Neuroprotective Effects, Biological Activities and Therapeutic Potential of Phytochemicals: A Comprehensive Review

A B S T R A C T

The incidence of neurological disorders is growing in the world together with an increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathology, which make necessary to search for new therapeutic agents. Natural products, most of them used in phytochemicals from herbal medicine, are considered promising alternatives for the treatment of neurodegenerative diseases. Numerous herbs have been applied to neurodegenerative disease treatments as complementary and alternative medicines. In the 21st century, omics-coupled functional pharmacology was developed for neurodegenerative drug discovery from natural products. In this article, we firstly provide the latest understanding of neurological disorders on risk factors, category, diagnosis and treatment, and then specially present an overview of natural products in neuroprotective effects research from chemical biology to pharmacological targets, and also discuss the natural products application and future challenge.

Keywords

Phytochemicals, neuroprotective effects, natural products, lead drug, pharmacological targets

Get access to the full version of this article.

Article Info

Article Type

Publication history

Copyright

Author Info

Shi Qiu Aihua Zhang Jian-hua Miao Hui Sun Guang-li Yan Fang-fang Wu Xi-jun Wang

Corresponding Author

Figures & Tables

Get access to the full version of this article.

References

1. Munuera CC (2011) [Assessment and management of dysphagia in children with neurological disorder]. Enferm Clin 21: 56-58. [Crossref]
2. Teive HA (2015) Non-progressive cerebellar ataxia with previous acute cerebellar injury of undetermined origin: a puzzling neurological disorder. Arq Neuropsiquiatr 73: 819-820. [Crossref]
3. Work SS, Colamonico JA, Bradley WG, Kaye RE (2011) Pseudobulbar affect: an under-recognized and under-treated neurological disorder. Adv Ther 28: 586-601. [Crossref]
4. Debadatta M, Mishra AK (2013) Meige's Syndrome: Rare Neurological Disorder Presenting as Conversion Disorder. Indian J Psychol Med 35: 317-318. [Crossref]
5. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD et al. (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: 2197-2223. [Crossref]
6. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C et al. (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: 2163-2196. [Crossref]
7. Brown MA, Potroz MG, Teh SW, Cho NJ (2016) Natural Products for the Treatment of Chlamydiaceae Infections. Microorganisms 4: E39. [Crossref]
8. Tundis R, Loizzo MR, Menichini F (2010) Natural products as alpha-amylase and alpha-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update. Mini Rev Med Chem 10: 315-331. [Crossref]
9. Sun YS, Li YJ, Xia Y, Xu F, Wang WW et al. (2016) Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation. Sci Rep 6: 34299. [Crossref]
10. Araujo AQ, Silva MT, Araujo AP (2016) Zika virus-associated neurological disorders: a review. Brain 139: 2122-2130. [Crossref]
11. Evzelman MA, Snimschikova IA, Koroleva LY (2015) Neurological disorders associated with HIV-infection. Zh Nevrol Psikhiatr Im S S Korsakova 115: 89-93.
12. Romanowski P, Kułakowska A, Drozdowski W (2004) Neurological disorders after carbon monoxide intoxication. Pol Merkur Lekarski 16: 592-594.
