Abstract
Emotional disorders such as anxiety and depression are widespread psychological diseases that affect up to 20% of the world’s population. There are many approaches to the discovery of novel agents for the treatment of depressive- and anxiety-like symptoms. However, the efficacy of existing drugs for emotional disorders is only exerted after a few weeks of treatment and have serious side effects. Due to this, new strategies to find suitable and safe options are being sought by many researchers. Among them, a lot of interest has been attracted by plant-derived natural compounds due to their wide range of beneficial effects for new agent development. Flavonoids are natural polyphenol-like compounds found commonly in plants, fruits, vegetables, and medicinal herbs. A diverse range of flavonoids have been studied to investigate their potential therapeutic activities for the treatment of brain-associated disorders, including anxiety and depression. The main aim of this review is to understand the associations between the various flavonoids and the emotional disorders and discuss the therapeutic effects of these natural compounds that were demonstrated during the conduction of recent studies. The current work shows advances in the latest research of some flavonoids as a potential candidate for the treatment of emotional disorders. We summarize their behavioral, molecular, physiological, and neurochemical effects in various in vitro and in vivo models. Therefore, in the present work, the latest studies were collected on the most important flavonoid compounds and their underlying mechanisms of action in emotion-related disorders were discussed.
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References
Ahad A, Ganai AA, Mujeeb M, Siddiqui WA (2014) Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats. Toxicol Appl Pharmacol 279:1–7. https://doi.org/10.1016/j.taap.2014.05.007
Ahmad B, Khan S (2020) Molecular mechanisms of anticancer activities of puerarin. Cancer Manag Res 12:79–90. https://doi.org/10.2147/cmar.s233567
Ahmad A, Ali T, Park HY, Badshah H, Rehman SU, Kim MO (2017) Neuroprotective effect of fisetin against amyloid-beta-induced cognitive/synaptic dysfunction, neuroinflammation, and neurodegeneration in adult mice. Mol Neurobiol 54:2269–2285. https://doi.org/10.1007/s12035-016-9795-4
Ahmad A, Ali T, Rehman SU, Kim MO (2019) Phytomedicine-based potent antioxidant, fisetin protects CNS-insult LPS-induced oxidative stress-mediated neurodegeneration and memory impairment. J Clin Med. https://doi.org/10.3390/jcm8060850
Amidfar M, Woelfer M, Réus GZ, Quevedo J, Walter M, Kim YK (2019) The role of NMDA receptor in neurobiology and treatment of major depressive disorder: evidence from translational research. Prog Neuropsychopharmacol Biol Psychiatry 94:109668. https://doi.org/10.1016/j.pnpbp.2019.109668
Atteritano M et al (2014) Genistein effects on quality of life and depression symptoms in osteopenic postmenopausal women: a 2-year randomized, double-blind, controlled study. Osteoporos Int 25:1123–1129. https://doi.org/10.1007/s00198-013-2512-5
Barreca D et al (2017) Flavanones: citrus phytochemical with health-promoting properties. Biofactors 43:495–506. https://doi.org/10.1002/biof.1363
Belmaker RH, Agam G (2008) Major depressive disorder. N Engl J Med 358:55–68. https://doi.org/10.1056/NEJMra073096
Bortolotto VC et al (2018) Chrysin reverses the depressive-like behavior induced by hypothyroidism in female mice by regulating hippocampal serotonin and dopamine. Eur J Pharmacol 822:78–84. https://doi.org/10.1016/j.ejphar.2018.01.017
Bueno-Antequera J, Munguía-Izquierdo D (2020) Exercise and depressive disorder. Adv Exp Med Biol 1228:271–287. https://doi.org/10.1007/978-981-15-1792-1_18
Cao LH, Qiao JY (2019) PI3K-AKT signaling activation and icariin: the potential effects on the perimenopausal depression-like rat model. Molecules. https://doi.org/10.3390/molecules24203700
Casilla-Lennon MM, Meltzer-Brody S, Steiner AZ (2016) The effect of antidepressants on fertility. Am J Obstet Gynecol 215:314.e311–314.e315. https://doi.org/10.1016/j.ajog.2016.01.170
