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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Phytosterols: Targeting Neuroinflammation in Neurodegeneration

Author(s): Raju Dash, Sarmistha Mitra, Md. Chayan Ali, Diyah Fatimah Oktaviani, Md. Abdul Hannan, Sung Min Choi and Il Soo Moon*

Volume 27, Issue 3, 2021

Published on: 27 June, 2020

Page: [383 - 401] Pages: 19

DOI: 10.2174/1381612826666200628022812

Price: $65


Plant-derived sterols, phytosterols, are well known for their cholesterol-lowering activity in serum and their anti-inflammatory activities. Recently, phytosterols have received considerable attention due to their beneficial effects on various non-communicable diseases, and recommended use as daily dietary components. The signaling pathways mediated in the brain by phytosterols have been evaluated, but little is known about their effects on neuroinflammation, and no clinical studies have been undertaken on phytosterols of interest. In this review, we discuss the beneficial roles of phytosterols, including their attenuating effects on inflammation, blood cholesterol levels, and hallmarks of the disease, and their regulatory effects on neuroinflammatory disease pathways. Despite recent advancements made in phytosterol pharmacology, some critical questions remain unanswered. Therefore, we have tried to highlight the potential of phytosterols as viable therapeutics against neuroinflammation and to direct future research with respect to clinical applications.

Keywords: Phytosterols, neuroinflammation, neurodegeneration, neuroprotection, anti-inflammatory, pharmacology.

Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science 2016; 353(6301): 777-83.
[] [PMID: 27540165]
Russo MV, McGavern DB. Inflammatory neuroprotection following traumatic brain injury. Science 2016; 353(6301): 783-5.
[] [PMID: 27540166]
Subhramanyam CS, Wang C, Hu Q, Dheen ST, Eds. Microglia-mediated neuroinflammation in neurodegenerative diseases Seminars in cell & developmental biology. Elsevier 2019.
Pennisi M, Crupi R, Di Paola R, et al. Inflammasomes, hormesis, and antioxidants in neuroinflammation: Role of NRLP3 in Alzheimer disease. J Neurosci Res 2017; 95(7): 1360-72.
[] [PMID: 27862176]
Su P, Zhang J, Wang D, et al. The role of autophagy in modulation of neuroinflammation in microglia. Neuroscience 2016; 319: 155-67.
[] [PMID: 26827945]
Voet S, Srinivasan S, Lamkanfi M, van Loo G. Inflammasomes in neuroinflammatory and neurodegenerative diseases. EMBO Mol Med 2019; 11(6)e10248
[] [PMID: 31015277]
Ambrogini P, Torquato P, Bartolini D, et al. Excitotoxicity, neuroinflammation and oxidant stress as molecular bases of epileptogenesis and epilepsy-derived neurodegeneration: The role of vitamin E. Biochimica et Biophysica Acta (BBA)-. Molecular Basis of Disease 2019; 1856(6): 1098-2.
Craft JM, Watterson DM, Van Eldik LJ. Neuroinflammation: a potential therapeutic target. Expert Opin Ther Targets 2005; 9(5): 887-900.
[] [PMID: 16185146]
Griffin WS, Sheng JG, Royston MC, et al. Glial-neuronal interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 1998; 8(1): 65-72.
[] [PMID: 9458167]
Bohlen CJ, Friedman BA, Dejanovic B, Sheng M. Microglia in brain development, homeostasis, and neurodegeneration. Annu Rev Genet 2019; 53: 263-88.
[] [PMID: 31518519]
Maiuolo J, Gliozzi M, Musolino V, et al. The “frail” brain blood barrier in neurodegenerative diseases: role of early disruption of endothelial cell-to-cell connections. Int J Mol Sci 2018; 19(9): 2693.
[] [PMID: 30201915]
Banati RB, Daniel SE, Blunt SB. Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson’s disease. Mov Disord 1998; 13(2): 221-7.
[] [PMID: 9539333]
El-Bakoush A, Olajide OA. Formononetin inhibits neuroinflammation and increases estrogen receptor beta (ERβ) protein expression in BV2 microglia. Int Immunopharmacol 2018; 61: 325-37.
[] [PMID: 29913427]
McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 1996; 47(2): 425-32.
[] [PMID: 8757015]
Ezzat SM, Jeevanandam J, Egbuna C, Kumar S, Ifemeje JC. Phytochemicals as Sources of Drugs Phytochemistry: An in-silico and in-vitro Update. Springer 2019; pp. 3-22.
Egbuna C, Kumar S, Ifemeje JC, Ezzat SM, Kaliyaperumal S. Phytochemicals as Lead Compounds for New Drug Discovery. Elsevier 2019.
Dash R, Arifuzzaman M, Mitra S, Abdul Hannan M, Absar N, Hosen SMZ. Unveiling the Structural Insights into the Selective Inhibition of Protein Kinase D1. Curr Pharm Des 2019; 25(10): 1059-74.
[] [PMID: 31131745]
Hosen SMZ, Rubayed M, Dash R, et al. Prospecting and structural insight into the binding of novel plant-derived molecules of leea indica as inhibitors of BACE1. Curr Pharm Des 2018; 24(33): 3972-9.
[] [PMID: 30398111]
Mitra S, Dash R. Natural products for the management and prevention of breast cancer. Evid Based Complement Alternat Med 2018; 20188324696
Hannan MA, Haque MN, Dash R, Alam M, Moon IS. 3β, 6β-dichloro-5-hydroxy-5α-cholestane facilitates neuronal development through modulating TrkA signaling regulated proteins in primary hippocampal neuron. Sci Rep 2019; 9(1): 18919.
[] [PMID: 31831796]
Quirós-Sauceda AE, Palafox-Carlos H, Sáyago-Ayerdi SG, et al. Dietary fiber and phenolic compounds as functional ingredients: interaction and possible effect after ingestion. Food Funct 2014; 5(6): 1063-72.
[] [PMID: 24740575]
Ostlund RE Jr. Phytosterols and cholesterol metabolism. Curr Opin Lipidol 2004; 15(1): 37-41.
[] [PMID: 15166807]
Dumolt JH, Rideout TC. The lipid-lowering effects and associated mechanisms of dietary phytosterol supplementation. Curr Pharm Des 2017; 23(34): 5077-85.
[PMID: 28745211]
Chawla R, Goel N. Phytosterol and its esters as novel food ingredients: A reviewAsian J Dairy Food Res 2016; 35(3)
Hannan MA, Sohag AAM, Dash R, et al. Phytosterols of marine algae: Insights into the potential health benefits and molecular pharmacology. Phytomedicine 2020; 69153201
[] [PMID: 32276177]
Cheng D, Spiro AS, Jenner AM, Garner B, Karl T. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice. J Alzheimers Dis 2014; 42(4): 1383-96.
[] [PMID: 25024347]
Dierckx T, Bogie JFJ, Hendriks JJA. The impact of phytosterols on the healthy and diseased brain. Curr Med Chem 2019; 26(37): 6750-65.
[] [PMID: 29984647]
Haque MN, Moon IS. Stigmasterol promotes neuronal migration via reelin signaling in neurosphere migration assays. Nutr Neurosci 2018; 23(9): 679-87.
[] [PMID: 30433855]
Haque MN, Bhuiyan MMH, Moon IS. Stigmasterol activates Cdc42-Arp2 and Erk1/2-Creb pathways to enrich glutamatergic synapses in cultures of brain neurons. Nutr Res 2018; 56: 71-8.
[] [PMID: 30055776]
Haque MN, Moon IS. Stigmasterol upregulates immediate early genes and promotes neuronal cytoarchitecture in primary hippocampal neurons as revealed by transcriptome analysis. Phytomedicine 2018; 46: 164-75.
