Natural Products for the Treatment of Neurodegenerative Diseases

doi:10.2174/0929867326666190527120614
摘要

神经退行性疾病是一种异质性疾病，其特征是中枢神经系统或周围神经系统的结构和功能的进行性退化。阿尔茨海默病(AD)、帕金森病(PD)和脊髓损伤(SCI)是常见的神经退行性疾病，多见于60岁以上人群。随着老龄化社会的迅速发展，全世界有6000多万人患有这些无法治愈的疾病。因此，寻找新的药物和治疗方法已成为一个越来越重要的研究课题。天然药物特别是中药的天然产物是药物的重要来源，受到药师的广泛关注。在这篇综述中，为了促进药师对这些有用的天然产物进行进一步的化学修饰，我们将汇集近年来对中药中具有神经保护作用的单一天然化合物的研究。
关键词: 天然产物，神经退行性疾病，阿尔茨海默病，帕金森病，脊髓损伤，清洁发展机制
« Previous Next »
[1] 
He, W.; Goodkind, D.; Kowal, P. An Aging World. U.S. Census Bureau, International. Population Reports., 2016.
[2] 
Cacabelos, R. Parkinson’s disease: from pathogenesis to pharmacogenomics. Int. J. Mol. Sci.,  2017, 18(3), 551.
[http://dx.doi.org/10.3390/ijms18030551 ] [PMID:  28273839] 
[3] 
Wu, T.Y.; Chen, C.P.; Jinn, T.R. Traditional Chinese medicines and Alzheimer’s disease. Taiwan. J. Obstet. Gynecol.,  2011, 50(2), 131-135.
[http://dx.doi.org/10.1016/j.tjog.2011.04.004 ] [PMID:  21791295] 
[4] 
Hempen, C.H.; Fischer, T. Materia medica for Chinese medicine: plants, minerals and animal products; Elsevier Health Sciences: London, 2009. 
[5] 
Law, B.Y.; Mok, S.W.; Wu, A.G.; Lam, C.W.; Yu, M.X.; Wong, V.K. New potential pharmacological functions of Chinese herbal medicines via regulation of autophagy. Molecules,  2016, 21(3), 359.
[http://dx.doi.org/10.3390/molecules21030359 ] [PMID:  26999089] 
[6] 
Yu, J.; Xie, J.; Mao, X.J.; Wei, H.; Zhao, S.L.; Ma, Y.G.; Li, N.; Zhao, R.H. Comparison of laxative and antioxidant activities of raw, processed and fermented Polygoni Multiflori radix. Chin. J. Nat. Med.,  2012, 10(1), 63-67.
[http://dx.doi.org/10.1016/S1875-5364(12)60014-4 ] [PMID:  23302534] 
[7] 
Sun, G.G.; Shih, J.H.; Chiou, S.H.; Hong, C.J.; Lu, S.W.; Pao, L.H. Chinese herbal medicines promote hippocampal neuroproliferation, reduce stress hormone levels, inhibit apoptosis, and improve behavior in chronically stressed mice. J. Ethnopharmacol.,  2016, 193, 159-168.
[http://dx.doi.org/10.1016/j.jep.2016.07.025 ] [PMID:  27416803] 
[8] 
Li, H.; Kang, T.; Qi, B.; Kong, L.; Jiao, Y.; Cao, Y.; Zhang, J.; Yang, J. Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of D-galactose/AlCl3 inducing rats model of Alzheimer’s disease. J. Ethnopharmacol.,  2016, 179, 162-169.
[http://dx.doi.org/10.1016/j.jep.2015.12.020 ] [PMID:  26721223] 
[9] 
Huang, J.L.; Jing, X.; Tian, X.; Qin, M.C.; Xu, Z.H.; Wu, D.P.; Zhong, Z.G. Neuroprotective properties of Panax notoginseng saponins via preventing oxidative stress injury in SAMP8 mice. Evid. Based Complement. Alternat. Med.,  2017, 2017,8713561.
[http://dx.doi.org/10.1155/2017/8713561 ] [PMID:  28250796] 
[10] 
Li, X.Z.; Zhang, S.N.; Wang, K.X.; Liu, S.M.; Lu, F. iTRAQ-based quantitative proteomics study on the neuroprotective effects of extract of Acanthopanax senticosus harm on SH-SY5Y cells overexpressing A53T mutant α-synuclein. Neurochem. Int.,  2014, 72, 37-47.
[http://dx.doi.org/10.1016/j.neuint.2014.04.012 ] [PMID:  24795107] 
[11] 
Qiu, J.; Wang, X.; Song, C. Neuroprotective and antioxidant lanostanoid triterpenes from the fruiting bodies of Ganoderma atrum. Fitoterapia,  2016, 109, 75-79.
[http://dx.doi.org/10.1016/j.fitote.2015.12.008 ] [PMID:  26709153] 
[12] 
Fang, F.; Peng, T.; Yang, S.; Wang, W.; Zhang, Y.; Li, H. Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of AKT. Int. J. Dev. Neurosci.,  2016, 52, 66-74.
[http://dx.doi.org/10.1016/j.ijdevneu.2016.05.004 ] [PMID:  27196502] 
[13] 
Zhang, B.; Li, Q.; Chu, X.; Sun, S.; Chen, S. Salidroside reduces tau hyperphosphorylation via up-regulating GSK-3β phosphorylation in a tau transgenic Drosophila model of Alzheimer’s disease. Transl. Neurodegener.,  2016, 5, 21.
[http://dx.doi.org/10.1186/s40035-016-0068-y ] [PMID:  27933142] 
[14] 
Jia, D.; Rao, C.; Xue, S.; Lei, J. Purification, characterization and neuroprotective effects of a polysaccharide from Gynostemma pentaphyllum. Carbohydr. Polym.,  2015, 122, 93-100.
[http://dx.doi.org/10.1016/j.carbpol.2014.12.032 ] [PMID:  25817647] 
[15] 
Zamani, Z.; Reisi, P.; Alaei, H.; Pilehvarian, A.A. Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic Alzheimer’s disease. Adv. Biomed. Res.,  2012, 1, 26.
[http://dx.doi.org/10.4103/2277-9175.98150 ] [PMID:  23210085] 
[16] 
Suk, K. Regulation of neuroinflammation by herbal medicine and its implications for neurodegenerative diseases. A focus on traditional medicines and flavonoids. Neurosignals,  2005, 14(1-2), 23-33.
[http://dx.doi.org/10.1159/000085383 ] [PMID:  15956812] 
[17] 
Adams, M.; Gmünder, F.; Hamburger, M. Plants traditionally used in age related brain disorders a survey of ethnobotanical literature. J. Ethnopharmacol.,  2007, 113(3), 363-381.
[http://dx.doi.org/10.1016/j.jep.2007.07.016 ] [PMID:  17720341] 
[18] 
McClatchey, W.C.; Mahady, G.B.; Bennett, B.C.; Shiels, L.; Savo, V. Ethnobotany as a pharmacological research tool and recent developments in CNS-active natural products from ethnobotanical sources. Pharmacol. Ther.,  2009, 123(2), 239-254.
[http://dx.doi.org/10.1016/j.pharmthera.2009.04.002 ] [PMID:  19422851] 
[19] 
Ho, Y.S.; So, K.F.; Chang, R.C.C. Anti-aging herbal medicine how and why can they be used in aging-associated neurodegenerative diseases? Ageing Res. Rev.,  2010, 9(3), 354-362.
[http://dx.doi.org/10.1016/j.arr.2009.10.001 ] [PMID:  19833234] 
[20] 
Guerrero, R.F.; García-Parrilla, M.C.; Puertas, B.; Cantos-Villar, E. Wine, resveratrol and health: a review. Nat. Prod. Commun.,  2009, 4(5), 635-658.
[http://dx.doi.org/10.1177/1934578X0900400503 ] [PMID:  19445315] 
[21] 
Zhang, X.S.; Li, W.; Wu, Q.; Wu, L.Y.; Ye, Z.N.; Liu, J.P.; Zhuang, Z.; Zhou, M-L.; Zhang, X.; Hang, C-H. Resveratrol attenuates acute inflammatory injury in experimental sub-arachnoid hemorrhage in rats via inhibition of TLR4 pathway. Int. J. Mol. Sci.,  2016, 17(8), 1131.
[http://dx.doi.org/10.3390/ijms17081331] 
[22] 
Della-Morte, D.; Dave, K.R.; DeFazio, R.A.; Bao, Y.C.; Raval, A.P.; Perez-Pinzon, M.A. Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway. Neuroscience,  2009, 159(3), 993-1002.
[http://dx.doi.org/10.1016/j.neuroscience.2009.01.017 ] [PMID:  19356683] 
[23] 
Lin, C.J.; Chen, T.H.; Yang, L.Y.; Shih, C.M. Resveratrol protects astrocytes against traumatic brain injury through inhibiting apoptotic and autophagic cell death. Cell Death Dis.,  2014, 5,e1147.
[http://dx.doi.org/10.1038/cddis.2014.123] 
[24] 
Rege, S.D.; Geetha, T.; Griffin, G.D.; Broderick, T.L.; Babu, J.R. Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front. Aging Neurosci.,  2014, 6, 218.
[http://dx.doi.org/10.3389/fnagi.2014.00218 ] [PMID:  25309423] 
[25] 
Shao, A.W.; Wu, H.J.; Chen, S.; Ammar, A.B.; Zhang, J.M.; Hong, Y. Resveratrol attenuates early brain injury after subarachnoid hemorrhage through inhibition of NF-kB-dependent inflammatory/MMP-9 pathway. CNS Neurosci. Ther.,  2014, 20(2), 182-185.
[http://dx.doi.org/10.1111/cns.12194 ] [PMID:  24279692] 
[26] 
Zhang, X.; Wu, Q.; Zhang, Q.; Lu, Y.; Liu, J.; Li, W.; Lv, S.; Zhou, M.; Zhang, X.; Hang, C. Resveratrol attenuates early brain injury after experimental subarachnoid hemorrhage via inhibition of NLRP3 inflammasome activation. Front. Neurosci.,  2017, 11, 611.
[http://dx.doi.org/10.3389/fnins.2017.00611 ] [PMID:  29163015] 
[27] 
Bertelli, A.A.; Giovannini, L.; Stradi, R.; Urien, S.; Tillement, J.P.; Bertelli, A. Kinetics of trans and cis-resveratrol (3,4′,5-trihydroxystilbene) after red wine oral administration in rats. Int. J. Clin. Pharmacol. Res.,  1996, 16(4-5), 77-81.
[PMID:  9172004] 
[28] 
Bertelli, A.A.; Giovannini, L.; Stradi, R.; Bertelli, A.; Tillement, J.P. Plasma, urine and tissue levels of trans- and cis-resveratrol (3,4′,5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats. Int. J. Tissue React.,  1996, 18(2-3), 67-71.
[PMID:  9172004] 
[29] 
Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E., Jr; Walle, U.K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos.,  2004, 32(12), 1377-1382.
[http://dx.doi.org/10.1124/dmd.104.000885 ] [PMID:  15333514] 
[30] 
Wang, D.; Hang, T.; Wu, C.; Liu, W. Identification of the major metabolites of resveratrol in rat urine by HPLC-MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2005, 829(1-2), 97-106.
[http://dx.doi.org/10.1016/j.jchromb.2005.09.040 ] [PMID:  16243591] 
[31] 
Soleas, G.J.; Angelini, M.; Grass, L.; Diamandis, E.P.; Goldberg, D.M. Absorption of trans-resveratrol in rats. Methods Enzymol.,  2001, 335, 145-154.
[http://dx.doi.org/10.1016/S0076-6879(01)35239-4 ] [PMID:  11400363] 
[32] 
Goldberg, D.M.; Yan, J.; Soleas, G.J. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin. Biochem.,  2003, 36(1), 79-87.
[http://dx.doi.org/10.1016/S0009-9120(02)00397-1 ] [PMID:  12554065] 
[33] 
Sehba, F.A.; Pluta, R.M.; Zhang, J.H. Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury. Mol. Neurobiol.,  2011, 43(1), 27-40.
[http://dx.doi.org/10.1007/s12035-010-8155-z ] [PMID:  21161614] 
[34] 
Li, J.; Chen, J.; Mo, H.; Chen, J.; Qian, C.; Yan, F.; Gu, C.; Hu, Q.; Wang, L.; Chen, G. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury after subarachnoid hemorrhage. Mol. Neurobiol.,  2016, 53(4), 2668-2678.
[http://dx.doi.org/10.1007/s12035-015-9318-8 ] [PMID:  26143258] 
[35] 
Chen, S.; Feng, H.; Sherchan, P.; Klebe, D.; Zhao, G.; Sun, X.; Zhang, J.; Tang, J.; Zhang, J.H. Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog. Neurobiol.,  2014, 115, 64-91.
[http://dx.doi.org/10.1016/j.pneurobio.2013.09.002 ] [PMID:  24076160] 
[36] 
Yuan, J.; Liu, W.; Zhu, H.; Zhang, X.; Feng, Y.; Chen, Y.; Feng, H.; Lin, J. Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice. J. Surg. Res.,  2017, 207, 85-91.