Catarino MD, Alves-Silva JM, Pereira OR, Cardoso SM (2015) Antioxidant capacities of flavones and benefits in oxidative-stress related diseases. Curr Top Med Chem 15:105–119
Chang WS et al (2016) Baicalin scavenged reactive oxygen species and protected human keratinocytes against UVB-induced cytotoxicity. In Vivo 30:605–610
Chen S, Jiang H (2016) Therapeutic effects of quercetin on inflammation, obesity, and Type 2 diabetes. Mediat Inflamm 2016:9340637. https://doi.org/10.1155/2016/9340637
Chen X, Cheng C, Zuo X, Huang W (2020) Astragalin alleviates cerebral ischemia-reperfusion injury by improving anti-oxidant and anti-inflammatory activities and inhibiting apoptosis pathway in rats. BMC Complement Med Ther 20:120. https://doi.org/10.1186/s12906-020-02902-x
Cheng Y, Leng W, Zhang J (2016) Protective effect of puerarin against oxidative stress injury of neural cells and related mechanisms. Med Sci Monit 22:1244–1249. https://doi.org/10.12659/msm.896058
Choubey P et al (2019) Ameliorative effect of fisetin against lipopolysaccharide and restraint stress-induced behavioral deficits via modulation of NF-κB and IDO-1. Psychopharmacology 236:741–752. https://doi.org/10.1007/s00213-018-5105-3
Chung PL, Huang CW (2020) Effect of depression and antidepressants on sexual dysfunction in men with diabetes: a national population-based cohort study. Neuropsychiatric 16:1105–1112. https://doi.org/10.2147/ndt.s242798
Dang YH et al (2014) Targeting of NMDA receptors in the treatment of major depression. Curr Pharm Des 20:5151–5159. https://doi.org/10.2174/1381612819666140110120435
Das S, Parveen S, Kundra CP, Pereira BM (2004) Reproduction in male rats is vulnerable to treatment with the flavonoid-rich seed extracts of Vitex negundo. Phytother Res 18:8–13. https://doi.org/10.1002/ptr.1352
de la Garza AL, Garza-Cuellar MA (2019) Maternal flavonoids intake reverts depression-like behaviour in rat female offspring. Nutrients. https://doi.org/10.3390/nu11030572
Devi KP et al (2015) Kaempferol and inflammation: from chemistry to medicine. Pharmacol Res 99:1–10. https://doi.org/10.1016/j.phrs.2015.05.002
Ding H, Wang H, Zhao Y, Sun D, Zhai X (2015) Protective effects of baicalin on Aβ1−42-induced learning and memory deficit, oxidative stress, and apoptosis in rat. Cell Mol Neurobiol 35:623–632. https://doi.org/10.1007/s10571-015-0156-z
El-Alfy AT, Abourashed EA, Matsumoto RR (2012) Nature against depression. Curr Med Chem 19:2229–2241. https://doi.org/10.2174/092986712800229096
Elder JK, Southern EM (1983) Measurement of DNA length by gel electrophoresis II: comparison of methods for relating mobility to fragment length. Anal Biochem 128:227–231. https://doi.org/10.1016/0003-2697(83)90369-x
Evans DL et al (2005) Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 58:175–189. https://doi.org/10.1016/j.biopsych.2005.05.001
Fang K et al (2020) Corrigendum: quercetin alleviates LPS-induced depression-like behavior in rats via regulating BDNF-related imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC. Front Pharmacol 11:518. https://doi.org/10.3389/fphar.2020.00518
Farkhondeh T, Jalali S, Ashrafizadeh M, Samarghandian S, Samini F (2020) Effects of chrysin on serum corticosterone levels and brain oxidative damages induced by immobilization in rat. Cardiovasc Hematol Disord Drug Targets 20:47–53. https://doi.org/10.2174/1871529x19666190618144440
Ferguson JM (2001) SSRI antidepressant medications: adverse effects and tolerability. Prim Care Companion J Clin Psychiatry 3:22–27. https://doi.org/10.4088/pcc.v03n0105
Filho CB et al (2013) Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test. Eur J Pharmacol 698:286–291. https://doi.org/10.1016/j.ejphar.2012.11.003
Filho CB et al (2015) Chronic unpredictable mild stress decreases BDNF and NGF levels and Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant effect of chrysin. Neuroscience 289:367–380. https://doi.org/10.1016/j.neuroscience.2014.12.048
Filho CB et al (2016) Chrysin promotes attenuation of depressive-like behavior and hippocampal dysfunction resulting from olfactory bulbectomy in mice. Chem Biol Interact 260:154–162. https://doi.org/10.1016/j.cbi.2016.11.005