[] [PMID: 30097115]
Jones PJH, Shamloo M, MacKay DS, et al. Progress and perspectives in plant sterol and plant stanol research. Nutr Rev 2018; 76(10): 725-46.
[] [PMID: 30101294]
Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology 2010; 129(2): 154-69.
[] [PMID: 20561356]
Smith JA, Das A, Ray SK, Banik NL. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull 2012; 87(1): 10-20.
[] [PMID: 22024597]
Höhn A, Jung T, Grune T. Pathophysiological importance of aggregated damaged proteins. Free Radic Biol Med 2014; 71: 70-89.
[] [PMID: 24632383]
Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell 2010; 140(6): 771-6.
[] [PMID: 20303867]
Petty MA, Lo EH. Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 2002; 68(5): 311-23.
[] [PMID: 12531232]
Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 2006; 1(3): 223-36.
[] [PMID: 18040800]
Liebner S, Dijkhuizen RM, Reiss Y, Plate KH, Agalliu D, Constantin G. Functional morphology of the blood-brain barrier in health and disease. Acta Neuropathol 2018; 135(3): 311-36.
[] [PMID: 29411111]
Wimmer I, Tietz S, Nishihara H, et al. PECAM-1 stabilizes blood-brain barrier integrity and favors paracellular T-cell diapedesis across the blood-brain barrier during neuroinflammation. Front Immunol 2019; 10: 711.
[] [PMID: 31024547]
McGeer PL, McGeer EG. Inflammation, autotoxicity and Alzheimer disease. Neurobiol Aging 2001; 22(6): 799-809.
[] [PMID: 11754986]
McGeer PL, McGeer EG. Local neuroinflammation and the progression of Alzheimer’s disease. J Neurovirol 2002; 8(6): 529-38.
[] [PMID: 12476347]
McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the Substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 1988; 38(8): 1285-91.
[] [PMID: 3399080]
Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease--a double-edged sword. Neuron 2002; 35(3): 419-32.
[] [PMID: 12165466]
Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 2009; 27: 119-45.
[] [PMID: 19302036]
Hunot S, Dugas N, Faucheux B, et al. FcepsilonRII/CD23 is expressed in Parkinson’s disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-α in glial cells. J Neurosci 1999; 19(9): 3440-7.
[] [PMID: 10212304]
Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 2007; 208(1): 1-25.
[] [PMID: 17720159]
Domingues HS, Portugal CC, Socodato R, Relvas JB. Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair. Front Cell Dev Biol 2016; 4: 71.
[PMID: 27551677]
Gengatharan A, Bammann RR, Saghatelyan A. The role of astrocytes in the generation, migration, and integration of new neurons in the adult olfactory bulb. Front Neurosci 2016; 10: 149.
[] [PMID: 27092050]
Lutgen V, Narasipura SD, Sharma A, Min S, Al-Harthi L. β-Catenin signaling positively regulates glutamate uptake and metabolism in astrocytes. J Neuroinflammation 2016; 13(1): 242.
[] [PMID: 27612942]
Potokar M, Jorgačevski J, Zorec R. Astrocyte aquaporin dynamics in health and disease. Int J Mol Sci 2016; 17(7): 1121.
[] [PMID: 27420057]
Reiner DJ, Mietlicki-Baase EG, McGrath LE, et al. Astrocytes regulate GLP-1 receptor-mediated effects on energy balance. J Neurosci 2016; 36(12): 3531-40.
[] [PMID: 27013681]
Ries M, Sastre M. Mechanisms of Aβ clearance and degradation by glial cells. Front Aging Neurosci 2016; 8: 160.
[] [PMID: 27458370]
Sofroniew MV. Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators. Neuroscientist 2014; 20(2): 160-72.
[] [PMID: 24106265]
Jha MK, Jo M, Kim J-H, Suk K. Microglia-astrocyte crosstalk: an intimate molecular conversation. Neuroscientist 2019; 25(3): 227-40.
[] [PMID: 29931997]
Anderson MA, Ao Y, Sofroniew MV. Heterogeneity of reactive astrocytes. Neurosci Lett 2014; 565: 23-9.
[] [PMID: 24361547]
Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19(8): 312-8.
[] [PMID: 8843599]
Hasseldam H, Rasmussen RS, Johansen FF. Oxidative damage and chemokine production dominate days before immune cell infiltration and EAE disease debut. J Neuroinflammation 2016; 13(1): 246.
[] [PMID: 27630002]
Bernhardi Rv. Neurodegenerative diseases-MAPK signalling pathways in neuroinflammation Encyclopedia of Neuroscience 2009; 2614-0.
Tretter L, Sipos I, Adam-Vizi V. Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson’s disease. Neurochem Res 2004; 29(3): 569-77.
[] [PMID: 15038604]
Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 2004; 58(1): 39-46.
[] [PMID: 14739060]
Loh KP, Huang SH, De Silva R, Tan BK, Zhu YZ, Zhun Zhu Y. Oxidative stress: apoptosis in neuronal injury. Curr Alzheimer Res 2006; 3(4): 327-37.
[] [PMID: 17017863]
Starkov AA. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci 2008; 1147: 37-52.
[] [PMID: 19076429]
Chen X, Guo C, Kong J. Oxidative stress in neurodegenerative diseases. Neural Regen Res 2012; 7(5): 376-85.
[PMID: 25774178]
Floyd RA, Hensley K. Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 2002; 23(5): 795-807.
[] [PMID: 12392783]
Borrás C, Sastre J, García-Sala D, Lloret A, Pallardó FV, Viña J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med 2003; 34(5): 546-52.
[] [PMID: 12614843]
Gilgun-Sherki Y, Melamed E, Offen D. Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 2001; 40(8): 959-75.
[] [PMID: 11406187]
Arora R. Herbal Medicine: A cancer chemopreventive and therapeutic perspective: Jaypee Brothers. Med Publ (Oulu) 2010.
Piironen V, Lindsay DG, Miettinen TA, Toivo J, Lampi AM. Plant sterols: biosynthesis, biological function and their importance to human nutrition. J Sci Food Agric 2000; 80(7): 939-66.
Normén L, Johnsson M, Andersson H, van Gameren Y, Dutta P. Plant sterols in vegetables and fruits commonly consumed in Sweden. Eur J Nutr 1999; 38(2): 84-9.
[] [PMID: 10352947]
Han JH, Yang YX, Feng MY. Contents of phytosterols in vegetables and fruits commonly consumed in China. Biomed Environ Sci 2008; 21(6): 449-53.
[] [PMID: 19263798]
Nguyen TT. The cholesterol-lowering action of plant stanol esters. J Nutr 1999; 129(12): 2109-12.
[] [PMID: 10573535]
Racette SB, Lin X, Lefevre M, et al. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study. Am J Clin Nutr 2010; 91(1): 32-8.
[] [PMID: 19889819]
Phillips KM, Ruggio DM, Ashraf-Khorassani M. Phytosterol composition of nuts and seeds commonly consumed in the United States. J Agric Food Chem 2005; 53(24): 9436-45.
[] [PMID: 16302759]
Ostlund RE Jr. Phytosterols in human nutrition. Annu Rev Nutr 2002; 22(1): 533-49.
[] [PMID: 12055357]
Racette SB, Lin X, Ma L, Ostlund RE Jr. Natural dietary phytosterols. J AOAC Int 2015; 98(3): 679-84.
[] [PMID: 26086252]
Ling WH, Jones PJ. Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci 1995; 57(3): 195-206.
[] [PMID: 7596226]
Ostlund RE Jr, McGill JB, Zeng C-M, et al. Gastrointestinal absorption and plasma kinetics of soy Δ(5)-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab 2002; 282(4): E911-6.
[] [PMID: 11882512]
Pollak OJ. Successive prevention of experimental hypercholesteremia and cholesterol atherosclerosis in the rabbit. Circulation 1953; 7(5): 696-701.