[http://dx.doi.org/10.1016/j.jss.2016.08.090 ] [PMID:  27979493] 
[37] 
Chen, S.; Ma, Q.; Krafft, P.R.; Hu, Q.; Rolland, W., II; Sherchan, P.; Zhang, J.; Tang, J.; Zhang, J.H. P2X7R/cryopyrin inflammasome axis inhibition reduces neuroinflammation after SAH. Neurobiol. Dis.,  2013, 58, 296-307.
[http://dx.doi.org/10.1016/j.nbd.2013.06.011 ] [PMID:  23816751] 
[38] 
Dong, Y.; Fan, C.; Hu, W.; Jiang, S.; Ma, Z.; Yan, X.; Deng, C.; Di, S.; Xin, Z.; Wu, G.; Yang, Y.; Reiter, R.J.; Liang, G. Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling. J. Pineal Res.,  2016, 60(3), 253-262.
[http://dx.doi.org/10.1111/jpi.12300 ] [PMID:  26639408] 
[39] 
Zhang, Z.; Zhang, Z.; Lu, H.; Yang, Q.; Wu, H.; Wang, J. Microglial polarization and inflammatory mediators after in-tracerebral hemorrhage. Mol. Neurobiol.,  2017, 54(3), 1874-1886.
[http://dx.doi.org/10.1007/s12035-016-9785-6 ] [PMID:  26894396] 
[40] 
Alam, P.; Siddiqi, K.; Chturvedi, S.K.; Khan, R.H. Protein aggregation: from background to inhibition strategies. Int. J. Biol. Macromol.,  2017, 103, 208-219.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.048 ] [PMID:  28522393] 
[41] 
Chaturvedi, S.K.; Siddiqi, M.K.; Alam, P.; Khan, R.H. Protein misfolding and aggregation: mechanism, factors and detection. Process Biochem.,  2016, 51(9), 1183-1192.
[http://dx.doi.org/10.1016/j.procbio.2016.05.015] 
[42] 
Kim, J.; Lee, H.J.; Lee, K.W. Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J. Neurochem.,  2010, 112(6), 1415-1430.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06562.x ] [PMID:  20050972] 
[43] 
Sun, A.Y.; Wang, Q.; Simonyi, A.; Sun, G.Y. Botanical phenolics and brain health. Neuromolecular Med.,  2008, 10(4), 259-274.
[http://dx.doi.org/10.1007/s12017-008-8052-z ] [PMID:  19191039] 
[44] 
Porat, Y.; Abramowitz, A.; Gazit, E. Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem. Biol. Drug Des.,  2006, 67(1), 27-37.
[http://dx.doi.org/10.1111/j.1747-0285.2005.00318.x ] [PMID:  16492146] 
[45] 
Luo, Y.; Smith, J.V.; Paramasivam, V.; Burdick, A.; Curry, K.J.; Buford, J.P.; Khan, I.; Netzer, W.J.; Xu, H.; Butko, P. Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc. Natl. Acad. Sci. USA,  2002, 99(19), 12197-12202.
[http://dx.doi.org/10.1073/pnas.182425199 ] [PMID:  12213959] 
[46] 
Luchsinger, J.A.; Tang, M.X.; Siddiqui, M.; Shea, S.; Mayeux, R. Alcohol intake and risk of dementia. J. Am. Geriatr. Soc.,  2004, 52(4), 540-546.
[http://dx.doi.org/10.1111/j.1532-5415.2004.52159.x ] [PMID:  15066068] 
[47] 
Wang, J.; Ho, L.; Zhao, W.; Ono, K.; Rosensweig, C.; Chen, L.; Humala, N.; Teplow, D.B.; Pasinetti, G.M. Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer’s disease. J. Neurosci.,  2008, 28(25), 6388-6392.
[http://dx.doi.org/10.1523/JNEUROSCI.0364-08.2008 ] [PMID:  18562609] 
[48] 
Wang, J.; Ho, L.; Zhao, Z.; Seror, I.; Humala, N.; Dickstein, D.L.; Thiyagarajan, M.; Percival, S.S.; Talcott, S.T.; Pasinetti, G.M. Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer’s disease. FASEB J.,  2006, 20(13), 2313-2320.
[http://dx.doi.org/10.1096/fj.06-6281com ] [PMID:  17077308] 
[49] 
Feng, Y.; Wang, X.P.; Yang, S.G.; Wang, Y.J.; Zhang, X.; Du, X.T.; Sun, X.X.; Zhao, M.; Huang, L.; Liu, R.T. Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation. Neurotoxicology,  2009, 30(6), 986-995.
[http://dx.doi.org/10.1016/j.neuro.2009.08.013 ] [PMID:  19744518] 
[50] 
Karuppagounder, S.S.; Pinto, J.T.; Xu, H.; Chen, H.L.; Beal, M.F.; Gibson, G.E. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem. Int.,  2009, 54(2), 111-118.
[http://dx.doi.org/10.1016/j.neuint.2008.10.008 ] [PMID:  19041676] 
[51] 
Cieślik-Boczula, K.; Trombik, P. Resveratrol modulates fibrillogenesis in a poly-l-lysine peptide. Int. J. Biol. Macromol.,  2019, 125, 630-641.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.12.100 ] [PMID:  30552924] 
[52] 
Spanos, G.K.; Wilde, E.A.; Bigler, E.D.; Cleavinger, H.B.; Fearing, M.A.; Levin, H.S.; Li, X.; Hunter, J.V. cerebellar atrophy after moderate-to-severe pediatric traumatic brain injury. AJNR Am. J. Neuroradiol.,  2007, 28(3), 537-542.
[PMID:  17353332] 
[53] 
Soto-Ares, G.; Vinchon, M.; Delmaire, C.; Abecidan, E.; Dhellemes, P.; Pruvo, J.P. Cerebellar atrophy after severe traumatic head injury in children. Childs Nerv. Syst.,  2001, 17(4-5), 263-269.
[http://dx.doi.org/10.1007/s003810000411 ] [PMID:  11398947] 
[54] 
Mar, F.M.; Bonni, A.; Sousa, M.M. Cell intrinsic control of axon regeneration. EMBO Rep.,  2014, 15(3), 254-263.
[http://dx.doi.org/10.1002/embr.201337723 ] [PMID:  24531721] 
[55] 
Shanan, N. GhasemiGharagoz, A.; Abdel-Kader, R.; Breitinger, H.G. The effect of pyrroloquinoline quinone and resveratrol on the survival and regeneration of cerebellar granular neurons. Neurosci. Lett.,  2019, 694, 192-197.
[http://dx.doi.org/10.1016/j.neulet.2018.12.002 ] [PMID:  30528876] 
[56] 
Zhang, F.; Shi, J.S.; Zhou, H.; Wilson, B.; Hong, J.S.; Gao, H.M. Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. Mol. Pharmacol.,  2010, 78(3), 466-477.
[http://dx.doi.org/10.1124/mol.110.064535 ] [PMID:  20554604] 
[57] 
Sun, D.; Yue, Q.; Guo, W.; Li, T.; Zhang, J.; Li, G.; Liu, Z.; Sun, J. Neuroprotection of resveratrol against neurotoxicity induced by methamphetamine in mouse mesencephalic dopaminergic neurons. Biofactors,  2015, 41(4), 252-260.
[http://dx.doi.org/10.1002/biof.1221 ] [PMID:  26212417] 
[58] 
Mahdavi, H.; Hadadi, Z.; Ahmadi, M.A. Review of the anti-oxidation, anti-inflammatory and anti-tumor properties of curcumin. Tradit. Integr. Med.,  2017, 2, 188-195.
[59] 
Gupta, S.C.; Patchva, S.; Aggarwal, B.B. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J.,  2013, 15(1), 195-218.
[http://dx.doi.org/10.1208/s12248-012-9432-8 ] [PMID:  23143785] 
[60] 
Brondino, N.; Re, S.; Boldrini, A.; Cuccomarino, A.; Lanati, N.; Barale, F.; Politi, P. Curcumin as a therapeutic agent in dementia: a mini systematic review of human studies. ScientificWorldJournal,  2014, 2014,174282.
[http://dx.doi.org/10.1155/2014/174282 ] [PMID:  24578620] 
[61] 
Serafini, M.M.; Catanzaro, M.; Rosini, M.; Racchi, M.; Lanni, C. Curcumin in Alzheimer’s disease: Can we think to new strategies and perspectives for this molecule? Pharmacol. Res.,  2017, 124, 146-155.
[http://dx.doi.org/10.1016/j.phrs.2017.08.004 ] [PMID:  28811228] 
[62] 
Maiti, P.; Dunbar, G.L. Use of curcumin, a natural polyphe-nol for targeting molecular pathways in treating age-related neurodegenerative diseases. Int. J. Mol. Sci.,  2018, 19(6), 19.
[http://dx.doi.org/10.3390/ijms19061637 ] [PMID:  29857538] 
[63] 
den Haan, J.; Morrema, T.H.J.; Rozemuller, A.J.; Bouwman, F.H.; Hoozemans, J.J.M. Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics. Acta Neuropathol. Commun.,  2018, 6(1), 75.
[http://dx.doi.org/10.1186/s40478-018-0577-2 ] [PMID:  30092839] 
[64] 
Samarghandian, S.; Azimi-Nezhad, M.; Farkhondeh, T.; Samini, F. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney. Biomed. Pharmacother.,  2017, 87, 223-229.
[http://dx.doi.org/10.1016/j.biopha.2016.12.105 ] [PMID:  28061405] 
[65] 
Ahmad, B.; Borana, M.S.; Chaudhary, A.P. Understanding curcumin-induced modulation of protein aggregation. Int. J. Biol. Macromol.,  2017, 100, 89-96.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.06.053 ] [PMID:  27327907] 
[66] 
Sarkar, B.; Dhiman, M.; Mittal, S.; Mantha, A.K. Curcumin revitalizes Amyloid beta (25-35)-induced and organophosphate pesticides pestered neurotoxicity in SH-SY5Y and IMR-32 cells via activation of APE1 and Nrf2. Metab. Brain Dis.,  2017, 32(6), 2045-2061.
[http://dx.doi.org/10.1007/s11011-017-0093-2 ] [PMID:  28861684] 
[67] 
Zhang, L.; Fang, Y.; Cheng, X.; Lian, Y.J.; Xu, H.L.; Zeng, Z.S.; Zhu, H.C. Curcumin exerts effects on the pathophysiology of Alzheimer’s disease by regulating PI(3,5)P2 and transient receptor potential mucolipin-1 expression. Front. Neurol.,  2017, 8, 531.
[http://dx.doi.org/10.3389/fneur.2017.00531 ] [PMID:  29062301] 
[68] 
Liaquat, L.; Batool, Z.; Sadir, S.; Rafiq, S.; Shahzad, S.; Perveen, T.; Haider, S. Naringenin-induced enhanced antioxidant defence system meliorates cholinergic neurotransmission and consolidates memory in male rats. Life Sci.,  2018, 194, 213-223.
[http://dx.doi.org/10.1016/j.lfs.2017.12.034 ] [PMID:  29287782] 
[69] 
Nguyen, T.T.; Vuu, M.D.; Huynh, M.A.; Yamaguchi, M.; Tran, L.T.; Dang, T.P.T. Curcumin effectively rescued Parkinson’s disease-like phenotypes in a novel drosophila melanogaster model with dUCH Knockdown. Oxid. Med. Cell. Longev., 2018.20182038267
[http://dx.doi.org/10.1155/2018/2038267 ] [PMID:  30057672] 
[70] 
Wang, Y.L.; Ju, B.; Zhang, Y.Z.; Yin, H.L.; Liu, Y.J.; Wang, S.S.; Zeng, Z.L.; Yang, X.P.; Wang, H.T.; Li, J.F. Protective effect of curcumin against oxidative stress-induced injury in rats with Parkinson’s disease through the Wnt/-catenin signaling pathway. Cell. Physiol. Biochem.,  2017, 43(6), 2226-2241.
[http://dx.doi.org/10.1159/000484302 ] [PMID:  29069652] 
[71] 
Snigdha, D.M.; Surjyanarayan, M.; Jayvadan, P. Intranasal mucoadhesive microemulsion for neuroprotective effect of curcumin in mPTP induced Parkinson model. Braz. J. Pharm. Sci.,  2017, 53(2)
[http://dx.doi.org/10.1590/s2175-97902017000215223 ] 
[72] 
Sevastre-Berghian, A.C.; Făgărăsan, V.; Toma, V.A.; Bâldea, I.; Olteanu, D.; Moldovan, R.; Decea, N.; Filip, G.A.; Clichici, S.V. Curcumin reverses the diazepam-induced cognitive impairment by modulation of oxidative stress and ERK 1/2/NF-B pathway in brain. Oxid. Med. Cell. Longev., 2017.20173037876
[http://dx.doi.org/10.1155/2017/3037876 ] [PMID:  29098059] 
[73] 
Motaghinejad, M.; Motevalian, M.; Fatima, S.; Hashemi, H.; Gholami, M. Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats. Biomed. Pharmacother.,  2017, 87, 721-740.
[http://dx.doi.org/10.1016/j.biopha.2016.12.020 ] [PMID:  28095363] 
[74] 
Motaghinejad, M.; Motevalian, M.; Fatima, S.; Faraji, F.; Mozaffari, S. The neuroprotective effect of curcumin against nicotine-induced neurotoxicity is mediated by CREB-BDNF signaling pathway. Neurochem. Res.,  2017, 42(10), 2921-2932.