Fornaro M, Rocchi G, Escelsior A, Contini P, Martino M (2013) Might different cytokine trends in depressed patients receiving duloxetine indicate differential biological backgrounds. J Affect Disord 145:300–307. https://doi.org/10.1016/j.jad.2012.08.007
Fu H et al (2019) The antidepressant effects of hesperidin on chronic unpredictable mild stress-induced mice. Eur J Pharmacol 853:236–246. https://doi.org/10.1016/j.ejphar.2019.03.035
Funaguchi N et al (2007) Narirutin inhibits airway inflammation in an allergic mouse model. Clin Exp Pharmacol Physiol 34:766–770. https://doi.org/10.1111/j.1440-1681.2007.04636.x
Gandolfo GM, Girelli G, Conti L, Perrone MP, Arista MC, Damico C (1992) Hemolytic anemia and thrombocytopenia induced by cyanidanol. Acta Haematol 88:96–99. https://doi.org/10.1159/000204660
Gao W, Wang W, Peng Y, Deng Z (2019) Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade. Metab Brain Dis 34:485–494. https://doi.org/10.1007/s11011-019-0389-5
Gautam J et al (2015) Neoflavonoid dalbergiphenol from heartwood of Dalbergia sissoo acts as bone savior in an estrogen withdrawal model for osteoporosis. Menopause 22:1246–1255. https://doi.org/10.1097/gme.0000000000000453
Gironés-Vilaplana A, Moreno DA, García-Viguera C (2014) Phytochemistry and biological activity of Spanish Citrus fruits. Food Funct 5:764–772. https://doi.org/10.1039/c3fo60700cB
Gong MJ, Han B, Wang SM, Liang SW, Zou ZJ (2016) Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats. J Pharm Biomed Anal 123:63–73. https://doi.org/10.1016/j.jpba.2016.02.001
Guan LP, Liu BY (2016) Antidepressant-like effects and mechanisms of flavonoids and related analogues. Eur J Med Chem 121:47–57. https://doi.org/10.1016/j.ejmech.2016.05.026
Guo LT et al (2019) Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway. J Neuroinflamm 16:95. https://doi.org/10.1186/s12974-019-1474-8
Heim KE, Tagliaferro AR, Bobilya DJ (2002) Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 13:572–584. https://doi.org/10.1016/s0955-2863(02)00208-5
Higa S et al (2003) Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils. J Allergy Clin Immunol 111:1299–1306. https://doi.org/10.1067/mai.2003.1456
Hollman PC (2004) Absorption, bioavailability, and metabolism of flavonoids. Pharm Biol 42:74–83
Hong SW, Yoo DH, Woo JY, Jeong JJ, Yang JH, Kim DH (2014) Soyasaponins Ab and Bb prevent scopolamine-induced memory impairment in mice without the inhibition of acetylcholinesterase. J Agric Food Chem 62:2062–2068. https://doi.org/10.1021/jf4046528
Hritcu L et al (2017) Antidepressant flavonoids and their relationship with oxidative stress. Oxidative Med Cell Longev 207:5762172. https://doi.org/10.1155/2017/5762172
Hu P et al (2017) Genistein, a dietary soy isoflavone, exerts antidepressant-like effects in mice: involvement of serotonergic system. Neurochem Int 108:426–435. https://doi.org/10.1016/j.neuint.2017.06.002
Huang G, Mei X, Hu J (2017) The antioxidant activities of natural polysaccharides. Curr Drug Targets 18:1296–1300. https://doi.org/10.2174/1389450118666170123145357
Huang Y, Sun M, Yang X, Ma A, Ma Y, Zhao A (2019) Baicalin relieves inflammation stimulated by lipopolysaccharide via upregulating TUG1 in liver cells. J Physiol Biochem 75:463–473. https://doi.org/10.1007/s13105-019-00698-0
Hussein RM, Mohamed WR, Omar HA (2018) A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3β-Nrf2 signaling pathway. Pestic Biochem Physiol 152:29–37. https://doi.org/10.1016/j.pestbp.2018.08.008
Iacopini P, Baldi M, Storchi P, Sebastiani L (2008) Catechin, epicatechin, quercetin, rutin and resveratrol in red grape: content, in vitro antioxidant activity and interactions. J Food Compos Anal 21:589–598
Jeon YD, Lee JH, Lee YM, Kim DK (2020) Puerarin inhibits inflammation and oxidative stress in dextran sulfate sodium-induced colitis mice model. Biomed Pharmacother 124:109847. https://doi.org/10.1016/j.biopha.2020.109847
Jung YH et al (2014) Strain differences in the chronic mild stress animal model of depression and anxiety in mice. Biomol Ther (Seoul) 22:453–459. https://doi.org/10.4062/biomolther.2014.058