[] [PMID: 13042923]
Best MM, Duncan CH, Van Loon EJ, Wathen JD. Lowering of serum cholesterol by the administration of a plant sterol. Circulation 1954; 10(2): 201-6.
[] [PMID: 13182752]
Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med 1995; 333(20): 1308-12.
[] [PMID: 7566021]
J Jansen PJ. Lütjohann D, Abildayeva K, et al. . Dietary plant sterols accumulate in the brain. Biochimica et Biophysica Acta (BBA)- 2006; 1761(4): 445-53.
Saeed AA, Genové G, Li T, et al. Increased flux of the plant sterols campesterol and sitosterol across a disrupted blood brain barrierSteroids 2015; 99(Pt B): 183-8
[] [PMID: 25683892]
Hąc-Wydro K, Wydro P, Dynarowicz-Łatka P, Paluch M. Cholesterol and phytosterols effect on sphingomyelin/phosphatidylcholine model membranes--thermodynamic analysis of the interactions in ternary monolayers. J Colloid Interface Sci 2009; 329(2): 265-72.
[] [PMID: 18922545]
Xu X, Bittman R, Duportail G, Heissler D, Vilcheze C, London E. Effect of the structure of natural sterols and sphingolipids on the formation of ordered sphingolipid/sterol domains (rafts). Comparison of cholesterol to plant, fungal, and disease-associated sterols and comparison of sphingomyelin, cerebrosides, and ceramide. J Biol Chem 2001; 276(36): 33540-6.
[] [PMID: 11432870]
Vanmierlo T, Rutten K, van Vark-van der Zee LC, et al. Cerebral accumulation of dietary derivable plant sterols does not interfere with memory and anxiety related behavior in Abcg5-/- mice. Plant Foods Hum Nutr 2011; 66(2): 149-56.
[] [PMID: 21431910]
Rui X, Wenfang L, Jing C, et al. Neuroprotective effects of phytosterol esters against high cholesterol-induced cognitive deficits in aged rat. Food Funct 2017; 8(3): 1323-32.
[] [PMID: 28256666]
Rader DJ. Liver X receptor and farnesoid X receptor as therapeutic targets. Am J Cardiol 2007; 100(11 A): n15-9.
[] [PMID: 18047847]
Kaneko E, Matsuda M, Yamada Y, Tachibana Y, Shimomura I, Makishima M. Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist. J Biol Chem 2003; 278(38): 36091-8.
[] [PMID: 12847102]
Calpe-Berdiel L, Escolà-Gil JC, Blanco-Vaca F. Phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of ATP-binding cassette transporter A1. Br J Nutr 2006; 95(3): 618-22.
[] [PMID: 16512948]
Sabeva NS, Liu J, Graf GA. The ABCG5 ABCG8 sterol transporter and phytosterols: implications for cardiometabolic disease. Curr Opin Endocrinol Diabetes Obes 2009; 16(2): 172-7.
[] [PMID: 19306529]
Gylling H, Nissinen MJ. Phytosterol therapy Dyslipidemias. Springer 2015; pp. 343-54.
Zhang J, Liu Q. Cholesterol metabolism and homeostasis in the brain. Protein Cell 2015; 6(4): 254-64.
[] [PMID: 25682154]
Nieweg K, Schaller H, Pfrieger FW. Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats. J Neurochem 2009; 109(1): 125-34.
[] [PMID: 19166509]
Björkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 2004; 24(5): 806-15.
[] [PMID: 14764421]
Liu Q, Trotter J, Zhang J, et al. Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J Neurosci 2010; 30(50): 17068-78.
[] [PMID: 21159977]
Vance JE, Karten B, Hayashi H. Lipid dynamics in neurons. Biochem Soc Trans 2006; 34(Pt 3): 399-403.
[] [PMID: 16709172]
Yao ZX, Papadopoulos V. Function of β-amyloid in cholesterol transport: a lead to neurotoxicity. FASEB J 2002; 16(12): 1677-9.
[] [PMID: 12206998]
Hayashi H, Campenot RB, Vance DE, Vance JE. Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures. J Biol Chem 2004; 279(14): 14009-15.
[] [PMID: 14709547]
Gamba P, Testa G, Gargiulo S, Staurenghi E, Poli G, Leonarduzzi G. Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease. Front Aging Neurosci 2015; 7: 119.
[] [PMID: 26150787]
Petrov AM, Kasimov MR, Zefirov AL. Brain cholesterol metabolism and its defects: linkage to neurodegenerative diseases and synaptic dysfunction. Acta Naturae 2016; 8(1): 58-73.
[] [PMID: 27099785]
Liao F, Yoon H, Kim J. Apolipoprotein E metabolism and functions in brain and its role in Alzheimer’s disease. Curr Opin Lipidol 2017; 28(1): 60-7.
[PMID: 27922847]
Björkhem I. Do oxysterols control cholesterol homeostasis? J Clin Invest 2002; 110(6): 725-30.
[] [PMID: 12235099]
Björkhem I, Leoni V, Svenningsson P. On the fluxes of side-chain oxidized oxysterols across blood-brain and blood-CSF barriers and origin of these steroids in CSF. (Review). J Steroid Biochem Mol Biol 2019; 188: 86-9.
[] [PMID: 30586624]
Dosch AR, Imagawa DK, Jutric Z. Bile metabolism and lithogenesis: An update. Surg Clin North Am 2019; 99(2): 215-29.
[] [PMID: 30846031]
Czuba E, Steliga A, Lietzau G, Kowiański P. Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions. Metab Brain Dis 2017; 32(4): 935-48.
[] [PMID: 28432486]
Testa G, Staurenghi E, Zerbinati C, et al. Changes in brain oxysterols at different stages of Alzheimer’s disease: Their involvement in neuroinflammation. Redox Biol 2016; 10: 24-33.
[] [PMID: 27687218]
Hascalovici JR, Vaya J, Khatib S, et al. Brain sterol dysregulation in sporadic AD and MCI: relationship to heme oxygenase-1. J Neurochem 2009; 110(4): 1241-53.
[] [PMID: 19522732]
Heverin M, Bogdanovic N, Lütjohann D, et al. Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer’s disease. J Lipid Res 2004; 45(1): 186-93.
[] [PMID: 14523054]
Dias IH, Polidori MC, Griffiths HR. Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier. Biochem Soc Trans 2014; 42(4): 1001-5.
[] [PMID: 25109993]
Marwarha G, Ghribi O. Does the oxysterol 27-hydroxycholesterol underlie Alzheimer’s disease-Parkinson’s disease overlap? Exp Gerontol 2015; 68: 13-8.
[] [PMID: 25261765]
Testa G, Gamba P, Badilli U, et al. Loading into nanoparticles improves quercetin’s efficacy in preventing neuroinflammation induced by oxysterols. PLoS One 2014; 9(5)e96795
[] [PMID: 24802026]
Prasanthi JR, Huls A, Thomasson S, Thompson A, Schommer E, Ghribi O. Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells. Mol Neurodegener 2009; 4(1): 1.
[] [PMID: 19126211]
Gamba P, Guglielmotto M, Testa G, et al. Up-regulation of β-amyloidogenesis in neuron-like human cells by both 24- and 27-hydroxycholesterol: protective effect of N-acetyl-cysteine. Aging Cell 2014; 13(3): 561-72.
[] [PMID: 24612036]
Zhang X, Xi Y, Yu H, et al. 27-hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice. Brain Pathol 2019; 29(4): 558-73.
[] [PMID: 30582229]
Marwarha G, Raza S, Prasanthi JR, Ghribi O. Gadd153 and NF-κB crosstalk regulates 27-hydroxycholesterol-induced increase in BACE1 and β-amyloid production in human neuroblastoma SH-SY5Y cells. PLoS One 2013; 8(8)e70773
[] [PMID: 23951005]
Chen S, Zhou C, Yu H, et al. 27-hydroxycholesterol contributes to lysosomal membrane permeabilization-mediated pyroptosis in co-cultured SH-SY5Y cells and C6 cells. Front Mol Neurosci 2019; 12: 14.
