Ampelopsin Improves Cognitive Impairment in Alzheimer’s Disease and Effects of Inflammatory Cytokines and Oxidative Stress in the Hippocampus

Page: [44 - 51] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Neuroinflammation and oxidative stress have significant effects on cognitive deficiency in the pathophysiological development of Alzheimer’s disease (AD). In the present study, we studied the influences of Ampelopsin (AMP) on proinflammatory cytokines (PICs, IL-1β, IL-6 and TNF-α), and products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, a product of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, a key biomarker of protein oxidation) in the hippocampus using a rat model of AD.

Methods: ELISA was used to examine PICs and oxidative stress production; and western blotting to examine NADPH oxidase (NOXs). The Spatial working memory tests and Morris water maze were utilized to assess cognitive functions.

Results: We observed amplification of IL-1β, IL-6 and TNF-α as well as 8-iso PGF2α and 8-OHdG in the hippocampus of AD rats. AMP attenuated upregulation of PICs and oxidative stress production. AMP also inhibited NOX4 in the AD rat hippocampus. Notably, AMP mostly improved learning performance in AD rat and this was linked to signal pathways of PIC and oxidative stress.

Conclusion: AMP plays a significant role in improving the memory deficiency in AD rats via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that AMP is likely to prospect in preventing and relieving development of the cognitive dysfunctions in AD as a complementary alternative intervention.

Keywords: Neuroinflammation, oxidative stress, hippocampus, Alzheimer's disease, ampelopsin, neurodegenerative disease.