13. Ramesh T, Sureka C, Bhuvana S, Begum VH (2015) Oxidative stress in the brain of cigarette smoke-induced noxiousness: neuroprotective role of Sesbania grandiflora. Metab Brain Dis 30: 573-582. [Crossref]
14. Sabourdy F, Astudillo L, Colacios C, Dubot P, Mrad M et al. (2015) Monogenic neurological disorders of sphingolipid metabolism. Biochim Biophys Acta 1851: 1040-1051. [Crossref]
15. Sazci A, Sazci G, Sazci B, Ergul E, Idrisoglu HA (2016) Nicotinamide-N-Methyltransferase gene rs694539 variant and migraine risk. J Headache Pain 17: 93. [Crossref]
16. Squitti R, Siotto M, Arciello M, Rossi L (2016) Non-ceruloplasmin bound copper and ATP7B gene variants in Alzheimer's disease. Metallomics 8: 863-873. [Crossref]
17. Mahley RW (2016) Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. J Mol Med (Berl) 94: 739-746. [Crossref]
18. Kajta M, Wójtowicz AK (2013) Impact of endocrine-disrupting chemicals on neural development and the onset of neurological disorders. Pharmacol Rep 65: 1632-1639. [Crossref]
19. Nandi Munshi D, Taplin CE (2015) Thyroid-related neurological disorders and complications in children. Pediatr Neurol 52: 373-382. [Crossref]
20. Liewluck T, Miravalle A (2015) Immune-Mediated Neurological Disorders. Curr Neurol Neurosci Rep 15: 61. [Crossref]
21. Benga I, Benga O (2012) Implications of water channel proteins in selected neurological disorders: epilepsies, muscular dystrophies, amyotrophic lateral sclerosis, neuromyelitis optica, Parkinson's disease, and spongiform encephalopathies. Mol Aspects Med 33: 590-604. [Crossref]
22. Howell KB, Kornberg AJ, Harvey AS, Ryan MM, Mackay MT et al. (2013) High resolution chromosomal microarray in undiagnosed neurological disorders. J Paediatr Child Health 49: 716-724. [Crossref]
23. Mott M, Pahigiannis K, Koroshetz W (2014) Small blood vessels: big health problems: National Institute of Neurological Disorders and Stroke update. Stroke 45: e257-e258. [Crossref]
24. Lathia JD, Mattson MP, Cheng A (2008) Notch: from neural development to neurological disorders. J Neurochem 107: 1471-1481. [Crossref]
25. Ji AL, Zhang X, Chen WW, Huang WJ (2017) Recent perspectives of metabolic alterations in neurological disorders. J Neurosurg Sci 61: 689-690. [Crossref]
26. Mateen FJ, Dua T, Shen GC, Reed GM, Shakir R et al. (2012) Neurological disorders in the 11th revision of the International Classification of Diseases: now open to public Feedback. Lancet Neurol 11: 484-485. [Crossref]
27. Rajakulendran S, Dua T, Harper M, Shakir R (2014) The classification of neurological disorders in the 11th revision of the International Classification of Diseases (ICD-11). J Neurol Neurosurg Psychiatry 85: 952-953. [Crossref]
28. Brigo F, Igwe SC, Nardone R, Lochner P, Tezzon F et al. (2015) Wikipedia and neurological disorders. J Clin Neurosci 22: 1170-1172. [Crossref]
29. Beghi E, Pupillo E, Giussani G (2016) Peculiarities of Neurological Disorders and Study Designs. Front Neurol Neurosci 39: 8-23. [Crossref]
30. Lamberg L (2001) Psychiatric symptoms common in neurological disorders. JAMA 286: 154-156. [Crossref]
31. Hansen CP, Amiri M (2015) Combined detection of depression and anxiety in epilepsy patients using the Neurological Disorders Depression Inventory for Epilepsy and the World Health Organization well-being index. Seizure 33: 41-45. [Crossref]
32. Agrawal N, Rickards H (2011) Detection and treatment of depression in neurological disorders. J Neurol Neurosurg Psychiatry 82: 828-829. [Crossref]