[] [PMID: 30881285]
Merino-Serrais P, Loera-Valencia R, Rodriguez-Rodriguez P, et al. 27-Hydroxycholesterol induces aberrant morphology and synaptic dysfunction in hippocampal neurons. Cereb Cortex 2019; 29(1): 429-46.
[] [PMID: 30395175]
Gamba P, Leonarduzzi G, Tamagno E, et al. Interaction between 24-hydroxycholesterol, oxidative stress, and amyloid-β in amplifying neuronal damage in Alzheimer’s disease: three partners in crime. Aging Cell 2011; 10(3): 403-17.
[] [PMID: 21272192]
Yamanaka K, Saito Y, Yamamori T, Urano Y, Noguchi N. 24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis. J Biol Chem 2011; 286(28): 24666-73.
[] [PMID: 21613228]
Paul SM, Doherty JJ, Robichaud AJ, et al. The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors. J Neurosci 2013; 33(44): 17290-300.
[] [PMID: 24174662]
Urano Y, Ochiai S, Noguchi N. Suppression of amyloid-β production by 24S-hydroxycholesterol via inhibition of intracellular amyloid precursor protein trafficking. FASEB J 2013; 27(10): 4305-15.
[] [PMID: 23839932]
Testa G, Staurenghi E, Giannelli S, et al. A silver lining for 24-hydroxycholesterol in Alzheimer’s disease: The involvement of the neuroprotective enzyme sirtuin 1. Redox Biol 2018; 17: 423-31.
[] [PMID: 29883958]
Testa G, Rossin D, Poli G, Biasi F, Leonarduzzi G. Implication of oxysterols in chronic inflammatory human diseases. Biochimie 2018; 153: 220-31.
[] [PMID: 29894701]
Morris MC, Evans DA, Bienias JL, et al. Dietary fats and the risk of incident Alzheimer disease. Arch Neurol 2003; 60(2): 194-200.
[] [PMID: 12580703]
Schönknecht P, Lütjohann D, Pantel J, et al. Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer’s disease compared to healthy controls. Neurosci Lett 2002; 324(1): 83-5.
[] [PMID: 11983301]
Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 1998; 95(11): 6460-4.
[] [PMID: 9600988]
Refolo LM, Malester B, LaFrancois J, et al. Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis 2000; 7(4): 321-31.
[] [PMID: 10964604]
Kojro E, Gimpl G, Lammich S, März W, Fahrenholz F. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α -secretase ADAM 10. Proc Natl Acad Sci USA 2001; 98(10): 5815-20.
[] [PMID: 11309494]
Choi JN, Choi Y-H, Lee J-M, et al. Anti-inflammatory effects of β-sitosterol-β-D-glucoside from Trachelospermum jasminoides (Apocynaceae) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Nat Prod Res 2012; 26(24): 2340-3.
[] [PMID: 22292934]
Valerio M, Awad AB. β-Sitosterol down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in J774A.1 murine macrophages. Int Immunopharmacol 2011; 11(8): 1012-7.
[] [PMID: 21356343]
Valerio MS, Minderman H, Mace T, Awad AB. β-Sitosterol modulates TLR4 receptor expression and intracellular MyD88-dependent pathway activation in J774A.1 murine macrophages. Cell Immunol 2013; 285(1-2): 76-83.
[] [PMID: 24121260]
Yoo M-S, Shin J-S, Choi H-E, et al. Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines via the inactivation of nuclear factor-κB and p38 mitogen-activated protein kinase in RAW264.7 macrophages. Food Chem 2012; 135(3): 967-75.
[] [PMID: 22953812]
Kim KA, Lee IA, Gu W, Hyam SR, Kim DH. β-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-κB pathway. Mol Nutr Food Res 2014; 58(5): 963-72.
[] [PMID: 24402767]
Awad AB, Toczek J, Fink CS. Phytosterols decrease prostaglandin release in cultured P388D1/MAB macrophages. Prostaglandins Leukot Essent Fatty Acids 2004; 70(6): 511-20.
[] [PMID: 15120714]
Moreno JJ. Effect of olive oil minor components on oxidative stress and arachidonic acid mobilization and metabolism by macrophages RAW 264.7. Free Radic Biol Med 2003; 35(9): 1073-81.
[] [PMID: 14572610]
Sabeva NS, McPhaul CM, Li X, Cory TJ, Feola DJ, Graf GA. Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells. J Nutr Biochem 2011; 22(8): 777-83.
[] [PMID: 21111593]
Jeong G-S, Li B, Lee D-S, et al. Cytoprotective and anti-inflammatory effects of spinasterol via the induction of heme oxygenase-1 in murine hippocampal and microglial cell lines. Int Immunopharmacol 2010; 10(12): 1587-94.
[] [PMID: 20933625]
Hannan MA, Dash R, Sohag AAM, Moon IS. Deciphering molecular mechanism of the neuropharmacological action of fucosterol through integrated system pharmacology and in silico analysis. Mar Drugs 2019; 17(11)E639
[] [PMID: 31766220]
Jung HA, Jin SE, Ahn BR, Lee CM, Choi JS. Anti-inflammatory activity of edible brown alga Eisenia bicyclis and its constituents fucosterol and phlorotannins in LPS-stimulated RAW264.7 macrophages. Food Chem Toxicol 2013; 59: 199-206.
[] [PMID: 23774261]
Karunaweera N, Raju R, Gyengesi E, Münch G. Plant polyphenols as inhibitors of NF-κB induced cytokine production-a potential anti-inflammatory treatment for Alzheimer’s disease? Front Mol Neurosci 2015; 8: 24.
[] [PMID: 26136655]
Mattson MP, Camandola S. NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest 2001; 107(3): 247-54.
[] [PMID: 11160145]
Cheon JH, Kim JS, Kim JM, Kim N, Jung HC, Song IS. Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking IkappaB kinase and ameliorates acute murine colitis. Inflamm Bowel Dis 2006; 12(12): 1152-61.
[] [PMID: 17119390]
Shishodia S, Aggarwal BB. Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J Biol Chem 2004; 279(45): 47148-58.
[] [PMID: 15322087]
Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993; 69(2): 238-49.
[PMID: 8350599]
Preetha SP, Kanniappan M, Selvakumar E, Nagaraj M, Varalakshmi P. Lupeol ameliorates aflatoxin B1-induced peroxidative hepatic damage in rats. Comp Biochem Physiol C Toxicol Pharmacol 2006; 143(3): 333-9.
[] [PMID: 16730236]
Badshah H, Ali T. Shafiq-ur Rehman, et al. Protective effect of lupeol against lipopolysaccharide-induced neuroinflammation via the p38/c-Jun N-terminal kinase pathway in the adult mouse brain. J Neuroimmune Pharmacol 2016; 11(1): 48-60.
[] [PMID: 26139594]
Saleem M, Afaq F, Adhami VM, Mukhtar H. Lupeol modulates NF-kappaB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice. Oncogene 2004; 23(30): 5203-14.
[] [PMID: 15122342]
Prabhu B, Balakrishnan D, Sundaresan S. Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats. Hum Exp Toxicol 2016; 35(6): 685-92.
[] [PMID: 26251508]
Bouic PJD, Clark A, Lamprecht J, et al. The effects of B-sitosterol (BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post marathon immune suppression and inflammation. Int J Sports Med 1999; 20(4): 258-62.
[] [PMID: 10376483]
Bouic PJ, Lamprecht JH. Plant sterols and sterolins: a review of their immune-modulating properties. Altern Med Rev 1999; 4(3): 170-7.