[http://dx.doi.org/10.1007/s11064-017-2323-8 ] [PMID:  28608236] 
[75] 
Ireson, C.R.; Jones, D.J.; Orr, S.; Coughtrie, M.W.; Boocock, D.J.; Williams, M.L.; Farmer, P.B.; Steward, W.P.; Gescher, A.J. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol. Biomarkers Prev.,  2002, 11(1), 105-111.
[PMID:  11815407] 
[76] 
Marczylo, T.H.; Steward, W.P.; Gescher, A.J. Rapid analysis of curcumin and curcumin metabolites in rat biomatrices using a novel ultraperformance liquid chromatography (UPLC) method. J. Agric. Food Chem.,  2009, 57(3), 797-803.
[http://dx.doi.org/10.1021/jf803038f ] [PMID:  19152267] 
[77] 
Marczylo, T.H.; Verschoyle, R.D.; Cooke, D.N.; Morazzoni, P.; Steward, W.P.; Gescher, A.J. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother. Pharmacol.,  2007, 60(2), 171-177.
[http://dx.doi.org/10.1007/s00280-006-0355-x ] [PMID:  17051370] 
[78] 
Baum, L.; Lam, C.W.; Cheung, S.K.; Kwok, T.; Lui, V.; Tsoh, J.; Lam, L.; Leung, V.; Hui, E.; Ng, C.; Woo, J.; Chiu, H.F.; Goggins, W.B.; Zee, B.C.; Cheng, K.F.; Fong, C.Y.; Wong, A.; Mok, H.; Chow, M.S.; Ho, P.C.; Ip, S.P.; Ho, C.S.; Yu, X.W.; Lai, C.Y.; Chan, M.H.; Szeto, S.; Chan, I.H.; Mok, V. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J. Clin. Psychopharmacol.,  2008, 28(1), 110-113.
[http://dx.doi.org/10.1097/jcp.0b013e318160862c ] [PMID:  18204357] 
[79] 
Ringman, J.M.; Frautschy, S.A.; Teng, E.; Begum, A.N.; Bardens, J.; Beigi, M.; Gylys, K.H.; Badmaev, V.; Heath, D.D.; Apostolova, L.G.; Porter, V.; Vanek, Z.; Marshall, G.A.; Hellemann, G.; Sugar, C.; Masterman, D.L.; Montine, T.J.; Cummings, J.L.; Cole, G.M. Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res. Ther.,  2012, 4(5), 43.
[http://dx.doi.org/10.1186/alzrt146 ] [PMID:  23107780] 
[80] 
Damar, U.; Gersner, R.; Johnstone, J.T.; Schachter, S.; Rotenberg, A. Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research. Expert Rev. Neurother.,  2016, 16(6), 671-680.
[http://dx.doi.org/10.1080/14737175.2016.1175303 ] [PMID:  27086593] 
[81] 
Zhao, Q.; Tang, X.C. Effects of huperzine A on acetylcholinesterase isoforms in vitro: comparison with tacrine, donepezil, rivastigmine and physostigmine. Eur. J. Pharmacol.,  2002, 455(2-3), 101-107.
[http://dx.doi.org/10.1016/S0014-2999(02)02589-X ] [PMID:  12445575] 
[82] 
Darbinyan, V.; Kteyan, A.; Panossian, A.; Gabrielian, E.; Wikman, G.; Wagner, H. Rhodiola rosea in stress induced fatigue a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine,  2000, 7(5), 365-371.
[http://dx.doi.org/10.1016/S0944-7113(00)80055-0 ] [PMID:  11081987] 
[83] 
Shevtsov, V.A.; Zholus, B.I.; Shervarly, V.I.; Vol’skij, V.B.; Korovin, Y.P.; Khristich, M.P.; Roslyakova, N.A.; Wikman, G. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine,  2003, 10(2-3), 95-105.
[http://dx.doi.org/10.1078/094471103321659780 ] [PMID:  12725561] 
[84] 
Sun, L.; Isaak, C.K.; Zhou, Y.; Petkau, J.C. O, K.; Liu, Y.; Siow, Y.L. Salidroside and tyrosol from Rhodiola protect H9c2 cells from ischemia/reperfusion-induced apoptosis. Life Sci.,  2012, 91(5-6), 151-158.
[http://dx.doi.org/10.1016/j.lfs.2012.06.026 ] [PMID:  22771701] 
[85] 
Qu, Z.Q.; Zhou, Y.; Zeng, Y.S.; Lin, Y.K.; Li, Y.; Zhong, Z.Q.; Chan, W.Y. Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat. PLoS One,  2012, 7(1)e29641
[http://dx.doi.org/10.1371/journal.pone.0029641 ] [PMID:  22235318] 
[86] 
Tang, H.; Gao, L.; Mao, J.; He, H.; Liu, J.; Cai, X.; Lin, H.; Wu, T. Salidroside protects against bleomycin-induced pulmonary fibrosis: activation of Nrf2-antioxidant signaling, and inhibition of NF-kB and TGF-β1/Smad-2/-3 pathways. Cell Stress Chaperones,  2016, 21(2), 239-249.
[http://dx.doi.org/10.1007/s12192-015-0654-4 ] [PMID:  26577463] 
[87] 
Zhu, L.; Chen, T.; Chang, X.; Zhou, R.; Luo, F.; Liu, J.; Zhang, K.; Wang, Y.; Yang, Y.; Long, H.; Liu, Y.; Yan, T.; Ma, C. Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-kB pathway. Neuropharmacology,  2016, 103, 134-142.
[http://dx.doi.org/10.1016/j.neuropharm.2015.12.007 ] [PMID:  26690894] 
[88] 
Fan, H.; Wu, P.F.; Zhang, L.; Hu, Z.L.; Wang, W.; Guan, X.L.; Luo, H.; Ni, M.; Yang, J.W.; Li, M.X.; Chen, J.G.; Wang, F. Methionine sulfoxide reductase A negatively controls microglia-mediated neuroinflammation via inhibiting ROS/MAPKs/NF-kB signaling pathways through a catalytic antioxidant function. Antioxid. Redox Signal.,  2015, 22(10), 832-847.
[http://dx.doi.org/10.1089/ars.2014.6022 ] [PMID:  25602783] 
[89] 
Xu, J.; Zhou, L.; Ji, L.; Chen, F.; Fortmann, K.; Zhang, K.; Liu, Q.; Li, K.; Wang, W.; Wang, H.; Xie, W.; Wang, Q.; Liu, J.; Zheng, B.; Zhang, P.; Huang, S.; Shi, T.; Zhang, B.; Dang, Y.; Chen, J.; O’Malley, B.W.; Moses, R.E.; Wang, P.; Li, L.; Xiao, J.; Hoffmann, A.; Li, X. The REGγ-proteasome forms a regulatory circuit with IkBε and NFkB in experimental colitis. Nat. Commun.,  2016, 7, 10761-10774.
[http://dx.doi.org/10.1038/ncomms10761 ] [PMID:  26899380] 
[90] 
Puneet, P.; Yap, C.T.; Wong, L.; Lam, Y.; Koh, D.R.; Moochhala, S.; Pfeilschifter, J.; Huwiler, A.; Melendez, A.J. SphK1 regulates proinflammatory responses associated with endotoxin and polymicrobial sepsis. Science,  2010, 328(5983), 1290-1294.
[http://dx.doi.org/10.1126/science.1188635 ] [PMID:  20522778] 
[91] 
Allagnat, F.; Fukaya, M.; Nogueira, T.C.; Delaroche, D.; Welsh, N.; Marselli, L.; Marchetti, P.; Haefliger, J.A.; Eizirik, D.L.; Cardozo, A.K. C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells. Cell Death Differ.,  2012, 19(11), 1836-1846.
[http://dx.doi.org/10.1038/cdd.2012.67 ] [PMID:  22653339] 
[92] 
Wang, C. Endoplasmic reticulum stress and NF-kB pathway in salidroside mediated neuroprotection: potential of salidroside in neurodegenerative diseases. Am. J. Chin. Med.,  2017, 45(7), 1-17.
[http://dx.doi.org/10.1142/S0192415X17500793] 
[93] 
Wang, S.; Wang, F.; Yang, H.; Li, R.; Guo, H.; Hu, L. Diosgenin glucoside provides neuroprotection by regulating microglial M1 polarization. Int. Immunopharmacol.,  2017, 50, 22-29.
[http://dx.doi.org/10.1016/j.intimp.2017.06.008 ] [PMID:  28623715] 
[94] 
Chen, Y.J.; Zheng, H.Y.; Huang, X.X.; Han, S.X.; Zhang, D.S.; Ni, J.Z.; He, X.Y. Neuroprotective effects of icariin on brain metabolism, mitochondrial functions, and cognition in triple-transgenic Alzheimer’s disease mice. CNS Neurosci. Ther.,  2016, 22(1), 63-73.
[http://dx.doi.org/10.1111/cns.12473 ] [PMID:  26584824] 
[95] 
Zong, N.; Li, F.; Deng, Y.; Shi, J.; Jin, F.; Gong, Q. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus. Behav. Brain Res.,  2016, 313, 111-119.
[http://dx.doi.org/10.1016/j.bbr.2016.06.055 ] [PMID:  27368415] 
[96] 
Xiong, D.; Deng, Y.; Huang, B.; Yin, C.; Liu, B.; Shi, J.; Gong, Q. Icariin attenuates cerebral ischemia-reperfusion injury through inhibition of inflammatory response mediated by NF-kB, PPARα and PPARγ in rats. Int. Immunopharmacol.,  2016, 30, 157-162.
[http://dx.doi.org/10.1016/j.intimp.2015.11.035 ] [PMID:  26679678] 
[97] 
Sheng, C.; Xu, P.; Zhou, K.; Deng, D.; Zhang, C.; Wang, Z. Icariin attenuates synaptic and cognitive deficits in an Aβ1-42-induced rat model of Alzheimer’s disease. Biomed Res. Int.,  2017, 2017,7464872.
[http://dx.doi.org/10.1155/2017/7464872 ] [PMID:  29057264] 
[98] 
Jin, J.; Wang, H.; Hua, X.; Chen, D.; Huang, C.; Chen, Z. An outline for the pharmacological effect of icariin in the nervous system. Eur. J. Pharmacol.,  2019, 842, 20-32.
[http://dx.doi.org/10.1016/j.ejphar.2018.10.006 ] [PMID:  30342950] 
[99] 
Li, X.A.; Ho, Y.S.; Chen, L.; Hsiao, W.L.W. The protective effects of icariin against the homocysteine-induced neurotoxicity in the primary embryonic cultures of rat cortical neurons. Molecules,  2016, 21(11), 1557.
[http://dx.doi.org/10.3390/molecules21111557 ] [PMID:  27879670] 
[100] 
Wen, X.; Huang, A.; Hu, J.; Zhong, Z.; Liu, Y.; Li, Z.; Pan, X.; Liu, Z. Neuroprotective effect of astaxanthin against glutamate-induced cytotoxicity in HT22 cells: Involvement of the Akt/GSK-3β pathway. Neuroscience,  2015, 303, 558-568.
[http://dx.doi.org/10.1016/j.neuroscience.2015.07.034 ] [PMID:  26197224] 
[101] 
Al-Amin, M.M.; Mahmud, W.; Pervin, M.S.; Ridwanul Islam, S.M.; Ashikur Rahman, M.; Zinchenko, A. Astaxanthin ameliorates scopolamine-induced spatial memory deficit via reduced cortical-striato-hippocampal oxidative stress. Brain Res.,  2019, 1710, 74-81.
[http://dx.doi.org/10.1016/j.brainres.2018.12.014 ] [PMID:  30552898] 
[102] 
Masoudi, A.; Dargahi, L.; Abbaszadeh, F.; Pourgholami, M.H.; Asgari, A.; Manoochehri, M.; Jorjani, M. Neuroprotective effects of astaxanthin in a rat model of spinal cord injury. Behav. Brain Res.,  2017, 329, 104-110.
[http://dx.doi.org/10.1016/j.bbr.2017.04.026 ] [PMID:  28442361] 
[103] 
El-Agamy, S.E.; Abdel-Aziz, A.K.; Wahdan, S.; Esmat, A.; Azab, S.S. Astaxanthin Ameliorates doxorubicin-induced cognitive impairment (chemobrain) in experimental rat model: impact on oxidative, inflammatory, and apoptotic machineries. Mol. Neurobiol.,  2018, 55(7), 5727-5740.
[http://dx.doi.org/10.1007/s12035-017-0797-7 ] [PMID:  29039023] 
[104] 
Wang, X.; Jiao, X.; Liu, Z.; Li, Y. Crocetin potentiates neurite growth in hippocampal neurons and facilitates functional recovery in rats with spinal cord injury. Neurosci. Bull.,  2017, 33(6), 695-702.