33. Reitz C (2012) Alzheimer’s disease and the amyloid cascade hypothesis: a critical review. Int J Alzheimers Dis 2012: 369808. [Crossref]
34. Cash DM, Rohrer JD, Ryan NS, Ourselin S, Fox NC (2014) Imaging endpoints f or clinical trials in Alzheimer’ s disease. Alzheimers Res Ther 6: 87. [Crossref]
35. Schrag A, Weintraub D, Schott JM (2017) Cognitive decline before diagnosis of Parkinson's disease - Authors' reply. Lancet Neurol 16: 262. [Crossref]
36. Abushouk AI, Negida A, Ahmed H, Abdel Daim MM (2017) Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: Future applications in Parkinson's disease. Biomed Pharmacother 85: 635-645. [Crossref]
37. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH et al. (2014) ILAE official report: a practical clinical definition of epilepsy. Epilepsia 55: 475-482. [Crossref]
38. Rotenstein LS, Ramos MA, Torre M, Segal JB, Peluso MJ (2016) Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation Among Medical Students: A Systematic Review and Meta-Analysis. JAMA 316: 2214-2236. [Crossref]
39. Dennis CL，Dowswell T (2013) Interventions (other than pharmacological，psychosocial or psychological) for treating antenatal depression. Cochrane Database Syst Rev 7: CD006795. [Crossref]
40. Bushnell CD (2008) Stroke and the female brain. Nat Clin Pract Neurol 4: 22-33. [Crossref]
41. Coupland AP, Thapar A, Qureshi MI, Jenkins H, Davies AH (2017) The definition of stroke. J R Soc Med 110: 9-12. [Crossref]
42. Camara Lemarroy CR, Ibarra Yruegas BE, Rodriguez Gutierrez R, Berrios Morales I, Ionete C et al. (2017) The varieties of psychosis in multiple sclerosis: A systematic review of cases. Mult Scler Relat Disord 12: 9-14. [Crossref]
43. Uccelli MM (2014) The impact of multiple sclerosis on family members: a review of the literature. Neurodegener Dis Manag 4: 177-185. [Crossref]
44. Benarroch EE (2014) The clinical approach to autonomic failure in neurological disorders. Nat Rev Neurol 10: 396-407. [Crossref]
45. Stone J (2016) Functional neurological disorders: the neurological assessment as treatment. Pract Neurol 16: 7-17. [Crossref]
46. Zhu M, Wu W, Chen S, Liu M, Wang L et al. (2014) [The etiology of neurological disorders in 1 188 elder patients with neuroimaging at geriatric outpatient clinic]. Zhonghua Nei Ke Za Zhi 53: 202-205. [Crossref]
47. Lee S, Mirsky DM, Beslow LA, Amlie-Lefond C, Danehy AR et al. (2017) Pathways for Neuroimaging of Neonatal Stroke. Pediatr Neurol 69: 37-48. [Crossref]
48. Goto J (2009) Guideline for gene diagnosis of neurological disorders. Rinsho Shinkeigaku 50: 812.
49. Guio Vega GP, Forero DA (2017) Functional genomics of candidate genes derived from genome-wide association studies for five common neurological diseases. Int J Neurosci 127: 118-123. [Crossref]
50. Howell KB, Kornberg AJ, Harvey AS, Ryan MM, Mackay MT et al. (2013) High resolution chromosomal microarray in undiagnosed neurological disorders. J Paediatr Child Health 49: 716-724. [Crossref]
51. Németh AH, Kwasniewska AC, Lise S, Parolin Schnekenberg R, Becker EB et al. (2013) Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model. Brain 136: 3106-3118. [Crossref]
52. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR et al. (2009) Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 106: 19096-19101. [Crossref]
53. Veeramah KR, O'Brien JE, Meisler MH, Cheng X, Dib-Hajj SD et al. (2012) De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am J Hum Genet 90: 502-510. [Crossref]