[1]
Burns A, Iliffe S. Alzheimer’s disease. BMJ 338: b158. (2009).
[http://dx.doi.org/10.1136/bmj.b158] [PMID: 19196745]
[2]
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med 362(4): 329-44. (2010).
[http://dx.doi.org/10.1056/NEJMra0909142] [PMID: 20107219]
[3]
Marttinen M, Takalo M, Natunen T, Wittrahm R, Gabbouj S, Kemppainen S, et al. Molecular mechanisms of synaptotoxicity and neuroinflammation in Alzheimer’s Disease. Front Neurosci 12: 963. (2018).
[http://dx.doi.org/10.3389/fnins.2018.00963] [PMID: 30618585]
[4]
Sharma P, Srivastava P, Seth A, Tripathi PN, Banerjee AG, Shrivastava SK. Comprehensive review of mechanisms of pathogenesis involved in Alzheimer’s disease and potential therapeutic strategies. Prog Neurobiol 174: 53-89. (2019).
[http://dx.doi.org/10.1016/j.pneurobio.2018.12.006] [PMID: 30599179]
[5]
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1(1) a006189 (2011).
[http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]
[6]
Piton M, Hirtz C, Desmetz C, Milhau J, Lajoix AD, Bennys K, et al. Alzheimer’s disease: advances in drug development. J Alzheimers Dis 65(1): 3-13. (2018).
[http://dx.doi.org/10.3233/JAD-180145] [PMID: 30040716]
[7]
Su F, Bai F, Zhang Z. Inflammatory cytokines and alzheimer’s disease: a review from the perspective of genetic polymorphisms. Neurosci Bull 32(5): 469-80. (2016).
[http://dx.doi.org/10.1007/s12264-016-0055-4] [PMID: 27568024]
[8]
Wang X, Li GJ, Hu HX, Ma C, Ma D-H, Liu X-L, et al. Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats. Transl Neurosci 7(1): 151-7. (2016).
[http://dx.doi.org/10.1515/tnsci-2016-0022] [PMID: 28123835]
[9]
Liu D, Zhao D, Zhao Y, Wang Y, Zhao Y, Wen C. Inhibition of microRNA-155 alleviates cognitive impairment in Alzheimer’s disease and involvement of neuroinflammation. Curr Alzheimer Res 16(6): 473-82. (2019).
[http://dx.doi.org/10.2174/1567205016666190503145207] [PMID: 31456514]
[10]
Sochocka M, Koutsouraki ES, Gasiorowski K, Leszek J. Vascular oxidative stress and mitochondrial failure in the pathobiology of Alzheimer’s disease: a new approach to therapy. CNS Neurol Disord Drug Targets 12(6): 870-81. (2013).
[http://dx.doi.org/10.2174/18715273113129990072] [PMID: 23469836]
[11]
Yan MH, Wang X, Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radic Biol Med 62: 90-101. (2013).
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.11.014] [PMID: 23200807]
[12]
Butterfield DA, Swomley AM, Sultana R. Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal 19(8): 823-35. (2013).
[http://dx.doi.org/10.1089/ars.2012.5027] [PMID: 23249141]
[13]
Zhou J, Xie G, Yan X. Encyclopedia of traditional chinese medicines – molecular structures, pharmacological activities, natural sources and applications. Springer Science & Business Media. (2011).
[14]
Hou X, Zhang J, Ahmad H, Zhang H, Xu Z, Wang T. Evaluation of antioxidant activities of ampelopsin and its protective effect in lipopolysaccharide-induced oxidative stress piglets. PLoS One 9(9) e108314 (2014).
[http://dx.doi.org/10.1371/journal.pone.0108314] [PMID: 25268121]
[15]
Liang X, Zhang T, Shi L, Kang C, Wan J, Zhou Y, et al. Ampelopsin protects endothelial cells from hyperglycemia-induced oxidative damage by inducing autophagy via the AMPK signaling pathway. Biofactors 41(6): 463-75. (2015).
[http://dx.doi.org/10.1002/biof.1248] [PMID: 26644014]
[16]
Weng L, Zhang H, Li X, Zhan H, Chen F, Han L, et al. Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia. Int Immunopharmacol 44: 1-8. (2017).
[http://dx.doi.org/10.1016/j.intimp.2016.12.018] [PMID: 27998743]
[17]
Swanson LW. Brain Maps: Structure of the rat brain, 2nd. New York: Elsevier. (1998).
[18]
Kou X, Shen K, An Y, Qi S, Dai WX, et al. Ampelopsin inhibits H2O2-induced apoptosis by ERK and Akt signaling pathways and up-regulation of heme oxygenase-1. Phytother Res 26(7): 988-94. (2012).
[http://dx.doi.org/10.1002/ptr.3671] [PMID: 22144097]
[19]
Pflieger A, Waffo Teguo P, Papastamoulis Y, Chaignepain S, Subra F, Munir S, et al. Natural stilbenoids isolated from grapevine exhibiting inhibitory effects against HIV-1 integrase and eukaryote MOS1 transposase in vitro activities. PLoS One 8(11) e81184 (2013).
[http://dx.doi.org/10.1371/journal.pone.0081184] [PMID: 24312275]
[20]
Qi S, Xin Y, Guo Y, Diao Y, Kou X, Luo L, et al. Ampelopsin reduces endotoxic inflammation via repressing ROS-mediated activation of PI3K/Akt/NF-κB signaling pathways. Int Immunopharmacol 12(1): 278-87. (2012).
[http://dx.doi.org/10.1016/j.intimp.2011.12.001] [PMID: 22193240]