Jung HA, Woo JJ, Jung MJ, Hwang GS, Choi JS (2009) Kaempferol glycosides with antioxidant activity from Brassica juncea. Arch Pharm Res 32:1379–1384. https://doi.org/10.1007/s12272-009-2006-3
Kanter M, Aktoz T, Aktas C, Ozen F, Yarali O, Kanter B (2016) Role of quercetin in cadmium-induced oxidative stress, testicular damage, and apoptosis in rats. Anal Quant Cytopathol Histpathol 38:45–51
Kessler RC, McGonagle KA, Nelson CB, Hughes M, Swartz M, Blazer DG (1994) Sex and depression in the National Comorbidity Survey. II: cohort effects. J Affect Disord 30:15–26. https://doi.org/10.1016/0165-0327(94)90147-3
Khalid S, Barfoot KL, May G, Lamport DJ, Reynolds SA, Williams CM (2017) Effects of acute blueberry flavonoids on mood in children and young adults. Nutrients. https://doi.org/10.3390/nu9020158
Khan H, Perviz S, Sureda A, Nabavi SM, Tejada S (2018) Current standing of plant derived flavonoids as an antidepressant. Food Chem Toxicol 119:176–188. https://doi.org/10.1016/j.fct.2018.04.052
Kim SK, Ko YH, Lee SY, Jang CG (2020) Memory-enhancing effects of 7,3’,4’-trihydroxyisoflavone by regulation of cholinergic function and BDNF signaling pathway in mice. Food Chem Toxicol 137:111160. https://doi.org/10.1016/j.fct.2020.111160
Kite GC, Green PW, Veitch NC, Groves MC, Gasson PE, Simmonds MS (2010) Dalnigrin, a neoflavonoid marker for the identification of Brazilian rosewood (Dalbergia nigra) in CITES enforcement. Phytochemistry 71:1122–1131. https://doi.org/10.1016/j.phytochem.2010.04.011
Ko YH et al (2018) The memory-enhancing effects of 7,8,4’-trihydroxyisoflavone, a major metabolite of daidzein, are associated with activation of the cholinergic system and BDNF signaling pathway in mice. Brain Res Bull 142:197–206. https://doi.org/10.1016/j.brainresbull.2018.07.012
Ko YH et al (2019a) Protective effects of 6,7,4’-trihydroxyisoflavone, a major metabolite of daidzein, on 6-hydroxydopamine-induced neuronal cell death in SH-SY5Y human neuroblastoma cells. Arch Pharm Res 42:1081–1091. https://doi.org/10.1007/s12272-019-01191-4
Ko YH, Kwon SH, Lee SY, Jang CG (2019b) Isoorientin improves scopolamine-induced cognitive impairments by restoring the cholinergic system, antioxidant defense, and p-CREB/BDNF signaling in the hippocampus and frontal cortex. Arch Pharm Res 42:722–731. https://doi.org/10.1007/s12272-019-01172-7
Ko YH et al (2019c) Lespedeza bicolor extract improves amyloid Beta25-35-induced memory impairments by upregulating BDNF and activating Akt, ERK, and CREB signaling in mice. Planta Med 85:1363–1373. https://doi.org/10.1055/a-1018-5402
Kohler O, Krogh J, Mors O, Benros ME (2016) Inflammation in depression and the potential for anti-inflammatory treatment. Curr Neuropharmacol 14:732–742. https://doi.org/10.2174/1570159x14666151208113700
Kosari-Nasab M, Shokouhi G, Ghorbanihaghjo A, Mesgari-Abbasi M, Salari AA (2019) Quercetin mitigates anxiety-like behavior and normalizes hypothalamus-pituitary-adrenal axis function in a mouse model of mild traumatic brain injury. Behav Pharmacol 30:282–289. https://doi.org/10.1097/fbp.0000000000000480
Lapidot T, Walker MD, Kanner J (2002) Antioxidant and prooxidant effects of phenolics on pancreatic beta-cells in vitro. J Agric Food Chem 50:7220–7225. https://doi.org/10.1021/jf020615a
Latendresse G, Elmore C, Deneris A (2017) Selective serotonin reuptake inhibitors as first-line antidepressant therapy for perinatal depression. J Midwifery Womens Health 62:317–328. https://doi.org/10.1111/jmwh.12607
Lee MH, Lin RD, Shen LY, Yang LL, Yen KY, Hou WC (2001) Monoamine oxidase B and free radical scavenging activities of natural flavonoids in Melastoma candidum D. Don. J Agric Food Chem 49:5551–5555. https://doi.org/10.1021/jf010622j
Lee B et al (2013) Chronic administration of catechin decreases depression and anxiety-like behaviors in a rat model using chronic corticosterone injections. Biomol Ther (Seoul) 21:313–322. https://doi.org/10.4062/biomolther.2013.004
Lee B, Sur B, Yeom M, Shim I, Lee H, Hahm DH (2014a) Erratum to “l-tetrahydropalmatine ameliorates development of anxiety and depression-related symptoms induced by single prolonged stress in rats” [biomol. Ther. 22 (2014) 213–222]. Biomol Ther (Seoul) 22:474. https://doi.org/10.4062/biomolther.2014.474
