[69] 
Yu, N.H.; Pei, H.; Huang, Y.P.; Li, Y.F. (-)-epigallocatechin-3-gallate inhibits arsenic-induced inflammation and apoptosis through suppression of oxidative stress in mice. Cell. Physiol. Biochem.,  2017, 41(5), 1788-1800.
[70] 
Shen, H.; Wu, N.; Liu, Z.; Zhao, H.; Zhao, M. Epigallocatechin-3-gallate alleviates paraquat-induced acute lung injury and inhibits upregulation of toll-like receptors. Life Sci.,  2017, 170, 25-32.
[http://dx.doi.org/10.1016/j.lfs.2016.11.021] [PMID:  27890776] 
[71] 
Li, M.; Liu, J.T.; Pang, X.M.; Han, C.J.; Mao, J.J. Epigallocatechin-3-gallate inhibits angiotensin II and interleukin-6-induced C-reactive protein production in macrophages. Pharmacol. Rep.,  2012, 64(4), 912-918.
[72] 
Xu, Z.; Wei, C.; Zhang, R.U.; Yao, J.; Zhang, D.; Wang, L. Epigallocatechin-3-gallate-induced inhibition of interleukin-6 release and adjustment of the regulatory T/T helper 17 cell balance in the treatment of colitis in mice. Exp. Ther. Med.,  2015, 10(6), 2231-2238.
[http://dx.doi.org/10.3892/etm.2015.2824] [PMID:  26668622] 
[73] 
Ku, W.C.; Chang, Y.L.; Wu, S.F.; Shih, H.N.; Tzeng, Y.M.; Kuo, H.R.; Chang, K.M.; Agrawal, D.C.; Liu, B.L.; Chang, C.A.; Huang, S.; Lee, M.J. A comparative proteomic study of secretomes in kaempferitrin-treated CTX TNA2 astrocytic cells. Phytomedicine,  2017, 36, 137-144.
[74] 
Im, M.; Kim, S.Y.; Sohn, K.C.; Choi, D.K.; Lee, Y.; Seo, Y.J.; Kim, C.D.; Hwang, Y.L.; Zouboulis, C.C.; Lee, J.H. Epigallocatechin-3-gallate suppresses IGF-I-induced lipogenesis and cytokine expression in SZ95 sebocytes. J. Invest. Dermatol.,  2012, 132(12), 2700-2708.
[http://dx.doi.org/10.1038/jid.2012.202] [PMID:  22763784] 
[75] 
Fabbri, R.; Macciocca, M.; Vicenti, R.; Caprara, G.; Piccinni, M.P.; Paradisi, R.; Terzano, P.; Papi, A.; Seracchioli, R. Epigallocatechin-3-gallate inhibits doxorubicin-induced inflammation on human ovarian tissue. Biosci. Rep.,  2019, 39(5), BSR20181424.
[http://dx.doi.org/10.1042/BSR20181424] [PMID:  30996116] 
[76] 
Othman, A.I.; El-Sawi, M.R.; El-Missiry, M.A.; Abukhalil, M.H. Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats. Biomed. Pharmacother.,  2017, 94, 362-373.
[http://dx.doi.org/10.1016/j.biopha.2017.07.129] [PMID:  28772214] 
[77] 
Mao, L.; Hochstetter, D.; Yao, L.; Zhao, Y.; Zhou, J.; Wang, Y.; Xu, P. Green Tea Polyphenol (-)-Epigallocatechin Gallate (EGCG) attenuates neuroinflammation in palmitic acid-stimulated bv-2 microglia and high-fat diet-induced obese mice. Int. J. Mol. Sci.,  2019, 20(20), E5081.
[http://dx.doi.org/10.3390/ijms20205081] [PMID:  31614951] 
[78] 
Wu, P.H.; Lin, S.K.; Lee, B.S.; Kok, S.H.; Wang, J.H.; Hou, K.L.; Yang, H.; Lai, E.H.; Wang, J.S.; Hong, C.Y. Epigallocatechin-3-gallate diminishes cytokine-stimulated Cyr61 expression in human osteoblastic cells: a therapeutic potential for arthritis. Rheumatology (Oxford),  2012, 51(11), 1953-1965.
[http://dx.doi.org/10.1093/rheumatology/kes174] [PMID:  22843790] 
[79] 
Singh, S.; Gupta, P.; Meena, A.; Luqman, S. Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders. Food Chem. Toxicol.,  2020, 145, 111708.
[http://dx.doi.org/10.1016/j.fct.2020.111708] [PMID:  32866514] 
[80] 
Semwal, R.B.; Semwal, D.K.; Combrinck, S.; Trill, J.; Gibbons, S.; Viljoen, A. Acacetin-A simple flavone exhibiting diverse pharmacological activities. Phytochem. Lett.,  2019, 32, 56-65.
[http://dx.doi.org/10.1016/j.phytol.2019.04.021] 
[81] 
Kwon, E.B.; Kang, M.J.; Ryu, H.W.; Lee, S.; Lee, J.W.; Lee, M.K.; Lee, H.S.; Lee, S.U.; Oh, S.R.; Kim, M.O. Acacetin enhances glucose uptake through insulin-independent GLUT4 translocation in L6 myotubes. Phytomedicine,  2020, 68, 153178.
[http://dx.doi.org/10.1016/j.phymed.2020.153178] [PMID:  32126492] 
[82] 
Wu, Y.; Song, F.; Li, Y.; Li, J.; Cui, Y.; Hong, Y.; Han, W.; Wu, W.; Lakhani, I.; Li, G.; Wang, Y. Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE. Mice. J. Cell. Mol. Med.,  2021, 25(1), 521-534.
[PMID:  33241629] 
[83] 
Li, S.; Lv, Q.; Sun, X.; Tang, T.; Deng, X.; Yin, Y.; Li, L. Acacetin inhibits Streptococcus pneumoniae virulence by targeting pneumolysin. J. Pharm. Pharmacol.,  2020, 72(8), 1092-1100.
[http://dx.doi.org/10.1111/jphp.13279] [PMID:  32390150] 
[84] 
Ni, H.; Whittaker, D.G.; Wang, W.; Giles, W.R.; Narayan, S.M.; Zhang, H. Synergistic anti-arrhythmic effects in human atria with combined use of sodium blockers and acacetin. Front. Physiol.,  2017, 8, 946.
[http://dx.doi.org/10.3389/fphys.2017.00946] [PMID:  29218016] 
[85] 
Liu, L.; Yang, J.; Zu, B.; Wang, J.; Sheng, K.; Zhao, L.; Xu, W. Acacetin regulated the reciprocal differentiation of Th17 cells and Treg cells and mitigated the symptoms of collagen-induced arthritis in mice. Scand. J. Immunol.,  2018, 88(4), e12712.
[http://dx.doi.org/10.1111/sji.12712] [PMID:  30176062] 
[86] 
Chen, W.P.; Yang, Z.G.; Hu, P.F.; Bao, J.P.; Wu, L.D. Acacetin inhibits expression of matrix metalloproteinases via a MAPK-dependent mechanism in fibroblast-like synoviocytes. J. Cell. Mol. Med.,  2015, 19(8), 1910-1915.
[http://dx.doi.org/10.1111/jcmm.12564] [PMID:  25856795] 
[87] 
Cho, H.I.; Park, J.H.; Choi, H.S.; Kwak, J.H.; Lee, D.U.; Lee, S.K.; Lee, S.M. Protective mechanisms of acacetin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice. J. Nat. Prod.,  2014, 77(11), 2497-2503.
[http://dx.doi.org/10.1021/np500537x] [PMID:  25382719] 
[88] 
Bu, J.; Shi, S.; Wang, H.Q.; Niu, X.S.; Zhao, Z.F.; Wu, W.D.; Zhang, X.L.; Ma, Z.; Zhang, Y.J.; Zhang, H.; Zhu, Y. Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway. Neural Regen. Res.,  2019, 14(4), 605-612.
[http://dx.doi.org/10.4103/1673-5374.247465] [PMID:  30632500] 
[89] 
Xin, C.; Guangliang, S.; Qing, Z.; Qingqing, L.; Hang, Y.; Yiming, Z.; Shu, L. Astilbin protects chicken peripheral blood lymphocytes from cadmium-induced necroptosis via oxidative stress and the PI3K/Akt pathway. Ecotoxicol. Environ. Saf.,  2020, 190, 110064.
[http://dx.doi.org/10.1016/j.ecoenv.2019.110064] [PMID:  31838230] 
[90] 
Wang, J.; Shi, Y.; Jing, S.; Dong, H.; Wang, D.; Wang, T. Astilbin inhibits the activity of sortase a from Streptococcus mutans. Molecules,  2019, 24(3), E465.
[http://dx.doi.org/10.3390/molecules24030465] [PMID:  30696091] 
[91] 
Jin, H.; Wang, Q.; Chen, K.; Xu, K.; Pan, H.; Chu, F.; Ye, Z.; Wang, Z.; Tickner, J.; Qiu, H.; Wang, C.; Kenny, J.; Xu, H.; Wang, T.; Xu, J. Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis. J. Cell. Mol. Med.,  2019, 23(12), 8355-8368.
[http://dx.doi.org/10.1111/jcmm.14713] [PMID:  31603626] 
[92] 
Chen, C.; Yang, M.; Chen, Y.; Wang, Y.; Wang, K.; Li, T.; Hu, Q.; Zhang, W.; Xia, J. Astilbin-induced inhibition of the PI3K/AKT signaling pathway decelerates the progression of osteoarthritis. Exp. Ther. Med.,  2020, 20(4), 3078-3083.
[http://dx.doi.org/10.3892/etm.2020.9048] [PMID:  32855675] 
[93] 
Bao, Y.; Li, H.; Li, Q.Y.; Li, Y.; Li, F.; Zhang, C.F.; Wang, C.Z.; Yuan, C.S. Therapeutic effects of Smilax glabra and Bolbostemma paniculatum on rheumatoid arthritis using a rat paw edema model. Biomed. Pharmacother.,  2018, 108, 309-315.
[http://dx.doi.org/10.1016/j.biopha.2018.09.004] [PMID:  30227323] 
[94] 
Ma, Y.; Gao, Z.; Xu, F.; Liu, L.; Luo, Q.; Shen, Y.; Wu, X.; Wu, X.; Sun, Y.; Wu, X.; Xu, Q. A novel combination of astilbin and low-dose methotrexate respectively targeting A2AAR and its ligand adenosine for the treatment of collagen-induced arthritis. Biochem. Pharmacol.,  2018, 153, 269-281.
[http://dx.doi.org/10.1016/j.bcp.2018.01.033] [PMID:  29410374] 
[95] 
Cai, Y.; Chen, T.; Xu, Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes. Inflamm. Res.,  2003, 52(8), 334-340.
[http://dx.doi.org/10.1007/s00011-003-1179-3] [PMID:  14504671] 
[96] 
Chen, F.; Zhu, X.; Sun, Z.; Ma, Y. Astilbin inhibits high glucose-induced inflammation and extracellular matrix accumulation by suppressing the tlr4/myd88/NF-κB pathway in rat glomerular mesangial cells. Front. Pharmacol.,  2018, 9, 1187.
[http://dx.doi.org/10.3389/fphar.2018.01187] [PMID:  30459606] 
[97] 
Xu, X.; Yan, G.; Chang, J.; Wang, P.; Yin, Q.; Liu, C.; Liu, S.; Zhu, Q.; Lu, F. Astilbin ameliorates deoxynivalenol-induced oxidative stress and apoptosis in intestinal porcine epithelial cells (IPEC-J2). JAT,  2020, 40(10), 1362-1372.
[http://dx.doi.org/10.1002/jat.3989] [PMID:  32324309] 
[98] 
Di, T.T.; Ruan, Z.T.; Zhao, J.X.; Wang, Y.; Liu, X.; Wang, Y.; Li, P. Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathway. Int. Immunopharmacol.,  2016, 32, 32-38.
[http://dx.doi.org/10.1016/j.intimp.2015.12.035] [PMID:  26784569] 
[99] 
Alblihed, M.A. Astragalin attenuates oxidative stress and acute inflammatory responses in carrageenan-induced paw edema in mice. Mol. Biol. Rep.,  2020, 47(9), 6611-6620.
[http://dx.doi.org/10.1007/s11033-020-05712-z] [PMID:  32770524] 
[100] 
Zhao, Z.W.; Zhang, M.; Wang, G.; Zou, J.; Gao, J.H.; Zhou, L.; Wan, X.J.; Zhang, D.W.; Yu, X.H.; Tang, C.K. Astragalin retards atherosclerosis by promoting cholesterol efflux and inhibiting the inflammatory response via up-regulating ABCA1 and ABCG1 expression in macrophages. J. Cardiovasc. Pharmacol.,  2021, 77(2), 217-227.
[101] 
Tong, Y.; Fu, H.; Xia, C.; Song, W.; Li, Y.; Zhao, J.; Zhang, X.; Gao, X.; Yong, J.; Liu, Q.; Yang, C.; Wang, H. Astragalin exerted antidepressant-like action through SIRT1 signaling modulated NLRP3 inflammasome deactivation. ACS Chem. Neurosci.,  2020, 11(10), 1495-1503.
[http://dx.doi.org/10.1021/acschemneuro.0c00156] [PMID:  32364698] 
[102] 
You, O.H.; Shin, E.A.; Lee, H.; Kim, J.H.; Sim, D.Y.; Kim, J.H.; Kim, Y.; Khil, J.H.; Baek, N.I.; Kim, S.H. Apoptotic effect of astragalin in melanoma skin cancers via activation of caspases and inhibition of Sry-related HMg-box gene 10. Phytother. Res.,  2017, 31(10), 1614-1620.
[http://dx.doi.org/10.1002/ptr.5895] [PMID:  28809055] 
[103] 
Rey, D.; Miranda Sulis, P.; Alves Fernandes, T.; Gonçalves, R.; Silva Frederico, M.J.; Costa, G.M.; Aragon, M.; Ospina, L.F.; Mena Barreto Silva, F.R. Astragalin augments basal calcium influx and insulin secretion in rat pancreatic islets. Cell Calcium,  2019, 80, 56-62.
[http://dx.doi.org/10.1016/j.ceca.2019.03.009] [PMID:  30965223] 
[104] 
Xu, T.; Feng, G.; Zhao, B.; Zhao, J.; Pi, Z.; Liu, S.; Song, F.; Liu, Z. A non-target urinary and serum metabolomics strategy reveals therapeutical mechanism of Radix astragali on adjuvant-induced arthritis rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2017, 1048, 94-101.