[http://dx.doi.org/10.1007/s12264-017-0157-7 ] [PMID:  28770439] 
[105] 
Li, Q.; Che, H-X.; Wang, C-C.; Zhang, L-Y.; Ding, L.; Xue, C-H.; Zhang, T-T.; Wang, Y-M. Cerebrosides from sea cucumber improved Aβ1-42-induced cognitive deficiency in a rat model of Alzheimer’s disease. Mol. Nutr. Food Res.,  2018, 63(5)
[http://dx.doi.org/10.1002/mnfr.201800707] 
[106] 
Guo, J.; Shang, E.X.; Duan, J.A.; Tang, Y.; Qian, D. Determination of ligustilide in the brains of freely moving rats using microdialysis coupled with ultra performance liquid chromatography/mass spectrometry. Fitoterapia,  2011, 82(3), 441-445.
[http://dx.doi.org/10.1016/j.fitote.2010.12.002 ] [PMID:  21156197] 
[107] 
Kuang, X.; Yao, Y.; Du, J.R.; Liu, Y.X.; Wang, C.Y.; Qian, Z.M. Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. Brain Res.,  2006, 1102(1), 145-153.
[http://dx.doi.org/10.1016/j.brainres.2006.04.110 ] [PMID:  16806112] 
[108] 
Wu, X.M.; Qian, Z.M.; Zhu, L.; Du, F.; Yung, W.H.; Gong, Q.; Ke, Y. Neuroprotective effect of ligustilide against ischaemia-reperfusion injury via up-regulation of erythropoietin and down-regulation of RTP801. Br. J. Pharmacol.,  2011, 164(2), 332-343.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01337.x ] [PMID:  21410687] 
[109] 
Peng, B.; Zhao, P.; Lu, Y.P.; Chen, M.M.; Sun, H.; Wu, X.M.; Zhu, L. Z-ligustilide activates the Nrf2/HO-1 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro. Brain Res.,  2013, 1520, 168-177.
[http://dx.doi.org/10.1016/j.brainres.2013.05.009 ] [PMID:  23688544] 
[110] 
Li, J.J.; Zhu, Q.; Lu, Y.P.; Zhao, P.; Feng, Z.B.; Qian, Z.M.; Zhu, L. Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain. Brain Res.,  2015, 1595, 19-28.
[http://dx.doi.org/10.1016/j.brainres.2014.10.012 ] [PMID:  25446001] 
[111] 
Zhang, D.W.; Wang, Z.L.; Qi, W.; Lei, W.; Zhao, G.Y. Cordycepin (3′-deoxyadenosine) down-regulates the proinflammatory cytokines in inflammation-induced osteoporosis model. Inflammation,  2014, 37(4), 1044-1049.
[http://dx.doi.org/10.1007/s10753-014-9827-z ] [PMID:  24493324] 
[112] 
Peng, J.; Wang, P.; Ge, H.; Qu, X.; Jin, X. Effects of cordycepin on the microglia overactivation induced impairments of growth and development of hippocampal cultured neurons. PLoS One,  2015, 10(5), e0125902.
[http://dx.doi.org/10.1371/journal.pone.0125902 ] [PMID:  25932642] 
[113] 
Cheng, Y.; Wei, Y.; Yang, W.; Song, Y.; Shang, H.; Cai, Y.; Wu, Z.; Zhao, W. Cordycepin confers neuroprotection in mice models of intracerebral hemorrhage via suppressing NLRP3 inflammasome activation. Metab. Brain Dis.,  2017, 32(4), 1133-1145.
[http://dx.doi.org/10.1007/s11011-017-0003-7 ] [PMID:  28401330] 
[114] 
Chen, C.; Liu, X.P.; Jiang, W.; Zeng, B.; Meng, W.; Huang, L.P.; Li, Y.P.; Sun, W.; Yuan, C.H.; Yao, L.H. Anti-effects of cordycepin to hypoxia-induced membrane depolarization on hippocampal CA1 pyramidal neuron. Eur. J. Pharmacol.,  2017, 796, 1-6.
[http://dx.doi.org/10.1016/j.ejphar.2016.12.021 ] [PMID:  27988284] 
[115] 
Song, H.; Huang, L.P.; Li, Y.; Liu, C.; Wang, S.; Meng, W.; Wei, S.; Liu, X.P.; Gong, Y.; Yao, L.H. Neuroprotective effects of cordycepin inhibit Aβ-induced apoptosis in hippocampal neurons. Neurotoxicology,  2018, 68, 73-80.
[http://dx.doi.org/10.1016/j.neuro.2018.07.008 ] [PMID:  30031108] 
[116] 
Kan, H.; Wang, Y.; Wang, D.; Sun, H.; Zhou, S.; Wang, H.; Guan, J.; Li, M. Cordycepin rescues lidocaine-induced neurotoxicity in dorsal root ganglion by interacting with inflammatory signaling pathway MMP3. Eur. J. Pharmacol.,  2018, 827, 88-93.
[http://dx.doi.org/10.1016/j.ejphar.2018.01.049 ] [PMID:  29382532] 
[117] 
Cheng, Y.; Yang, C.; Zhao, J.; Tse, H.F.; Rong, J. Proteomic identification of calcium-binding chaperone calreticulin as a potential mediator for the neuroprotective and neuritogenic activities of fruit-derived glycoside amygdalin. J. Nutr. Biochem.,  2015, 26(2), 146-154.
[http://dx.doi.org/10.1016/j.jnutbio.2014.09.012 ] [PMID:  25465157] 
[118] 
Lv, C.; Wang, L.; Liu, X.; Yan, S.; Yan, S.S.; Wang, Y.; Zhang, W. Multi-faced neuroprotective effects of geniposide depending on the RAGE-mediated signaling in an Alzheimer mouse model. Neuropharmacology,  2015, 89, 175-184.
[http://dx.doi.org/10.1016/j.neuropharm.2014.09.019 ] [PMID:  25261783] 
[119] 
Chen, Y.; Zhang, Y.; Li, L.; Hölscher, C. Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson’s disease. Eur. J. Pharmacol.,  2015, 768, 21-27.
[http://dx.doi.org/10.1016/j.ejphar.2015.09.029 ] [PMID:  26409043] 
[120] 
Su, C.; Yang, X.; Lou, J. Geniposide reduces α-synuclein by blocking microRNA-21/lysosome-associated membrane protein 2A interaction in Parkinson disease models. Brain Res.,  2016, 1644, 98-106.
[http://dx.doi.org/10.1016/j.brainres.2016.05.011 ] [PMID:  27173998] 
[121] 
Xia, Y.; Kong, L.; Yao, Y.; Jiao, Y.; Song, J.; Tao, Z.; You, Z.; Yang, J. Osthole confers neuroprotection against cortical stab wound injury and attenuates secondary brain injury; J. Neuroinflamm, 2015. 
[http://dx.doi.org/10.1186/s12974-015-0373-x] 
[122] 
Li, K.; Ding, D.; Zhang, M. Neuroprotection of osthole against cerebral ischemia/reperfusion injury through an anti-apoptotic pathway in rats. Biol. Pharm. Bull.,  2016, 39(3), 336-342.
[http://dx.doi.org/10.1248/bpb.b15-00699 ] [PMID:  26934926] 
[123] 
Li, X.; Zhao, Y.; Liu, P.; Zhu, X.; Chen, M.; Wang, H.; Lu, D.; Qi, R. Senegenin inhibits hypoxia/reoxygenation-induced neuronal apoptosis by upregulating RhoGDIα. Mol. Neurobiol.,  2015, 52(3), 1561-1571.
[http://dx.doi.org/10.1007/s12035-014-8948-6 ] [PMID:  25367882] 
[124] 
Pi, T.; Zhou, X.W.; Cai, L.; Zhang, W.; Su, C.F.; Wu, W.T.; Ren, X.M.; Luo, H.M. PI3K/Akt signaling pathway is involved in the neurotrophic effect of senegenin. Mol. Med. Rep.,  2016, 13(2), 1257-1262.
[http://dx.doi.org/10.3892/mmr.2015.4652 ] [PMID:  26647727] 
[125] 
Jesky, R.; Chen, H. The neuritogenic and neuroprotective potential of senegenin against AB-induced neurotoxicity in PC-12 cells. BMC Complement. Altern. Med.,  2016, 16, 26.
[http://dx.doi.org/10.1186/s12906-016-1006-3 ] [PMID:  26803813] 
[126] 
Park, J.H.; Park, Ok.; Cho, J.H.; Chen, B.H.; Kim, I.H.; Ahn, J.H.; Lee, J.C.; Yan, B.C.; Yoo, K.Y.; Lee, C.H.; Hwang, I.K.; Kwon, S.H.; Lee, Y.L.; Won, M.H.; Choi, J.H. Anti-inflammatory effect of tanshinone I in neuroprotection against cerebral ischemia-reperfusion injury in the gerbil hippocampus. Neurochem. Res.,  2014, 39(7), 1300-1312.
[http://dx.doi.org/10.1007/s11064-014-1312-4 ] [PMID:  24760430] 
[127] 
Dai, C.; Liu, Y.; Dong, Z. Tanshinone I alleviates motor and cognitive impairments via suppressing oxidative stress in the neonatal rats after hypoxicischemic brain damage. Mol. Brain,  2017, 10
[http://dx.doi.org/10.1186/s13041-017-0332-9]] 
[128] 
de Oliveira, M.R.; Schuck, P.F.; Bosco, S.M.D. Tanshinone I induces mitochondrial protection through an Nrf2-dependent mechanism in Paraquat-Treated Human neuroblas-toma SH-SY5Y cells. Mol. Neurobiol.,  2017, 54(6), 4597-4608.
[http://dx.doi.org/10.1007/s12035-016-0009-x ] [PMID:  27389776] 
[129] 
Jing, X.; Wei, X.; Ren, M.; Wang, L.; Zhang, X.; Lou, H. Neuroprotective effects of Tanshinone I against 6-OHDA-induced oxidative stress in cellular and mouse model of Parkinson’s disease through upregulating Nrf2. Neurochem. Res.,  2016, 41(4), 779-786.
[http://dx.doi.org/10.1007/s11064-015-1751-6 ] [PMID:  26537816] 
[130] 
Guo, Z.; Shao, L.; Du, Q.; Park, K.S.; Geller, D.A. Identification of a classic cytokine-induced enhancer upstream in the human iNOS promoter. FASEB J.,  2007, 21(2), 535-542.
[http://dx.doi.org/10.1096/fj.06-6739com ] [PMID:  17158780] 
[131] 
Rojo, A.I.; Salinas, M.; Martín, D.; Perona, R.; Cuadrado, A. Regulation of Cu/Zn-superoxide dismutase expression via the phosphatidylinositol 3 kinase/Akt pathway and nuclear factor-kappaB. J. Neurosci.,  2004, 24(33), 7324-7334.
[http://dx.doi.org/10.1523/JNEUROSCI.2111-04.2004 ] [PMID:  15317858] 
[132] 
Nie, J.; Tian, Y.; Zhang, Y.; Lu, Y.L.; Li, L-S.; Shi, J.S. Dendrobium alkaloids prevent Aβ25-35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice. PeerJ,  2016, 4,e2739.
[http://dx.doi.org/10.7717/peerj.2739 ] [PMID:  27994964] 
[133] 
Zhang, W.; Wu, Q.; Lu, Y.L.; Gong, Q.H.; Zhang, F.; Shi, J.S. Protective effects of Dendrobium nobile Lindl. alkaloids on amyloid beta (25-35)-induced neuronal injury. Neural Regen. Res.,  2017, 12(7), 1131-1136.
[http://dx.doi.org/10.4103/1673-5374.211193 ] [PMID:  28852396] 
[134] 
Li, L.S.; Lu, Y.L.; Nie, J.; Xu, Y.Y.; Zhang, W.; Yang, W.J.; Gong, Q.H.; Lu, Y.F.; Lu, Y.; Shi, J.S. Dendrobium nobile Lindl alkaloid, a novel autophagy inducer, protects against axonal degeneration induced by Aβ25-35 in hippocampus neurons in vitro. CNS Neurosci. Ther.,  2017, 23(4), 329-340.
[http://dx.doi.org/10.1111/cns.12678 ] [PMID:  28261990] 
[135] 
Park, S.; Kim, D.S.; Kang, S. Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: vanillin and 4-hydroxybenzaldehyde are the bioactive candidates. Eur. J. Nutr.,  2011, 50(2), 107-118.
[http://dx.doi.org/10.1007/s00394-010-0120-0 ] [PMID:  20577883] 
[136] 
Liu, B.; Li, F.; Shi, J.; Yang, D.; Deng, Y.; Gong, Q. Gastrodin ameliorates subacute phase cerebral ischemiareperfusion injury by inhibiting inflammation and apoptosis in rats. Mol. Med. Rep.,  2016, 14(5), 4144-4152.
[http://dx.doi.org/10.3892/mmr.2016.5785 ] [PMID:  27748849] 
[137] 
Lin, L.C.; Chen, Y.F.; Lee, W.C.; Wu, Y.T.; Tsai, T.H. Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood, brain and bile by microdialysis coupled to LC-MS/MS. J. Pharm. Biomed. Anal.,  2008, 48(3), 909-917.
[http://dx.doi.org/10.1016/j.jpba.2008.07.013 ] [PMID:  18757149] 
[138] 
Zeng, X.; Zhang, S.; Zhang, L.; Zhang, K.; Zheng, X. A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro. Planta Med.,  2006, 72(15), 1359-1365.