54. Berisavac II, Pavlović AM, Trajković JJ Šternić NM, Bumbaširević LG (2015) Drug treatment of vertigo in neurological disorders. Neurol India 63: 933-939. [Crossref]
55. Kapoor S (2014) Bexarotene and its potential role in the treatment of neurological disorders: beyond its role as an anti-cancer agent. J Drugs Dermatol 13: 240. [Crossref]
56. Bonouvrié L, Becher J, Soudant D, Buizer A, van Ouwerkerk W et al. (2016) The effect of intrathecal baclofen treatment on activities of daily life in children and young adults with cerebral palsy and progressive neurological disorders. Eur J Paediatr Neurol 20: 538-544. [Crossref]
57. Li P, Zhang Q, Robichaud AJ, Lee T, Tomesch J et al. (2014) Discovery of a tetracyclic quinoxaline derivative as a potent and orally active multifunctional drug candidate for the treatment of neuropsychiatric and neurological disorders. J Med Chem 57: 2670-2682. [Crossref]
58. Jatana N, Apoorva N, Malik S, Sharma A, Latha N (2013) Inhibitors of catechol-O-methyltransferase in the treatment of neurological disorders. Cent Nerv Syst Agents Med Chem 13: 166-194. [Crossref]
59. Li G, Jorgensen M, Campbell BM, Doller D (2016) Recent Developments in Group I Metabotropic Glutamate Receptor Allosteric Modulators for the Treatment of Psychiatric and Neurological Disorders (2014-May 2015). Curr Top Med Chem 16: 3470-3526. [Crossref]
60. Li G, Jørgensen M, Campbell BM (2013) Metabotropic glutamate receptor 5-negative allosteric modulators for the treatment of psychiatric and neurological disorders (2009-July 2013). Pharm Pat Anal 2: 767-802.
61. Reuillon T, Ward SE, Beswick P (2016) AMPA Receptor Positive Allosteric Modulators: Potential for the Treatment of Neuropsychiatric and Neurological Disorders. Curr Top Med Chem 16: 3536-3565. [Crossref]
62. Shaw AE, Bamburg JR (2017) Peptide regulation of cofilin activity in the CNS: A novel therapeutic approach for treatment of multiple neurological disorders. Pharmacol Ther 175:17-27. [Crossref]
63. Brinker T, Spader H (2014) A translational view of peptide treatment of neurological disorders. Curr Med Chem 21: 2583-2590. [Crossref]
64. Ong WY, Farooqui T, Kokotos G, Farooqui AA (2015) Synthetic and natural inhibitors of phospholipases A2: their importance for understanding andtreatment of neurological disorders. ACS Chem Neurosci 6: 814-831. [Crossref]
65. Devinsky O, Whalley BJ, Di Marzo V (2015) Cannabinoids in the Treatment of Neurological Disorders. Neurotherapeutics 12: 689-691. [Crossref]
66. Kamran N, Candolfi M, Baker GJ, Ayala MM, Dzaman M et al. (2016) Gene Therapy for the Treatment of Neurological Disorders: Central Nervous System Neoplasms. Methods Mol Biol 1382: 467-482. [Crossref]
67. Gessler DJ, Gao G (2016,) Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders. Methods Mol Biol 1382: 429-465. [Crossref]
68. McEachin ZT, Donsante A, Boulis N (2016) Gene Therapy for the Treatment of Neurological Disorders: Amyotrophic Lateral Sclerosis. Methods Mol Biol 1382: 399-408. [Crossref]
69. Baba M, Itaka K, Kondo K, Yamasoba T, Kataoka K (2015) Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles. J Control Release 201: 41-48. [Crossref]
70. Jette N, Reid AY, Wiebe S (2014) Surgical management of epilepsy. CMAJ 186: 997-1004. [Crossref]
71. Ohkubo A1, Okado T, Kurashima N, Maeda T, Miyamoto S et al. (2014) Removal kinetics of antibodies against glutamic acid decarboxylase by various plasmapheresis modalities in the treatment of neurological disorders. Ther Apher Dial 18: 231-237. [Crossref]