[http://dx.doi.org/10.1016/j.jchromb.2017.01.040] [PMID:  28232289] 
[105] 
Jia, Q.; Wang, T.; Wang, X.; Xu, H.; Liu, Y.; Wang, Y.; Shi, Q.; Liang, Q. Astragalin suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis and in human fibroblast-like synoviocytes. Front. Pharmacol.,  2019, 10, 94.
[http://dx.doi.org/10.3389/fphar.2019.00094] [PMID:  30809149] 
[106] 
Ma, Z.; Piao, T.; Wang, Y.; Liu, J. Astragalin inhibits IL-1β-induced inflammatory mediators production in human osteoarthritis chondrocyte by inhibiting NF-κB and MAPK activation. Int. Immunopharmacol.,  2015, 25(1), 83-87.
[http://dx.doi.org/10.1016/j.intimp.2015.01.018] [PMID:  25637445] 
[107] 
Peng, L.; Gao, X.; Nie, L.; Xie, J.; Dai, T.; Shi, C.; Tao, L.; Wang, Y.; Tian, Y.; Sheng, J. Astragalin attenuates Dextran Sulfate Sodium (DSS)-induced acute experimental colitis by alleviating gut microbiota dysbiosis and inhibiting NF-κB activation in mice. Front. Immunol.,  2020, 11, 2058.
[http://dx.doi.org/10.3389/fimmu.2020.02058] [PMID:  33042117] 
[108] 
Soromou, L.W.; Chen, N.; Jiang, L.; Huo, M.; Wei, M.; Chu, X.; Millimouno, F.M.; Feng, H.; Sidime, Y.; Deng, X. Astragalin attenuates lipopolysaccharide-induced inflammatory responses by down-regulating NF-κB signaling pathway. Biochem. Biophys. Res. Commun.,  2012, 419(2), 256-261.
[http://dx.doi.org/10.1016/j.bbrc.2012.02.005] [PMID:  22342978] 
[109] 
Qu, D.; Han, J.; Ren, H.; Yang, W.; Zhang, X.; Zheng, Q.; Wang, D. Cardioprotective effects of astragalin against myocardial ischemia/reperfusion injury in isolated rat heart. Oxid. Med. Cell. Longev.,  2016, 2016, 8194690.
[http://dx.doi.org/10.1155/2016/8194690] [PMID:  26788251] 
[110] 
Wang, Z.; Ma, L.; Su, M.; Zhou, Y.; Mao, K.; Li, C.; Peng, G.; Zhou, C.; Shen, B.; Dou, J. Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling. Cell Death Dis.,  2018, 9(2), 217.
[http://dx.doi.org/10.1038/s41419-017-0223-0] [PMID:  29440765] 
[111] 
Huang, T.; Liu, Y.; Zhang, C. Pharmacokinetics and bioavailability enhancement of baicalin: a review. Eur. J. Drug Metab. Pharmacokinet.,  2019, 44(2), 159-168.
[http://dx.doi.org/10.1007/s13318-018-0509-3] [PMID:  30209794] 
[112] 
Xin, X.; Zhang, M.; Li, X.F.; Zhao, G. Biocatalytic synthesis of lipophilic baicalin derivatives as antimicrobial agents. J. Agric. Food Chem.,  2019, 67(42), 11684-11693.
[http://dx.doi.org/10.1021/acs.jafc.9b04667] [PMID:  31564105] 
[113] 
Dinda, B.; Dinda, S.; DasSharma, S.; Banik, R.; Chakraborty, A.; Dinda, M. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur. J. Med. Chem.,  2017, 131, 68-80.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.004] [PMID:  28288320] 
[114] 
Wang, J.; Song, H.; Wu, X.; Zhang, S.; Gao, X.; Li, F.; Zhu, X.; Chen, Q. Steroidal saponins from Vernonia amygdalina Del. and their biological activity. Molecules,  2018, 23(3), 579.
[http://dx.doi.org/10.3390/molecules23030579] [PMID:  29510543] 
[115] 
Xu, M.; Li, X.; Song, L. Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway. Pharm. Biol.,  2020, 58(1), 655-663.
[http://dx.doi.org/10.1080/13880209.2020.1779318] [PMID:  32649845] 
[116] 
Yang, X.; Zhang, Q.; Gao, Z.; Yu, C.; Zhang, L. Baicalin alleviates IL-1β-induced inflammatory injury via down-regulating miR-126 in chondrocytes. Biomed. Pharmacother.,  2018, 99, 184-190.
[http://dx.doi.org/10.1016/j.biopha.2018.01.041] [PMID:  29331857] 
[117] 
Luo, W.; Wang, C.Y.; Jin, L. Baicalin downregulates Porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling. PLoS One,  2012, 7(12), e51008.
[http://dx.doi.org/10.1371/journal.pone.0051008] [PMID:  23239998] 
[118] 
Liao, C.C.; Day, Y.J.; Lee, H.C.; Liou, J.T.; Chou, A.H.; Liu, F.C. Baicalin attenuates IL-17-mediated acetaminophen-induced liver injury in a mouse model. PLoS One,  2016, 11(11), e0166856.
[http://dx.doi.org/10.1371/journal.pone.0166856] [PMID:  27855209] 
[119] 
Liu, T.; Dai, W.; Li, C.; Liu, F.; Chen, Y.; Weng, D.; Chen, J. Baicalin alleviates silica-induced lung inflammation and fibrosis by inhibiting the Th17 response in C57BL/6 Mice. J. Nat. Prod.,  2015, 78(12), 3049-3057.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00868] [PMID:  26605988] 
[120] 
Yimam, M.; Brownell, L.; Pantier, M.; Jia, Q. UP446, analgesic and anti-inflammatory botanical composition. Pharmacognosy Res.,  2013, 5(3), 139-145.
[http://dx.doi.org/10.4103/0974-8490.112406] [PMID:  23901209] 
[121] 
Yang, X.; Yang, J.; Zou, H. Baicalin inhibits IL-17-mediated joint inflammation in murine adjuvant-induced arthritis. Clin. Dev. Immunol.,  2013, 2013, 268065.
[http://dx.doi.org/10.1155/2013/268065] [PMID:  23840239] 
[122] 
Wang, H.Z.; Wang, H.H.; Huang, S.S.; Zhao, H.; Cao, Y.G.; Wang, G.Z.; Wang, D.; Wang, Z.G.; Liu, Y.H. Inhibitory effect of baicalin on collagen-induced arthritis in rats through the nuclear factor-κB pathway. J. Pharmacol. Exp. Ther.,  2014, 350(2), 435-443.
[http://dx.doi.org/10.1124/jpet.114.215145] [PMID:  24893986] 
[123] 
Sun, F.; Gu, W. Baicalin attenuates collagen-induced arthritis via inhibition of JAK2-STAT3 signaling and regulation of Th17 cells in mice. J. Cell Commun. Signal.,  2019, 13(1), 65-73.
[http://dx.doi.org/10.1007/s12079-018-0475-1] [PMID:  29942991] 
[124] 
Xu, J.; Liu, J.; Yue, G.; Sun, M.; Li, J.; Xiu, X.; Gao, Z. Therapeutic effect of the natural compounds baicalein and baicalin on autoimmune diseases. Mol. Med. Rep.,  2018, 18(1), 1149-1154.
[http://dx.doi.org/10.3892/mmr.2018.9054] [PMID:  29845272] 
[125] 
Deng, M.; Chen, H.; Long, J.; Song, J.; Xie, L.; Li, X. Calycosin: A review of its pharmacological effects and application prospects. Expert Rev. Anti Infect. Ther.,  2021, 19(7), 911-925.
[PMID:  33346681] 
[126] 
El-Kott, A.F.; Al-Kahtani, M.A.; Shati, A.A. Calycosin induces apoptosis in adenocarcinoma HT29 cells by inducing cytotoxic autophagy mediated by SIRT1/AMPK-induced inhibition of Akt/mTOR. Clin. Exp. Pharmacol. Physiol.,  2019, 46(10), 944-954.
[http://dx.doi.org/10.1111/1440-1681.13133] [PMID:  31276230] 
[127] 
Jia, Z.; Wang, X.; Wang, X.; Wei, P.; Li, L.; Wu, P.; Hong, M. Calycosin alleviates allergic contact dermatitis by repairing epithelial tight junctions via down-regulating HIF-1α. J. Cell. Mol. Med.,  2018, 22(9), 4507-4521.
[http://dx.doi.org/10.1111/jcmm.13763] [PMID:  29993193] 
[128] 
Nong, Y.; Liang, Y.; Liang, X.; Li, Y.; Yang, B. Pharmacological targets and mechanisms of calycosin against meningitis. Aging (Albany NY),  2020, 12(19), 19468-19492.
[http://dx.doi.org/10.18632/aging.103886] [PMID:  33031061] 
[129] 
Ma, W.; Nomura, M.; Takahashi-Nishioka, T.; Kobayashi, S. Combined effects of fangchinoline from Stephania tetrandra Radix and formononetin and calycosin from Astragalus membranaceus Radix on hyperglycemia and hypoinsulinemia in streptozotocin-diabetic mice. Biol. Pharm. Bull.,  2007, 30(11), 2079-2083.
[http://dx.doi.org/10.1248/bpb.30.2079] [PMID:  17978479] 
[130] 
Su, X.; Huang, Q.; Chen, J.; Wang, M.; Pan, H.; Wang, R.; Zhou, H.; Zhou, Z.; Liu, J.; Yang, F.; Li, T.; Liu, L. Calycosin suppresses expression of pro-inflammatory cytokines via the activation of p62/Nrf2-linked heme oxygenase 1 in rheumatoid arthritis synovial fibroblasts. Pharmacol., Res.,  2016, 113(Pt A), 695-704.
[131] 
Ma, R.; Yuan, F.; Wang, S.; Liu, Y.; Fan, T.; Wang, F. Calycosin alleviates cerulein-induced acute pancreatitis by inhibiting the inflammatory response and oxidative stress via the p38 MAPK and NF-κB signal pathways in mice. Biomed. Pharmacother.,  2018, 105, 599-605.
[http://dx.doi.org/10.1016/j.biopha.2018.05.080] [PMID:  29890468] 
[132] 
Dong, L.; Yin, L.; Chen, R.; Zhang, Y.; Hua, S.; Quan, H.; Fu, X. Anti-inflammatory effect of Calycosin glycoside on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells. Gene,  2018, 675, 94-101.
[http://dx.doi.org/10.1016/j.gene.2018.06.057] [PMID:  29936264] 
[133] 
Ping, C.P.; Tengku Mohamad, T.A.S.; Akhtar, M.N.; Perimal, E.K.; Akira, A.; Israf Ali, D.A.; Sulaiman, M.R. Antinociceptive effects of cardamonin in mice: possible involvement of TRPv1 glutamate, and opioid receptors. Molecules,  2018, 23(9), E2237.
[http://dx.doi.org/10.3390/molecules23092237] [PMID:  30177603] 
[134] 
Jin, J.; Qiu, S.; Wang, P.; Liang, X.; Huang, F.; Wu, H.; Zhang, B.; Zhang, W.; Tian, X.; Xu, R.; Shi, H.; Wu, X. Cardamonin inhibits breast cancer growth by repressing HIF-1α;-dependent metabolic reprogramming. J. Exp. Clin. Cancer Res.,  2019, 38(1), 377.
[http://dx.doi.org/10.1186/s13046-019-1351-4] [PMID:  31455352] 
[135] 
Nawaz, J.; Rasul, A.; Shah, M.A.; Hussain, G.; Riaz, A.; Sarfraz, I.; Zafar, S.; Adnan, M.; Khan, A.H.; Selamoglu, Z. Cardamonin: a new player to fight cancer via multiple cancer signaling pathways. Life Sci.,  2020, 250, 117591.
[http://dx.doi.org/10.1016/j.lfs.2020.117591] [PMID:  32224026] 
[136] 
Niu, P.; Zhang, Y.; Shi, D.; Chen, Y.; Deng, J. Cardamonin ameliorates insulin resistance induced by high insulin and high glucose through the mTOR and signal pathway. Planta Med.,  2013, 79(6), 452-458.
[http://dx.doi.org/10.1055/s-0032-1328325] [PMID:  23512499] 
[137] 
Daimary, U.D.; Parama, D.; Rana, V.; Banik, K.; Kumar, A.; Harsha, C.; Kunnumakkara, A.B. Emerging roles of cardamonin, a multitargeted nutraceutical in the prevention and treatment of chronic diseases. Curr. Res. Pharmacol. Drug Discov.,  2021, 2, 100008.
[http://dx.doi.org/10.1016/j.crphar.2020.100008] 
[138] 
Benchabane, S.; Belguendouz, H.; Behairi, N.; Arroul-Lammali, A.; Boudjelida, A.; Youinou, P.; Touil-Boukoffa, C. Cardamonin inhibits pro-inflammatory cytokine production and suppresses NO pathway in PBMCs from patients with primary Sjögren’s syndrome. Immunopharmacol. Immunotoxicol.,  2018, 40(2), 126-133.
[http://dx.doi.org/10.1080/08923973.2017.1418881] [PMID:  29303022] 
[139] 
Voon, F.L.; Sulaiman, M.R.; Akhtar, M.N.; Idris, M.F.; Akira, A.; Perimal, E.K.; Israf, D.A.; Ming-Tatt, L. Cardamonin (2′4′-dihydroxy-6′-methoxychalcone) isolated from Boesenbergia rotunda (L.) Mansf. inhibits CFA-induced rheumatoid arthritis in rats. Eur. J. Pharmacol.,  2017, 794, 127-134.
[http://dx.doi.org/10.1016/j.ejphar.2016.11.009] [PMID:  27845065] 
[140] 
Jia, D.; Tan, Y.; Liu, H.; Ooi, S.; Li, L.; Wright, K.; Bennett, S.; Addison, C.L.; Wang, L. Cardamonin reduces chemotherapy-enriched breast cancer stem-like cells in vitro and in vivo. Oncotarget,  2016, 7(1), 771-785.
[http://dx.doi.org/10.18632/oncotarget.5819] [PMID:  26506421] 
[141] 
Ren, G.; Sun, A.; Deng, C.; Zhang, J.; Wu, X.; Wei, X.; Mani, S.; Dou, W.; Wang, Z. The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis. Am. J. Physiol. Gastrointest. Liver Physiol.,  2015, 309(7), G517-G527.