[http://dx.doi.org/10.1055/s-2006-951709 ] [PMID:  17089323] 
[139] 
Xu, X.; Lu, Y.; Bie, X. Protective effects of gastrodin on hypoxia-induced toxicity in primary cultures of rat cortical neurons. Planta Med.,  2007, 73(7), 650-654.
[http://dx.doi.org/10.1055/s-2007-981523 ] [PMID:  17583824] 
[140] 
Dai, J.N.; Zong, Y.; Zhong, L.M.; Li, Y.M.; Zhang, W.; Bian, L.G.; Ai, Q.L.; Liu, Y.D.; Sun, J.; Lu, D. Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PLoS One,  2011, 6(7),e21891.
[http://dx.doi.org/10.1371/journal.pone.0021891 ] [PMID:  21765922] 
[141] 
Wang, X.; Tan, Y.; Zhang, F. Ameliorative effect of gastrodin on 3,3′-iminodipropionitrile-induced memory impairment in rats. Neurosci. Lett.,  2015, 594, 40-45.
[http://dx.doi.org/10.1016/j.neulet.2015.03.049 ] [PMID:  25817367] 
[142] 
Zhao, X.; Zou, Y.; Xu, H.; Fan, L.; Guo, H.; Li, X.; Li, G.; Zhang, X.; Dong, M. Gastrodin protect primary cultured rat hippocampal neurons against amyloid-beta peptide-induced neurotoxicity via ERK1/2-Nrf2 pathway. Brain Res.,  2012, 1482, 13-21.
[http://dx.doi.org/10.1016/j.brainres.2012.09.010 ] [PMID:  22982592] 
[143] 
Wang, X.L.; Xing, G.H.; Hong, B.; Li, X.M.; Zou, Y.; Zhang, X.J.; Dong, M.X. Gastrodin prevents motor deficits and oxidative stress in the MPTP mouse model of Parkinson’s disease: involvement of ERK1/2-Nrf2 signaling pathway. Life Sci.,  2014, 114(2), 77-85.
[http://dx.doi.org/10.1016/j.lfs.2014.08.004 ] [PMID:  25132361] 
[144] 
Cole, T.B.; Wenzel, H.J.; Kafer, K.E.; Schwartzkroin, P.A.; Palmiter, R.D. Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc. Natl. Acad. Sci. USA,  1999, 96(4), 1716-1721.
[http://dx.doi.org/10.1073/pnas.96.4.1716 ] [PMID:  9990090] 
[145] 
Koh, J.Y.; Suh, S.W.; Gwag, B.J.; He, Y.Y.; Hsu, C.Y.; Choi, D.W. The role of zinc in selective neuronal death after transient global cerebral ischemia. Science,  1996, 272(5264), 1013-1016.
[http://dx.doi.org/10.1126/science.272.5264.1013 ] [PMID:  8638123] 
[146] 
Sheline, C.T.; Behrens, M.M.; Choi, D.W. Zinc-induced cortical neuronal death: contribution of energy failure attributable to loss of NAD(+) and inhibition of glycolysis. J. Neurosci.,  2000, 20(9), 3139-3146.
[http://dx.doi.org/10.1523/JNEUROSCI.20-09-03139.2000 ] [PMID:  10777777] 
[147] 
Noh, K.M.; Kim, Y.H.; Koh, J.Y. Mediation by membrane protein kinase C of zinc-induced oxidative neuronal injury in mouse cortical cultures. J. Neurochem.,  1999, 72(4), 1609-1616.
[http://dx.doi.org/10.1046/j.1471-4159.1999.721609.x ] [PMID:  10098868] 
[148] 
Bishop, G.M.; Dringen, R.; Robinson, S.R. Zinc stimulates the production of toxic reactive oxygen species (ROS) and inhibits glutathione reductase in astrocytes. Free Radic. Biol. Med.,  2007, 42(8), 1222-1230.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.01.022 ] [PMID:  17382203] 
[149] 
Suh, S.W.; Aoyama, K.; Alano, C.C.; Anderson, C.M.; Hamby, A.M.; Swanson, R.A. Zinc inhibits astrocyte glutamate uptake by activation of poly(ADP-ribose) polymerase-1. Mol. Med.,  2007, 13(7-8), 344-349.
[http://dx.doi.org/10.2119/2007-00043.Suh ] [PMID:  17728843] 
[150] 
Rossi, D.J.; Brady, J.D.; Mohr, C. Astrocyte metabolism and signaling during brain ischemia. Nat. Neurosci.,  2007, 10(11), 1377-1386.
[http://dx.doi.org/10.1038/nn2004 ] [PMID:  17965658] 
[151] 
Li, J.; Liu, W.; Ding, S.; Xu, W.; Guan, Y.; Zhang, J.H.; Sun, X.; Sun, X. Hyperbaric oxygen preconditioning induces tolerance against brain ischemia-reperfusion injury by upregulation of antioxidant enzymes in rats. Brain Res.,  2008, 1210, 223-229.
[http://dx.doi.org/10.1016/j.brainres.2008.03.007 ] [PMID:  18407255] 
[152] 
Abramov, A.Y.; Jacobson, J.; Wientjes, F.; Hothersall, J.; Canevari, L.; Duchen, M.R. Expression and modulation of an NADPH oxidase in mammalian astrocytes. J. Neurosci.,  2005, 25(40), 9176-9184.
[http://dx.doi.org/10.1523/JNEUROSCI.1632-05.2005 ] [PMID:  16207877] 
[153] 
Nawashiro, H.; Brenner, M.; Fukui, S.; Shima, K.; Hallenbeck, J.M. High susceptibility to cerebral ischemia in GFAP-null mice. J. Cereb. Blood Flow Metab.,  2000, 20(7), 1040-1044.
[http://dx.doi.org/10.1097/00004647-200007000-00003 ] [PMID:  10908037] 
[154] 
Luo, L.; Kim, S.W.; Lee, H.K.; Kim, I.D.; Lee, H.; Lee, J.K. Gastrodin exerts robust neuroprotection in the postischemic brain via its protective effect against Zn2+-toxicity and its anti-oxidative effects in astrocytes. Anim Cells Syst (Seoul),  2018, 22(6), 429-437.
[http://dx.doi.org/10.1080/19768354.2018.1549099 ] [PMID:  30533266] 
[155] 
Liu, S-J.; Liu, X-Y.; Li, J-H.; Guo, J.; Li, F.; Gui, Y.; Li, X-H.; Yang, L.; Wu, C-Y.; Yuan, Y.; Li, J-J. Gastrodin attenuates microglia activation through renin-angiotensin system and Sirtuin3 pathway. Neurochem. Int.,  2018, 120, 49-63.
[http://dx.doi.org/10.1016/j.neuint.2018.07.012 ] [PMID:  30075231] 
[156] 
Liu, B.; Gao, J.M.; Li, F.; Gong, Q.H.; Shi, J.S. Gastrodin attenuates bilateral common carotid artery occlusion-induced cognitive deficits via regulating Aβ-related proteins and reducing autophagy and apoptosis in rats. Front. Pharmacol.,  2018, 9, 405.
[http://dx.doi.org/10.3389/fphar.2018.00405 ] [PMID:  29755351] 
[157] 
Smith, E.E. Clinical presentations and epidemiology of vascular dementia. Clin. Sci. (Lond.),  2017, 131(11), 1059-1068.
[http://dx.doi.org/10.1042/CS20160607 ] [PMID:  28515342] 
[158] 
Yang, X.; Li, F.; Yang, Y.; Shen, J.; Zou, R.; Zhu, P.; Zhang, C.; Yang, Z.; Li, P. Efficacy and safety of echinaco-side in a rat osteopenia model. Evid. Based Complement. Alternat. Med.,  2013, 2013926928
[http://dx.doi.org/10.1155/2013/926928]] 
[159] 
Wu, Y.; Li, L.; Wen, T.; Li, Y.Q. Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity in rats. Toxicology,  2007, 232(1-2), 50-56.
[http://dx.doi.org/10.1016/j.tox.2006.12.013 ] [PMID:  17222497] 
[160] 
Jia, Y.; Guan, Q.; Jiang, Y.; Salh, B.; Guo, Y.; Tu, P.; Du, C. Amelioration of dextran sulphate sodium-induced colitis in mice by echinacoside-enriched extract of Cistanche tubulosa. Phytother. Res.,  2014, 28(1), 110-119.
[http://dx.doi.org/10.1002/ptr.4967 ] [PMID:  23512684] 
[161] 
Xie, H.; Zhu, H.; Cheng, C.; Liang, Y.; Wang, Z. Echinacoside retards cellular senescence of human fibroblastic cells MRC-5. Pharmazie,  2009, 64(11), 752-754.
[PMID:  20099521] 
[162] 
Zhu, M.; Lu, C.; Li, W. Transient exposure to echinacoside is sufficient to activate Trk signaling and protect neuronal cells from rotenone. J. Neurochem.,  2013, 124(4), 571-580.
[http://dx.doi.org/10.1111/jnc.12103 ] [PMID:  23189969] 
[163] 
Kalia, L.V.; Lang, A.E. Parkinson’s disease. Lancet,  2015, 386(9996), 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3 ] [PMID:  25904081] 
[164] 
Ahmed, H.; Abushouk, A.I.; Gabr, M.; Negida, A.; Abdel-Daim, M.M. Parkinson’s disease and pesticides: a meta-analysis of disease connection and genetic alterations. Biomed. Pharmacother.,  2017, 90, 638-649.
[http://dx.doi.org/10.1016/j.biopha.2017.03.100 ] [PMID:  28412655] 
[165] 
Abushouk, A.I.; Negida, A.; Ahmed, H.; Abdel-Daim, M.M. Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: future applications in Parkinson’s disease. Biomed. Pharmacother.,  2017, 85, 635-645.
[http://dx.doi.org/10.1016/j.biopha.2016.11.074 ] [PMID:  27890431] 
[166] 
Herskovits, A.Z.; Guarente, L. SIRT1 in neurodevelopment and brain senescence. Neuron,  2014, 81(3), 471-483.
[http://dx.doi.org/10.1016/j.neuron.2014.01.028 ] [PMID:  24507186] 
[167] 
Zhao, Q.; Gao, J.; Li, W.; Cai, D. Neurotrophic and neurorescue effects of Echinacoside in the subacute MPTP mouse model of Parkinson’s disease. Brain Res.,  2010, 1346, 224-236.
[http://dx.doi.org/10.1016/j.brainres.2010.05.018 ] [PMID:  20478277] 
[168] 
Zhang, Y.; Long, H.; Zhou, F.; Zhu, W.; Ruan, J.; Zhao, Y.; Lu, Y. Echinacoside’s nigrostriatal dopaminergic protection against 6-OHDA-Induced endoplasmic reticulum stress through reducing the accumulation of Seipin. J. Cell. Mol. Med.,  2017, 21(12), 3761-3775.
[http://dx.doi.org/10.1111/jcmm.13285 ] [PMID:  28767194] 
[169] 
Wei, L.L.; Chen, H.; Jiang, Y.; Tu, P.F.; Zhong, M.; Du, J.; Liu, F.; Wang, L.; Liu, C.Y. Effects of echinacoside on histio-central levels of active mass in middle cerebral artery occlusion rats. Biomed. Environ. Sci.,  2012, 25(2), 238-244.
[http://dx.doi.org/10.3967/0895-3988.2012.02.017 ] [PMID:  22998833] 
[170] 
Chen, H.; Jing, F.C.; Li, C.L.; Tu, P.F.; Zheng, Q.S.; Wang, Z.H. Echinacoside prevents the striatal extracellular levels of monoamine neurotransmitters from diminution in 6-hydroxydopamine lesion rats. J. Ethnopharmacol.,  2007, 114(3), 285-289.
[http://dx.doi.org/10.1016/j.jep.2007.07.035 ] [PMID:  17951018] 
[171] 
Chang, C.; Xia, B.; Tang, L.; Wu, W.; Tang, J.; Liang, Y.; Yang, H.; Zhang, Z.; Lu, Y.; Chen, G.; Yang, Y.; Zhao, Y. Echinacoside protects against MPTP/MPP+-induced neuro-toxicity via regulating autophagy pathway mediated by Sirt1. Metab. Brain Dis.,  2019, 34(1), 203-212.
[http://dx.doi.org/10.1007/s11011-018-0330-3 ] [PMID:  30426321] 
[172] 
Wang, S.N.; Li, Q.; Jing, M.H.; Alba, E.; Yang, X.H.; Sabaté, R.; Han, Y.F.; Pi, R.B.; Lan, W.J.; Yang, X.B.; Chen, J.K. Natural xanthones from garcinia mangostana with multifunctional activities for the therapy of Alzheimer’s Disease. Neurochem. Res.,  2016, 41(7), 1806-1817.
[http://dx.doi.org/10.1007/s11064-016-1896-y ] [PMID:  27038926] 
[173] 
Li, F.Q.; Wang, T.; Pei, Z.; Liu, B.; Hong, J.S. Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons. J. Neural Transm. (Vienna),  2005, 112(3), 331-347.
[http://dx.doi.org/10.1007/s00702-004-0213-0 ] [PMID:  15503194] 
[174] 
Zhang, Z.; Cui, W.; Li, G.; Yuan, S.; Xu, D.; Hoi, M.P.; Lin, Z.; Dou, J.; Han, Y.; Lee, S.M. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways. J. Agric. Food Chem.,  2012, 60(33), 8171-8182.