Lee DS et al (2014b) The neoflavonoid latifolin isolated from MeOH extract of Dalbergia odorifera attenuates inflammatory responses by inhibiting NF-κB activation via Nrf2-mediated heme oxygenase-1 expression. Phytother Res 28:1216–1223. https://doi.org/10.1002/ptr.5119
Lee B, Choi GM, Sur B (2020a) Antidepressant-like effects of hesperidin in animal model of post-traumatic stress disorder. Chin J Integr Med . https://doi.org/10.1007/s11655-020-2724-4
Lee B, Choi GM, Sur B (2020b) Silibinin prevents depression-like behaviors in a single prolonged stress rat model: the possible role of serotonin. BMC Complement Med Ther 20:70. https://doi.org/10.1186/s12906-020-2868-y
León-González AJ, Acero N, Muñoz-Mingarro D, Navarro I, Martín-Cordero C (2015) Chalcones as promising lead compounds on cancer therapy. Curr Med Chem 22:3407–3425. https://doi.org/10.2174/0929867322666150729114829
Li Y et al (2016) Quercetin, inflammation and immunity. Nutrients 8:167. https://doi.org/10.3390/nu8030167
Li Y et al (2018a) Narirutin produces antidepressant-like effects in a chronic unpredictable mild stress mouse model. Neuroreport 29:1264–1268. https://doi.org/10.1097/wnr.0000000000001102
Li YJ et al (2018b) Silibinin exerts antidepressant effects by improving neurogenesis through BDNF/TrkB pathway. Behav Brain Res 348:184–191. https://doi.org/10.1016/j.bbr.2018.04.025
Li LF, Yang J, Ma SP, Qu R (2013a) Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression. Eur J Pharmacol 711:42–49. https://doi.org/10.1016/j.ejphar.2013.04.008
Li YC, Shen JD, Li J, Wang R, Jiao S, Yi LT (2013b) Chronic treatment with baicalin prevents the chronic mild stress-induced depressive-like behavior: involving the inhibition of cyclooxygenase-2 in rat brain. Prog Neuropsychopharmacol Biol Psychiatry 40:138–143. https://doi.org/10.1016/j.pnpbp.2012.09.007
Lieberman HD, Fogelman JP, Ramsay DL, Cohen DE (2002) Allergic contact dermatitis to propolis in a violin maker. J Am Acad Dermatol 46:S30–S31. https://doi.org/10.1067/mjd.2002.106349
Lim H, Heo MY, Kim HP (2019) Flavonoids: broad spectrum agents on chronic inflammation. Biomol Ther (Seoul) 27:241–253. https://doi.org/10.4062/biomolther.2019.034
Lim JO et al (2020) Silibinin attenuates silica dioxide nanoparticles-induced inflammation by suppressing TXNIP/MAPKs/AP-1 signaling. Cells. https://doi.org/10.3390/cells9030678
Linde K et al (2015) Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis. Ann Fam Med 13:69–79. https://doi.org/10.1370/afm.1687
Liu X, Liu C (2017) Baicalin ameliorates chronic unpredictable mild stress-induced depressive behavior: involving the inhibition of NLRP3 inflammasome activation in rat prefrontal cortex. Int Immunopharmacol 48:30–34. https://doi.org/10.1016/j.intimp.2017.04.019
Liu CS, Adibfar A, Herrmann N, Gallagher D, Lanctôt KL (2017a) Evidence for inflammation-associated depression. Curr Top Behav Neurosci 31:3–30. https://doi.org/10.1007/7854_2016_2
Liu RH, Lin S, Zhang PZ, Chen LY, Huang HL, Mei DY (2017b) [Neoflavonoids and their pharmacological activities in Dalbergia genus]. Zhongguo Zhong Yao Za Zhi 42:4707–4715. https://doi.org/10.19540/j.cnki.cjcmm.20170928.013
Liu CH et al (2019a) Role of inflammation in depression relapse. J Neuroinflammation 16:90. https://doi.org/10.1186/s12974-019-1475-7
Liu L et al (2019b) Icariin and icaritin ameliorated hippocampus neuroinflammation via inhibiting HMGB1-related pro-inflammatory signals in lipopolysaccharide-induced inflammation model in C57BL/6 J mice. Int Immunopharmacol 68:95–105. https://doi.org/10.1016/j.intimp.2018.12.055
Liu P et al (2020) Silibinin ameliorates STZ-induced impairment of memory and learning by up- regulating insulin signaling pathway and attenuating apoptosis. Physiol Behav 213:112689. https://doi.org/10.1016/j.physbeh.2019.112689
López-Lázaro M (2009) Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 9:31–59. https://doi.org/10.2174/138955709787001712
Ma K, Zhang H, Baloch Z (2016) Pathogenetic and therapeutic applications of tumor necrosis factor-α (TNF-α) in major depressive disorder: a systematic review. Int J Mol Sci. https://doi.org/10.3390/ijms17050733