[PMID: 10383481]
Gabay O, Sanchez C, Salvat C, et al. Stigmasterol: a phytosterol with potential anti-osteoarthritic properties. Osteoarthritis Cartilage 2010; 18(1): 106-16.
[] [PMID: 19786147]
Valerio M, Liu HB, Heffner R, et al. Phytosterols ameliorate clinical manifestations and inflammation in experimental autoimmune encephalomyelitis. Inflamm Res 2011; 60(5): 457-65.
[] [PMID: 21136279]
Catani MV, Gasperi V, Bisogno T, Maccarrone M. Essential dietary bioactive lipids in neuroinflammatory diseases. Antioxid Redox Signal 2018; 29(1): 37-60.
[] [PMID: 28637354]
Micallef MA, Garg ML. Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals. Atherosclerosis 2009; 204(2): 476-82.
[] [PMID: 18977480]
Desai F, Ramanathan M, Fink CS, Wilding GE, Weinstock-Guttman B, Awad AB. Comparison of the immunomodulatory effects of the plant sterol β-sitosterol to simvastatin in peripheral blood cells from multiple sclerosis patients. Int Immunopharmacol 2009; 9(1): 153-7.
[] [PMID: 19022404]
Loizou S, Lekakis I, Chrousos GP, Moutsatsou P. Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol Nutr Food Res 2010; 54(4): 551-8.
[] [PMID: 19937850]
Brüll F, Mensink RP, van den Hurk K, Duijvestijn A, Plat J. TLR2 activation is essential to induce a Th1 shift in human peripheral blood mononuclear cells by plant stanols and plant sterols. J Biol Chem 2010; 285(5): 2951-8.
[] [PMID: 19948716]
Bouic PJ. Sterols and sterolins: new drugs for the immune system? Drug Discov Today 2002; 7(14): 775-8.
[] [PMID: 12547034]
Calpe-Berdiel L, Escolà-Gil JC, Benítez S, et al. Dietary phytosterols modulate T-helper immune response but do not induce apparent anti-inflammatory effects in a mouse model of acute, aseptic inflammation. Life Sci 2007; 80(21): 1951-6.
[] [PMID: 17382351]
Breytenbach U, Clark A, Lamprecht J, Bouic P. Flow cytometric analysis of the Th1-Th2 balance in healthy individuals and patients infected with the human immunodeficiency virus (HIV) receiving a plant sterol/sterolin mixture. Cell Biol Int 2001; 25(1): 43-9.
[] [PMID: 11237407]
Bouic PJ, Etsebeth S, Liebenberg RW, Albrecht CF, Pegel K, Van Jaarsveld PP. beta-Sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulatory vitamin combination. Int J Immunopharmacol 1996; 18(12): 693-700.
[] [PMID: 9172012]
Lee TH, Jung M, Bang M-H, Chung DK, Kim J. Inhibitory effects of a spinasterol glycoside on lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines via down-regulating MAP kinase pathways and NF-κB activation in RAW264.7 macrophage cells. Int Immunopharmacol 2012; 13(3): 264-70.
[] [PMID: 22595195]
Ju SM, Song HY, Lee SJ, et al. Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-β-D-glucose via blockade of NF-kappaB and STAT1 activation in the HaCaT cells. Biochem Biophys Res Commun 2009; 387(1): 115-20.
[] [PMID: 19576177]
Jung M, Lee TH, Oh HJ, et al. Inhibitory effect of 5,6-dihydroergosteol-glucoside on atopic dermatitis-like skin lesions via suppression of NF-κB and STAT activation. J Dermatol Sci 2015; 79(3): 252-61.
[] [PMID: 26100037]
Calpe-Berdiel L, Escolà-Gil JC, Ribas V, Navarro-Sastre A, Garcés-Garcés J, Blanco-Vaca F. Changes in intestinal and liver global gene expression in response to a phytosterol-enriched diet. Atherosclerosis 2005; 181(1): 75-85.
[] [PMID: 15939057]
Navarro A, De las Heras B, Villar A. Anti-inflammatory and immunomodulating properties of a sterol fraction from Sideritis foetens Clem. Biol Pharm Bull 2001; 24(5): 470-3.
[] [PMID: 11379762]
Park E-H, Kahng J-H, Lee SH, Shin K-H. An anti-inflammatory principle from cactus. Fitoterapia 2001; 72(3): 288-90.
[] [PMID: 11295308]
Surh Y-J, Chun K-S, Cha H-H, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κ B activation. Mutat Res 2001; 480-481: 243-68.
[] [PMID: 11506818]
Tanabe T, Tohnai N. Cyclooxygenase isozymes and their gene structures and expression. Prostaglandins Other Lipid Mediat 2002; 68-69: 95-114.
[] [PMID: 12432912]
Mestre JR, Mackrell PJ, Rivadeneira DE, Stapleton PP, Tanabe T, Daly JM. Redundancy in the signaling pathways and promoter elements regulating cyclooxygenase-2 gene expression in endotoxin-treated macrophage/monocytic cells. J Biol Chem 2001; 276(6): 3977-82.
[] [PMID: 11092878]
Kang Y-J, Wingerd BA, Arakawa T, Smith WL. Cyclooxygenase-2 gene transcription in a macrophage model of inflammation. J Immunol 2006; 177(11): 8111-22.
[] [PMID: 17114486]
Nagasaka R, Chotimarkorn C, Shafiqul IM, Hori M, Ozaki H, Ushio H. Anti-inflammatory effects of hydroxycinnamic acid derivatives. Biochem Biophys Res Commun 2007; 358(2): 615-9.
[] [PMID: 17499610]
Limtrakul P, Yodkeeree S, Pitchakarn P, Punfa W. Suppression of inflammatory responses by black rice extract in RAW 264.7 macrophage cells via downregulation of NF-kB and AP-1 signaling pathways. Asian Pac J Cancer Prev 2015; 16(10): 4277-83.
[] [PMID: 26028086]
Shin SY, Kim H-W, Jang H-H, et al. γ-Oryzanol suppresses COX-2 expression by inhibiting reactive oxygen species-mediated Erk1/2 and Egr-1 signaling in LPS-stimulated RAW264.7 macrophages. Biochem Biophys Res Commun 2017; 491(2): 486-92.
[] [PMID: 28728842]
Yang C, Yu L, Li W, Xu F, Cohen JC, Hobbs HH. Disruption of cholesterol homeostasis by plant sterols. J Clin Invest 2004; 114(6): 813-22.
[] [PMID: 15372105]
Courtney R, Landreth GE. LXR regulation of brain cholesterol: from development to disease. Trends Endocrinol Metab 2016; 27(6): 404-14.
[] [PMID: 27113081]
Sonoda J, Pei L, Evans RM. Nuclear receptors: decoding metabolic disease. FEBS Lett 2008; 582(1): 2-9.
[] [PMID: 18023286]
Janowski BA, Grogan MJ, Jones SA, et al. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci USA 1999; 96(1): 266-71.
[] [PMID: 9874807]
Joseph SB, Tontonoz P. LXRs: new therapeutic targets in atherosclerosis? Curr Opin Pharmacol 2003; 3(2): 192-7.
[] [PMID: 12681243]
Maqdasy S, Trousson A, Tauveron I, Volle DH, Baron S, Lobaccaro J-MA. Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system. Mol Aspects Med 2016; 49: 31-46.
[] [PMID: 27091047]
Liu C-C, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 2013; 9(2): 106-18.
[] [PMID: 23296339]
Vitali C, Wellington CL, Calabresi L. HDL and cholesterol handling in the brain. Cardiovasc Res 2014; 103(3): 405-13.
[] [PMID: 24907980]
Fessler MB. The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease. Pharmacol Ther 2018; 181: 1-12.
[] [PMID: 28720427]
Ghisletti S, Huang W, Ogawa S, et al. Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol Cell 2007; 25(1): 57-70.