72. Sarma AA, Crocker B, Cash SS, Truccolo W (2016) A modular, closed-loop platform for intracranial stimulation in people with neurological disorders. Conf Proc IEEE Eng Med Biol Soc 2016: 3139-3142. [Crossref]
73. Barral S, Kurian MA (2016) Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders. Front Mol Neurosci 9: 78. [Crossref]
74. Taylor CJ, Jhaveri DJ, Bartlett PF (2013) The therapeutic potential of endogenous hippocampal stem cells for the treatment of neurological disorders. Front Cell Neurosci 7: 5. [Crossref]
75. Chhabra R, Tosi G, Grabrucker AM (2015) Emerging Use of Nanotechnology in the Treatment of Neurological Disorders. Curr Pharm Des 21: 3111-3130. [Crossref]
76. Wang Q, Meng J, Dong A, Yu JZ, Zhang GX et al. (2016) The Pharmacological Effects and Mechanism of Tripterygium wilfordii Hook F in Central NervousSystem Autoimmunity. J Altern Complement Med 22: 496-502. [Crossref]
77. WANG Zhe, LI Wei, LI Jingyuan (2016) Metabolomics Study on the Therapeutic Effect of Valeriana amurensis extracts on Alzheimer 's Disease Mice. China Medical Herald 21: 4-7.
78. Jin G, He XR, Chen LP (2014) The protective effect of ginko bilboa leaves injection on the brain dopamine in the rat model of cerebral ischemia/reperfusion injury. Afr Health Sci 14: 725-728. [Crossref]
79. Li S, Li S, Liu C, Liu C, Zhang Y (2017) Extraction and isolation of potential anti-stroke compounds from flowers of Pueraria lobataguided by in vitro PC12 cell model. J Chromatogr B Analyt Technol Biomed Life Sci 1048: 111-120. [Crossref]
80. Subash S, Essa MM, Braidy N, Al Jabri A, Vaishnav R et al. (2016) Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning skills in a transgenic mice model of Alzheimer’s disease. Nutr Neurosci 19: 475-483. [Crossref]
81. Li Ji Le (2016) Clinical Research on Treatment of Early Alzheimer 's Disease with Di Dang soup. HENAN TRADITIONAL CHINESE MEDICINE 36: 1318-1321.
82. Jiang YM, Li XJ, Meng ZZ, Liu YY, Hong BZ et al. (2016) Effects of Xiao Yao san on Stress-Induced Anxiety-Like Behavior in Rats: Involvement of CRF1 Receptor. Evid Based Complement Alternat Med 2016: 1238426. [Crossref]
83. Chu H, Zhang A, Han Y, Lu S, Kong L et al. (2016) Metabolomics approach to explore the effects of Kai-Xin-San on Alzheimer’s disease using UPLC/ESI-QTOF mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1015-1016: 50-61. [Crossref]
84. Zhou W, Cheng X, Zhang Y (2016) Effect of Liuwei Dihuang decoction, a traditional Chinese medicinal prescription, on the neuroendocrine immunomodulation network. Pharmacol Ther 162: 170-178. [Crossref]
85. Cao G, Zhou H, Jiang N, Han Y, Hu Y et al. (2016) YiQiFuMai Powder Injection Ameliorates Cerebral Ischemia by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis. Oxid Med Cell Longev 2016: 5493279. [Crossref]
86. Li L, Yang N, Nin L, Zhao Z, Chen L et al. (2015) Chinese herbal medicine formula tao hong si wu decoction protects against cerebral ischemia-reperfusion injury via PI3K/Akt and the Nrf2 signaling pathway. J Nat Med 69: 76-85. [Crossref]
87. Wang ZY, Liu JG, Li H, Yang HM (2016) Pharmacological Effects of Active Components of Chinese Herbal Medicine in the Treatment of Alzheimer's Disease: A Review. Am J Chin Med 44: 1525-1541. [Crossref]
88. More SV, Kumar H, Kang SM, Song SY, Lee Ket al. (2013) Advances in neuroprotective ingredients of medicinal herbs by using cellular and animal models of Parkinson's disease. Evid Based Complement Alternat Med 2013: 957875. [Crossref]