Macedo D et al (2017) Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness. J Affect Disord 208:22–32. https://doi.org/10.1016/j.jad.2016.09.012
Maj J, Rogóz Z, Skuza G, Sowińska H (1992) Effects of MK-801 and antidepressant drugs in the forced swimming test in rats. Eur Neuropsychopharmacol 2:37–41. https://doi.org/10.1016/0924-977x(92)90034-6
Marín L, Gutiérrez-Del-Río I, Entrialgo-Cadierno R, Villar CJ, Lombó F (2018) De novo biosynthesis of myricetin, kaempferol and quercetin in Streptomyces albus and Streptomyces coelicolor. Plos One 13:e0207278. https://doi.org/10.1371/journal.pone.0207278
Mathew B et al (2019) Perspective design of chalcones for the management of CNS disorders: a mini-review. CNS Neurol Disord Drug Targets 18:432–445. https://doi.org/10.2174/1871527318666190610111246
Mei ZR, Tan XP, Liu SZ, Huang HH (2016) [Puerarin alleviates cognitive impairment and tau hyperphosphorylation in APP/PS1 transgenic mice]. Zhongguo Zhong Yao Za Zhi 41:3285–3289. https://doi.org/10.4268/cjcmm20161727
Meng F, Wang Y, Liu R, Gao M, Du G (2014) Pinocembrin alleviates memory impairment in transient global cerebral ischemic rats. Exp Ther Med 8:1285–1290. https://doi.org/10.3892/etm.2014.1923
Mlcek J, Jurikova T, Skrovankova S, Sochor J (2016) Quercetin and its anti-allergic immune response. Molecules. https://doi.org/10.3390/molecules21050623
Murrough JW, Abdallah CG, Mathew SJ (2017) Targeting glutamate signalling in depression: progress and prospects. Nat Rev Drug Discov 16:472–486. https://doi.org/10.1038/nrd.2017.16
Nabavi SF et al (2015) Luteolin as an anti-inflammatory and neuroprotective agent: a brief review. Brain Res Bull 119:1–11. https://doi.org/10.1016/j.brainresbull.2015.09.002
Nabavi SM, Daglia M, Braidy N, Nabavi SF (2017) Natural products, micronutrients, and nutraceuticals for the treatment of depression: a short review. Nutr Neurosci 20:180–194. https://doi.org/10.1080/1028415x.2015.1103461
Nabeshima T, Kim HC (2013) Involvement of genetic and environmental factors in the onset of depression. Exp Neurobiol 22:235–243. https://doi.org/10.5607/en.2013.22.4.235
Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59:1151–1159. https://doi.org/10.1016/j.biopsych.2005.09.018
Noto C, Rizzo LB, Mansur RB, McIntyre RS, Maes M, Brietzke E (2014) Targeting the inflammatory pathway as a therapeutic tool for major depression. Neuroimmunomodulation 21:131–139. https://doi.org/10.1159/000356549
Pan Y, Wang FM, Qiang LQ, Zhang DM, Kong LD (2010) Icariin attenuates chronic mild stress-induced dysregulation of the LHPA stress circuit in rats. Psychoneuroendocrinology 35:272–283. https://doi.org/10.1016/j.psyneuen.2009.06.020
Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M (2015) Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res 29:323–331. https://doi.org/10.1002/ptr.5256
Park HY, Ha SK, Eom H, Choi I (2013) Narirutin fraction from citrus peels attenuates alcoholic liver disease in mice. Food Chem Toxicol 55:637–644. https://doi.org/10.1016/j.fct.2013.01.060
Patil PO, Bari SB, Firke SD, Deshmukh PK, Donda ST, Patil DA (2013) A comprehensive review on synthesis and designing aspects of coumarin derivatives as monoamine oxidase inhibitors for depression and Alzheimer’s disease. Bioorg Med Chem 21:2434–2450. https://doi.org/10.1016/j.bmc.2013.02.017
Patil P, Thakur A, Sharma A (2020) Natural products and their derivatives as multifunctional ligands against Alzheimer’s disease. Drug Dev Res 81:165–183. https://doi.org/10.1002/ddr.21587
Pei B, Sun J (2018) Pinocembrin alleviates cognition deficits by inhibiting inflammation in diabetic mice. J Neuroimmunol 314:42–49. https://doi.org/10.1016/j.jneuroim.2017.11.006
Peluso I, Palmery M (2015) Flavonoids at the pharma-nutrition interface: is a therapeutic index in demand? Biomed Pharmacother 71:102–107. https://doi.org/10.1016/j.biopha.2015.02.028
Pérez-Cano FJ, Castell M (2016) Flavonoids, inflammation and immune system. Nutrients. https://doi.org/10.3390/nu8100659
Pine DS (1999) Pathophysiology of childhood anxiety disorders. Biol Psychiatry 46:1555–1566 i: 10.1016/s0006-3223(99)00115-8 ) : do