[http://dx.doi.org/10.1021/jf301511m ] [PMID:  22838648] 
[175] 
Chen, S.F.; Hsu, C.W.; Huang, W.H.; Wang, J.Y. Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br. J. Pharmacol.,  2008, 155(8), 1279-1296.
[http://dx.doi.org/10.1038/bjp.2008.345 ] [PMID:  18776918] 
[176] 
Liu, C.; Wu, J.; Xu, K.; Cai, F.; Gu, J.; Ma, L.; Chen, J. Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway. J. Neurochem.,  2010, 112(6), 1500-1512.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06561.x ] [PMID:  20050973] 
[177] 
Lee, J.H.; Lee, S.R. The effect of Baicalein on hippocampal neuronal damage and metalloproteinase activity following transient global cerebral ischaemia. Phytother. Res.,  2012, 26(11), 1614-1619.
[http://dx.doi.org/10.1002/ptr.4644 ] [PMID:  22344890] 
[178] 
Lee, E.; Park, H.R.; Ji, S.T.; Lee, Y.; Lee, J. Baicalein attenuates astroglial activation in the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson’s disease model by downregulating the activations of nuclear factor-kB, ERK, and JNK. J. Neurosci. Res.,  2014, 92(1), 130-139.
[http://dx.doi.org/10.1002/jnr.23307 ] [PMID:  24166733] 
[179] 
Wang, S.Y.; Wang, H.H.; Chi, C.W.; Chen, C.F.; Liao, J.F. Effects of baicalein on β-amyloid peptide-(25-35)-induced amnesia in mice. Eur. J. Pharmacol.,  2004, 506(1), 55-61.
[http://dx.doi.org/10.1016/j.ejphar.2004.10.029 ] [PMID:  15588624] 
[180] 
Liu, C.; Wu, J.; Gu, J.; Xiong, Z.; Wang, F.; Wang, J.; Wang, W.; Chen, J. Baicalein improves cognitive deficits induced by chronic cerebral hypoperfusion in rats. Pharmacol. Biochem. Behav.,  2007, 86(3), 423-430.
[http://dx.doi.org/10.1016/j.pbb.2006.11.005 ] [PMID:  17289131] 
[181] 
Chang, Y.; Lu, C.W.; Lin, T.Y.; Huang, S.K.; Wang, S.J. Baicalein, a Constituent of Scutellaria baicalensis, Reduces Glutamate Release and Protects Neuronal Cell Against Kainic Acid-Induced Excitotoxicity in Rats. Am. J. Chin. Med.,  2016, 44(5), 943-962.
[http://dx.doi.org/10.1142/S0192415X1650052X ] [PMID:  27430911] 
[182] 
Wang, S.; Wang, H.; Guo, H.; Kang, L.; Gao, X.; Hu, L. Neuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation. Neuroscience,  2011, 185, 150-160.
[http://dx.doi.org/10.1016/j.neuroscience.2011.04.005 ] [PMID:  21524691] 
[183] 
Fang, M.; Yuan, Y.; Lu, J.; Li, H.E.; Zhao, M.; Ling, E.A.; Wu, C.Y. Scutellarin promotes microglia-mediated astrogliosis coupled with improved behavioral function in cerebral ischemia. Neurochem. Int.,  2016, 97, 154-171.
[http://dx.doi.org/10.1016/j.neuint.2016.04.007 ] [PMID:  27105682] 
[184] 
Yuan, Y.; Fang, M.; Wu, C.Y.; Ling, E.A. Scutellarin as a potential therapeutic agent for microglia-mediated neuroinflammation in cerebral ischemia. Neuromolecular Med.,  2016, 18(3), 264-273.
[http://dx.doi.org/10.1007/s12017-016-8394-x ] [PMID:  27103430] 
[185] 
Baluchnejadmojarad, T.; Zeinali, H.; Roghani, M. Scutellarin alleviates lipopolysaccharide-induced cognitive deficits in the rat: Insights into underlying mechanisms. Int. Immunopharmacol.,  2018, 54, 311-319.
[http://dx.doi.org/10.1016/j.intimp.2017.11.033 ] [PMID:  29190543] 
[186] 
Zeng, Y.Q.; Cui, Y.B.; Gu, J.H.; Liang, C.; Zhou, X.F. Scutellarin mitigates Aβ-induced neurotoxicity and improves behavior impairments in AD mice. Molecules,  2018, 23(4), 869.
[http://dx.doi.org/10.3390/molecules23040869 ] [PMID:  29642616] 
[187] 
Xian, Y.F.; Ip, S.P.; Lin, Z.X.; Mao, Q.Q.; Su, Z.R.; Lai, X.P. Protective effects of pinostrobin on β-amyloid-induced neurotoxicity in PC12 cells. Cell. Mol. Neurobiol.,  2012, 32(8), 1223-1230.
[http://dx.doi.org/10.1007/s10571-012-9847-x ] [PMID:  22565301] 
[188] 
Lang, A.E.; Lozano, A.M. Parkinson’s disease. First of two parts. N. Engl. J. Med.,  1998, 339(15), 1044-1053.
[http://dx.doi.org/10.1056/NEJM199810083391506 ] [PMID:  9761807] 
[189] 
Lang, A.E.; Lozano, A.M. Parkinson’s disease. Second of two parts. N. Engl. J. Med.,  1998, 339(16), 1130-1143.
[http://dx.doi.org/10.1056/NEJM199810153391607 ] [PMID:  9770561] 
[190] 
Jenner, P. Genetic susceptibility and the occurrence of Parkinson’s disease. Parkinsonism Relat. Disord.,  1999, 5(4), 173-177.
[http://dx.doi.org/10.1016/S1353-8020(99)00034-6 ] [PMID:  18591137] 
[191] 
Bayir, H.; Kapralov, A.A.; Jiang, J.; Huang, Z.; Tyurina, Y.Y.; Tyurin, V.A.; Zhao, Q.; Belikova, N.A.; Vlasova, I.I.; Maeda, A.; Zhu, J.; Na, H.M.; Mastroberardino, P.G.; Sparvero, L.J.; Amoscato, A.A.; Chu, C.T.; Greenamyre, J.T.; Kagan, V.E. Peroxidase mechanism of lipid-dependent cross-linking of synuclein with cytochrome C: protection against apoptosis versus delayed oxidative stress in Parkinson disease. J. Biol. Chem.,  2009, 284(23), 15951-15969.
[http://dx.doi.org/10.1074/jbc.M900418200 ] [PMID:  19351880] 
[192] 
Kumar, H.; Koppula, S.; Kim, I.S.; More, S.V.; Kim, B.W.; Choi, D.K. Nuclear factor erythroid 2-related factor 2 signaling in Parkinson disease: a promising multi therapeutic target against oxidative stress, neuroinflammation and cell death. CNS Neurol. Disord. Drug Targets,  2012, 11(8), 1015-1029.
[http://dx.doi.org/10.2174/1871527311211080012 ] [PMID:  23244425] 
[193] 
Beal, M.F. Experimental models of Parkinson’s disease. Nat. Rev. Neurosci.,  2001, 2(5), 325-334.
[http://dx.doi.org/10.1038/35072550 ] [PMID:  11331916] 
[194] 
Langston, J.W.; Irwin, I. MPTP: current concepts and controversies. Clin. Neuropharmacol.,  1986, 9(6), 485-507.
[http://dx.doi.org/10.1097/00002826-198612000-00001 ] [PMID:  3542203] 
[195] 
Keane, P.C.; Kurzawa, M.; Blain, P.G.; Morris, C.M. Mitochondrial dysfunction in Parkinson’s disease. Parkinsons Dis.,  2011, 2011,716871.
[http://dx.doi.org/10.4061/2011/716871 ] [PMID:  21461368] 
[196] 
Gan, L.; Johnson, J.A. Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim. Biophys. Acta,  2014, 1842(8), 1208-1218.
[http://dx.doi.org/10.1016/j.bbadis.2013.12.011 ] [PMID:  24382478] 
[197] 
Pajares, M.; Cuadrado, A.; Rojo, A.I. Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases. Redox Biol.,  2017, 11, 543-553.
[http://dx.doi.org/10.1016/j.redox.2017.01.006 ] [PMID:  28104575] 
[198] 
Li, C.; Tang, B.; Feng, Y.; Tang, F.; Pui-Man Hoi, M.; Su, Z.; Ming-Yuen Lee, S. Pinostrobin exerts neuroprotective actions in neuro-toxininduced Parkinson’s disease models through Nrf2 induction. J. Agric. Food Chem.,  2018, 66(31), 8307-8318.
[http://dx.doi.org/10.1021/acs.jafc.8b02607 ] [PMID:  29961319] 
[199] 
Steer, T.E.; Johnson, I.T.; Gee, J.M.; Gibson, G.R. Metabolism of the soybean isoflavone glycoside genistin in vitro by human gut bacteria and the effect of prebiotics. Br. J. Nutr.,  2003, 90(3), 635-642.
[http://dx.doi.org/10.1079/BJN2003949 ] [PMID:  13129470] 
[200] 
Ma, W.; Yuan, L.; Yu, H.; Ding, B.; Xi, Y.; Feng, J.; Xiao, R. Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by β-amyloid peptides 25-35 in PC12 cells. Int. J. Dev. Neurosci.,  2010, 28(4), 289-295.
[http://dx.doi.org/10.1016/j.ijdevneu.2010.03.003 ] [PMID:  20362658] 
[201] 
Yu, H.L.; Li, L.; Zhang, X.H.; Xiang, L.; Zhang, J.; Feng, J.F.; Xiao, R. Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by β-amyloid 31-35. Br. J. Nutr.,  2009, 102(5), 655-662.
[http://dx.doi.org/10.1017/S0007114509243042 ] [PMID:  19331699] 
[202] 
Lamartiniere, C.A.; Moore, J.; Holland, M.; Barnes, S. Neonatal genistein chemoprevents mammary cancer. Proc. Soc. Exp. Biol. Med.,  1995, 208(1), 120-123.
[http://dx.doi.org/10.3181/00379727-208-43843 ] [PMID:  7892285] 
[203] 
Uckun, F.M.; Evans, W.E.; Forsyth, C.J.; Waddick, K.G.; Ahlgren, L.T.; Chelstrom, L.M.; Burkhardt, A.; Bolen, J.; Myers, D.E. Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases. Science,  1995, 267(5199), 886-891.
[http://dx.doi.org/10.1126/science.7531365 ] [PMID:  7531365] 
[204] 
Zhu, J.T.; Choi, R.C.; Chu, G.K.; Cheung, A.W.; Gao, Q.T.; Li, J.; Jiang, Z.Y.; Dong, T.T.X.; Tsim, K.W.K. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing β-amyloid-induced cell death. J. Agric. Food Chem.,  2007, 55(6), 2438-2445.
[http://dx.doi.org/10.1021/jf063299z ] [PMID:  17323972] 
[205] 
Zhu, J.T.; Choi, R.C.; Xie, H.Q.; Zheng, K.Y.; Guo, A.J.; Bi, C.W.; Lau, D.T.W.; Li, J.; Dong, T.T.X.; Lau, B.W.C.; Chen, J.J.; Tsim, K.W.K. Hibifolin, a flavonol glycoside, prevents β-amyloid-induced neurotoxicity in cultured cortical neurons. Neurosci. Lett.,  2009, 461(2), 172-176.
[http://dx.doi.org/10.1016/j.neulet.2009.06.010 ] [PMID:  19539722] 
[206] 
Choi, R.C.; Zhu, J.T.; Leung, K.W.; Chu, G.K.; Xie, H.Q.; Chen, V.P.; Zheng, K.Y.Z.; Lau, D.T.W.; Dong, T.T.; Chow, P.C.; Han, Y.F.; Wang, Z.T.; Tsim, K.W. A flavonol glycoside, isolated from roots of Panax notoginseng, reduces amyloid-β-induced neurotoxicity in cultured neurons: signaling transduction and drug development for Alzheimer’s disease. J. Alzheimers Dis.,  2010, 19(3), 795-811.
[http://dx.doi.org/10.3233/JAD-2010-1293 ] [PMID:  20157237] 
[207] 
Xu, H.N.; Li, L.X.; Wang, Y.X.; Wang, H.G.; An, D.; Heng, B.; Liu, Y.Q. Genistein inhibits Aβ25-35-induced SH-SY5Y cell damage by modulating the expression of apoptosis-related proteins and Ca2+ influx through iono-tropic glutamate receptors. Phytother. Res.,  2018, 1-11.
[208] 
Dagytė, G.; Den Boer, J.A.; Trentani, A. The cholinergic system and depression. Behav. Brain Res.,  2011, 221(2), 574-582.
[http://dx.doi.org/10.1016/j.bbr.2010.02.023 ] [PMID:  20170685] 
[209] 
Bon, S.; Massoulié, J. Quaternary associations of acetylcholinesterase. I. Oligomeric associations of T subunits with and without the amino-terminal domain of the collagen tail. J. Biol. Chem.,  1997, 272(5), 3007-3015.