[http://dx.doi.org/10.1152/ajpgi.00133.2015] [PMID:  26251468] 
[142] 
Chen, H.; Shi, D.; Niu, P.; Zhu, Y.; Zhou, J. Anti-inflammatory effects of cardamonin in ovarian cancer cells are mediated via mTOR suppression. Planta Med.,  2018, 84(16), 1183-1190.
[http://dx.doi.org/10.1055/a-0626-7426] [PMID:  29772587] 
[143] 
Li, Y.Y.; Huang, S.S.; Lee, M.M.; Deng, J.S.; Huang, G.J. Anti-inflammatory activities of cardamonin from Alpinia katsumadai through heme oxygenase-1 induction and inhibition of NF-κB and MAPK signaling pathway in the carrageenan-induced paw edema. Int. Immunopharmacol.,  2015, 25(2), 332-339.
[http://dx.doi.org/10.1016/j.intimp.2015.02.002] [PMID:  25681284] 
[144] 
Chow, Y.L.; Lee, K.H.; Vidyadaran, S.; Lajis, N.H.; Akhtar, M.N.; Israf, D.A.; Syahida, A. Cardamonin from Alpinia rafflesiana inhibits inflammatory responses in IFN-γ/LPS-stimulated BV2 microglia via NF-κB signalling pathway. Int. Immunopharmacol.,  2012, 12(4), 657-665.
[http://dx.doi.org/10.1016/j.intimp.2012.01.009] [PMID:  22306767] 
[145] 
Wei, Z.; Yang, J.; Xia, Y.F.; Huang, W.Z.; Wang, Z.T.; Dai, Y. Cardamonin protects septic mice from acute lung injury by preventing endothelial barrier dysfunction. J. Biochem. Mol. Toxicol.,  2012, 26(7), 282-290.
[http://dx.doi.org/10.1002/jbt.21420] [PMID:  22696397] 
[146] 
Lee, M.Y.; Seo, C.S.; Lee, J.A.; Shin, I.S.; Kim, S.J.; Ha, H.; Shin, H.K. Alpinia katsumadai H.(AYATA) seed extract inhibit LPS-induced inflammation by induction of heme oxygenase-1 in RAW264.7 cells. Inflammation,  2012, 35(2), 746-757.
[http://dx.doi.org/10.1007/s10753-011-9370-0] [PMID:  21830094] 
[147] 
Mirzaei, H.; Shakeri, A.; Rashidi, B.; Jalili, A.; Banikazemi, Z.; Sahebkar, A. Phytosomal curcumin: a review of pharmacokinetic, experimental and clinical studies. Biomed. Pharmacother.,  2017, 85, 102-112.
[http://dx.doi.org/10.1016/j.biopha.2016.11.098] [PMID:  27930973] 
[148] 
Lestari, M.L.; Indrayanto, G. Curcumin. Profiles Drug Subst. Excip. Relat. Methodol.,  2014, 39, 113-204.
[http://dx.doi.org/10.1016/B978-0-12-800173-8.00003-9] [PMID:  24794906] 
[149] 
Akbik, D.; Ghadiri, M.; Chrzanowski, W.; Rohanizadeh, R. Curcumin as a wound healing agent. Life Sci.,  2014, 116(1), 1-7.
[http://dx.doi.org/10.1016/j.lfs.2014.08.016] [PMID:  25200875] 
[150] 
Unlu, A.; Nayir, E.; Dogukan Kalenderoglu, M.; Kirca, O.; Ozdogan, M. Curcumin (turmeric) and cancer. J. BUON,  2016, 21(5), 1050-1060.
[PMID:  27837604] 
[151] 
Nabavi, S.F.; Thiagarajan, R.; Rastrelli, L.; Daglia, M.; Sobarzo-Sánchez, E.; Alinezhad, H.; Nabavi, S.M. Curcumin: a natural product for diabetes and its complications. Curr. Top. Med. Chem.,  2015, 15(23), 2445-2455.
[http://dx.doi.org/10.2174/1568026615666150619142519] [PMID:  26088351] 
[152] 
Moghadamtousi, S.Z.; Kadir, H.A.; Hassandarvish, P.; Tajik, H.; Abubakar, S.; Zandi, K. A review on antibacterial, antiviral, and antifungal activity of curcumin. BioMed Res. Int.,  2014, 2014, 186864.
[PMID:  24877064] 
[153] 
Wang, Q.; Ye, C.; Sun, S.; Li, R.; Shi, X.; Wang, S.; Zeng, X.; Kuang, N.; Liu, Y.; Shi, Q.; Liu, R. Curcumin attenuates collagen-induced rat arthritis via anti-inflammatory and apoptotic effects. Int. Immunopharmacol.,  2019, 72, 292-300.
[http://dx.doi.org/10.1016/j.intimp.2019.04.027] [PMID:  31005039] 
[154] 
Zheng, Z.; Sun, Y.; Liu, Z.; Zhang, M.; Li, C.; Cai, H. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. Drug Des. Devel. Ther.,  2015, 9, 4931-4942.
[PMID:  26345159] 
[155] 
Kloesch, B.; Becker, T.; Dietersdorfer, E.; Kiener, H.; Steiner, G. Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes. Int. Immunopharmacol.,  2013, 15(2), 400-405.
[http://dx.doi.org/10.1016/j.intimp.2013.01.003] [PMID:  23347846] 
[156] 
Ghandadi, M.; Sahebkar, A. Curcumin: an effective inhibitor of interleukin-6. Curr. Pharm. Des.,  2017, 23(6), 921-931.
[http://dx.doi.org/10.2174/1381612822666161006151605] [PMID:  27719643] 
[157] 
Gong, Z.; Zhao, S.; Zhou, J.; Yan, J.; Wang, L.; Du, X.; Li, H.; Chen, Y.; Cai, W.; Wu, J. Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production. Mol. Immunol.,  2018, 104, 11-19.
[http://dx.doi.org/10.1016/j.molimm.2018.09.004] [PMID:  30396035] 
[158] 
Kumar, P.; Sulakhiya, K.; Barua, C.C.; Mundhe, N. TNF-α; IL-6 and IL-10 expressions, responsible for disparity in action of curcumin against cisplatin-induced nephrotoxicity in rats. Mol. Cell. Biochem.,  2017, 431(1-2), 113-122.
[http://dx.doi.org/10.1007/s11010-017-2981-5] [PMID:  28258441] 
[159] 
Li, Y.; Zhang, J.; Liu, H.; Yuan, J.; Yin, Y.; Wang, T.; Cheng, B.; Sun, S.; Guo, Z. Curcumin ameliorates glyoxylate-induced calcium oxalate deposition and renal injuries in mice. Phytomedicine,  2019, 61, 152861.
[http://dx.doi.org/10.1016/j.phymed.2019.152861] [PMID:  31029908] 
[160] 
Huang, G.; Xu, Z.; Huang, Y.; Duan, X.; Gong, W.; Zhang, Y.; Fan, J.; He, F. Curcumin protects against collagen-induced arthritis via suppression of BAFF production. J. Clin. Immunol.,  2013, 33(3), 550-557.
[http://dx.doi.org/10.1007/s10875-012-9839-0] [PMID:  23184090] 
[161] 
Dai, Q.; Zhou, D.; Xu, L.; Song, X. Curcumin alleviates rheumatoid arthritis-induced inflammation and synovial hyperplasia by targeting mTOR pathway in rats. Drug Des. Devel. Ther.,  2018, 12, 4095-4105.
[http://dx.doi.org/10.2147/DDDT.S175763] [PMID:  30584274] 
[162] 
Moon, D.O.; Kim, M.O.; Choi, Y.H.; Park, Y.M.; Kim, G.Y. Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model. Int. Immunopharmacol.,  2010, 10(5), 605-610.
[http://dx.doi.org/10.1016/j.intimp.2010.02.011] [PMID:  20188213] 
[163] 
Jackson, J.K.; Higo, T.; Hunter, W.L.; Burt, H.M. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm. Res.,  2006, 55(4), 168-175.
[http://dx.doi.org/10.1007/s00011-006-0067-z] [PMID:  16807698] 
[164] 
Yang, M.; Akbar, U.; Mohan, C. Curcumin in autoimmune and rheumatic diseases. Nutrients,  2019, 11(5), E1004.
[http://dx.doi.org/10.3390/nu11051004] [PMID:  31052496] 
[165] 
Asteriou, E.; Gkoutzourelas, A.; Mavropoulos, A.; Katsiari, C.; Sakkas, L.I.; Bogdanos, D.P. Curcumin for the management of periodontitis and early acpa-positive rheumatoid arthritis: killing two birds with one stone. Nutrients,  2018, 10(7), E908.
[http://dx.doi.org/10.3390/nu10070908] [PMID:  30012973] 
[166] 
Piovezana Bossolani, G.D.; Silva, B.T.; Colombo Martins Perles, J.V.; Lima, M.M.; Vieira Frez, F.C.; Garcia de Souza, S.R.; Sehaber-Sierakowski, C.C.; Bersani-Amado, C.A.; Zanoni, J.N. Rheumatoid arthritis induces enteric neurodegeneration and jejunal inflammation, and quercetin promotes neuroprotective and anti-inflammatory actions. Life Sci.,  2019, 238, 116956.
[http://dx.doi.org/10.1016/j.lfs.2019.116956] [PMID:  31622607] 
[167] 
Cho, E.; Chung, E.Y.; Jang, H.Y.; Hong, O.Y.; Chae, H.S.; Jeong, Y.J.; Kim, S.Y.; Kim, B.S.; Yoo, D.J.; Kim, J.S.; Park, K.H. Anti-cancer effect of cyanidin-3-glucoside from mulberry via caspase-3 cleavage and DNA fragmentation in vitro and in vivo. Anticancer. Agents Med. Chem.,  2017, 17(11), 1519-1525.
[http://dx.doi.org/10.2174/1871520617666170327152026] [PMID:  28356020] 
[168] 
Zhang, P.; Liu, S.; Zhao, Z.; You, L.; Harrison, M.D.; Zhang, Z. Enzymatic acylation of cyanidin-3-glucoside with fatty acid methyl esters improves stability and antioxidant activity. Food Chem.,  2021, 343, 128482.
[http://dx.doi.org/10.1016/j.foodchem.2020.128482] [PMID:  33160770] 
[169] 
Matsukawa, T.; Inaguma, T.; Han, J.; Villareal, M.O.; Isoda, H. Cyanidin-3-glucoside derived from black soybeans ameliorate type 2 diabetes through the induction of differentiation of preadipocytes into smaller and insulin-sensitive adipocytes. J. Nutr. Biochem.,  2015, 26(8), 860-867.
[http://dx.doi.org/10.1016/j.jnutbio.2015.03.006] [PMID:  25940979] 
[170] 
Molonia, M.S.; Occhiuto, C.; Muscarà, C.; Speciale, A.; Bashllari, R.; Villarroya, F.; Saija, A.; Cimino, F.; Cristani, M. Cyanidin-3-O-glucoside restores insulin signaling and reduces inflammation in hypertrophic adipocytes. Arch. Biochem. Biophys.,  2020, 691, 108488.
[http://dx.doi.org/10.1016/j.abb.2020.108488] [PMID:  32692982] 
[171] 
Sun, Y.; Li, L. Cyanidin-3-glucoside inhibits inflammatory activities in human fibroblast-like synoviocytes and in mice with collagen-induced arthritis. Clin. Exp. Pharmacol. Physiol.,  2018, 45(10), 1038-1045.
[http://dx.doi.org/10.1111/1440-1681.12970] [PMID:  29779214] 
[172] 
Park, K.H.; Gu, D.R.; So, H.S.; Kim, K.J.; Lee, S.H. Dual role of cyanidin-3-glucoside on the differentiation of bone cells. J. Dent. Res.,  2015, 94(12), 1676-1683.
[http://dx.doi.org/10.1177/0022034515604620] [PMID:  26350961] 
[173] 
Xiao, X.N.; Wang, F.; Yuan, Y.T.; Liu, J.; Liu, Y.Z.; Yi, X. Antibacterial activity and mode of action of dihydromyricetin from Ampelopsis grossedentata leaves against food-borne bacteria. Molecules,  2019, 24(15), E2831.
[http://dx.doi.org/10.3390/molecules24152831] [PMID:  31382605] 
[174] 
Gandhi, G.R.; Vasconcelos, A.B.S.; Wu, D.T.; Li, H.B.; Antony, P.J.; Li, H.; Geng, F.; Gurgel, R.Q.; Narain, N.; Gan, R.Y. Citrus flavonoids as promising phytochemicals targeting diabetes and related complications: a systematic review of in vitro and in vivo studies. Nutrients,  2020, 12(10), E2907.
[http://dx.doi.org/10.3390/nu12102907] [PMID:  32977511] 
[175] 
Kaewmool, C.; Udomruk, S.; Phitak, T.; Pothacharoen, P.; Kongtawelert, P. Cyanidin-3-O-glucoside protects PC12 cells against neuronal apoptosis mediated by LPS-stimulated BV2 microglial activation. Neurotox. Res.,  2020, 37(1), 111-125.
[http://dx.doi.org/10.1007/s12640-019-00102-1] [PMID:  31485933] 
[176] 
Xia, Y.; Tian, L.M.; Liu, Y.; Guo, K.S.; Lv, M.; Li, Q.T.; Hao, S.Y.; Ma, C.H.; Chen, Y.X.; Tanaka, M.; Bai, W.B.; Qiu, C.H. Low dose of cyanidin-3-O-glucoside alleviated dextran sulfate sodium-induced colitis, mediated by CD169+ macrophage pathway. Inflamm. Bowel Dis.,  2019, 25(9), 1510-1521.
[http://dx.doi.org/10.1093/ibd/izz090] [PMID:  31107535] 
[177] 
Yan, X.; Wu, L.; Li, B.; Meng, X.; Dai, H.; Zheng, Y.; Fu, J. Cyanidin-3-O-glucoside attenuates acute lung injury in sepsis rats. J. Surg. Res.,  2015, 199(2), 592-600.
[http://dx.doi.org/10.1016/j.jss.2015.06.013] [PMID:  26152793] 
[178] 
Shen, X.; Li, G.; Deng, X.; Wang, J.; Zhang, P. Cyanidin 3-O-glucoside chloride attenuates Streptococcus suis-induced inflammation by inhibiting MAPK and NF-κB signaling pathways in murine macrophage J774 cells. J. Microbiol. Biotechnol., 2019. Online ahead of print
[http://dx.doi.org/10.4014/jmb.1904.04036] [PMID:  31030450] 
[179] 
Zhang, Y.; Lian, F.; Zhu, Y.; Xia, M.; Wang, Q.; Ling, W.; Wang, X.D. Cyanidin-3-O-beta-glucoside inhibits LPS-induced expression of inflammatory mediators through decreasing IkappaBalpha phosphorylation in THP-1 cells. Inflamm. Res.,  2010, 59(9), 723-730.