89. Zhang X, Hong YL, Xu DS, Feng Y, Zhao LJ et al. (2014) A review of experimental research on herbal compounds in amyotrophic lateral sclerosis. Phytother Res 28: 9-21. [Crossref]
90. Kean RJ, Lamport DJ, Dodd GF, Freeman JE, Williams CM et al. (2015) Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults. Am J Clin Nutr101: 506-514. [Crossref]
91. Bensalem J, Servant L, Alfos S, Gaudout D, Layé S et al. (2016) Dietary Polyphenol Supplementation Prevents Alterations of Spatial Navigation in Middle-Aged Mice. Front Behav Neurosci 10: 9. [Crossref]
92. Nabavi SF, Daglia M, D'Antona G, Sobarzo Sánchez E, Talas ZS et al. (2015) Natural compounds used as therapies targeting to amyotrophic lateral sclerosis. Curr Pharm Biotechnol 16: 211-218. [Crossref]
93. Goozee KG, Shah TM, Sohrabi HR, Rainey Smith SR, Brown B et al. (2016) Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease. Br J Nutr 115: 449-465. [Crossref]
94. Gaballah HH, Zakaria SS, Elbatsh MM, Tahoon NM et al. (2016) Modulatory effects of resveratrol on endoplasmic reticulum stress-associated apoptosis and oxido-inflammatory markers in a rat model of rotenone-induced Parkinson's disease. Chem Biol Interact 251: 10-16. [Crossref]
95. Wang ZH, Zhang JL, Duan YL, Zhang QS, Li GF et al. (2015) MicroRNA-214 participates in the neuroprotective effect of Resveratrol via inhibiting α-synuclein expression in MPTP-induced Parkinson's disease mouse. Biomed Pharmacother 74: 252-256. [Crossref]
96. Jiang YF, Liu ZQ, Cui W, Zhang WT, Gong JP et al. (2015) Antioxidant effect of salvianolic acid B on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury. Chin J Integr Med 21: 516-522. [Crossref]
97. Wang Y, Chen G, Yu X, Li Y, Zhang L et al. (2016) Salvianolic Acid B Ameliorates Cerebral Ischemia/Reperfusion Injury Through Inhibiting TLR4/MyD88 Signaling Pathway. Inflammation 39: 1503-1513. [Crossref]
98. Zhang L, Feng H, He Y, Zhao J, Chen Y et al. (2017) Ginseng saponin Rb1 enhances hematopoietic function and dendritic cells differentiation. Acta Biochim Biophys Sin (Shanghai) 49: 746-749. [Crossref]
99. Zhuo X, Sun H, Wang S, Guo X, Ding H et al. (2017) Ginseng Stem-and-Leaf Saponin (GSLS)- Enhanced Protective Immune Responses Induced by Toxoplasma gondii Heat Shocked Protein 70 (HSP70) Against Toxoplasmosis in Mice. J Parasitol 103: 111-117. [Crossref]
100.  Liu MY, Ren YP, Zhang LJ, Ding JY (2016) Pretreatment with Ginseng Fruit Saponins Affects Serotonin Expression in an Experimental Comorbidity Model of Myocardial Infarction and Depression. Aging Dis 7: 680-686. [Crossref]
101.  He DF, Ren YP, Liu MY (2016) Effects of Ginseng Fruit Saponins on Serotonin System in Sprague-Dawley Rats with Myocardial Infarction, Depression, and Myocardial Infarction Complicated with Depression. Chin Med J (Engl) 129: 2913-2919. [Crossref]
102. Yan ZQ, Chen J, Xing GX, Huang JG, Hou XH et al. (2015) Salidroside prevents Cognitive impairment induced by chronic cerebral hypoperfusion in rats. J Int Med Res 43: 402-411. [Crossref]
103.  WANG XJ, WANG DX, XU CJ (2016) Therapeutic effect of asiaticoside on Alzheimer's disease. CHINA MEDICINE AND PHARMACY 6: 37-39.
104.  Cao G, Jiang N, Hu Y, Zhang Y, Wang G et al. (2016) Ruscogenin Attenuates Cerebral Ischemia-Induced Blood-Brain Barrier Dysfunction by Suppressing TXNIP/NLRP3 Inflammasome Activation and the MAPK Pathway. Int J Mol Sci 17: E1418. [Crossref]
