<strong><strong>Recent Development of the Flavonoids on the Treatment of Alzheimer’s Disease</strong></strong>

Abstract

Abstract:Flavonoids, a class of secondary metabolites present in plants, are the active ingredients of a variety of herbals. An increasing body of evidences demonstrate that the flavonoids could significantly improve the cognitive function of Alzheimer’s diseases (AD) in animal models and alleviate the progression of AD, exerting positive therapeutic effect. The mechanism is complex, including suppressing inflammatory modulators production, inhibiting Aβ aggregation and tau protein phosphorylation, and reducing the generation of free radical generation through multiple intracellular signaling pathways. Summarizing the relationship between the structure and their biological actions of the flavonoids and the possible mechanisms in the treatment of AD, the aim of this review, is to obtain a further understanding of how flavonoids participate in relieving the progression of AD and providing some inspiration for the flavonoids applying in AD treatment.

Key words:Alzheimer&,rsquo,s disease,flavonoids compound,neuroinflammation,A&,beta,oxidative stress

CLC Number:

R964

ZHOU Si-bai, LI Jin-ze, LIU Rui, ZHANG Tian-tai.Recent Development of the Flavonoids on the Treatment of Alzheimer’s Disease[J]. Acta Neuropharmacologica, 2015, 5(1): 51-58.

References

Sander Hougee, Annemarie Sanders, Joyce Faber, et al. Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages [J]. Bioch Pharmacol, 2005, 69(2): 241-248.

[2] Robert J Williams, Jeremy P E Spencer. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease [J]. Free Radic Biol Med, 2012, 52(1): 35-45.

[3] Kristopher Beking, Amandio Vieira. Flavonoid intake and disability-adjusted life years due to Alzheimer's and related dementias: a population-based study involving twenty-three developed countries[J]. Public Health Nutr, 2010, 13(9): 1403-1409.

[4] Jayasena T, Anne Poljak, George A Smythe, et al. The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer's disease [J]. Ageing Res Rev, 2013, 12(4): 867-883.

[5] Claudine Manach, Augustin Scalbert, Christine Morand, et al. Polyphenols: food sources and bioavailability [J]. Am J Clin Nutr, 2004, 79(5): 727-747.

[6] Mainen J Moshi, Ramadhani S O Nondo1, Emmanuel E Haule, et al. Antimicrobial activity, acute toxicity and cytoprotective effect of Crassocephalum vitellinum (Benth.) S. Moore extract in a rat ethanol-HCl gastric ulcer model [J]. BMC Resh Notes, 2014, 7(1):91.

[7] Brian Giunta, Francisco Fernandez, William V Nikolic, et al. Inflammaging as a prodrome to Alzheimer's disease [J]. J Neuroinflammation, 2008, 5:51.

[8] Zeng Qiao-hui, Zhang Xue-wu, Xu Xi-lin, et al. Antioxidant and anticomplement functions of flavonoids extracted from Penthorum chinense Pursh [J]. Food Funct, 2013, 4(12): 1811-1818.

[9] Kenjiro Ono, Yuji Yoshiike, Akihiko Takashima, et al. Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease [J]. J Neurochem, 2003, 87(1): 172-181.

[10] Georgine Agullo, Laurence Gamet-Payrastre, Stephane Manenti, et al. Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: A comparison with tyrosine kinase and protein kinase C inhibition [J]. Biochem Pharmacol, 1997, 53(11): 1649-1657.

[11] Jeremy P E Spencer. Flavonoids and brain health: multiple effects underpinned by common mechanisms [J]. Genes Nutr, 2009, 4(4): 243-250.

[12] Ehab E Tuppo, Hugo R Arias. The role of inflammation in Alzheimer's disease [J]. Int J Biochem Cell Biol, 2005, 37(2): 289-305.

[13] Clive Ballard Mycpsych, Serge Gauthier, Anne Corbett, et al. Alzheimer's disease [J]. Lancet, 2011, 377(9770): 1019-1031.

[14] Filipa I Baptista, Ana G Henriques, Artur M S Silva, et al. Flavonoids as therapeutic compounds targeting key proteins involved in Alzheimer's disease [J]. ACS Chem Neurosci, 2014, 5(2): 83-92.

[15] Jose Miguel Rubio-Perez, Juana Maria Morillas-Ruiz. A review: inflammatory process in Alzheimer's disease, role of cytokines [J]. Scientific World J, 2012, 2012:756357.