[] [PMID: 17218271]
Lee JH, Park SM, Kim OS, et al. Differential SUMOylation of LXRalpha and LXRbeta mediates transrepression of STAT1 inflammatory signaling in IFN-γ-stimulated brain astrocytes. Mol Cell 2009; 35(6): 806-17.
[] [PMID: 19782030]
Ito A, Hong C, Rong X, et al. LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling. eLife 2015; 4e08009
[] [PMID: 26173179]
Thomas DG, Doran AC, Fotakis P, et al. LXR suppresses inflammatory gene expression and neutrophil migration through cis-repression and cholesterol efflux. Cell Rep 2018; 25(13): 3774-3785.e4.
[] [PMID: 30590048]
Kim OS, Lee CS, Joe EH, Jou I. Oxidized low density lipoprotein suppresses lipopolysaccharide-induced inflammatory responses in microglia: oxidative stress acts through control of inflammation. Biochem Biophys Res Commun 2006; 342(1): 9-18.
[] [PMID: 16466690]
Zhang-Gandhi CX, Drew PD. Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes. J Neuroimmunol 2007; 183(1-2): 50-9.
[] [PMID: 17175031]
Secor McVoy JR, Oughli HA, Oh U. Liver X receptor-dependent inhibition of microglial nitric oxide synthase 2. J Neuroinflammation 2015; 12(1): 27.
[] [PMID: 25889344]
Wu CH, Chen CC, Lai CY, et al. Treatment with TO901317, a synthetic liver X receptor agonist, reduces brain damage and attenuates neuroinflammation in experimental intracerebral hemorrhage. J Neuroinflammation 2016; 13(1): 62.
[] [PMID: 26968836]
Paterniti I, Campolo M, Siracusa R, et al. Liver X receptors activation, through TO901317 binding, reduces neuroinflammation in Parkinson’s disease. PLoS One 2017; 12(4)e0174470
[] [PMID: 28369131]
Eckert GP, Vardanian L, Rebeck GW, Burns MP. Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317. Neurosci Lett 2007; 423(1): 47-52.
[] [PMID: 17662526]
Abildayeva K, Jansen PJ, Hirsch-Reinshagen V, et al. 24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux. J Biol Chem 2006; 281(18): 12799-808.
[] [PMID: 16524875]
Meffre D, Shackleford G, Hichor M, et al. Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum. Proc Natl Acad Sci USA 2015; 112(24): 7587-92.
[] [PMID: 26023184]
Makoukji J, Shackleford G, Meffre D, et al. Interplay between LXR and Wnt/β-catenin signaling in the negative regulation of peripheral myelin genes by oxysterols. J Neurosci 2011; 31(26): 9620-9.
[] [PMID: 21715627]
Plat J, Mensink RP. Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FASEB J 2002; 16(10): 1248-53.
[] [PMID: 12153993]
Chen Z, Liu J, Fu Z, et al. 24(S)-Saringosterol from edible marine seaweed Sargassum fusiforme is a novel selective LXRβ agonist. J Agric Food Chem 2014; 62(26): 6130-7.
[] [PMID: 24927286]
Bogie J, Hoeks C, Schepers M, et al. Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer’s disease mouse model. Sci Rep 2019; 9(1): 4908.
[] [PMID: 30894635]
Plat J, Nichols JA, Mensink RP. Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation. J Lipid Res 2005; 46(11): 2468-76.
[] [PMID: 16150823]
Hoang MH, Jia Y, Jun HJ, Lee JH, Lee BY, Lee SJ. Fucosterol is a selective liver X receptor modulator that regulates the expression of key genes in cholesterol homeostasis in macrophages, hepatocytes, and intestinal cells. J Agric Food Chem 2012; 60(46): 11567-75.
[] [PMID: 23116181]
El Kharrassi Y, Samadi M, Lopez T, et al. Biological activities of Schottenol and Spinasterol, two natural phytosterols present in argan oil and in cactus pear seed oil, on murine miroglial BV2 cells. Biochem Biophys Res Commun 2014; 446(3): 798-804.
[] [PMID: 24582563]
Kim HJ, Fan X, Gabbi C, et al. Liver X receptor β (LXRbeta): a link between β-sitosterol and amyotrophic lateral sclerosis-Parkinson’s dementia. Proc Natl Acad Sci USA 2008; 105(6): 2094-9.
[] [PMID: 18238900]
Spann NJ, Garmire LX, McDonald JG, et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 2012; 151(1): 138-52.
[] [PMID: 23021221]
Vanmierlo T, Husche C, Schött HF, Pettersson H, Lütjohann D. Plant sterol oxidation products--analogs to cholesterol oxidation products from plant origin? Biochimie 2013; 95(3): 464-72.
[] [PMID: 23009926]
Joseph SB, Bradley MN, Castrillo A, et al. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 2004; 119(2): 299-309.
[] [PMID: 15479645]
Belandia B, Parker MG. Nuclear receptors: a rendezvous for chromatin remodeling factors. Cell 2003; 114(3): 277-80.
[] [PMID: 12914692]
McKenna NJ, O’Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 2002; 108(4): 465-74.
[] [PMID: 11909518]
Klinge CM. Estrogen receptor interaction with co-activators and co-repressors. Steroids 2000; 65(5): 227-51.
[] [PMID: 10751636]
Norris JD, Paige LA, Christensen DJ, et al. Peptide antagonists of the human estrogen receptor. Science 1999; 285(5428): 744-6.
[] [PMID: 10426998]
Pike AC. Lessons learnt from structural studies of the oestrogen receptor. Best Pract Res Clin Endocrinol Metab 2006; 20(1): 1-14.
[] [PMID: 16522516]
Brzozowski AM, Pike AC, Dauter Z, et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997; 389(6652): 753-8.
[] [PMID: 9338790]
Paige LA, Christensen DJ, Grøn H, et al. Estrogen receptor (ER) modulators each induce distinct conformational changes in ER α and ER β. Proc Natl Acad Sci USA 1999; 96(7): 3999-4004.
[] [PMID: 10097152]
Cyr M, Calon F, Morissette M, Grandbois M, Di Paolo T, Callier S. Drugs with estrogen-like potency and brain activity: potential therapeutic application for the CNS. Curr Pharm Des 2000; 6(12): 1287-312.
[] [PMID: 10903393]
Dhandapani KM, Brann DW. Protective effects of estrogen and selective estrogen receptor modulators in the brain. Biol Reprod 2002; 67(5): 1379-85.
[] [PMID: 12390866]
Littleton-Kearney MT, Ostrowski NL, Cox DA, Rossberg MI, Hurn PD. Selective estrogen receptor modulators: tissue actions and potential for CNS protection. CNS Drug Rev 2002; 8(3): 309-30.
[] [PMID: 12353060]
DonCarlos LL, Azcoitia I, Garcia-Segura LM. In search of neuroprotective therapies based on the mechanisms of estrogens. Expert Rev Endocrinol Metab 2007; 2(3): 387-97.
[] [PMID: 30743812]
Prokai L, Simpkins JW. Structure-nongenomic neuroprotection relationship of estrogens and estrogen-derived compounds. Pharmacol Ther 2007; 114(1): 1-12.
[] [PMID: 17336390]
Stein B, Yang MX. Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol Cell Biol 1995; 15(9): 4971-9.
[] [PMID: 7651415]
Guzeloglu-Kayisli O, Halis G, Taskiran S, Kayisli UA, Arici A. DNA-binding ability of NF-kappaB is affected differently by ERalpha and ERbeta and its activation results in inhibition of estrogen responsiveness. Reprod Sci 2008; 15(5): 493-505.
[] [PMID: 18579858]
Galien R, Garcia T. Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF-kappaB site. Nucleic Acids Res 1997; 25(12): 2424-9.