[http://dx.doi.org/10.1007/s00011-010-0183-7] [PMID:  20309718] 
[180] 
Fu, Y.; Wei, Z.; Zhou, E.; Zhang, N.; Yang, Z. Cyanidin-3-O-β-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model. J. Lipid Res.,  2014, 55(6), 1111-1119.
[http://dx.doi.org/10.1194/jlr.M047340] [PMID:  24752550] 
[181] 
Tsuda, T.; Horio, F.; Osawa, T. Cyanidin 3-O-beta-D-glucoside suppresses nitric oxide production during a zymosan treatment in rats. J. Nutr. Sci. Vitaminol. (Tokyo),  2002, 48(4), 305-310.
[http://dx.doi.org/10.3177/jnsv.48.305] [PMID:  12489822] 
[182] 
Jiang, M.; Zhu, M.; Wang, L.; Yu, S. Anti-tumor effects and associated molecular mechanisms of myricetin. Biomed. Pharmacother.,  2019, 120, 109506.
[http://dx.doi.org/10.1016/j.biopha.2019.109506] [PMID:  31586904] 
[183] 
Li, T.; Zhu, J.; Deng, F.; Wu, W.; Zheng, Z.; Lv, C.; Li, Y.; Xiang, W.; Lu, X.; Qin, S. Microarray based functional analysis of myricetin and proteomic study on its anti-inflammatory property. BioMed Res. Int.,  2019, 2019, 3746326.
[http://dx.doi.org/10.1155/2019/3746326] [PMID:  30956980] 
[184] 
Zhang, K.; Ma, Z.; Wang, J.; Xie, A.; Xie, J. Myricetin attenuated MPP(+)-induced cytotoxicity by anti-oxidation and inhibition of MKK4 and JNK activation in MES23.5 cells. Neuropharmacology,  2011, 61(1-2), 329-335.
[http://dx.doi.org/10.1016/j.neuropharm.2011.04.021] [PMID:  21549720] 
[185] 
Yuan, X.; Liu, Y.; Hua, X.; Deng, X.; Sun, P.; Yu, C.; Chen, L.; Yu, S.; Liu, S.; Pang, H. Myricetin ameliorates the symptoms of collagen-induced arthritis in mice by inhibiting cathepsin K activity. Immunopharmacol. Immunotoxicol.,  2015, 37(6), 513-519.
[http://dx.doi.org/10.3109/08923973.2015.1096942] [PMID:  26525510] 
[186] 
Vargas-Ruiz, R.; Montiel-Ruiz, R.M.; Herrera-Ruiz, M.; González-Cortazar, M.; Ble-González, E.A.; Jiménez-Aparicio, A.R.; Jiménez-Ferrer, E.; Zamilpa, A. Effect of phenolic compounds from Oenothera rosea on the kaolin-carrageenan induced arthritis model in mice. J. Ethnopharmacol.,  2020, 253, 112711.
[http://dx.doi.org/10.1016/j.jep.2020.112711] [PMID:  32097698] 
[187] 
Lee, Y.S.; Choi, E.M. Myricetin inhibits IL-1beta-induced inflammatory mediators in SW982 human synovial sarcoma cells. Int. Immunopharmacol.,  2010, 10(7), 812-814.
[http://dx.doi.org/10.1016/j.intimp.2010.04.010] [PMID:  20403460] 
[188] 
Kan, X.; Liu, B.; Guo, W.; Wei, L.; Lin, Y.; Guo, Y.; Gong, Q.; Li, Y.; Xu, D.; Cao, Y.; Huang, B.; Dong, A.; Ma, H.; Fu, S.; Liu, J. Myricetin relieves LPS-induced mastitis by inhibiting inflammatory response and repairing the blood-milk barrier. J. Cell. Physiol., 2019. Online Ahead of Print
[http://dx.doi.org/10.1002/jcp.28288] [PMID:  30746687] 
[189] 
Hassan, S.M.; Khalaf, M.M.; Sadek, S.A.; Abo-Youssef, A.M. Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. Pharm. Biol.,  2017, 55(1), 766-774.
[http://dx.doi.org/10.1080/13880209.2016.1275704] [PMID:  28064632] 
[190] 
Wang, F.; Song, Z.Y.; Qu, X.J.; Li, F.; Zhang, L.; Li, W.B.; Cui, S.X. M10, a novel derivative of myricetin, prevents ulcerative colitis and colorectal tumor through attenuating robust endoplasmic reticulum stress. Carcinogenesis,  2018, 39(7), 889-899.
[http://dx.doi.org/10.1093/carcin/bgy057] [PMID:  29757351] 
[191] 
Sun, J.; Sun, J.; Zhou, X. Protective functions of myricetin in LPS-induced cardiomyocytes H9c2 cells injury by regulation of MALAT1. Eur. J. Med. Res.,  2019, 24(1), 20.
[http://dx.doi.org/10.1186/s40001-019-0378-5] [PMID:  31027517] 
[192] 
Chen, S.; Fan, B. Myricetin protects cardiomyocytes from LPS-induced injury. Herz,  2018, 43(3), 265-274.
[http://dx.doi.org/10.1007/s00059-017-4556-3] [PMID:  28357449] 
[193] 
Martínez-Coria, H.; Mendoza-Rojas, M.X.; Arrieta-Cruz, I.; López-Valdés, H.E. Preclinical research of dihydromyricetin for brain aging and neurodegenerative diseases. Front. Pharmacol.,  2019, 10, 1334.
[http://dx.doi.org/10.3389/fphar.2019.01334] [PMID:  31780947] 
[194] 
Zhang, J.; Chen, Y.; Luo, H.; Sun, L.; Xu, M.; Yu, J.; Zhou, Q.; Meng, G.; Yang, S. Recent update on the pharmacological effects and mechanisms of dihydromyricetin. Front. Pharmacol.,  2018, 9, 1204.
[http://dx.doi.org/10.3389/fphar.2018.01204] [PMID:  30410442] 
[195] 
Luo, Y.; Lu, S.; Dong, X.; Xu, L.; Sun, G.; Sun, X. Dihydromyricetin protects human umbilical vein endothelial cells from injury through ERK and Akt mediated Nrf2/HO-1 signaling pathway. Apoptosis,  2017, 22(8), 1013-1024.
[http://dx.doi.org/10.1007/s10495-017-1381-3] [PMID:  28612103] 
[196] 
Liu, T.T.; Zeng, Y.; Tang, K.; Chen, X.; Zhang, W.; Xu, X.L. Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice. Atherosclerosis,  2017, 262, 39-50.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.003] [PMID:  28500865] 
[197] 
Fan, T.F.; Wu, T.F.; Bu, L.L.; Ma, S.R.; Li, Y.C.; Mao, L.; Sun, Z.J.; Zhang, W.F. Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma. Oncotarget,  2016, 7(37), 59691-59703.
[http://dx.doi.org/10.18632/oncotarget.10836] [PMID:  27474168] 
[198] 
Liang, H.; He, K.; Li, T.; Cui, S.; Tang, M.; Kang, S.; Ma, W.; Song, L. Mechanism and antibacterial activity of vine tea extract and dihydromyricetin against Staphylococcus aureus. Sci. Rep.,  2020, 10(1), 21416.
[http://dx.doi.org/10.1038/s41598-020-78379-y] [PMID:  33293561] 
[199] 
Wu, T.C.; Chan, S.T.; Chang, C.N.; Yu, P.S.; Chuang, C.H.; Yeh, S.L. Quercetin and chrysin inhibit nickel-induced invasion and migration by downregulation of TLR4/NF-κB signaling in A549 cells. Chem. Biol. Interact.,  2018, 292, 101-109.
[http://dx.doi.org/10.1016/j.cbi.2018.07.010] [PMID:  30016632] 
[200] 
Chu, J.; Wang, X.; Bi, H.; Li, L.; Ren, M.; Wang, J. Dihydromyricetin relieves rheumatoid arthritis symptoms and suppresses expression of pro-inflammatory cytokines via the activation of Nrf2 pathway in rheumatoid arthritis model. Int. Immunopharmacol.,  2018, 59, 174-180.
[http://dx.doi.org/10.1016/j.intimp.2018.04.001] [PMID:  29656207] 
[201] 
Wang, Y.C.; Liu, Q.X.; Zheng, Q.; Liu, T.; Xu, X.E.; Liu, X.H.; Gao, W.; Bai, X.J.; Li, Z.F. Dihydromyricetin alleviates sepsis-induced acute lung injury through inhibiting NLRP3 inflammasome-dependent pyroptosis in mice model. Inflammation,  2019, 42(4), 1301-1310.
[http://dx.doi.org/10.1007/s10753-019-00990-7] [PMID:  30887396] 
[202] 
Qiu, P.; Dong, Y.; Li, B.; Kang, X.J.; Gu, C.; Zhu, T.; Luo, Y.Y.; Pang, M.X.; Du, W.F.; Ge, W.H. Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury. Toxicol. Lett.,  2017, 274, 31-41.
[http://dx.doi.org/10.1016/j.toxlet.2017.04.009] [PMID:  28419832] 
[203] 
Sureda, A.; Sanches Silva, A.; Sánchez-Machado, D.I.; López-Cervantes, J.; Daglia, M.; Nabavi, S.F.; Nabavi, S.M. Hypotensive effects of genistein: from chemistry to medicine. Chem. Biol. Interact.,  2017, 268, 37-46.
[http://dx.doi.org/10.1016/j.cbi.2017.02.012] [PMID:  28242380] 
[204] 
Xie, J.; Liu, J.; Chen, T.M.; Lan, Q.; Zhang, Q.Y.; Liu, B.; Dai, D.; Zhang, W.D.; Hu, L.P.; Zhu, R.Z. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World J. Gastroenterol.,  2015, 21(18), 5473-5481.
[http://dx.doi.org/10.3748/wjg.v21.i18.5473] [PMID:  25987769] 
[205] 
Wu, B.; Lin, J.; Luo, J.; Han, D.; Fan, M.; Guo, T.; Tao, L.; Yuan, M.; Yi, F. Dihydromyricetin protects against diabetic cardiomyopathy in streptozotocin-induced diabetic mice. BioMed Res. Int.,  2017, 2017, 3764370.
[http://dx.doi.org/10.1155/2017/3764370] [PMID:  28421194] 
[206] 
Zhou, M.Q.; Shao, L.; Wu, J.; Peng, N.; Jin, L.P.; Wei, G.Z.; Cheng, W.; Deng, C.J. Dihydromyricetin protects against lipopolysaccharide induced cardiomyocyte injury through the toll like receptor 4/nuclear factor κB pathway. Mol. Med. Rep.,  2017, 16(6), 8983-8988.
[http://dx.doi.org/10.3892/mmr.2017.7742] [PMID:  29039483] 
[207] 
Choi, J.; Lee, D.H.; Park, S.Y.; Seol, J.W. Diosmetin inhibits tumor development and block tumor angiogenesis in skin cancer. Biomed. Pharmacother.,  2019, 117, 109091.
[http://dx.doi.org/10.1016/j.biopha.2019.109091] [PMID:  31228803] 
[208] 
Kasiri, N.; Rahmati, M.; Ahmadi, L.; Eskandari, N.; Motedayyen, H. Therapeutic potential of quercetin on human breast cancer in different dimensions. Inflammopharmacology,  2020, 28(1), 39-62.
[http://dx.doi.org/10.1007/s10787-019-00660-y] [PMID:  31754939] 
[209] 
Qi, W.; Lin, C.; Fan, K.; Chen, Z.; Liu, L.; Feng, X.; Zhang, H.; Shao, Y.; Fang, H.; Zhao, C.; Zhang, R.; Cai, D. Hesperidin inhibits synovial cell inflammation and macrophage polarization through suppression of the PI3K/AKT pathway in complete Freund’s adjuvant-induced arthritis in mice. Chem. Biol. Interact.,  2019, 306, 19-28.
[http://dx.doi.org/10.1016/j.cbi.2019.04.002] [PMID:  30954464] 
[210] 
Cheriet, T.; Ben-Bachir, B.; Thamri, O.; Seghiri, R.; Mancini, I. Isolation and biological properties of the natural flavonoids pectolinarin and pectolinarigenin-a review. Antibiotics (Basel),  2020, 9(7), E417.
[http://dx.doi.org/10.3390/antibiotics9070417] [PMID:  32708783] 
[211] 
Yang, Y.; Gong, X.B.; Huang, L.G.; Wang, Z.X.; Wan, R.Z.; Zhang, P.; Zhang, Q.Y.; Chen, Z.; Zhang, B.S. Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice. Oncotarget,  2017, 8(19), 30723-30733.
[http://dx.doi.org/10.18632/oncotarget.15413] [PMID:  28430612] 
[212] 
Patel, K.; Gadewar, M.; Tahilyani, V.; Patel, D.K. A review on pharmacological and analytical aspects of diosmetin: a concise report. Chin. J. Integr. Med.,  2013, 19(10), 792-800.
[http://dx.doi.org/10.1007/s11655-013-1595-3] [PMID:  24092244] 
[213] 
Hawas, U.W.; Abou El-Kassem, L.T.; Thalassiolin, D. Thalassiolin D: a new flavone O-glucoside Sulphate from the seagrass Thalassia hemprichii. Nat. Prod. Res.,  2017, 31(20), 2369-2374.
[http://dx.doi.org/10.1080/14786419.2017.1308367] [PMID:  28355883] 
[214] 
Gomez-Chang, E.; Uribe-Estanislao, G.V.; Martinez-Martinez, M.; Gálvez-Mariscal, A.; Romero, I. Anti-helicobacter pylori potential of three edible plants known as quelites in Mexico. J. Med. Food,  2018, 21(11), 1150-1157.
[http://dx.doi.org/10.1089/jmf.2017.0137] [PMID:  30036109] 
[215] 
Park, Y.; Moon, B.H.; Yang, H.; Lee, Y.; Lee, E.; Lim, Y. Complete assignments of NMR data of 13 hydroxymethoxyflavones. Magn. Reson. Chem.,  2007, 45(12), 1072-1075.