[16] Katerina Vafeiadou, David Vauzour, Hung Yi Lee, et al. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury [J]. Arc Biochem Biophys, 2009, 484(1): 100-109.

[17] Wu Ling-Hsuan, Lin Ching-ju, Lin Yu-shu, et al. Naringenin suppresses neuroinflammatory responses through inducing suppressor of cytokine signaling 3 expression [J]. Mol Neurobiol, 2015, Doi: 10.1007/s12035-014-9042-9.

[18] Ravikanth Velagapudi, Mutallib Aderogba, Olumayokun A Olajide. Tiliroside, a dietary glycosidic flavonoid, inhibits TRAF-6/NF-kappaB/p38-mediated neuroinflammation in activated BV2 microglia [J]. Biochim Biophys Acta, 2014, 1840(12): 3311-3319.

[19] Zeng Ke-wu, Fu Hong, Liu Geng-xin, et al. Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-kappaB and JNK/p38 MAPK pathways [J]. Int Immunopharmacol, 2010, 10(6): 668-678.

[20] Xi Zhong-xin, Chen Wan-sheng, Wu Zhi-jun, et al. Anti-complementary activity of flavonoids from Gnaphalium affine D. Don [J]. Food Chem, 2012, 130(1): 165-170.

[21] Amod P Kulkarni, Laurie A Kellaway, Girish J Kotwal. Herbal complement inhibitors in the treatment of neuroinflammation: future strategy for neuroprotection [J]. Ann N Y Acad Sci, 2005, 1056:413-429.

[22] Amod P Kulkarni, Yohannes T Ghebremariam, Girish J Kotwal. Curcumin inhibits the classical and the alternate pathways of complement activation [J]. Ann N Y Acad Sci, 2005, 1056:100-112.

[23] Bonnie M Bradt, William P Kolb, Neil R Cooper. Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide [J]. J Exp Med, 1998, 188(3): 431-438.

[24] Hiroko Ushikubo, Yui Tanimoto, Kazuho Abe, et al. 3,3',4',5'-tetrahydroxyflavone induces formation of large aggregates of amyloid beta protein [J]. Biol Pharm Bull, 2014, 37(5): 748-754.

[25] Peter J Crouch, Susan-Marie E Harding, Anthony R White, et al. Mechanisms of A beta mediated neurodegeneration in Alzheimer's disease [J]. Int J Biochem Cell Biol, 2008, 40(2): 181-198.

[26] Joseph Rogers, Ron Strohmeyer, C J Kovelowski, et al. Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide [J]. Glia, 2002, 40(2): 260-269.

[27] Junko Kimura, Kiyomitsu Nemoto, Akihito Yokosuka, et al. 6-demethoxynobiletin, a nobiletin-analog citrus flavonoid, enhances extracellular signal-regulated kinase phosphorylation in PC12D cells [J]. Biol Pharm Bull, 2013, 36(10): 1646-1649.

[28] Hiroshi Onozuka, Akira Nakajima, Kentaro Matsuzaki, et al. Nobiletin, a citrus flavonoid, improves memory impairment and abeta pathology in a transgenic mouse model of Alzheimer's disease [J]. J Pharmacol Exp Ther, 2008, 326(3): 739-744.

[29] Mie Hirohata, Kenjiro Ono, Jun-ichi Takasaki, et al. Anti-amyloidogenic effects of soybean isoflavones in vitro: Fluorescence spectroscopy demonstrating direct binding to abeta monomers, oligomers and fibrils [J]. Biochim Biophys Acta, 2012, 1822(8): 1316-1324.

[30] Kavon Rezai-Zadeh, R Douglas Shytle, Bai Yun, et al. Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer's disease beta-amyloid production [J]. J Cell Mol Med, 2009, 13(3): 574-588.

[31] Zheng Nan, Yuan Peng, Li Chang-hao, et al. Luteolin Reduces BACE1 expression through NF-kappaB and estrogen receptor mediated pathways in HEK293 and SH-SY5Y Cells [J]. J Alzheimers Dis, 2015, 44: 561-572.

[32] Zeng Ke-wu, Ko Hyeonseok, Yang Hyun K O, et al. Icariin attenuates β-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells [J]. Neuropharmacology, 2010, 59(6): 542-550.

[33] Bess Frost, Jürgen Götz, Mel B Feany, et al. Connecting the dots between tau dysfunction and neurodegeneration [J]. Trends Cell Biol, 2015, 25(1): 46-53.