[http://dx.doi.org/10.1074/jbc.272.5.3007 ] [PMID:  9006949] 
[210] 
Xie, H.Q.; Liang, D.; Leung, K.W.; Chen, V.P.; Zhu, K.Y.; Chan, W.K.; Choi, R.C.Y.; Massoulié, J.; Tsim, K.W.K. Targeting acetylcholinesterase to membrane rafts: a function mediated by the proline-rich membrane anchor (PRiMA) in neurons. J. Biol. Chem.,  2010, 285(15), 11537-11546.
[http://dx.doi.org/10.1074/jbc.M109.038711 ] [PMID:  20147288] 
[211] 
Chen, V.P.; Choi, R.C.; Chan, W.K.; Leung, K.W.; Guo, A.J.; Chan, G.K.; Luk, W.K.W.; Tsim, K.W.K. The assembly of proline-rich membrane anchor (PRiMA)-linked acetylcholinesterase enzyme: glycosylation is required for enzymatic activity but not for oligomerization. J. Biol. Chem.,  2011, 286(38), 32948-32961.
[http://dx.doi.org/10.1074/jbc.M111.261248 ] [PMID:  21795704] 
[212] 
Newhouse, P.; Albert, K.; Astur, R.; Johnson, J.; Naylor, M.; Dumas, J. Tamoxifen improves cholinergically modulated cognitive performance in postmenopausal women. Neuropsychopharmacology,  2013, 38(13), 2632-2643.
[http://dx.doi.org/10.1038/npp.2013.172 ] [PMID:  23867982] 
[213] 
Hammond, R.; Nelson, D.; Gibbs, R.B. GPR30 co-localizes with cholinergic neurons in the basal forebrain and enhances potassium-stimulated acetylcholine release in the hippocampus. Psychoneuroendocrinology,  2011, 36(2), 182-192.
[http://dx.doi.org/10.1016/j.psyneuen.2010.07.007 ] [PMID:  20696528] 
[214] 
Thomas, P.; Dong, J. Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption. J. Steroid Biochem. Mol. Biol.,  2006, 102(1-5), 175-179.
[http://dx.doi.org/10.1016/j.jsbmb.2006.09.017 ] [PMID:  17088055] 
[215] 
Liu, E.Y.L.; Xu, M.L.; Jin, Y.; Wu, Q.; Dong, T.T.X.; Tsim, K.W.K. Genistein, a phytoestrogen in soybean, induces the expression of acetylcholinesterase via G protein-coupled receptor 30 in PC12 cells. Front. Mol. Neurosci.,  2018, 11, 59.
[http://dx.doi.org/10.3389/fnmol.2018.00059 ] [PMID:  29535608] 
[216] 
Wang, G.Q.; Zhang, B.; He, X.M.; Li, D.D.; Shi, J.S.; Zhang, F. Naringenin targets on astroglial Nrf2 to support dopaminergic neurons. Pharmacol. Res.,  2019, 139, 452-459.
[http://dx.doi.org/10.1016/j.phrs.2018.11.043 ] [PMID:  30527894] 
[217] 
Sugumar, M.; Sevanan, M.; Sekar, S. Neuroprotective effect of Naringenin against MPTP induced oxidative stress. Int. J. Neurosci., 2018.
[PMID:  30433834] 
[218] 
Md, S.; Gan, S.Y.; Haw, Y.H.; Ho, C.L.; Wong, S.; Choudhury, H. In vitro neuroprotective effects of naringenin nanoemulsion against B-amyloid toxicity through the regulation of amyloi-dogenesis and tau phosphorylation. Int. J. Biol. Macromol,  2018, 118(Pt A), 1211-1219.
[http://dx.doi.org/0.1016/j.ijbiomac.2018.06.190] [PMID:  30001606] 
[219] 
Brichta, L.; Greengard, P.; Flajolet, M. Advances in the pharmacological treatment of Parkinson’s disease: targeting neurotransmitter systems. Trends Neurosci.,  2013, 36(9), 543-554.
[http://dx.doi.org/10.1016/j.tins.2013.06.003 ] [PMID:  23876424] 
[220] 
Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature,  2006, 443(7113), 787-795.
[http://dx.doi.org/10.1038/nature05292 ] [PMID:  17051205] 
[221] 
Dias, V.; Junn, E.; Mouradian, M.M. The role of oxidative stress in Parkinson’s disease. J. Parkinsons Dis.,  2013, 3(4), 461-491.
[http://dx.doi.org/10.3233/JPD-130230 ] [PMID:  24252804] 
[222] 
Li, X.Z.; Zhang, S.N.; Liu, S.M.; Lu, F. Recent advances in herbal medicines treating Parkinson’s disease. Fitoterapia,  2013, 84, 273-285.
[http://dx.doi.org/10.1016/j.fitote.2012.12.009 ] [PMID:  23266574] 
[223] 
Shui, G.; Bao, Y.M.; Jiang, B.; An, L.J. Protective effect of protocatechuic acid from Alpinia oxyphylla on hydrogen peroxide-induced oxidative PC12 cell death. Eur. J. Pharmacol.,  2006, 538(1-3), 73-79.
[http://dx.doi.org/10.1016/j.ejphar.2006.03.065 ] [PMID:  16678817] 
[224] 
Guan, S.; Jiang, B.; Bao, Y.M.; An, L.J. Protocatechuic acid suppresses MPP+ -induced mitochondrial dysfunction and apoptotic cell death in PC12 cells. Food Chem. Toxicol.,  2006, 44(10), 1659-1666.
[http://dx.doi.org/10.1016/j.fct.2006.05.004 ] [PMID:  16806628] 
[225] 
Liu, Y.M.; Jiang, B.; Bao, Y.M.; An, L.J. Protocatechuic acid inhibits apoptosis by mitochondrial dysfunction in rotenone-induced PC12 cells. Toxicol. In Vitro,  2008, 22(2), 430-437.
[http://dx.doi.org/10.1016/j.tiv.2007.10.012 ] [PMID:  18082360] 
[226] 
Zhang, Z.J.; Cheang, L.C.; Wang, M.W.; Li, G.H.; Chu, I.K.; Lin, Z.X.; Lee, S.M. Ethanolic extract of fructus Alpinia oxyphylla protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish. Cell. Mol. Neurobiol.,  2012, 32(1), 27-40.
[http://dx.doi.org/10.1007/s10571-011-9731-0 ] [PMID:  21744117] 
[227] 
Zhang, Z.; Li, G.; Szeto, S.S.W.; Chong, C.M.; Quan, Q.; Huang, C.; Cui, W.; Guo, B.; Wang, Y.; Han, Y.; Michael Siu, K.W.; Yuen Lee,  S.M.; Chu, I.K. Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease. Free Radic. Biol. Med.,  2015, 84, 331-343.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.030 ] [PMID:  25769424] 
[228] 
Hirai, A.; Terano, T.; Hamazaki, T.; Sajiki, J.; Saito, H.; Tahara, K.; Tamura, Y.; Kumagai, A. Studies on the mechanism of antiaggregatory effect of Moutan Cortex. Thromb. Res.,  1983, 31(1), 29-40.
[http://dx.doi.org/10.1016/0049-3848(83)90005-1 ] [PMID:  6412397] 
[229] 
Himaya, S.W.; Ryu, B.; Qian, Z.J.; Kim, S.K. Paeonol from Hippocampus kuda Bleeler suppressed the neuro-inflammatory responses in vitro via NF-kB and MAPK signaling pathways. Toxicol. In Vitro,  2012, 26(6), 878-887.
[http://dx.doi.org/10.1016/j.tiv.2012.04.022 ] [PMID:  22542583] 
[230] 
Du, Q.; Feng, G.Z.; Shen, L.; Cui, J.; Cai, J.K. Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma. Can. J. Physiol. Pharmacol.,  2010, 88(10), 1010-1016.
[http://dx.doi.org/10.1139/Y10-077 ] [PMID:  20962901] 
[231] 
Siu, D. A new way of targeting to treat coronary artery disease. J. Cardiovasc. Med. (Hagerstown),  2010, 11(1), 1-6.
[http://dx.doi.org/10.2459/JCM.0b013e32832e0af3 ] [PMID:  19829140] 
[232] 
Wu, J.B.; Song, N.N.; Wei, X.B.; Guan, H.S.; Zhang, X.M. Protective effects of paeonol on cultured rat hippocampal neurons against oxygen-glucose deprivation-induced injury. J. Neurol. Sci.,  2008, 264(1-2), 50-55.
[http://dx.doi.org/10.1016/j.jns.2007.06.057 ] [PMID:  17942121] 
[233] 
Su, S.Y.; Cheng, C.Y.; Tsai, T.H.; Hsiang, C.Y.; Ho, T.Y.; Hsieh, C.L. Paeonol attenuates H2O2-induced NF-kB-associated amyloid precursor protein expression. Am. J. Chin. Med.,  2010, 38(6), 1171-1192.
[http://dx.doi.org/10.1142/S0192415X1000855X ] [PMID:  21061469] 
[234] 
Hsieh, C.L.; Cheng, C.Y.; Tsai, T.H.; Lin, I.H.; Liu, C.H.; Chiang, S.Y.; Lin, J.G.; Lao, C.J.; Tang, N.Y. Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats. J. Ethnopharmacol.,  2006, 106(2), 208-215.
[http://dx.doi.org/10.1016/j.jep.2005.12.027 ] [PMID:  16458462] 
[235] 
Chou, T.C. Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia. Br. J. Pharmacol.,  2003, 139(6), 1146-1152.
[http://dx.doi.org/10.1038/sj.bjp.0705360 ] [PMID:  12871833] 
[236] 
Tseng, Y.T.; Hsu, Y.Y.; Shih, Y.T.; Lo, Y.C. Paeonol attenuates microglia-mediated inflammation and oxidative stress-induced neurotoxicity in rat primary microglia and cortical neurons. Shock,  2012, 37(3), 312-318.
[http://dx.doi.org/10.1097/SHK.0b013e31823fe939 ] [PMID:  22089194] 
[237] 
Lin, C.; Lin, H.Y.; Chen, J.H.; Tseng, W.P.; Ko, P.Y.; Liu, Y.S.; Yeh, W.L.; Lu, D.Y. Effects of paeonol on anti-neuroinflammatory responses in microglial cells. Int. J. Mol. Sci.,  2015, 16(4), 8844-8860.
[http://dx.doi.org/10.3390/ijms16048844 ] [PMID:  25906473] 
[238] 
Kim, S.R.; Lee, M.K.; Koo, K.A.; Kim, S.H.; Sung, S.H.; Lee, N.G.; Markelonis, G.J.; Oh, T.H.; Yang, J.H.; Kim, Y.C. Dibenzocyclooctadiene lignans from Schisandra chinensis protect primary cultures of rat cortical cells from glutamate-induced toxicity. J. Neurosci. Res.,  2004, 76(3), 397-405.
[http://dx.doi.org/10.1002/jnr.20089 ] [PMID:  15079869] 
[239] 
Gu, B.H.; Minh, N.V.; Lee, S.H.; Lim, S.W.; Lee, Y.M.; Lee, K.S.; Kim, D.K. Deoxyschisandrin inhibits H2O2-induced apoptotic cell death in intestinal epithelial cells through nuclear factor-kappaB. Int. J. Mol. Med.,  2010, 26(3), 401-406.
[PMID:  20664957] 
[240] 
Hu, D.; Li, C.; Han, N.; Miao, L.; Wang, D.; Liu, Z.; Wang, H.; Yin, J. Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates AB1-4 2-induced memory impairment in mice. Planta Med.,  2012, 78(12), 1332-1336.
[http://dx.doi.org/10.1055/s-0032-1315019 ] [PMID:  22773410] 
[241] 
Giridharan, V.V.; Thandavarayan, R.A.; Sato, S.; Ko, K.M.; Konishi, T. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice. Free Radic. Res.,  2011, 45(8), 950-958.
[http://dx.doi.org/10.3109/10715762.2011.571682 ] [PMID:  21615274] 
[242] 
Ko, K.M.; Chen, N.; Leung, H.Y.; Leong, E.P.; Poon, M.K.; Chiu, P.Y. Long-term schisandrin B treatment mitigates age-related impairments in mitochondrial antioxidant status and functional ability in various tissues, and improves the survival of aging C57BL/6J mice. Biofactors,  2008, 34(4), 331-342.
[http://dx.doi.org/10.1002/biof.5520340408 ] [PMID:  19850987] 
[243] 
Lee, T.H.; Jung, C.H.; Lee, D.H. Neuroprotective effects of Schisandrin B against transient focal cerebral ischemia in Sprague-Dawley rats. Food Chem. Toxicol.,  2012, 50(12), 4239-4245.
[http://dx.doi.org/10.1016/j.fct.2012.08.047 ] [PMID:  22960133] 
[244] 
Sa, F.; Zhang, L.Q.; Chong, C.M.; Guo, B.J.; Li, S.; Zhang, Z.J.; Zheng, Y.; Hoi, P.M.; Lee, S.M.Y. Discovery of novel anti-parkinsonian effect of schisantherin A in in vitro and in vivo. Neurosci. Lett.,  2015, 593, 7-12.