105.  FAN Yue，WU Xiaoguang，MIAO Hong (2015) Effect of Scutellaria Barbata Flavonoids on β-Amyloid Protein-induced Injury in Rats Astrocytes［J］．Herald of Medicine 34: 141-145.
106.  YIN Xue li, GUI Li, LI Zhen (2015) Effects of puerarin preconditioning on neuronal injury in hippocampal CA1 region of rats with focal cerebral ischemia - reperfusion and its mechanism. J Anhui Med University 50: 723-726.
107.  LIU Xiao ling，LI Wen yan，GAO Tian, et al. (2015) Study on experimental autoimmune encephalomyelitis with oxymatrine on rats model［J］．Chin J Biochem Pharm 35: 22-24.
108.  Liu J, Chen Q, Jian Z, Xiong X, Shao L et al. (2016) Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway. Biomed Res Int 2016: 2816056. [Crossref]
109.  SONG WS, ZHANG YL, SUN W (2016) Research on effects and mechanisms of oleanolic acid on waking silent synapses in Alzheimer’ s disease rat hippocampus. CJTCM P 31: 3471-3474.
110.  Huang S, Mao J, Ding K, Zhou Y, Zeng X et al. (2017) Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease. Stem Cell Reports 8: 84-94. [Crossref]
111.  KONG L，YAO Y，JIAO Y (2015) Protective Effects of Osthole on the Nerves of Model Mice with Craniocerebral Injury［J］. China Pharmacy 26: 3046-3049.
112.  LI C，LI Z， JI W (2015) Effect of physcion on the expression of Bcl-2 and Bax in rats after brain injury［J］．Chin J Neurosurg Dis Res 14: 200-203.
113.  Lin L, Chang LL，Liu GL (2016) Effects of Crocin on Spatial Learning and Memory and LTP in Hippocampus on Rat’s with Alzheimer disease. Chin J Neuroanat 32: 482-486.
114.  Karami M, Bathaie SZ, Tiraihi T, Habibi Rezaei M, Arabkheradmand J et al. (2013) Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP). Phytomedicine 21: 62-67. [Crossref]
115.  Lee SH, Ko IG, Kim SE, Hwang L, Jin JJ et al. (2016) Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils. J Exerc Rehabil 12: 69-78. [Crossref]
116.  Zeng Y, Guo W, Xu G, Wang Q, Feng L et al. (2016) Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington's disease. Drug Des Devel Ther 13: 1443-1451. [Crossref]
117.  Koster KP, Smith C, Valencia Olvera AC, Thatcher GR, Tai LM et al. (2017) Rexinoids as therapeutics for Alzheimer disease: role of APOE. Curr Top Med Chem 17: 708-720. [Crossref]
118.  Huang Q, Du X, He X, Yu Q, Hu K et al. (2016) JNK- mediated activation of ATF2 contributes to dopaminergic neurodegeneration in the MPTP mouse model of Parkinson’s disease. Exp Neurol 277: 296-304. [Crossref]
119.  Mortari MR, Cunha AOS (2013) New perspectives in drug discovery using neuroactive molecules from the venom of arthropods. In: Baptista GR, editor. An Integrative View of the Molecular Recognit ion and Toxinology - From Analytical Procedures to Biomedical Applications p. 91-117.
120.  Fuentes VM, Gomes FMM, Campos GAA, Silva JC, Biolchi AM et al. (2015) Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders. J Venom Anim Toxins incl Trop Dis 21: 31. [Crossref]
121.  Choi DY, Choi H (2015) Natural products from marine organisms with neuroprotective activity in the experimental models of Alzheimer's disease, Parkinson's disease and ischemic brain stroke: their molecular targets and action mechanisms. Arch Pharm Res 38: 139-170. [Crossref]
122.  Olasehinde TA, Olaniran AO, Okoh AI (2017) Therapeutic Potentials of Microalgae in the Treatment of Alzheimer's Disease. Molecules 22: E480. [Crossref]
123.  Wu DT, Deng Y, Chen LX, Zhao J, Bzhelyansky A et al. (2017) Evaluation on quality consistency of Ganoderma lucidum dietary supplements collected in the United States. Sci Rep 7: 7792. [Crossref]