[http://dx.doi.org/10.1002/mrc.2063] [PMID:  17987643] 
[216] 
Shao, S.; Fu, F.; Wang, Z.; Song, F.; Li, C.; Wu, Z.X.; Ding, J.; Li, K.; Xiao, Y.; Su, Y.; Lin, X.; Yuan, G.; Zhao, J.; Liu, Q.; Xu, J. Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice. J. Cell. Physiol.,  2019, 234(8), 12701-12713.
[http://dx.doi.org/10.1002/jcp.27887] [PMID:  30515812] 
[217] 
Chen, Y.; Wang, Y.; Liu, M.; Zhou, B.; Yang, G. Diosmetin exhibits anti-proliferative and anti-inflammatory effects on TNF-α;-stimulated human rheumatoid arthritis fibroblast-like synoviocytes through regulating the Akt and NF-κB signaling pathways. Phytother. Res.,  2020, 34(6), 1310-1319.
[http://dx.doi.org/10.1002/ptr.6596] [PMID:  31833613] 
[218] 
Liu, Q.; Ci, X.; Wen, Z.; Peng, L. Diosmetin alleviates lipopolysaccharide-induced acute lung injury through activating the Nrf2 pathway and inhibiting the NLRP3 inflammasome. Biomol. Ther. (Seoul),  2018, 26(2), 157-166.
[http://dx.doi.org/10.4062/biomolther.2016.234] [PMID:  28365974] 
[219] 
Yu, G.; Wan, R.; Yin, G.; Xiong, J.; Hu, Y.; Xing, M.; Cang, X.; Fan, Y.; Xiao, W.; Qiu, L.; Wang, X.; Hu, G. Diosmetin ameliorates the severity of cerulein-induced acute pancreatitis in mice by inhibiting the activation of the nuclear factor-κ. B. Int. J. Clin. Exp. Pathol.,  2014, 7(5), 2133-2142.
[PMID:  24966921] 
[220] 
Lephart, E.D. Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms. Ageing Res. Rev.,  2016, 31, 36-54.
[http://dx.doi.org/10.1016/j.arr.2016.08.001] [PMID:  27521253] 
[221] 
Tanaka, Y.; Kimura, S.; Ishii, Y.; Tateda, K. Equol inhibits growth and spore formation of Clostridioides difficile. J. Appl. Microbiol.,  2019, 127(3), 932-940.
[http://dx.doi.org/10.1111/jam.14353] [PMID:  31211883] 
[222] 
Yang, Z.P.; Zhao, Y.; Huang, F.; Chen, J.; Yao, Y.H.; Li, J.; Wu, X.N. Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway. World J. Gastroenterol.,  2015, 21(36), 10385-10399.
[http://dx.doi.org/10.3748/wjg.v21.i36.10385] [PMID:  26420965] 
[223] 
Martin, D.; Song, J.; Mark, C.; Eyster, K. Understanding the cardiovascular actions of soy isoflavones: potential novel targets for antihypertensive drug development. Cardiovasc. Hematol. Disord. Drug Targets,  2008, 8(4), 297-312.
[http://dx.doi.org/10.2174/187152908786786214] [PMID:  19202595] 
[224] 
Lin, I.C.; Yamashita, S.; Murata, M.; Kumazoe, M.; Tachibana, H. Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mice. J. Nutr. Biochem.,  2016, 32, 101-106.
[http://dx.doi.org/10.1016/j.jnutbio.2016.02.012] [PMID:  27142742] 
[225] 
Deng, Z.; Hassan, S.; Rafiq, M.; Li, H.; He, Y.; Cai, Y.; Kang, X.; Liu, Z.; Yan, T. Pharmacological activity of eriodictyol: the major natural polyphenolic flavanone. eCAM,  2020, 2020, 6681352.
[226] 
Bai, J.; Wang, Y.; Zhu, X.; Shi, J. Eriodictyol inhibits high glucose-induced extracellular matrix accumulation, oxidative stress, and inflammation in human glomerular mesangial cells. Phytother. Res.,  2019, 33(10), 2775-2782.
[http://dx.doi.org/10.1002/ptr.6463] [PMID:  31373419] 
[227] 
Dunstan, M.S.; Robinson, C.J.; Jervis, A.J.; Yan, C.; Carbonell, P.; Hollywood, K.A.; Currin, A.; Swainston, N.; Feuvre, R.L.; Micklefield, J.; Faulon, J.L.; Breitling, R.; Turner, N.; Takano, E.; Scrutton, N.S. Engineering Escherichia coli towards de novo production of gatekeeper (2S)-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol. Syn. Biol.,  2020, 5(1), ysaa012.
[228] 
Habtemariam, S. The Nrf2/HO-1 axis as targets for flavanones: neuroprotection by pinocembrin, naringenin, and eriodictyol. Oxid. Med. Cell. Longev.,  2019, 2019, 4724920.
[http://dx.doi.org/10.1155/2019/4724920] [PMID:  31814878] 
[229] 
Hameed, A.; Hafizur, R.M.; Hussain, N.; Raza, S.A.; Rehman, M.; Ashraf, S.; Ul-Haq, Z.; Khan, F.; Abbas, G.; Choudhary, M.I. Eriodictyol stimulates insulin secretion through cAMP/PKA signaling pathway in mice islets. Eur. J. Pharmacol.,  2018, 820, 245-255.
[http://dx.doi.org/10.1016/j.ejphar.2017.12.015] [PMID:  29229531] 
[230] 
Kwon, E.Y.; Choi, M.S. Dietary eriodictyol alleviates adiposity, hepatic steatosis, insulin resistance, and inflammation in diet-induced obese mice. Int. J. Mol. Sci.,  2019, 20(5), E1227.
[http://dx.doi.org/10.3390/ijms20051227] [PMID:  30862092] 
[231] 
Sun, Y.Z.; Chen, J.F.; Shen, L.M.; Zhou, J.; Wang, C.F. Anti-atherosclerotic effect of hesperidin in LDLr-/- mice and its possible mechanism. Eur. J. Pharmacol.,  2017, 815, 109-117.
[http://dx.doi.org/10.1016/j.ejphar.2017.09.010] [PMID:  28899694] 
[232] 
Lei, Z.; Ouyang, L.; Gong, Y.; Wang, Z.; Yu, B. Effect of eriodictyol on collagen-induced arthritis in rats by Akt/HIF-1α; pathway. Drug Des. Devel. Ther.,  2020, 14, 1633-1639.
[http://dx.doi.org/10.2147/DDDT.S239662] [PMID:  32425508] 
[233] 
Liu, Y.; Yan, X. Eriodictyol inhibits survival and inflammatory responses and promotes apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through AKT/FOXO1 signaling. J. Cell. Biochem.,  2019, 120(9), 14628-14635.
[http://dx.doi.org/10.1002/jcb.28724] [PMID:  31009103] 
[234] 
Li, D.; Lu, N.; Han, J.; Chen, X.; Hao, W.; Xu, W.; Liu, X.; Ye, L.; Zheng, Q. Eriodictyol attenuates myocardial ischemia-reperfusion injury through the activation of JAK2. Front. Pharmacol.,  2018, 9, 33.
[http://dx.doi.org/10.3389/fphar.2018.00033] [PMID:  29441020] 
[235] 
Daily, J.W.; Ko, B.S.; Ryuk, J.; Liu, M.; Zhang, W.; Park, S. Equol decreases hot flashes in postmenopausal women: a systematic review and meta-analysis of randomized clinical trials. J. Med. Food,  2019, 22(2), 127-139.
[http://dx.doi.org/10.1089/jmf.2018.4265] [PMID:  30592686] 
[236] 
Kim, J.S.; Lee, S.G.; Min, K.; Kwon, T.K.; Kim, H.J.; Nam, J.O. Eupatilin inhibits adipogenesis through suppression of PPARγ activity in 3T3-L1 cells. Biomed. Pharmacother.,  2018, 103, 135-139.
[http://dx.doi.org/10.1016/j.biopha.2018.03.073] [PMID:  29649628] 
[237] 
Wu, Z.; Zou, B.; Zhang, X.; Peng, X. Eupatilin regulates proliferation and cell cycle of cervical cancer by regulating hedgehog signalling pathway. Cell Biochem. Funct.,  2020, 38(4), 428-435.
[http://dx.doi.org/10.1002/cbf.3493] [PMID:  31926121] 
[238] 
Serttas, R.; Koroglu, C.; Erdogan, S. Eupatilin inhibits the proliferation and migration of prostate cancer cells through modulation of PTEN and NF-κB signaling. Anticancer. Agents Med. Chem.,  2021, 21(3), 372-382.
[PMID:  32781972] 
[239] 
Kim, T.J.; Kim, E.R.; Hong, S.N.; Kim, Y.H.; Lee, Y.C.; Kim, H.S.; Kim, K.; Chang, D.K. Effectiveness of acid suppressants and other mucoprotective agents in reducing the risk of occult gastrointestinal bleeding in nonsteroidal anti-inflammatory drug users. Sci. Rep.,  2019, 9(1), 11696.
[http://dx.doi.org/10.1038/s41598-019-48173-6] [PMID:  31406189] 
[240] 
Sapkota, A.; Gaire, B.P.; Cho, K.S.; Jeon, S.J.; Kwon, O.W.; Jang, D.S.; Kim, S.Y.; Ryu, J.H.; Choi, J.W. Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. PLoS One,  2017, 12(2), e0171479.
[http://dx.doi.org/10.1371/journal.pone.0171479] [PMID:  28178289] 
[241] 
Kim, J.; Kim, Y.; Yi, H.; Jung, H.; Rim, Y.A.; Park, N.; Jung, S.M.; Park, S.H.; Ju, J.H. Eupatilin ameliorates collagen induced arthritis. J. Korean Med. Sci.,  2015, 30(3), 233-239.
[http://dx.doi.org/10.3346/jkms.2015.30.3.233] [PMID:  25729243] 
[242] 
Zhang, Y.; Qin, L.; Xie, J.; Li, J.; Wang, C. Eupatilin prevents behavioral deficits and dopaminergic neuron degeneration in a Parkinson’s disease mouse model. Life Sci.,  2020, 253, 117745.
[http://dx.doi.org/10.1016/j.lfs.2020.117745] [PMID:  32376269] 
[243] 
Song, E.H.; Chung, K.S.; Kang, Y.M.; Lee, J.H.; Lee, M.; An, H.J. Eupatilin suppresses the allergic inflammatory response in vitro and in vivo. Phytomedicine,  2018, 42, 1-8.
[http://dx.doi.org/10.1016/j.phymed.2017.08.027] [PMID:  29655675] 
[244] 
Park, W.S.; Paik, K.; Yang, K.J.; Kim, J.O. Eupatilin ameliorates cerulein-induced pancreatitis via inhibition of the protein kinase D1 signaling pathway in vitro. Pancreas,  2020, 49(2), 281-289.
[http://dx.doi.org/10.1097/MPA.0000000000001488] [PMID:  32011533] 
[245] 
Pal, H.C.; Pearlman, R.L.; Afaq, F. Fisetin and its role in chronic diseases. Adv. Exp. Med. Biol.,  2016, 928, 213-244.
[http://dx.doi.org/10.1007/978-3-319-41334-1_10] [PMID:  27671819] 
[246] 
Maher, P. Modulation of the neuroprotective and anti-inflammatory activities of the flavonol fisetin by the transition metals iron and copper. Antioxidants (Basel, Switzerland),  2020, 9(11), 1113.
[247] 
Sinha, R.; Srivastava, S.; Joshi, A.; Joshi, U.J.; Govil, G. In-vitro anti-proliferative and anti-oxidant activity of galangin, fisetin and quercetin: role of localization and intermolecular interaction in model membrane. Eur. J. Med. Chem.,  2014, 79, 102-109.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.002] [PMID:  24727463] 
[248] 
Nabavi, S.F.; Braidy, N.; Habtemariam, S.; Sureda, A.; Manayi, A.; Nabavi, S.M. Neuroprotective effects of fisetin in Alzheimer’s and Parkinson’s diseases: from chemistry to medicine. Curr. Top. Med. Chem.,  2016, 16(17), 1910-1915.
[http://dx.doi.org/10.2174/1568026616666160204121725] [PMID:  26845554] 
[249] 
Garg, S.; Khan, S.I.; Malhotra, R.K.; Sharma, M.K.; Kumar, M.; Kaur, P.; Nag, T.C. RumaRay; Bhatia, J.; Arya, D.S. The molecular mechanism involved in cardioprotection by the dietary flavonoid fisetin as an agonist of PPAR-γ in a murine model of myocardial infarction. Arch. Biochem. Biophys.,  2020, 694, 108572.
[http://dx.doi.org/10.1016/j.abb.2020.108572] [PMID:  32926843] 
[250] 
Lee, J.D.; Huh, J.E.; Jeon, G.; Yang, H.R.; Woo, H.S.; Choi, D.Y.; Park, D.S. Flavonol-rich RVHxR from Rhus verniciflua Stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models. Int. Immunopharmacol.,  2009, 9(3), 268-276.
[http://dx.doi.org/10.1016/j.intimp.2008.11.005] [PMID:  19111632] 
[251] 
Kumar, R.; Kumar, R.; Khurana, N.; Singh, S.K.; Khurana, S.; Verma, S.; Sharma, N.; Kapoor, B.; Vyas, M.; Khursheed, R.; Awasthi, A.; Kaur, J.; Corrie, L. Enhanced oral bioavailability and neuroprotective effect of fisetin through its SNEDDS against rotenone-induced Parkinson’s disease rat model. Food Chem. Toxicol.,  2020, 144, 111590.
[http://dx.doi.org/10.1016/j.fct.2020.111590] [PMID:  32710995] 
[252] 
Seo, S.H.; Jeong, G.S. Fisetin inhibits TNF-α;-induced inflammatory action and hydrogen peroxide-induced oxidative damage in human keratinocyte HaCaT cells through PI3K/AKT/Nrf-2-mediated heme oxygenase-1 expression. Int. Immunopharmacol.,  2015, 29(2), 246-253.
[http://dx.doi.org/10.1016/j.intimp.2015.11.014] [PMID:  26590114] 
[253] 
Li, P.; Chen, D.; Huang, Y. Fisetin administration improves LPS-induced acute otitis media in mouse in vivo. Int. J. Mol. Med.,  2018, 42(1), 237-247.
[http://dx.doi.org/10.3892/ijmm.2018.3585] [PMID:  29568876] 
[254] 
Xin, X.; Chen, C.; Hu, Y.Y.; Feng, Q. Protective effect of genistein on nonalcoholic fatty liver disease (NAFLD). Biomed. Pharmacother.,  2019, 117, 109047.