Qiu ZK, Zhong DS, He JL, Liu X, Chen JS, Nie H (2018) The anxiolytic-like effects of puerarin are associated with the changes of monoaminergic neurotransmitters and biosynthesis of allopregnanolone in the brain. Metab Brain Dis 33:167–175. https://doi.org/10.1007/s11011-017-0127-9
Rasul A, Millimouno FM, Ali Eltayb W, Ali M, Li J, Li X (2013) Pinocembrin: a novel natural compound with versatile pharmacological and biological activities. Biomed Res Int 2013:379850. https://doi.org/10.1155/2013/379850
Şahin TD, Gocmez SS, Duruksu G, Yazir Y, Utkan T (2020) Resveratrol and quercetin attenuate depressive-like behavior and restore impaired contractility of vas deferens in chronic stress-exposed rats: involvement of oxidative stress and inflammation. Naunyn Schmiedebergs Arch Pharmacol 393:761–775. https://doi.org/10.1007/s00210-019-01781-5
Salin O et al (2011) Corn mint (Mentha arvensis) extract diminishes acute Chlamydia pneumoniae infection in vitro and in vivo. J Agric Food Chem 59:12836–12842. https://doi.org/10.1021/jf2032473
Santangelo RM et al (2012) Novel NMDA receptor modulators: an update. Expert Opin Ther Pat 22:1337–1352. https://doi.org/10.1517/13543776.2012.728587
Shafabakhsh R, Asemi Z (2019) Quercetin: a natural compound for ovarian cancer treatment. J Ovarian Res 12:55. https://doi.org/10.1186/s13048-019-0530-4
Sharma R et al (2015) A review on mechanisms of anti tumor activity of chalcones. Anticancer Agents Med Chem 16:200–211. https://doi.org/10.2174/1871520615666150518093144
Song C, Wang H (2011) Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 35:760–768. https://doi.org/10.1016/j.pnpbp.2010.06.020
Song HY et al (2019) A hydroxyethyl derivative of chrysin exhibits anti-inflammatory activity in dendritic cells and protective effects against dextran sodium salt-induced colitis in mice. Int Immunopharmacol 77:105958. https://doi.org/10.1016/j.intimp.2019.105958
Souza LC et al (2013) Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice. Prog Neuropsychopharmacol Biol Psychiatry 40:103–109. https://doi.org/10.1016/j.pnpbp.2012.09.003
Stanika RI, Pivovarova NB, Brantner CA, Watts CA, Winters CA, Andrews SB (2009) Coupling diverse routes of calcium entry to mitochondrial dysfunction and glutamate excitotoxicity. Proc Natl Acad Sci USA 106:9854–9859. https://doi.org/10.1073/pnas.0903546106
Sun ZB et al (2015) Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study. Osteoporos Int 26:187–197. https://doi.org/10.1007/s00198-014-2809-z
Tak CR et al (2017) The impact of exposure to antidepressant medications during pregnancy on neonatal outcomes: a review of retrospective database cohort studies. Eur J Clin Pharmacol 73:1055–1069. https://doi.org/10.1007/s00228-017-2269-4
Taliaz D, Stall N, Dar DE, Zangen A (2010) Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol Psychiatry 15:80–92. https://doi.org/10.1038/mp.2009.67
Tian J, Wu X, Zhang M, Zhou Z, Liu Y (2018) Comparative study on the effects of apple peel polyphenols and apple flesh polyphenols on cardiovascular risk factors in mice. Clin Exp Hypertens 40:65–72. https://doi.org/10.1080/10641963.2017.1313851
Tong Y et al (2020) Astragalin exerted antidepressant-like action through SIRT1 signaling modulated NLRP3 inflammasome deactivation. ACS Chem Neurosci 11:1495–1503. https://doi.org/10.1021/acschemneuro.0c00156
Tousen Y, Ishiwata H, Ishimi Y, Ikegami S (2015) Equol, a metabolite of daidzein, is more efficient than daidzein for bone formation in growing female rats. Phytother Res 29:1349–1354. https://doi.org/10.1002/ptr.5387
Vaváková M, Ďuračková Z (2015) Markers of oxidative stress and neuroprogression in depression disorder. Oxidative Med Cell Longev 2015:898393. https://doi.org/10.1155/2015/898393
Wang Y et al (2017) Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice. J Neurochem 143:561–568. https://doi.org/10.1111/jnc.14226
Wang W, Zheng L, Xu L, Tu J, Gu X (2020) Pinocembrin mitigates depressive-like behaviors induced by chronic unpredictable mild stress through ameliorating neuroinflammation and apoptosis. Mol Med 26:53. https://doi.org/10.1186/s10020-020-00179-x