[21]
Zhang B, Dong S, Cen X, Wang X, Liu X, Zhang H, et al. Ampelopsin sodium exhibits antitumor effects against bladder carcinoma in orthotopic xenograft models. Anticancer Drugs 23(6): 590-6. (2012).
[http://dx.doi.org/10.1097/CAD.0b013e32835019f9] [PMID: 22241170]
[22]
Zhou Y, Shu F, Liang X, Chang H, Shi L, Peng X, et al. Ampelopsin induces cell growth inhibition and apoptosis in breast cancer cells through ROS generation and endoplasmic reticulum stress pathway. PLoS One 9(2) e89021 (2014).
[http://dx.doi.org/10.1371/journal.pone.0089021] [PMID: 24551210]
[23]
Kim JY, Jeong HY, Lee HK, Kim S-H, Hwang BY, Bae K, et al. Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxicity in cultured neurons. Phytomedicine 19(2): 150-9. (2012).
[http://dx.doi.org/10.1016/j.phymed.2011.06.015] [PMID: 21778042]
[24]
Ye XL, Lu LQ, Li W, Lou Q, Guo HG, Shi QJ. Oral administration of ampelopsin protects against acute brain injury in rats following focal cerebral ischemia. Exp Ther Med 13(5): 1725-34. (2017).
[http://dx.doi.org/10.3892/etm.2017.4197] [PMID: 28565759]
[25]
Dung HV, Cuong TD, Chinh NM, Quyen D, Kim JA, Su J, et al. Compounds from the aerial parts of Piper bavinum and their anti-cholinesterase activity. Arch Pharm Res 38(5): 677-82. (2015).
[http://dx.doi.org/10.1007/s12272-014-0432-3] [PMID: 25005067]
[26]
Papastamoulis Y, Richard T, Nassra M, Badoc A, Krisa S, Harakat D, et al. Viniphenol A, a complex resveratrol hexamer from Vitis vinifera stalks: structural elucidation and protective effects against amyloid-β-induced toxicity in PC12 cells. J Nat Prod 77(2): 213-7. (2014).
[http://dx.doi.org/10.1021/np4005294] [PMID: 24521157]
[27]
Lecanu L, Papadopoulos V. Modeling Alzheimer’s disease with non-transgenic rat models. Alzheimers Res Ther 5(3): 17. (2013).
[http://dx.doi.org/10.1186/alzrt171] [PMID: 23634826]
[28]
Lecanu L, Greeson J, Papadopoulos V. Beta-amyloid and oxidative stress jointly induce neuronal death, amyloid deposits, gliosis, and memory impairment in the rat brain. Pharmacology 76(1): 19-33. (2006).
[http://dx.doi.org/10.1159/000088929] [PMID: 16224201]
[29]
Nakamura S, Murayama N, Noshita T, Annoura H, Ohno T. Progressive brain dysfunction following intracerebroventricular infusion of beta(1-42)-amyloid peptide. Brain Res 912(2): 128-36. (2001).
[http://dx.doi.org/10.1016/S0006-8993(01)02704-4] [PMID: 11532428]
[30]
Rose-John S, Heinrich PC. Soluble receptors for cytokines and growth factors: generation and biological function. Biochem J 300(Pt 2): 281-90. (1994).
[http://dx.doi.org/10.1042/bj3000281] [PMID: 8002928]
[31]
Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58(3): 573-81. (1989).
[http://dx.doi.org/10.1016/0092-8674(89)90438-8] [PMID: 2788034]
[32]
MacEwan DJ. TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 14(6): 477-92. (2002).
[http://dx.doi.org/10.1016/S0898-6568(01)00262-5] [PMID: 11897488]
[33]
Probert L. TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects. Neuroscience 302: 2-22. (2015).
[http://dx.doi.org/10.1016/j.neuroscience.2015.06.038] [PMID: 26117714]
[34]
Altenhöfer S, Kleikers PW, Radermacher KA, Scheurer P, Hermans JJR, Schiffers P, et al. The NOX toolbox: validating the role of NADPH oxidases in physiology and disease. Cell Mol Life Sci 69(14): 2327-43. (2012).
[http://dx.doi.org/10.1007/s00018-012-1010-9] [PMID: 22648375]
[35]
Salvemini D, Little JW, Doyle T, Neumann WL. Roles of reactive oxygen and nitrogen species in pain. Free Radic Biol Med 51(5): 951-66. (2011).
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.01.026] [PMID: 21277369]
[36]
Lam GY, Huang J, Brumell JH. The many roles of NOX2 NADPH oxidase-derived ROS in immunity. Semin Immunopathol 32(4): 415-30. (2010).
[http://dx.doi.org/10.1007/s00281-010-0221-0] [PMID: 20803017]
[37]
Gavazzi G, Banfi B, Deffert C, Fiette L, Schappi M, Herrmann F, et al. Decreased blood pressure in NOX1-deficient mice. FEBS Lett 580(2): 497-504. (2006).
[http://dx.doi.org/10.1016/j.febslet.2005.12.049] [PMID: 16386251]
[38]
Suzuki Y, Hattori K, Hamanaka J, Murase T, Egashira Y, Mishiro K, et al. Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia. Sci Rep 2: 896. (2012).
[http://dx.doi.org/10.1038/srep00896] [PMID: 23193438]
[39]
Kallenborn-Gerhardt W, Schröder K, Del Turco D, Lu R, Kynast K, Kosowski J, et al. NADPH oxidase-4 maintains neuropathic pain after peripheral nerve injury. J Neurosci 32(30): 10136-45. (2012).
[http://dx.doi.org/10.1523/JNEUROSCI.6227-11.2012] [PMID: 22836249]