[http://dx.doi.org/10.1016/j.biopha.2019.109047] [PMID:  31176163] 
[255] 
Nagaraju, G.P.; Zafar, S.F.; El-Rayes, B.F. Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases. Nutr. Rev.,  2013, 71(8), 562-572.
[http://dx.doi.org/10.1111/nure.12044] [PMID:  23865800] 
[256] 
Chae, H.S.; Xu, R.; Won, J.Y.; Chin, Y.W.; Yim, H. Molecular targets of genistein and its related flavonoids to exert anticancer effects. Int. J. Mol. Sci.,  2019, 20(10), E2420.
[http://dx.doi.org/10.3390/ijms20102420] [PMID:  31100782] 
[257] 
Wu, Z.M.; Ni, G.L.; Shao, A.M.; Cui, R. Genistein alleviates anxiety-like behaviors in post-traumatic stress disorder model through enhancing serotonergic transmission in the amygdala. Psychiatry Res.,  2017, 255, 287-291.
[http://dx.doi.org/10.1016/j.psychres.2017.05.051] [PMID:  28600997] 
[258] 
Verdrengh, M.; Collins, L.V.; Bergin, P.; Tarkowski, A. Phytoestrogen genistein as an anti-staphylococcal agent. Microbes Infect.,  2004, 6(1), 86-92.
[http://dx.doi.org/10.1016/j.micinf.2003.10.005] [PMID:  14738897] 
[259] 
Mohammad-Shahi, M.; Haidari, F.; Rashidi, B.; Saei, A.A.; Mahboob, S.; Rashidi, M.R. Comparison of the effects of genistein and daidzein with dexamethasone and soy protein on rheumatoid arthritis in rats. Bioimpacts,  2011, 1(3), 161-170.
[PMID:  23678422] 
[260] 
Wang, J.; Zhang, Q.; Jin, S.; He, D.; Zhao, S.; Liu, S. Genistein modulate immune responses in collagen-induced rheumatoid arthritis model. Maturitas,  2008, 59(4), 405-412.
[http://dx.doi.org/10.1016/j.maturitas.2008.04.003] [PMID:  18499367] 
[261] 
Hu, Y.; Li, J.; Qin, L.; Cheng, W.; Lai, Y.; Yue, Y.; Ren, P.; Pan, X.; Zhang, P. study in treatment of collagen-induced arthritis in DBA/1 mice model by genistein. Curr. Pharm. Des.,  2016, 22(46), 6975-6981.
[http://dx.doi.org/10.2174/1381612822666161025150403] [PMID:  27784235] 
[262] 
Li, J.; Li, J.; Yue, Y.; Hu, Y.; Cheng, W.; Liu, R.; Pan, X.; Zhang, P. Genistein suppresses tumor necrosis factor α;-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor κB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells. Drug Des. Devel. Ther.,  2014, 8, 315-323.
[http://dx.doi.org/10.2147/DDDT.S52354] [PMID:  24669186] 
[263] 
Yang, R.; Jia, Q.; Liu, X.F.; Ma, S.F. Effect of genistein on myocardial fibrosis in diabetic rats and its mechanism. Mol. Med. Rep.,  2018, 17(2), 2929-2936.
[PMID:  29257312] 
[264] 
Zhu, Q.; Zhang, W.; Mu, D.; Zhou, H.; Wu, S.; Zou, H. Effects of genistein on lipopolysaccharide-induced injury of mouse alveolar epithelial cells and its mechanism. Biosci. Biotechnol. Biochem.,  2020, 84(3), 544-551.
[http://dx.doi.org/10.1080/09168451.2019.1697197] [PMID:  31791192] 
[265] 
Ortega-Santos, C.P.; Al-Nakkash, L.; Whisner, C.M. Exercise and/or genistein treatment impact gut microbiota and inflammation after 12 weeks on a high-fat, high-sugar diet in C57BL/6 Mice. Nutrients,  2020, 12(11), E3410.
[http://dx.doi.org/10.3390/nu12113410] [PMID:  33172007] 
[266] 
Bao, Y.; Sun, Y.W.; Ji, J.; Gan, L.; Zhang, C.F.; Wang, C.Z.; Yuan, C.S. Genkwanin ameliorates adjuvant-induced arthritis in rats through inhibiting JAK/STAT and NF-κB signaling pathways. Phytomedicine,  2019, 63, 153036.
[http://dx.doi.org/10.1016/j.phymed.2019.153036] [PMID:  31401534] 
[267] 
Hakobyan, A.; Arabyan, E.; Kotsinyan, A.; Karalyan, Z.; Sahakyan, H.; Arakelov, V.; Nazaryan, K.; Ferreira, F.; Zakaryan, H. Inhibition of African swine fever virus infection by genkwanin. Antiviral Res.,  2019, 167, 78-82.
[http://dx.doi.org/10.1016/j.antiviral.2019.04.008] [PMID:  30991087] 
[268] 
Wang, X.; Song, Z.J.; He, X.; Zhang, R.Q.; Zhang, C.F.; Li, F.; Wang, C.Z.; Yuan, C.S. Antitumor and immunomodulatory activity of genkwanin on colorectal cancer in the APC(Min/+) mice. Int. Immunopharmacol.,  2015, 29(2), 701-707.
[http://dx.doi.org/10.1016/j.intimp.2015.09.006] [PMID:  26388189] 
[269] 
Shu, Y.; Liang, Y.; Liang, Z.; Zhao, X.; Zhu, X.; Feng, W.; Liang, J.; Ito, Y. Studies on a simple and efficient method for large-scale preparation of genkwanin from Daphne genkwa SIEB. ET ZUCC. Using normal-phase flash chromatography. J. Liq. Chromatogr. Relat. Technol.,  2014, 37(6), 773-785.
[http://dx.doi.org/10.1080/10826076.2012.749501] [PMID:  24489458] 
[270] 
Lucarini, R.; Tozatti, M.G.; Silva, M.L.; Gimenez, V.M.; Pauletti, P.M.; Groppo, M.; Turatti, I.C.; Cunha, W.R.; Martins, C.H. Antibacterial and anti-inflammatory activities of an extract, fractions, and compounds isolated from Gochnatia pulchra aerial parts. Braz. J. Med. Biol. Res.,  2015, 48(9), 822-830.
[http://dx.doi.org/10.1590/1414-431x20154410] [PMID:  26200228] 
[271] 
Sun, Y.W.; Bao, Y.; Yu, H.; Chen, Q.J.; Lu, F.; Zhai, S.; Zhang, C.F.; Li, F.; Wang, C.Z.; Yuan, C.S. Anti-rheumatoid arthritis effects of flavonoids from Daphne genkwa. Int. Immunopharmacol.,  2020, 83, 106384.
[http://dx.doi.org/10.1016/j.intimp.2020.106384] [PMID:  32199350] 
[272] 
Gao, Y.; Liu, F.; Fang, L.; Cai, R.; Zong, C.; Qi, Y. Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages. PLoS One,  2014, 9(5), e96741.
[http://dx.doi.org/10.1371/journal.pone.0096741] [PMID:  24800851] 
[273] 
Li, C.; Schluesener, H. Health-promoting effects of the citrus flavanone hesperidin. Crit. Rev. Food Sci. Nutr.,  2017, 57(3), 613-631.
[http://dx.doi.org/10.1080/10408398.2014.906382] [PMID:  25675136] 
[274] 
Ahmad, S.; Alam, K.; Hossain, M.M.; Fatima, M.; Firdaus, F.; Zafeer, M.F.; Arif, Z.; Ahmed, M.; Nafees, K.A. Anti-arthritogenic and cardioprotective action of hesperidin and daidzein in collagen-induced rheumatoid arthritis. Mol. Cell. Biochem.,  2016, 423(1-2), 115-127.
[http://dx.doi.org/10.1007/s11010-016-2830-y] [PMID:  27704466] 
[275] 
Ahmed, Y.M.; Messiha, B.A.; Abo-Saif, A.A. Protective effects of simvastatin and hesperidin against complete freund’s adjuvant-induced rheumatoid arthritis in rats. Pharmacology,  2015, 96(5-6), 217-225.
[http://dx.doi.org/10.1159/000439538] [PMID:  26345515] 
[276] 
Li, R.; Li, J.; Cai, L.; Hu, C.M.; Zhang, L. Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms. J. Pharm. Pharmacol.,  2008, 60(2), 221-228.
[http://dx.doi.org/10.1211/jpp.60.2.0011] [PMID:  18237470] 
[277] 
Elhelaly, A.E.; AlBasher, G.; Alfarraj, S.; Almeer, R.; Bahbah, E.I.; Fouda, M.M.A. Bungău, S.G.; Aleya, L.; Abdel-Daim, M.M. Protective effects of hesperidin and diosmin against acrylamide-induced liver, kidney, and brain oxidative damage in rats. Environ. Sci. Pollut. Res. Int.,  2019, 26(34), 35151-35162.
[http://dx.doi.org/10.1007/s11356-019-06660-3] [PMID:  31686333] 
[278] 
Zhou, Z.; Kandhare, A.D.; Kandhare, A.A.; Bodhankar, S.L. Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-beta1/Smad3/AMPK and IkappaBalpha/NF-kappaB pathways. EXCLI J.,  2019, 18, 723-745.
[PMID:  31611754] 
[279] 
Guazelli, C.F.S.; Fattori, V.; Ferraz, C.R.; Borghi, S.M.; Casagrande, R.; Baracat, M.M.; Verri, W.A., Jr Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis. Chem. Biol. Interact.,  2021, 333, 109315.
[http://dx.doi.org/10.1016/j.cbi.2020.109315] [PMID:  33171134] 
[280] 
Qian, X.; Zhu, F. Hesperetin protects crayfish Procambarus clarkii against white spot syndrome virus infection. Fish Shellfish Immunol.,  2019, 93, 116-123.
[http://dx.doi.org/10.1016/j.fsi.2019.07.029] [PMID:  31302287] 
[281] 
Kaul, T.N.; Middleton, E., Jr; Ogra, P.L. Antiviral effect of flavonoids on human viruses. J. Med. Virol.,  1985, 15(1), 71-79.
[http://dx.doi.org/10.1002/jmv.1890150110] [PMID:  2981979] 
[282] 
Lin, Z.; Fu, C.; Yan, Z.; Wu, Y.; Zhan, J.; Lou, Z.; Liao, X.; Pan, J. The protective effect of hesperetin in osteoarthritis: an in vitro and in vivo study. Food Funct.,  2020, 11(3), 2654-2666.
[http://dx.doi.org/10.1039/C9FO02552A] [PMID:  32159191] 
[283] 
Alshatwi, A.A.; Ramesh, E.; Periasamy, V.S.; Subash-Babu, P. The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways. Fundam. Clin. Pharmacol.,  2013, 27(6), 581-592.
[http://dx.doi.org/10.1111/j.1472-8206.2012.01061.x] [PMID:  22913657] 
[284] 
Wang, Y.; Liu, S.; Dong, W.; Qu, X.; Huang, C.; Yan, T.; Du, J. Combination of hesperetin and platinum enhances anticancer effect on lung adenocarcinoma. Biomed. Pharmacother.,  2019, 113, 108779.
[http://dx.doi.org/10.1016/j.biopha.2019.108779] [PMID:  30889488] 
[285] 
Liu, H.; Dong, Y.; Gao, Y.; Zhao, L.; Cai, C.; Qi, D.; Zhu, M.; Zhao, L.; Liu, C.; Guo, F.; Xiao, J.; Huang, H. Hesperetin suppresses RANKL-induced osteoclastogenesis and ameliorates lipopolysaccharide-induced bone loss. J. Cell. Physiol.,  2019, 234(7), 11009-11022.
[http://dx.doi.org/10.1002/jcp.27924] [PMID:  30548260] 
[286] 
Li, R.; Cai, L.; Xie, X.F.; Peng, L.; Wu, T.N.; Li, J. 7,3′-dimethoxy hesperetin inhibits inflammation by inducing synovial apoptosis in rats with adjuvant-induced arthritis. Immunopharmacol. Immunotoxicol.,  2013, 35(1), 139-146.
[http://dx.doi.org/10.3109/08923973.2012.723010] [PMID:  22978269] 
[287] 
Choi, E.M.; Lee, Y.S. Effects of hesperetin on the production of inflammatory mediators in IL-1beta treated human synovial cells. Cell. Immunol.,  2010, 264(1), 1-3.
[http://dx.doi.org/10.1016/j.cellimm.2010.05.006] [PMID:  20538267] 
[288] 
Shirzad, M.; Heidarian, E.; Beshkar, P.; Gholami-Arjenaki, M. Biological effects of hesperetin on interleukin-6/phosphorylated signal transducer and activator of transcription 3 pathway signaling in prostate cancer PC3 cells. Pharmacognosy Res.,  2017, 9(2), 188-194.
[PMID:  28539744] 
[289] 
Polat, F.R.; Karaboga, I.; Polat, M.S.; Erboga, Z.; Yilmaz, A.; Güzel, S. Effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid-induced experimental colitis model. Cell. Mol. Biol.,  2018, 64(11), 58-65.
[http://dx.doi.org/10.14715/cmb/2018.64.11.11] [PMID:  30213290] 
[290] 
Zhang, J.; Lei, H.; Hu, X.; Dong, W. Hesperetin ameliorates DSS-induced colitis by maintaining the epithelial barrier via blocking RIPK3/MLKL necroptosis signaling. Eur. J. Pharmacol.,  2020, 873, 172992.
[http://dx.doi.org/10.1016/j.ejphar.2020.172992] [PMID:  32035144] 
[291] 
Ku, S.K.; Zhou, W.; Lee, W.; Han, M.S.; Na, M.; Bae, J.S. Anti-inflammatory effects of hyperoside in human endothelial cells and in mice. Inflammation,  2015, 38(2), 784-799.
[http://dx.doi.org/10.1007/s10753-014-9989-8] [PMID:  25097077] 
[292] 
Zhou, Y.Q.; Zhao, Y.T.; Zhao, X.Y.; Liang, C.; Xu, Y.W.; Li, L.; Liu, Y.; Yang, H.B. Hyperoside suppresses lipopolysaccharide-induced inflammation and apoptosis in human umbilical vein endothelial cells. Curr. Med. Sci.,  2018, 38(2), 222-228.
[http://dx.doi.org/10.1007/s11596-018-1869-2] [PMID:  30074179] 
[293] 
Huang, J.; Tong, X.; Zhang, L.; Zhang, Y.; Wang, L.; Wang, D.; Zhang, S.; Fan, H. Hyperoside attenuates bleomycin-induced pulmonary fibrosis development in mice. Front. Pharmacol.,  2020, 11, 550955.