124.  Guillemin GJ, Essa MM, Song BJ, Manivasagam T (2017) Dietary Supplements/Antioxidants: Impact on Redox Status in Brain Diseases. Oxid Med Cell Longev 2017: 5048432. [Crossref]
125.  Saboor Yaraghi AA, Harirchian MH, Mohammadzadeh Honarvar N, Bitarafan S, Abdolahi M et al. (2015) The Effect of Vitamin A Supplementation on FoxP3 and TGF-β Gene Expression in Avonex-Treated Multiple Sclerosis Patients. J Mol Neurosci 56: 608-612. [Crossref]
126.  Raszewski G, Chwedorowicz R, Chwedorowicz A, Gustaw Rothenberg K (2016) Homocysteine, antioxidant vitamins and lipids as biomarkers of neurodegeneration in Alzheimer’s disease versus non-Alzheimer’s dementia. Ann Agric Environ Med 23: 193-196. [Crossref]
127.  Chen H, Liu S, Ji L, Wu T, Ma F et al. (2015) Associations between Alzheimer’s disease and blood homocysteine, vitamin B12, and folate: a case control study. Curr Alzheimer Res 12: 88-94. [Crossref]
128.  Eagappan K, Sasikumar S (2015) Functional nutrition is a deterimental factor in biological aging. International Journal of Pharmaceutical Sciences Review and Research 32: 153-161.
129.  Liu Y, Li YW, Tang YL, Liu X, Jiang JH et al. (2013) Vitamin D: preventive and therapeutic potential in Parkinson's disease. Curr Drug Metab 14: 989-993. [Crossref]
130.  Sundström P, Salzer J (2015) Vitamin D and multiple sclerosis-from epidemiology to prevention. Acta Neurol Scand 132: 56-61. [Crossref]
131.  Molnár MF, Török R, Szalárdy L, Sümegi E, Vécsei L et al. (2016) High-dose 1,25-dihydroxyvitamin D supplementation elongates the lifespan of Huntington's disease transgenic mice. Acta Neurobiol Exp (Wars) 76: 176-181. [Crossref]
132.  Okereke OI, Singh A (2016) The role of vitamin D in the prevention of late-life depression. J Affect Disord 198: 1-14. [Crossref]
133.  Grimm MO, Stahlmann CP, Mett J, Haupenthal VJ, Zimmer VC et al. (2015) Vitamin E: curse or benefit in Alzheimer’s disease? A systematic investigation of the impact of 𝛼-, 𝛾- and 𝛿-tocopherol on A𝛽 generation and degradation in neuroblastoma cells. J Nutr Health Aging 19: 646-656. [Crossref]
134.  Yary T, Lehto SM, Tolmunen T, Tuomainen TP, Kauhanen J et al. (2016) Dietary magnesium intake and the incidence of depression: A 20-year follow-up study. J Affect Disord 193: 94-98. [Crossref]
135.  Fitzgerald KC, O'Reilly ÉJ, Fondell E, Falcone GJ, McCullough ML et al. (2013) Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: pooled results from 5 cohort studies. Ann Neurol 73: 236-245. [Crossref]
136.  Vauzour D, Martinsen A, Layé S (2015) Neuroinflammatory processes in cognitive disorders: is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects? Neurochem Int 89: 63-74. [Crossref]
137.  Fitzgerald KC, O'Reilly ÉJ, Falcone GJ, McCullough ML, Park Y et al. (2014) Dietary ω-3 polyunsaturated fatty acid intake and risk for amyotrophic lateral sclerosis. JAMA Neurol 71: 1102-1110. [Crossref]
138.  Parkinson Study Group SURE PD Investigators, Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, et al. (2014) Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol 71: 141-150. [Crossref]
139.  Yu S, Wang C, Cheng Q, Xu H, Zhang S et al. (2014) An active component of Achyranthes bidentata polypeptides provides neuroprotection through inhibition of mitochondrial-dependent apoptotic pathway in cultured neurons and in animal models of cerebral ischemia. PLoS One 9: e109923. [Crossref]