Wu J et al (2011) Icariin attenuates social defeat-induced down-regulation of glucocorticoid receptor in mice. Pharmacol Biochem Behav 98:273–278. https://doi.org/10.1016/j.pbb.2011.01.008
Xia R, Xu G, Huang Y, Sheng X, Xu X, Lu H (2018) Hesperidin suppresses the migration and invasion of non-small cell lung cancer cells by inhibiting the SDF-1/CXCR-4 pathway. Life Sci 201:111–120. https://doi.org/10.1016/j.lfs.2018.03.046
Xu M et al (2019) Schisantherin B improves the pathological manifestations of mice caused by behavior desperation in different ages-depression with cognitive impairment. Biomol Ther (Seoul) 27:160–167. https://doi.org/10.4062/biomolther.2018.074
Xu AL, Jiang MC, Chen XH, Chen WF (2016) Icariin protects against MPP(+)-induced neurotoxicity in MES23.5 cells. Sheng Li Xue Bao 68:585–591
Yan WJ et al (2015) Protective effects of silibinin and its possible mechanism of action in mice exposed to chronic unpredictable mild stress. Biomol Ther (Seoul) 23:245–250. https://doi.org/10.4062/biomolther.2014.138
Yeung DK, Leung SW, Xu YC, Vanhoutte PM, Man RY (2006) Puerarin, an isoflavonoid derived from Radix puerariae, potentiates endothelium-independent relaxation via the cyclic AMP pathway in porcine coronary artery. Eur J Pharmacol 552:105–111. https://doi.org/10.1016/j.ejphar.2006.08.078
Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C (2003) Interaction between flavonoids and the blood-brain barrier: in vitro studies. J Neurochem 85:180–192. https://doi.org/10.1046/j.1471-4159.2003.01652.x
Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ (2004) Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med 36:592–604. https://doi.org/10.1016/j.freeradbiomed.2003.11.023
Zaheer K, Humayoun Akhtar M (2017) An updated review of dietary isoflavones: nutrition, processing, bioavailability and impacts on human health. Crit Rev Food Sci Nutr 57:1280–1293. https://doi.org/10.1080/10408398.2014.989958
Zarate CA Jr et al (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864. https://doi.org/10.1001/archpsyc.63.8.856
Zarzecki MS, Araujo SM, Bortolotto VC, de Paula MT, Jesse CR, Prigol M (2014) Hypolipidemic action of chrysin on Triton WR-1339-induced hyperlipidemia in female C57BL/6 mice. Toxicol Rep 1:200–208. https://doi.org/10.1016/j.toxrep.2014.02.003
Zhang CY et al (2018) Baicalin exerts neuroprotective effects via inhibiting activation of GSK3β/NF-κB/NLRP3 signal pathway in a rat model of depression. Int Immunopharmacol 64:175–182. https://doi.org/10.1016/j.intimp.2018.09.001
Zhang B et al (2019) Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner. J Neuroinflamm 16:92. https://doi.org/10.1186/s12974-019-1472-x
Zheng M, Fan Y, Shi D, Liu C (2013) Antidepressant-like effect of flavonoids extracted from Apocynum venetum leaves on brain monoamine levels and dopaminergic system. J Ethnopharmacol 147:108–113. https://doi.org/10.1016/j.jep.2013.02.015
Zhong J, Li G (2019) Baicalin ameliorates chronic mild stress-induced depression-like behaviors in mice and attenuates inflammatory cytokines and oxidative stress. Braz J Med Biol Res 52:e8434. https://doi.org/10.1590/1414-431x20198434
Zhou B, Xing C (2015) Diverse molecular targets for chalcones with varied bioactivities. Med Chem (Los Angeles) 5:388–404. https://doi.org/10.4172/2161-0444.1000291
Zhou LT, Wang KJ, Li L, Li H, Geng M (2015) Pinocembrin inhibits lipopolysaccharide-induced inflammatory mediators production in BV2 microglial cells through suppression of PI3K/Akt/NF-κB pathway. Eur J Pharmacol 761:211–216. https://doi.org/10.1016/j.ejphar.2015.06.003
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This work was supported by Grants (NRF-2020R1F1A1072302) from the Basic Science Research Program through the National Research Foundation of South Korea.
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Ko, YH., Kim, SK., Lee, SY. et al. Flavonoids as therapeutic candidates for emotional disorders such as anxiety and depression. Arch. Pharm. Res. 43, 1128–1143 (2020). https://doi.org/10.1007/s12272-020-01292-5
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DOI: https://doi.org/10.1007/s12272-020-01292-5