[http://dx.doi.org/10.3389/fphar.2020.550955] [PMID:  33192501] 
[294] 
Han, J.; Xuan, J.L.; Hu, H.R.; Chen, Z.W. Protective effect against myocardial ischemia reperfusion injuries induced by hyperoside preconditioning and its relationship with PI3K/Akt signaling pathway in rats. Zhongguo Zhongyao Zazhi,  2015, 40(1), 118-123.
[PMID:  25993800] 
[295] 
Yang, L.; Shen, L.; Li, Y.; Li, Y.; Yu, S.; Wang, S. Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway. J. Inflamm. (Lond.),  2017, 14, 25.
[http://dx.doi.org/10.1186/s12950-017-0172-5] [PMID:  29162986] 
[296] 
Jin, X.N.; Yan, E.Z.; Wang, H.M.; Sui, H.J.; Liu, Z.; Gao, W.; Jin, Y. Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis. Acta Pharmacol. Sin.,  2016, 37(5), 674-686.
[http://dx.doi.org/10.1038/aps.2016.7] [PMID:  27041460] 
[297] 
Del Carmen Juárez-Vázquez, M.; Josabad Alonso-Castro, A.; García-Carrancá, A. Kaempferitrin induces immunostimulatory effects in vitro. J. Ethnopharmacol.,  2013, 148(1), 337-340.
[http://dx.doi.org/10.1016/j.jep.2013.03.072] [PMID:  23588095] 
[298] 
Mello, C.D.S.; Valente, L.M.M.; Wolff, T.; Lima-Junior, R.S.; Fialho, L.G.; Marinho, C.F.; Azeredo, E.L.; Oliveira-Pinto, L.M.; Pereira, R.C.A.; Siani, A.C.; Kubelka, C.F. Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7. Mem. Inst. Oswaldo Cruz,  2017, 112(6), 458-468.
[http://dx.doi.org/10.1590/0074-02760160323] [PMID:  28591408] 
[299] 
Zhang, Y.; Peng, L.; Li, W.; Dai, T.; Nie, L.; Xie, J.; Ai, Y.; Li, L.; Tian, Y.; Sheng, J. Polyphenol extract of Moringa oleifera leaves alleviates colonic inflammation in dextran sulfate sodium-treated mice. Evid. Based Complement. Alternat. Med.,  2020, 2020, 6295402.
[http://dx.doi.org/10.1155/2020/6295402] [PMID:  33299453] 
[300] 
Wang, J.; Zhao, Q. Kaempferitrin inhibits proliferation, induces apoptosis, and ameliorates inflammation in human rheumatoid arthritis fibroblast-like synoviocytes. Phytother. Res.,  2019, 33(6), 1726-1735.
[http://dx.doi.org/10.1002/ptr.6364] [PMID:  31155798] 
[301] 
Imran, M.; Rauf, A.; Abu-Izneid, T.; Nadeem, M.; Shariati, M.A.; Khan, I.A.; Imran, A.; Orhan, I.E.; Rizwan, M.; Atif, M.; Gondal, T.A.; Mubarak, M.S. Luteolin, a flavonoid, as an anticancer agent: a review. Biomed. Pharmacother.,  2019, 112, 108612.
[http://dx.doi.org/10.1016/j.biopha.2019.108612] [PMID:  30798142] 
[302] 
Aziz, N.; Kim, M.Y.; Cho, J.Y. Anti-inflammatory effects of luteolin: a review of in vitro, in vivo, and in silico studies. J. Ethnopharmacol.,  2018, 225, 342-358.
[http://dx.doi.org/10.1016/j.jep.2018.05.019] [PMID:  29801717] 
[303] 
Ahmadi, S.M.; Farhoosh, R.; Sharif, A.; Rezaie, M. Structure-antioxidant activity relationships of luteolin and catechin. J. Food Sci.,  2020, 85(2), 298-305.
[http://dx.doi.org/10.1111/1750-3841.14994] [PMID:  31957877] 
[304] 
Impellizzeri, D.; Esposito, E.; Di Paola, R.; Ahmad, A.; Campolo, M.; Peli, A.; Morittu, V.M.; Britti, D.; Cuzzocrea, S. Erratum to: Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice. Arthritis Res. Ther.,  2016, 18(1), 101.
[http://dx.doi.org/10.1186/s13075-016-0999-9] [PMID:  27149951] 
[305] 
Choi, E.M.; Lee, Y.S. Luteolin suppresses IL-1beta-induced cytokines and MMPs production via p38 MAPK, JNK, NF-kappaB and AP-1 activation in human synovial sarcoma cell line, SW982. Food Chem. Toxicol.,  2010, 48(10), 2607-2611.
[http://dx.doi.org/10.1016/j.fct.2010.06.029] [PMID:  20600535] 
[306] 
Hou, Y.; Wu, J.; Huang, Q.; Guo, L. Luteolin inhibits proliferation and affects the function of stimulated rat synovial fibroblasts. Cell Biol. Int.,  2009, 33(2), 135-147.
[http://dx.doi.org/10.1016/j.cellbi.2008.10.005] [PMID:  18992831] 
[307] 
Zhang, B.C.; Li, Z.; Xu, W.; Xiang, C.H.; Ma, Y.F. Luteolin alleviates NLRP3 inflammasome activation and directs macrophage polarization in lipopolysaccharide-stimulated RAW264.7 cells. Am. J. Transl. Res.,  2018, 10(1), 265-273.
[PMID:  29423011] 
[308] 
Boeing, T.; de Souza, P.; Speca, S.; Somensi, L.B.; Mariano, L.N.B.; Cury, B.J.; Ferreira Dos Anjos, M.; Quintão, N.L.M.; Dubuqoy, L.; Desreumax, P.; da Silva, L.M.; de Andrade, S.F. Luteolin prevents irinotecan-induced intestinal mucositis in mice through antioxidant and anti-inflammatory properties. Br. J. Pharmacol.,  2020, 177(10), 2393-2408.
[http://dx.doi.org/10.1111/bph.14987] [PMID:  31976547] 
[309] 
Yan, Y.; Jun, C.; Lu, Y.; Jiangmei, S. Combination of metformin and luteolin synergistically protects carbon tetrachloride-induced hepatotoxicity: mechanism involves antioxidant, anti-inflammatory, antiapoptotic, and Nrf2/HO-1 signaling pathway. Biofactors,  2019, 45(4), 598-606.
[http://dx.doi.org/10.1002/biof.1521] [PMID:  31336028] 
[310] 
Lee, G.J.; Cho, I.A.; Oh, J.S.; Seo, Y.S.; You, J.S.; Kim, S.G.; Kim, J.S. Anticatabolic effects of morin through the counteraction of interleukin-1β-induced inflammation in rat primary chondrocytes. Cells Tissues Organs,  2019, 207(1), 21-33.
[http://dx.doi.org/10.1159/000500323] [PMID:  31256148] 
[311] 
Lee, M.H.; Cha, H.J.; Choi, E.O.; Han, M.H.; Kim, S.O.; Kim, G.Y.; Hong, S.H.; Park, C.; Moon, S.K.; Jeong, S.J.; Jeong, M.J.; Kim, W.J.; Choi, Y.H. Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2 mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts. Int. J. Mol. Med.,  2017, 39(3), 672-680.
[http://dx.doi.org/10.3892/ijmm.2017.2871] [PMID:  28204816] 
[312] 
Jiang, B.; Geng, Q.; Li, T.; Mohammad Firdous, S.; Zhou, X. Morin attenuates STZ-induced diabetic retinopathy in experimental animals. Saudi J. Biol. Sci.,  2020, 27(8), 2139-2142.
[http://dx.doi.org/10.1016/j.sjbs.2020.06.001] [PMID:  32714041] 
[313] 
Qu, Y.; Wang, C.; Liu, N.; Gao, C.; Liu, F. Morin Exhibits anti-inflammatory effects on IL-1β-stimulated human osteoarthritis chondrocytes by activating the Nrf2 signaling pathway. Cell. Physiol. Biochem.,  2018, 51(4), 1830-1838.
[http://dx.doi.org/10.1159/000495684] [PMID:  30504721] 
[314] 
Sultana, F.; Neog, M.K.; Rasool, M. Targeted delivery of morin, a dietary bioflavanol encapsulated mannosylated liposomes to the macrophages of adjuvant-induced arthritis rats inhibits inflammatory immune response and osteoclastogenesis. Eur. J. Pharm. Biopharm.,  2017, 115, 229-242.
[http://dx.doi.org/10.1016/j.ejpb.2017.03.009] [PMID:  28315446] 
[315] 
Zeng, N.; Tong, B.; Zhang, X.; Dou, Y.; Wu, X.; Xia, Y.; Dai, Y.; Wei, Z. Antiarthritis effect of morin is associated with inhibition of synovial angiogensis. Drug Dev. Res.,  2015, 76(8), 463-473.
[http://dx.doi.org/10.1002/ddr.21282] [PMID:  26769128] 
[316] 
Jiang, A.; Zhang, Y.; Zhang, X.; Wu, D.; Liu, Z.; Li, S.; Liu, X.; Han, Z.; Wang, C.; Wang, J.; Wei, Z.; Guo, C.; Yang, Z. Morin alleviates LPS-induced mastitis by inhibiting the PI3K/AKT, MAPK, NF-κB and NLRP3 signaling pathway and protecting the integrity of blood-milk barrier. Int. Immunopharmacol.,  2020, 78, 105972.
[http://dx.doi.org/10.1016/j.intimp.2019.105972] [PMID:  31711938] 
[317] 
Kandemir, F.M.; Yıldırım, S.; Kucukler, S.; Caglayan, C.; Darendelioğlu, E.; Dortbudak, M.B. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: a multi-biomarker approach. Food Chem. Toxicol.,  2020, 138, 111190.
[http://dx.doi.org/10.1016/j.fct.2020.111190] [PMID:  32068001] 
[318] 
Jiang, K.; Shi, J.; Shi, J. Morin alleviates vincristine-induced neuropathic pain via nerve protective effect and inhibition of NF-κB pathway in rats. Cell. Mol. Neurobiol.,  2019, 39(6), 799-808.
[http://dx.doi.org/10.1007/s10571-019-00679-3] [PMID:  31011938] 
[319] 
Ola, M.S.; Aleisa, A.M.; Al-Rejaie, S.S.; Abuohashish, H.M.; Parmar, M.Y.; Alhomida, A.S.; Ahmed, M.M. Flavonoid, morin inhibits oxidative stress, inflammation and enhances neurotrophic support in the brain of streptozotocin-induced diabetic rats. Neurol. Sci.,  2014, 35(7), 1003-1008.
[http://dx.doi.org/10.1007/s10072-014-1628-5] [PMID:  24413816] 
[320] 
Goh, J.X.H.; Tan, L.T.; Goh, J.K.; Chan, K.G.; Pusparajah, P.; Lee, L.H.; Goh, B.H. Nobiletin and derivatives: functional compounds from citrus fruit peel for colon cancer chemoprevention. Cancers (Basel),  2019, 11(6), 867.
[http://dx.doi.org/10.3390/cancers11060867] [PMID:  31234411] 
[321] 
Wu, X.; Song, M.; Rakariyatham, K.; Zheng, J.; Guo, S.; Tang, Z.; Zhou, S.; Xiao, H. Anti-inflammatory effects of 4'-demethylnobiletin, a major metabolite of nobiletin. J. Funct. Foods,  2015, 19(Pt A), 278-287.
[322] 
Yang, G.; Li, S.; Yuan, L.; Yang, Y.; Pan, M.H. Effect of nobiletin on the MAPK/NF-κB signaling pathway in the synovial membrane of rats with arthritis induced by collagen. Food Funct.,  2017, 8(12), 4668-4674.
[http://dx.doi.org/10.1039/C7FO01311F] [PMID:  29160881] 
[323] 
Bunbupha, S.; Apaijit, K.; Maneesai, P.; Prasarttong, P.; Pakdeechote, P. Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats. Life Sci.,  2020, 260, 118398.
[http://dx.doi.org/10.1016/j.lfs.2020.118398] [PMID:  32920004] 
[324] 
Liu, Z.; Han, Y.; Zhao, F.; Zhao, Z.; Tian, J.; Jia, K. Nobiletin suppresses high-glucose-induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF-κB pathway. J. Cell. Biochem.,  2019, 120(3), 3467-3473.
[http://dx.doi.org/10.1002/jcb.27621] [PMID:  30499124] 
[325] 
Yang, G.; Li, S.; Yang, Y.; Yuan, L.; Wang, P.; Zhao, H.; Ho, C.T.; Lin, C.C. Nobiletin and 5-Hydroxy-6,7,8,3′4′-pentamethoxyflavone Ameliorate 12- O-Tetradecanoylphorbol-13-acetate-induced psoriasis-like mouse skin lesions by regulating the expression of Ki-67 and proliferating cell nuclear antigen and the differentiation of CD4+ T cells through mitogen-activated protein kinase signaling pathways. J. Agric. Food Chem.,  2018, 66(31), 8299-8306.
[http://dx.doi.org/10.1021/acs.jafc.8b02524] [PMID:  30058806] 
[326] 
Li, W.; Wang, X.; Niu, X.; Zhang, H.; He, Z.; Wang, Y.; Zhi, W.; Liu, F. Protective effects of nobiletin against endotoxic shock in mice through inhibiting TNF-α; IL-6, and HMGB1 and regulating NF-κB pathway. Inflammation,  2016, 39(2), 786-797.
[http://dx.doi.org/10.1007/s10753-016-0307-5] [PMID:  26846885] 
[327] 
Güvenç, M.; Cellat, M.; Uyar, A.; Özkan, H. Gokcek,İ.; İsler, C.T.; Yakan, A. Nobiletin protects from renal ischemia-reperfusion injury in rats by suppressing inflammatory cytokines and regulating iNOS-eNOS expressions. Inflammation,  2020, 43(1), 336-346.
[http://dx.doi.org/10.1007/s10753-019-01123-w] [PMID:  31705353] 
[328] 
Bi, J.; Zhang, H.; Lu, J.; Lei, W. Nobiletin ameliorates isoflurane-induced cognitive impairment via antioxidant, anti-inflammatory and anti-apoptotic effects in aging rats. Mol. Med. Rep.,  2016, 14(6), 5408-5414.