[http://dx.doi.org/10.1016/j.neulet.2015.03.016 ] [PMID:  25770828] 
[245] 
Tang, B.; Qu, Y.; Wang, D.; Mu, D. Targeting hypoxia inducible factor-1α: a novel mechanism of ginsenoside Rg1 for brain repair after hypoxia/ischemia brain damage. CNS Neurol. Disord. Drug Targets,  2011, 10(2), 235-238.
[http://dx.doi.org/10.2174/187152711794480456 ] [PMID:  20874696] 
[246] 
Chen, B.; Cheng, Q.; Yang, K.; Lyden, P.D. Thrombin mediates severe neurovascular injury during ischemia. Stroke,  2010, 41(10), 2348-2352.
[http://dx.doi.org/10.1161/STROKEAHA.110.584920 ] [PMID:  20705928] 
[247] 
Cossi, M.J.; Gobron, C.; Preux, P.M.; Niama, D.; Chabriat, H.; Houinato, D. Stroke: prevalence and disability in Cotonou, Benin. Cerebrovasc. Dis.,  2012, 33(2), 166-172.
[http://dx.doi.org/10.1159/000334195 ] [PMID:  22222467] 
[248] 
Sanderson, T.H.; Reynolds, C.A.; Kumar, R.; Przyklenk, K.; Hüttemann, M. Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol. Neurobiol.,  2013, 47(1), 9-23.
[http://dx.doi.org/10.1007/s12035-012-8344-z ] [PMID:  23011809] 
[249] 
Desilles, J.P.; Rouchaud, A.; Labreuche, J.; Meseguer, E.; Laissy, J.P.; Serfaty, J.M.; Lapergue, B.; Klein, I.F.; Guidoux, C.; Cabrejo, L.; Sirimarco, G.; Lavallée, P.C.; Schouman-Claeys, E.; Amarenco, P.; Mazighi, M. Blood-brain barrier disruption is associated with increased mortality after endovascular therapy. Neurology,  2013, 80(9), 844-851.
[http://dx.doi.org/10.1212/WNL.0b013e31828406de ] [PMID:  23365060] 
[250] 
Hacke, W.; Schwab, S.; Horn, M.; Spranger, M.; De Georgia, M.; von Kummer, R. ‘Malignant’ middle cerebral artery territory infarction: clinical course and prognostic signs. Arch. Neurol.,  1996, 53(4), 309-315.
[http://dx.doi.org/10.1001/archneur.1996.00550040037012 ] [PMID:  8929152] 
[251] 
O’Collins, V.E.; Macleod, M.R.; Donnan, G.A.; Howells, D.W. Evaluation of combination therapy in animal models of cerebral ischemia. J. Cereb. Blood Flow Metab.,  2012, 32(4), 585-597.
[http://dx.doi.org/10.1038/jcbfm.2011.203 ] [PMID:  22293990] 
[252] 
van der Worp, H.B.; Howells, D.W.; Sena, E.S.; Porritt, M.J.; Rewell, S.; O’Collins, V.; Macleod, M.R. Can animal models of disease reliably inform human studies? PLoS Med.,  2010, 7(3),e1000245.
[http://dx.doi.org/10.1371/journal.pmed.1000245 ] [PMID:  20361020] 
[253] 
Li, X.J.; Hou, J.C.; Sun, P.; Li, P.T.; He, R.Q.; Liu, Y.; Zhao, L.Y.; Hua, Q. Neuroprotective effects of tongluojiunao in neurons exposed to oxygen and glucose deprivation. J. Ethnopharmacol.,  2012, 141(3), 927-933.
[http://dx.doi.org/10.1016/j.jep.2012.03.042 ] [PMID:  22472112] 
[254] 
Huang, T.; Fang, F.; Chen, L.; Zhu, Y.; Zhang, J.; Chen, X.; Yan, S.S. Ginsenoside Rg1 attenuates oligomeric Aβ(1-42)-induced mitochondrial dysfunction. Curr. Alzheimer Res.,  2012, 9(3), 388-395.
[http://dx.doi.org/10.2174/156720512800107636 ] [PMID:  22381145] 
[255] 
Jiang, B.; Xiong, Z.; Yang, J.; Wang, W.; Wang, Y.; Hu, Z.L.; Wang, F.; Chen, J.G. Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. Br. J. Pharmacol.,  2012, 166(6), 1872-1887.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01902.x ] [PMID:  22335772] 
[256] 
Rui, W.; Wang, G.J.; Wu, X.L.; Zhou, F.; Li, Y.N. Ginseno-side Rg1 attenuates structural disruption of the blood-brain barrier to protect the central nervous system in ischemia/reperfusion. Chin. J. Nat. Med.,  2013, 11(1), 30-37.
[http://dx.doi.org/10.1016/S1875-5364(13)60004-7 ] 
[257] 
Xie, C.L.; Li, J.H.; Wang, W.W.; Zheng, G.Q.; Wang, L.X. Neuroprotective effect of ginsenoside-Rg1 on cerebral ischemia/reperfusion injury in rats by downregulating protease-activated receptor-1 expression. Life Sci.,  2015, 121, 145-151.
[http://dx.doi.org/10.1016/j.lfs.2014.12.002 ] [PMID:  25498890] 
[258] 
Radad, K.; Gille, G.; Moldzio, R.; Saito, H.; Rausch, W.D. Ginsenosides Rb1 and Rg1 effects on mesencephalic dopaminergic cells stressed with glutamate. Brain Res.,  2004, 1021(1), 41-53.
[http://dx.doi.org/10.1016/j.brainres.2004.06.030 ] [PMID:  15328030] 
[259] 
Chen, X.C.; Zhu, Y.G.; Zhu, L.A.; Huang, C.; Chen, Y.; Chen, L.M.; Fang, F.; Zhou, Y.C.; Zhao, C.H. Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. Eur. J. Pharmacol.,  2003, 473(1), 1-7.
[http://dx.doi.org/10.1016/S0014-2999(03)01945-9 ] [PMID:  12877931] 
[260] 
Chen, X.C.; Zhou, Y.C.; Chen, Y.; Zhu, Y.G.; Fang, F.; Chen, L.M. Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress. Acta Pharmacol. Sin.,  2005, 26(1), 56-62.
[http://dx.doi.org/10.1111/j.1745-7254.2005.00019.x ] [PMID:  15659115] 
[261] 
Xu, L.; Chen, W.F.; Wong, M.S. Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson’s disease through the IGF-I receptor signalling pathway. Br. J. Pharmacol.,  2009, 158(3), 738-748.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00361.x ] [PMID:  19703168] 
[262] 
Castelo-Branco, G.; Arenas, E. Function of Wnts in dopaminergic neuron development. Neurodegener. Dis.,  2006, 3(1-2), 5-11.
[http://dx.doi.org/10.1159/000092086 ] [PMID:  16909030] 
[263] 
Castelo-Branco, G.; Wagner, J.; Rodriguez, F.J.; Kele, J.; Sousa, K.; Rawal, N.; Pasolli, H.A.; Fuchs, E.; Kitajewski, J.; Arenas, E. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc. Natl. Acad. Sci. USA,  2003, 100(22), 12747-12752.
[http://dx.doi.org/10.1073/pnas.1534900100 ] [PMID:  14557550] 
[264] 
Inestrosa, N.C.; Arenas, E. Emerging roles of Wnts in the adult nervous system. Nat. Rev. Neurosci.,  2010, 11(2), 77-86.
[http://dx.doi.org/10.1038/nrn2755 ] [PMID:  20010950] 
[265] 
Dun, Y.; Yang, Y.; Xiong, Z.; Feng, M.; Zhang, Y.; Wang, M.; Xiang, J.; Li, G.; Ma, R. Induction of Dickkopf-1 contributes to the neurotoxicity of MPP+ in PC12 cells via inhibition of the canonical Wnt signaling pathway. Neuropharmacology,  2013, 67, 168-175.
[http://dx.doi.org/10.1016/j.neuropharm.2012.10.031 ] [PMID:  23164620] 
[266] 
Scott, E.L.; Brann, D.W. Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease. Brain Res.,  2013, 1514, 63-74.
[http://dx.doi.org/10.1016/j.brainres.2012.12.015 ] [PMID:  23261660] 
[267] 
Parish, C.L.; Thompson, L.H. Modulating Wnt signaling to improve cell replacement therapy for Parkinson’s disease. J. Mol. Cell Biol.,  2014, 6(1), 54-63.
[http://dx.doi.org/10.1093/jmcb/mjt045 ] [PMID:  24334258] 
[268] 
Zhou, T.; Zu, G.; Zhang, X.; Wang, X.; Li, S.; Gong, X.; Liang, Z.; Zhao, J. Neuroprotective effects of ginsenoside Rg1 through the Wnt/β-catenin signaling pathway in both in vivo and in vitro models of Parkinson’s disease. Neuropharmacology,  2016, 101, 480-489.
[http://dx.doi.org/10.1016/j.neuropharm.2015.10.024 ] [PMID:  26525190] 
[269] 
Gu, B.; Nakamichi, N.; Zhang, W.S.; Nakamura, Y.; Kambe, Y.; Fukumori, R.; Takuma, K.; Yamada, K.; Takarada, T.; Taniura, H.; Yoneda, Y. Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N-methyl-D-aspartate receptors composed of an NR1/NR2B subunit assembly. J. Neurosci. Res.,  2009, 87(9), 2145-2156.
[http://dx.doi.org/10.1002/jnr.22021 ] [PMID:  19224577] 
[270] 
Chen, F.; Eckman, E.A.; Eckman, C.B. Reductions in levels of the Alzheimer’s amyloid β peptide after oral administration of ginsenosides. FASEB J.,  2006, 20(8), 1269-1271.
[http://dx.doi.org/10.1096/fj.05-5530fje ] [PMID:  16636099] 
[271] 
Yang, L.; Hao, J.; Zhang, J.; Xia, W.; Dong, X.; Hu, X.; Kong, F.; Cui, X. Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin. J. Pharm. Pharmacol.,  2009, 61(3), 375-380.
[http://dx.doi.org/10.1211/jpp.61.03.0013 ] [PMID:  19222911] 
[272] 
Wang, Y.H.; Du, G.H. Ginsenoside Rg1 inhibits beta-secretase activity in vitro and protects against Abeta-induced cytotoxicity in PC12 cells. J. Asian Nat. Prod. Res.,  2009, 11(7), 604-612.
[http://dx.doi.org/10.1080/10286020902843152 ] [PMID:  20183297] 
[273] 
Li, L.; Liu, Z.; Liu, J.; Tai, X.; Hu, X.; Liu, X.; Wu, Z.; Zhang, G.; Shi, M.; Zhao, G. Ginsenoside Rd attenuates beta-amyloid-induced tau phosphorylation by altering the functional balance of glycogen synthase kinase 3beta and protein phosphatase 2A. Neurobiol. Dis.,  2013, 54, 320-328.
[http://dx.doi.org/10.1016/j.nbd.2013.01.002 ] [PMID:  23321003] 
[274] 
Li, W.; Chu, Y.; Zhang, L.; Yin, L.; Li, L. Ginsenoside Rg1 attenuates tau phosphorylation in SK-N-SH induced by Aβ-stimulated THP-1 supernatant and the involvement of p38 pathway activation. Life Sci.,  2012, 91(15-16), 809-815.
[http://dx.doi.org/10.1016/j.lfs.2012.08.028 ] [PMID:  22982182] 
[275] 
Fang, F.; Chen, X.; Huang, T.; Lue, L.F.; Luddy, J.S.; Yan, S.S.D. Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model. Biochim. Biophys. Acta,  2012, 1822(2), 286-292.
[http://dx.doi.org/10.1016/j.bbadis.2011.10.004 ] [PMID:  22015470] 
[276] 
Lee, S.T.; Chu, K.; Sim, J.Y.; Heo, J.H.; Kim, M. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis. Assoc. Disord.,  2008, 22(3), 222-226.
[http://dx.doi.org/10.1097/WAD.0b013e31816c92e6 ] [PMID:  18580589] 
[277] 
Petkov, V.D.; Mosharrof, A.H. Effects of standardized ginseng extract on learning, memory and physical capabilities. Am. J. Chin. Med.,  1987, 15(1-2), 19-29.
[http://dx.doi.org/10.1142/S0192415X87000047 ] [PMID:  3687838] 
[278] 
Liu, J.; Yan, X.; Li, L.; Zhu, Y.; Qin, K.; Zhou, L.; Sun, D.; Zhang, X.; Ye, R.; Zhao, G. Ginsennoside rd attenuates cognitive dysfunction in a rat model of Alzheimer’s disease. Neurochem. Res.,  2012, 37(12), 2738-2747.
[http://dx.doi.org/10.1007/s11064-012-0866-2 ] [PMID:  22903450] 
[279] 
Yan, S.; Li, Z.; Li, H.; Arancio, O.; Zhang, W. Notoginsenoside R1 increases neuronal excitability and ameliorates synaptic and memory dysfunction following amyloid elevation. Sci. Rep.,  2014, 4, 6352.
[http://dx.doi.org/10.1038/srep06352 ] [PMID:  25213453] 
Rights & Permissions Print Cite
Article Metrics
99
6
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867326666190527120614	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

治疗神经退行性疾病的天然产物

摘要

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

当代药物化学

治疗神经退行性疾病的天然产物

摘要

Call for Papers in Thematic Issues

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Related Journals

Related Books

Related Articles