[34] Zhao Bao-lu. Natural antioxidants protect neurons in Alzheimer's disease and Parkinson's disease [J]. Neurochem Res, 2009, 34(4): 630-638.

[35] Jana Hroudová, Namrata Singh, Zdeněk Fišar. Mitochondrial dysfunctions in neurodegenerative diseases: relevance to Alzheimer's disease [J]. BioMed Res Int, 2014, 2014:175062.

[36] Choi Dong-Young, Lee Young-Jung, Hong Jin Tae, et al. Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer's disease [J]. Brain Res Bull, 2012, 87(2-3): 144-153.

[37] Hsieh Hsi-Lung, Wang Hui-Hsin, Wu Wen-Bin, et al. Transforming growth factor-β1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-κB pathways [J]. J Neuroinflammation, 2010, 7(1): 88.

[38] Joungil Choi, Craig C Conrad, Christina A Malakowsky, et al. Flavones from scutellaria baicalensis georgi attenuate apoptosis and protein oxidation in neuronal cell lines [J]. Biochim Biophys Acta, 2002, 1571(3): 201-210.

[39] Korbecki J, Baranowska-Bosiacka I, Gutowska I, et al. The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid [J]. J Physiol Pharmacol, 2013, 64(4): 409-421.

[40] Yavuz Cakir, Scott W Ballinger. Reactive species-mediated regulation of cell signaling and the cell cycle: the role of MAPK [J]. Antioxid Redox Signal, 2005, 7(5-6): 726-740.

[41] Silvia A Mandel, Tamar Amit, Limor Kalfon, et al. Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG) [J]. J Alzheimers Dis, 2008, 15(2): 211-222.

[42] Jennifer M Walker, Diana Klakotskaia, Deepa Ajit, et al. Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer's disease mouse model [J]. J Alzheimers Dis, 2015, 44(2): 561-572.

[43] Gao Zhong-hou, Huang Kai-xun, Xu Hui-bi. Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells [J]. Pharmacol Res, 2001, 43(2): 173-178.

[44] Obulesu M, Lakshmi M Jhansi. Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues [J]. Neurochem Res, 2014, 39(12): 2301-2312.

[45] Bradley T Hyman, Yuan Jun-ying. Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology [J]. Nat Rev Neurosci, 2012, 13(6): 395-406.

[46] Mark P Mattson. Apoptosis in neurodegenerative disorders [J]. Nat Rev Mol Cell Biol, 2000, 1(2): 120-129.

[47] Fossati S, Ghiso J, Rostagno A. Insights into caspase-mediated apoptotic pathways induced by amyloid-beta in cerebral microvascular endothelial cells [J]. Neurodegener Dis, 2012, 10(1-4): 324-328.

[48] Ghavami S, Shojaei S, Yeganeh B, et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders [J]. Prog Neurobiol, 2014, 112: 24-49.

[49] Song Juhyun, Kyung Ah Park, Won Taek Lee, et al. Apoptosis signal regulating kinase 1 (ASK1): potential as a therapeutic target for Alzheimer's disease [J]. Int J Mol Sci, 2014, 15(2): 2119-2129.

[50] Zhao Le, Wang Jun-li, Wang Yan-rui, et al. Apigenin attenuates copper-mediated beta-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model [J]. Brain Res, 2013, 1492:33-45.

[51] Kulasekaran Gopinath, Dharmalingam Prakash, Ganapasam Sudhandiran. Neuroprotective effect of naringin, a dietary flavonoid against 3-nitropropionic acid-induced neuronal apoptosis [J]. Neurochem Int, 2011, 59(7): 1066-1073.

[52] Mahmud Tareq Hassan Khan, Iikay Erdogan Orhan, Fatma Sezer Senol, et al. Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies [J]. Chem Biol Interact, 2009, 181(3): 383-389.

[53] Vauzour D, Vafeiadou K, Rodriguez-Mateos A, et al. The neuroprotective potential of flavonoids: a multiplicity of effects [J]. Genes Nutr, 2008, 3(3-4): 115-126.

[54] Jeremy P E Spencer, David Vauzour, Catarina Rendeiro. Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects [J]. Arch Biochem Biophys, 2009, 492(1-2): 1-9.

[55] Xiao Jian-bo, Chen Ting-ting, Cao Hui. Flavonoid glycosylation and biological benefits [J]. Biotechnol Adv, 2014, doi: 10.1016/j.biotechadv.2014.05.004.