[http://dx.doi.org/10.3892/mmr.2016.5919] [PMID:  27840933] 
[329] 
Elumalai, P.; Lakshmi, S. Role of quercetin benefits in neurodegeneration. Adv. Neurobiol.,  2016, 12, 229-245.
[http://dx.doi.org/10.1007/978-3-319-28383-8_12] [PMID:  27651256] 
[330] 
Wang, Y.L.; Gao, J.M.; Xing, L.Z. Therapeutic potential of Oroxylin A in rheumatoid arthritis. Int. Immunopharmacol.,  2016, 40, 294-299.
[http://dx.doi.org/10.1016/j.intimp.2016.09.006] [PMID:  27643663] 
[331] 
Yang, X.; Zhang, F.; Wang, Y.; Cai, M.; Wang, Q.; Guo, Q.; Li, Z.; Hu, R. Oroxylin A inhibits colitis-associated carcinogenesis through modulating the IL-6/STAT3 signaling pathway. Inflamm. Bowel Dis.,  2013, 19(9), 1990-2000.
[http://dx.doi.org/10.1097/MIB.0b013e318293c5e0] [PMID:  23823704] 
[332] 
Hui, H.; Yang, H.; Dai, Q.; Wang, Q.; Yao, J.; Zhao, K.; Guo, Q.; Lu, N. Oroxylin A inhibits ATRA-induced IL-6 expression involved in retinoic acid syndrome by down-regulating CHOP Gene,  2014, 551(2), 230-235.
[http://dx.doi.org/10.1016/j.gene.2014.08.061] [PMID:  25192658] 
[333] 
Hui, H.; Yang, H.; Dai, Q.; Wang, Q.; Yao, J.; Zhao, K.; Guo, Q.; Lu, N. Corrigendum to “Oroxylin A inhibits ATRA-induced IL-6 expression involved in retinoic acid syndrome by down-regulating CHOP”. Gene,  2020, 722, 144118. [Gene 551 (2014) 230-235]
[http://dx.doi.org/10.1016/j.gene.2019.144118] [PMID:  31629555] 
[334] 
Liu, P.W.; Chen, M.F.; Tsai, A.P.; Lee, T.J. STAT1 mediates oroxylin a inhibition of iNOS and pro-inflammatory cytokines expression in microglial BV-2 cells. PLoS One,  2012, 7(12), e50363.
[http://dx.doi.org/10.1371/journal.pone.0050363] [PMID:  23236370] 
[335] 
Zhu, R.; Zeng, G.; Chen, Y.; Zhang, Q.; Liu, B.; Liu, J.; Chen, H.; Li, M. Oroxylin A accelerates liver regeneration in CCl4-induced acute liver injury mice. PLoS One,  2013, 8(8), e71612.
[http://dx.doi.org/10.1371/journal.pone.0071612] [PMID:  23951204] 
[336] 
Jang, M.; Kim, K.H.; Kim, G.H. Antioxidant capacity of thistle (Cirsium japonicum) in various drying methods and their protection effect on neuronal pc12 cells and Caenorhabditis elegans. Antioxidants (Basel, Switzerland),  2020, 9(3), 200.
[337] 
Lim, H.; Son, K.H.; Chang, H.W.; Bae, K.; Kang, S.S.; Kim, H.P. Anti-inflammatory activity of pectolinarigenin and pectolinarin isolated from Cirsium chanroenicum. Biol. Pharm. Bull.,  2008, 31(11), 2063-2067.
[http://dx.doi.org/10.1248/bpb.31.2063] [PMID:  18981574] 
[338] 
Wang, L.; Wang, N.; Zhao, Q.; Zhang, B.; Ding, Y. Pectolinarin inhibits proliferation, induces apoptosis, and suppresses inflammation in rheumatoid arthritis fibroblast-like synoviocytes by inactivating the phosphatidylinositol 3 kinase/protein kinase B pathway. J. Cell. Biochem.,  2019, 120(9), 15202-15210.
[http://dx.doi.org/10.1002/jcb.28784] [PMID:  31020684] 
[339] 
de Oliveira, M.R. Phloretin-induced cytoprotective effects on mammalian cells: a mechanistic view and future directions. Biofactors,  2016, 42(1), 13-40.
[PMID:  26826024] 
[340] 
Mendes, R.A.E.; Silva, B.L.S.; Takeara, R.; Freitas, R.G.; Brown, A.; de Souza, G.L.C. Probing the antioxidant potential of phloretin and phlorizin through a computational investigation. J. Mol. Model.,  2018, 24(4), 101.
[http://dx.doi.org/10.1007/s00894-018-3632-9] [PMID:  29569097] 
[341] 
Kim, J.; Durai, P.; Jeon, D.; Jung, I.D.; Lee, S.J.; Park, Y.M.; Kim, Y. Phloretin as a potent natural TLR2/1 inhibitor suppresses tlr2-induced inflammation. Nutrients,  2018, 10(7), E868.
[http://dx.doi.org/10.3390/nu10070868] [PMID:  29976865] 
[342] 
Choi, B.Y. Biochemical basis of anti-cancer-effects of phloretin-a natural dihydrochalcone. Molecules,  2019, 24(2), E278.
[http://dx.doi.org/10.3390/molecules24020278] [PMID:  30642127] 
[343] 
Wu, M.; Li, P.; An, Y.; Ren, J.; Yan, D.; Cui, J.; Li, D.; Li, M.; Wang, M.; Zhong, G. Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. Pharmacol. Res.,  2019, 150, 104489.
[http://dx.doi.org/10.1016/j.phrs.2019.104489] [PMID:  31689519] 
[344] 
Zhang, G.; Yang, G.; Liu, J. Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson’s disease in mice. Life Sci.,  2019, 232, 116600.
[http://dx.doi.org/10.1016/j.lfs.2019.116600] [PMID:  31251998] 
[345] 
Huang, W.C.; Dai, Y.W.; Peng, H.L.; Kang, C.W.; Kuo, C.Y.; Liou, C.J. Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α;-induced HaCaT human keratinocytes. Int. Immunopharmacol.,  2015, 27(1), 32-37.
[http://dx.doi.org/10.1016/j.intimp.2015.04.024] [PMID:  25929446] 
[346] 
Huang, W.C.; Lai, C.L.; Liang, Y.T.; Hung, H.C.; Liu, H.C.; Liou, C.J. Phloretin attenuates LPS-induced acute lung injury in mice via modulation of the NF-κB and MAPK pathways. Int. Immunopharmacol.,  2016, 40, 98-105.
[http://dx.doi.org/10.1016/j.intimp.2016.08.035] [PMID:  27588909] 
[347] 
Wu, C.S.; Lin, S.C.; Li, S.; Chiang, Y.C.; Bracci, N.; Lehman, C.W.; Tang, K.T.; Lin, C.C. Phloretin alleviates dinitrochlorobenzene-induced dermatitis in BALB/c mice. Int. J. Immunopathol. Pharmacol.,  2020, 34, 2058738420929442.
[http://dx.doi.org/10.1177/2058738420929442] [PMID:  32571120] 
[348] 
Wang, S.P.; Lin, S.C.; Li, S.; Chao, Y.H.; Hwang, G.Y.; Lin, C.C. Potent antiarthritic properties of phloretin in murine collageninduced arthritis. eCAM,  2016, 2016, 9831263.
[349] 
Carullo, G.; Cappello, A.R.; Frattaruolo, L.; Badolato, M.; Armentano, B.; Aiello, F. Quercetin and derivatives: useful tools in inflammation and pain management. Future Med. Chem.,  2017, 9(1), 79-93.
[http://dx.doi.org/10.4155/fmc-2016-0186] [PMID:  27995808] 
[350] 
Haleagrahara, N.; Miranda-Hernandez, S.; Alim, M.A.; Hayes, L.; Bird, G.; Ketheesan, N. Therapeutic effect of quercetin in collagen-induced arthritis. Biomed. Pharmacother.,  2017, 90, 38-46.
[http://dx.doi.org/10.1016/j.biopha.2017.03.026] [PMID:  28342364] 
[351] 
Zhao, J.; Chen, B.; Peng, X.; Wang, C.; Wang, K.; Han, F.; Xu, J. Quercetin suppresses migration and invasion by targeting miR-146a/GATA6 axis in fibroblast-like synoviocytes of rheumatoid arthritis. Immunopharmacol. Immunotoxicol.,  2020, 42(3), 221-227.
[http://dx.doi.org/10.1080/08923973.2020.1742732] [PMID:  32216502] 
[352] 
Guazelli, C.F.S.; Staurengo-Ferrari, L.; Zarpelon, A.C.; Pinho-Ribeiro, F.A.; Ruiz-Miyazawa, K.W.; Vicentini, F.T.M.C.; Vignoli, J.A.; Camilios-Neto, D.; Georgetti, S.R.; Baracat, M.M.; Casagrande, R.; Verri, W.A., Jr Quercetin attenuates zymosan-induced arthritis in mice. Biomed. Pharmacother.,  2018, 102, 175-184.
[http://dx.doi.org/10.1016/j.biopha.2018.03.057] [PMID:  29554596] 
[353] 
Borghi, S.M.; Mizokami, S.S.; Pinho-Ribeiro, F.A.; Fattori, V.; Crespigio, J.; Clemente-Napimoga, J.T.; Napimoga, M.H.; Pitol, D.L.; Issa, J.P.M.; Fukada, S.Y.; Casagrande, R.; Verri, W.A., Jr The flavonoid quercetin inhibits titanium dioxide (TiO2)-induced chronic arthritis in mice. J. Nutr. Biochem.,  2018, 53, 81-95.
[http://dx.doi.org/10.1016/j.jnutbio.2017.10.010] [PMID:  29197723] 
[354] 
Yuan, K.; Zhu, Q.; Lu, Q.; Jiang, H.; Zhu, M.; Li, X.; Huang, G.; Xu, A. Quercetin alleviates rheumatoid arthritis by inhibiting neutrophil inflammatory activities. J. Nutr. Biochem.,  2020, 84, 108454.
[http://dx.doi.org/10.1016/j.jnutbio.2020.108454] [PMID:  32679549] 
[355] 
Peng, S.; Hu, C.; Liu, X.; Lei, L.; He, G.; Xiong, C.; Wu, W. Rhoifolin regulates oxidative stress and proinflammatory cytokine levels in Freund’s adjuvant-induced rheumatoid arthritis via inhibition of NF-κ. B. Braz. J. Med. Biol. Res.,  2020, 53(6), e9489.
[http://dx.doi.org/10.1590/1414-431x20209489] [PMID:  32401927] 
[356] 
Tewtrakul, S.; Tungcharoen, P.; Sudsai, T.; Karalai, C.; Ponglimanont, C.; Yodsaoue, O. Antiinflammatory and wound healing effects of Saesalpinia sappan L. Phytother. Res.,  2015, 29(6), 850-856.
[http://dx.doi.org/10.1002/ptr.5321] [PMID:  25760294] 
[357] 
Jung, E.G.; Han, K.I.; Kwon, H.J.; Patnaik, B.B.; Kim, W.J.; Hur, G.M.; Nam, K.W.; Han, M.D. Anti-inflammatory activity of sappanchalcone isolated from Caesalpinia sappan L. in a collagen-induced arthritis mouse model. Arch. Pharm. Res.,  2015, 38(6), 973-983.
[http://dx.doi.org/10.1007/s12272-015-0557-z] [PMID:  25586964] 
[358] 
Washiyama, M.; Sasaki, Y.; Hosokawa, T.; Nagumo, S. Anti-inflammatory constituents of Sappan Lignum. Biol. Pharm. Bull.,  2009, 32(5), 941-944.
[http://dx.doi.org/10.1248/bpb.32.941] [PMID:  19420769] 
[359] 
Jeong, G.S.; Lee, D.S.; Li, B.; Lee, H.J.; Kim, E.C.; Kim, Y.C. Effects of sappanchalcone on the cytoprotection and anti-inflammation via heme oxygenase-1 in human pulp and periodontal ligament cells. Eur. J. Pharmacol.,  2010, 644(1-3), 230-237.
[http://dx.doi.org/10.1016/j.ejphar.2010.06.059] [PMID:  20621084] 
[360] 
Chen, H.; Hayek, S.; Rivera Guzman, J.; Gillitt, N.D.; Ibrahim, S.A.; Jobin, C.; Sang, S. The microbiota is essential for the generation of black tea theaflavins-derived metabolites. PLoS One,  2012, 7(12), e51001.
[http://dx.doi.org/10.1371/journal.pone.0051001] [PMID:  23227227] 
[361] 
Tu, Y.Y.; Tang, A.B.; Watanabe, N. The theaflavin monomers inhibit the cancer cells growth in vitro. Acta Biochim. Biophys. Sin. (Shanghai),  2004, 36(7), 508-512.
[http://dx.doi.org/10.1093/abbs/36.7.508] [PMID:  15248026] 
[362] 
Ding, Y.; Chen, B.; Gao, Z.; Suo, H.; Xiao, H. Pre-treated theaflavin-3,3′-digallate has a higher inhibitory effect on the HCT116 cell line. Food Nutr. Res.,  2017, 61(1), 1400340.
[http://dx.doi.org/10.1080/16546628.2017.1400340] [PMID:  29200992] 
[363] 
Teng, Z.; Guo, Y.; Liu, X.; Zhang, J.; Niu, X.; Yu, Q.; Deng, X.; Wang, J. Theaflavin-3,3´-digallate increases the antibacterial activity of β-lactam antibiotics by inhibiting metallo-β-lactamase activity. J. Cell. Mol. Med.,  2019, 23(10), 6955-6964.
[http://dx.doi.org/10.1111/jcmm.14580] [PMID:  31392792] 
[364] 
Liu, W.; Li, J. Theaflavin-3, 3′-digallate attenuates rheumatoid inflammation in mice through the nuclear factor-κB and MAPK pathways. Arch. Immunol. Ther. Exp. (Warsz.),  2019, 67(3), 153-160.
[http://dx.doi.org/10.1007/s00005-019-00536-7] [PMID:  30874838] 
[365] 
Hosokawa, Y.; Hosokawa, I.; Ozaki, K.; Nakanishi, T.; Nakae, H.; Matsuo, T. Tea polyphenols inhibit IL-6 production in tumor necrosis factor superfamily 14-stimulated human gingival fibroblasts. Mol. Nutr. Food Res.,  2010, 54(Suppl. 2), S151-S158.
[http://dx.doi.org/10.1002/mnfr.200900549] [PMID: 20461739] 
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DOI https://dx.doi.org/10.2174/1568026622666220107105233	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
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