[] [PMID: 9171095]
Evans MJ, Eckert A, Lai K, Adelman SJ, Harnish DC. Reciprocal antagonism between estrogen receptor and NF-kappaB activity in vivo. Circ Res 2001; 89(9): 823-30.
[] [PMID: 11679413]
Xing D, Oparil S, Yu H, et al. Estrogen modulates NFκB signaling by enhancing IκBα levels and blocking p65 binding at the promoters of inflammatory genes via estrogen receptor-β. PLoS One 2012; 7(6)e36890
[] [PMID: 22723832]
Dodel RC, Du Y, Bales KR, Gao F, Paul SM. Sodium salicylate and 17β-estradiol attenuate nuclear transcription factor NF-kappaB translocation in cultured rat astroglial cultures following exposure to amyloid A β(1-40) and lipopolysaccharides. J Neurochem 1999; 73(4): 1453-60.
[] [PMID: 10501189]
Simoncini T, Maffei S, Basta G, et al. Estrogens and glucocorticoids inhibit endothelial vascular cell adhesion molecule-1 expression by different transcriptional mechanisms. Circ Res 2000; 87(1): 19-25.
[] [PMID: 10884367]
Wen Y, Yang S, Liu R, et al. Estrogen attenuates nuclear factor-kappa B activation induced by transient cerebral ischemia. Brain Res 2004; 1008(2): 147-54.
[] [PMID: 15145751]
Liu CJ, Lo JF, Kuo CH, et al. Akt mediates 17β-estradiol and/or estrogen receptor-α inhibition of LPS-induced tumor necresis factor-α expression and myocardial cell apoptosis by suppressing the JNK1/2-NFkappaB pathway. J Cell Mol Med 2009; 13(9B): 3655-67.
[] [PMID: 20196785]
Wu WF, Tan XJ, Dai YB, Krishnan V, Warner M, Gustafsson JÅ. Targeting estrogen receptor β in microglia and T cells to treat experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2013; 110(9): 3543-8.
[] [PMID: 23401502]
Kumar S, Patel R, Moore S, et al. Estrogen receptor β ligand therapy activates PI3K/Akt/mTOR signaling in oligodendrocytes and promotes remyelination in a mouse model of multiple sclerosis. Neurobiol Dis 2013; 56: 131-44.
[] [PMID: 23603111]
Harden JL, Egilmez NK. Indoleamine 2,3-dioxygenase and dendritic cell tolerogenicity. Immunol Invest 2012; 41(6-7): 738-64.
[] [PMID: 23017144]
McGaha TL, Huang L, Lemos H, et al. Amino acid catabolism: a pivotal regulator of innate and adaptive immunity. Immunol Rev 2012; 249(1): 135-57.
[] [PMID: 22889220]
Rosenblum ER, Stauber RE, Van Thiel DH, Campbell IM, Gavaler JS. Assessment of the estrogenic activity of phytoestrogens isolated from bourbon and beer. Alcohol Clin Exp Res 1993; 17(6): 1207-9.
[] [PMID: 8116832]
Mellanen P, Petänen T, Lehtimäki J, et al. Wood-derived estrogens: studies in vitro with breast cancer cell lines and in vivo in trout. Toxicol Appl Pharmacol 1996; 136(2): 381-8.
[] [PMID: 8619247]
Baker VA, Hepburn PA, Kennedy SJ, et al. Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays. Food Chem Toxicol 1999; 37(1): 13-22.
[] [PMID: 10069478]
Sato H, Nishida S, Tomoyori H, Sato M, Ikeda I, Imaizumi K. Oxysterol regulation of estrogen receptor α-mediated gene expression in a transcriptional activation assay system using HeLa cells. Biosci Biotechnol Biochem 2004; 68(8): 1790-3.
[] [PMID: 15322366]
Newill H, Loske R, Wagner J, Johannes C, Lorenz RL, Lehmann L. Oxidation products of stigmasterol interfere with the action of the female sex hormone 17β-estradiol in cultured human breast and endometrium cell lines. Mol Nutr Food Res 2007; 51(7): 888-98.
[] [PMID: 17579897]
Bouic PJ. The role of phytosterols and phytosterolins in immune modulation: a review of the past 10 years. Curr Opin Clin Nutr Metab Care 2001; 4(6): 471-5.
[] [PMID: 11706278]
Kimura Y, Yasukawa K, Takido M, Akihisa T, Tamura T. Inhibitory effect of some oxygenated stigmastane-type sterols on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Biol Pharm Bull 1995; 18(11): 1617-9.
[] [PMID: 8593493]
Tremblay L, Van Der Kraak G. Use of a series of homologous in vitro and in vivo assays to evaluate the endocrine modulating actions of β-sitosterol in rainbow trout. Aquat Toxicol 1998; 43(2-3): 149-62.
Tremblay L, Kraak GVD. Comparison between the effects of the phytosterol sitosterol and pulp and paper mill effluents on sexually immature rainbow trout. Environ Toxicol Chem 1999; 18(2): 329-36.
MacLatchy DL, Van Der Kraak GJ. The phytoestrogen β-sitosterol alters the reproductive endocrine status of goldfish. Toxicol Appl Pharmacol 1995; 134(2): 305-12.
[] [PMID: 7570607]
MacLatchy D, Peters L, Nickle J, Van Der Kraak G. Exposure to β‐sitosterol alters the endocrine status of goldfish differently than 17β‐estradiol. Environ Toxicol Chem 1997; 16(9): 1895-904.
Leusch FD, MacLatchy DL. In vivo implants of β-sitosterol cause reductions of reactive cholesterol pools in mitochondria isolated from gonads of male goldfish (Carassius auratus). Gen Comp Endocrinol 2003; 134(3): 255-63.
[] [PMID: 14636632]
Furukawa T, Bai C-X, Kaihara A, et al. Ginsenoside Re, a main phytosterol of Panax ginseng, activates cardiac potassium channels via a nongenomic pathway of sex hormones. Mol Pharmacol 2006; 70(6): 1916-24.
[] [PMID: 16985185]
Lee YJ, Chung E, Lee KY, Lee YH, Huh B, Lee SK. Ginsenoside-Rg1, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor. Mol Cell Endocrinol 1997; 133(2): 135-40.
[] [PMID: 9406859]
Cho J, Park W, Lee S, Ahn W, Lee Y. Ginsenoside-Rb1 from Panax ginseng C.A. Meyer activates estrogen receptor-α and -β, independent of ligand binding. J Clin Endocrinol Metab 2004; 89(7): 3510-5.
[] [PMID: 15240639]
Theoharides TC, Asadi S, Patel AB. Focal brain inflammation and autism. J Neuroinflammation 2013; 10: 46.
[] [PMID: 23570274]
Fuster-Matanzo A, Llorens-Martín M, Hernández F, Avila J. Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediators Inflamm 2013; 2013260925
[] [PMID: 23690659]
Koutsilieri E, Lutz MB, Scheller C. Autoimmunity, dendritic cells and relevance for Parkinson’s disease. J Neural Transm (Vienna) 2013; 120(1): 75-81.
[] [PMID: 22699458]
Stertz L, Magalhães PV, Kapczinski F. Is bipolar disorder an inflammatory condition? The relevance of microglial activation. Curr Opin Psychiatry 2013; 26(1): 19-26.
[] [PMID: 23196997]
Wang J, Wu F, Shi C. Substitution of membrane cholesterol with β-sitosterol promotes nonamyloidogenic cleavage of endogenous amyloid precursor protein. Neuroscience 2013; 247: 227-33.
[] [PMID: 23707801]
Shi C, Wu F, Zhu XC, Xu J. Incorporation of β-sitosterol into the membrane increases resistance to oxidative stress and lipid peroxidation via estrogen receptor-mediated PI3K/GSK3β signaling. Biochim Biophys Acta 2013; 1830(3): 2538-44.