[56] Xiao Jian-bo, Tamar S Muzashvili, Milen I Georgiev. Advances in the biotechnological glycosylation of valuable flavonoids [J]. Biotechnol Adv, 2014, 32(6): 1145-1156.

[57] Giuseppe Galati, Peter J O'brien. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties [J]. Free Radic Biol Med, 2004, 37(3): 287-303.

[58] Arjan Scheepens, Kee Tan, James W. Paxton. Improving the oral bioavailability of beneficial polyphenols through designed synergies [J]. Genes Nutr, 2010, 5(1):75-87.

[1]	XIE bin, HUANG Zhi-yuan, LIN Duo-duo, YANG Fu-long, XIE Yi-bin.Effect of Acupuncture Combined with Medicine on Depressive Symptoms of Alzheimer’s Disease[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 5-8.
[2]	SUN Li-cong, ZHANG Dan-shen.Research Progress on Potential Treatment of Alzheimer’s Disease with Alkaloids[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 33-37.
[3]	WANG Si-yi, LI Xian-xiang, LIU Yi-zhou, DU Shuang, GE Chao, LIU Si-si.Current Situation and Prospect of Alzeimer’s Disease Treatment[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 38-42.
[4]	ZHAO Yu-wei, ZHEN Yan-jie, DAI Yue-ying, SHEN Li-xia.Study on the Neuroprotective Mechanism of Quercetin in Alzheimer’s Disease[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 55-64.
[5]	HAI Ji-tao, LUO Huan-min.Progress on the Relationship between Pathogenic Microorganisms and Alzheimer’s Disease[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(4): 58-64.
[6]	ZHANG Hao-ting, SONG Gui-qin, CUI Ruo-tong, HAO Min, WANG Wen-dong.Mining Target Genes of Alzheimer’s Disease Associated with Biological Clock by Bioinformatics Analysis[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(3): 1-7.
[7]	YANG Xu-hua, DU Shuang, SHEN Li-xia, HAO Jun-rong.Research Progress in Drug Treatment of Alzheimer’s Disease[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(3): 47-53.
[8]	LIN Si-mei, ZHOU Hong, YANG Bao-xue.The Relationship between Hyperuricemia and Chronic Kidney Disease[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(2): 55-64.
[9]	ZHEN Yan-jie, GUO Tong-lin, ZHAO Yu-wei, SHEN Li-xia.Study Progress on Phytoestrogen-Mediated Mitochondrial Pathway’s Neuroprotective Effects in Alzheimer’s Disease[J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(1): 40-46.
[10]	YANG-Lin，AI-Jing.Research Progress of Brain-Derived Estrogen in Alzheimer’s Disease[J]. Acta Neuropharmacologica, 2019, 9(5): 50-64.
[11]	ZHANG Shuai，AI Jing.Glutamate Dysfunction and Alzheimer’s Disease[J]. Acta Neuropharmacologica, 2018, 8(6): 9-20.
[12]	王奇.Bushen-Yizhi Formula Inhibits the NLRP3/NFκB Mediated Neuroinflammation and Improves the Motor Dysfunction in a Mouse Model of Parkinson's Disease[J]. Acta Neuropharmacologica, 2018, 8(5): 71-72.
[13]	CUI Su-ying, SONG Jin-zhi, CUI Xiang-yu, HU Xiao, DING Hui, YE Hui, ZHANG Yong-he.Intracerebroventricular Streptozocin-induced Alzheimer’s Disease-like Sleep Disorders: Role of the GABAergic System in the Parabrachial Complex[J]. Acta Neuropharmacologica, 2018, 8(5): 96-97.
[14]	YU Li-li1，2，XU Li1，WANG Yi-nuo1，XUE Lu-ning1，Gou Ji-wei1，LI Hong-bo1，HOU Xue-qin1，ZHANG Han-ting1.Effects of Osthole on Learning and Memory and the Estrogen Pathway in Ovariectomized Rats[J]. Acta Neuropharmacologica, 2018, 8(4): 7-8.
[15]	LIU Cai-hong，WU Xian，TANG Su-su，HONG Hao*.Involvement of TGR5 in Aβ-Induced Neurotoxicity in Vivo[J]. Acta Neuropharmacologica, 2018, 8(4): 11-12.

Recent Development of the Flavonoids on the Treatment of Alzheimer’s Disease

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles15

Recommended Articles

Metrics