[] [PMID: 23266618]
Burg VK, Grimm HS, Rothhaar TL, et al. Plant sterols the better cholesterol in Alzheimer’s disease? A mechanistical study. J Neurosci 2013; 33(41): 16072-87.
[] [PMID: 24107941]
Ayaz M, Junaid M, Ullah F, et al. Anti-Alzheimer’s studies on β-sitosterol isolated from Polygonum hydropiper L. Front Pharmacol 2017; 8: 697.
[] [PMID: 29056913]
Jung HA, Ali MY, Choi RJ, Jeong HO, Chung HY, Choi JS. Kinetics and molecular docking studies of fucosterol and fucoxanthin, BACE1 inhibitors from brown algae Undaria pinnatifida and Ecklonia stolonifera. Food Chem Toxicol 2016; 89: 104-11.
[] [PMID: 26825629]
Ben Halima S, Rajendran L. Membrane anchored and lipid raft targeted β-secretase inhibitors for Alzheimer’s disease therapy. J Alzheimers Dis 2011; 24(s2)(Suppl. 2): 143-52.
[] [PMID: 21460437]
Suzuki N, Cheung TT, Cai X-D, et al. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 1994; 264(5163): 1336-40.
[] [PMID: 8191290]
Ledesma MD, Abad-Rodriguez J, Galvan C, et al. Raft disorganization leads to reduced plasmin activity in Alzheimer’s disease brains. EMBO Rep 2003; 4(12): 1190-6.
[] [PMID: 14618158]
Pérez-Cañamás A, Sarroca S, Melero-Jerez C, et al. A diet enriched with plant sterols prevents the memory impairment induced by cholesterol loss in senescence-accelerated mice. Neurobiol Aging 2016; 48: 1-12.
[] [PMID: 27622776]
Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 2001; 81(2): 741-66.
[] [PMID: 11274343]
Jansen D, Janssen CI, Vanmierlo T, et al. Cholesterol and synaptic compensatory mechanisms in Alzheimer’s disease mice brain during aging. J Alzheimers Dis 2012; 31(4): 813-26.
[] [PMID: 22717611]
Jones L, Holmans PA, Hamshere ML, et al. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer’s disease. PLoS One 2010; 5(11)e13950
[] [PMID: 21085570]
Kölsch H, Heun R, Jessen F, et al. Alterations of cholesterol precursor levels in Alzheimer’s disease. Biochim Biophys Acta 2010; 1801(8): 945-50.
[] [PMID: 20226877]
Jiang Q, Lee CY, Mandrekar S, et al. ApoE promotes the proteolytic degradation of Abeta. Neuron 2008; 58(5): 681-93.
[] [PMID: 18549781]
Vanmierlo T, Rutten K, Dederen J, et al. Liver X receptor activation restores memory in aged AD mice without reducing amyloid. Neurobiol Aging 2011; 32(7): 1262-72.
[] [PMID: 19674815]
Lei C, Lin R, Wang J, et al. Amelioration of amyloid β-induced retinal inflammatory responses by a LXR agonist TO901317 is associated with inhibition of the NF-κB signaling and NLRP3 inflammasome. Neuroscience 2017; 360: 48-60.
[] [PMID: 28760679]
Stachel SJ, Zerbinatti C, Rudd MT, et al. Identification and in vivo evaluation of liver X receptor β-Selective agonists for the potential treatment of alzheimer’s disease. J Med Chem 2016; 59(7): 3489-98.
[] [PMID: 27011007]
Sandoval-Hernández AG, Hernández HG, Restrepo A, et al. Liver X receptor agonist modifies the DNA methylation profile of synapse and neurogenesis-related genes in the triple transgenic mouse model of Alzheimer’s disease. J Mol Neurosci 2016; 58(2): 243-53.
[] [PMID: 26553261]
Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest 2006; 116(3): 607-14.
[] [PMID: 16511593]
Bensinger SJ, Tontonoz P. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 2008; 454(7203): 470-7.
[] [PMID: 18650918]
Hong C, Tontonoz P. Liver X receptors in lipid metabolism: opportunities for drug discovery. Nat Rev Drug Discov 2014; 13(6): 433-44.
[] [PMID: 24833295]
Nelissen K, Mulder M, Smets I, et al. Liver X receptors regulate cholesterol homeostasis in oligodendrocytes. J Neurosci Res 2012; 90(1): 60-71.
[] [PMID: 21972082]
Sodhi RK, Singh N. Liver X receptors: emerging therapeutic targets for Alzheimer’s disease. Pharmacol Res 2013; 72: 45-51.
[] [PMID: 23542729]
Zelcer N, Khanlou N, Clare R, et al. Attenuation of neuroinflammation and Alzheimer’s disease pathology by liver x receptors. Proc Natl Acad Sci USA 2007; 104(25): 10601-6.
[] [PMID: 17563384]
Repa JJ, Liang G, Ou J, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 2000; 14(22): 2819-30.
[] [PMID: 11090130]
Kim GH, Oh G-S, Yoon J, Lee GG, Lee K-U, Kim S-W. Hepatic TRAP80 selectively regulates lipogenic activity of liver X receptor. J Clin Invest 2015; 125(1): 183-93.
[] [PMID: 25437875]
Schultz JR, Tu H, Luk A, et al. Role of LXRs in control of lipogenesis. Genes Dev 2000; 14(22): 2831-8.
[] [PMID: 11090131]
Mulder M. Sterols in the central nervous system. Curr Opin Clin Nutr Metab Care 2009; 12(2): 152-8.
[] [PMID: 19202386]
Park SJ, Kim DH, Jung JM, et al. The ameliorating effects of stigmasterol on scopolamine-induced memory impairments in mice. Eur J Pharmacol 2012; 676(1-3): 64-70.
[] [PMID: 22173129]
Mohibbullah M, Hannan MA, Choi J-Y, et al. The edible marine alga gracilariopsis chorda alleviates hypoxia/reoxygenation-induced oxidative stress in cultured hippocampal neurons. J Med Food 2015; 18(9): 960-71.
[] [PMID: 26106876]
Vanmierlo T, Bogie JFJ, Mailleux J, et al. Plant sterols: Friend or foe in CNS disorders? Prog Lipid Res 2015; 58: 26-39.
[] [PMID: 25623279]
Vanmierlo T, Weingärtner O, van der Pol S, et al. Dietary intake of plant sterols stably increases plant sterol levels in the murine brain. J Lipid Res 2012; 53(4): 726-35.
[] [PMID: 22279184]
Báez-Becerra C, Filipello F, Sandoval-Hernández A, Arboleda H, Arboleda G. Liver X receptor agonist GW3965 regulates synaptic function upon amyloid beta exposure in hippocampal neurons. Neurotox Res 2018; 33(3): 569-79.
[] [PMID: 29297151]
Haque MN, Hannan MA, Dash R, Moon IS. Natural LXRβ agonist stigmasterol confers protection against excitotoxicity after hypoxia-reoxygenation (H/R) injury via regulation of mitophagy in primary hippocampal neurons. bioRxiv 2019.707059
Adcox C, Boyd L, Oehrl L, Allen J, Fenner G. Comparative effects of phytosterol oxides and cholesterol oxides in cultured macrophage-derived cell lines. J Agric Food Chem 2001; 49(4): 2090-5.
[] [PMID: 11308372]
Tabata RC, Wilson JM, Ly P, et al. Chronic exposure to dietary sterol glucosides is neurotoxic to motor neurons and induces an ALS-PDC phenotype. Neuromolecular Med 2008; 10(1): 24-39.
[] [PMID: 18196479]
Panov A, Kubalik N, Brooks BR, Shaw CA. In vitro effects of cholesterol β-D-glucoside, cholesterol and cycad phytosterol glucosides on respiration and reactive oxygen species generation in brain mitochondria. J Membr Biol 2010; 237(2-3): 71-7.
[] [PMID: 20938651]

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