Protective roles of isoastilbin against Alzheimer's disease via Nrf2‑mediated antioxidation and anti‑apoptosis

Yu,Hong; Yuan,Bo; Chu,Qiubo; Wang,Chunyue; Bi,Hui

doi:10.3892/ijmm.2019.4058

Protective roles of isoastilbin against Alzheimer's disease via Nrf2‑mediated antioxidation and anti‑apoptosis

Authors:
- Hong Yu
- Bo Yuan
- Qiubo Chu
- Chunyue Wang
- Hui Bi
View Affiliations

Affiliations: Department of Otolaryngology Head and Neck Surgery, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Urology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China, School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China, Department of Anesthesiology, Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: January 10, 2019 https://doi.org/10.3892/ijmm.2019.4058
Pages: 1406-1416
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

By analyzing the L‑glutamic acid (L‑Glu)‑induced apoptosis of PC12 cells and an AlCl3 combined with D‑galactose (D‑gal)‑developed Alzheimer's disease (AD) mouse model, the protective effects of isoastilbin (IAB) against AD were systematically investigated in the present study. Pre‑incubation with IAB for 3 h prior to treatment with 25 mM L‑Glu decreased cell viability and inhibited apoptosis, suppressed the accumulation of intracellular reactive oxygen species, and restored mitochondrial membrane potential in PC12 cells induced by L‑Glu. In mice with AD, the reduced escape latency time in the water maze test, suppressed chronic movement in the center area of an open field test and enhanced ability to seek hidden food in a Y maze test indicated that abnormal behaviors had improved after 28 days of treatment with IAB. Furthermore, IAB reduced the deposition of amyloid β (Aβ) and the expression of phosphorylated‑Tau in the mouse brain and enhanced the serum levels of Aβ. IAB ameliorated the oxidative stress via modulating the levels of associated enzymes and improved the functioning of the central cholinergic system, as indicated by an increase in acetylcholine and choline acetyltransferase concentrations. The expression levels of acetylcholine esterase were reduced in the mouse brain in response to IAB pre‑treatment. In cells and brain tissue, IAB regulated the expression levels of pro‑ and anti‑apoptotic proteins and enhanced the nuclear levels of NF‑E2p45‑related factor 2 (Nrf2); subsequently, IAB further enhanced the expression of superoxide dismutase 1, catalase, and heme oxygenase‑1 and ‑2. The findings of the present study indicated that the protection of IAB against AD is at least partially associated with its antioxidation and anti‑apoptotic properties.

View Figures

View References

1	Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C and Collin F: Oxidative stress and the amyloid beta peptide in Alzheimer's disease. Redox Biol. 14:450–464. 2018. View Article : Google Scholar
2	Coimbra JRM, Marques DFF, Baptista SJ, Pereira CMF, Moreira PI, Dinis TCP, Santos AE and Salvador JAR: Highlights in BACE1 Inhibitors for Alzheimer's disease treatment. Front Chem. 6:1782018. View Article : Google Scholar : PubMed/NCBI
3	Rosello A, Warnes G and Meier UC: Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: To die or not to die-that is the question. Clin Exp Immunol. 168:52–57. 2012. View Article : Google Scholar : PubMed/NCBI
4	Angelova PR and Abramov AY: Role of mitochondrial ROS in the brain: From physiology to neurodegeneration. FEBS Lett. 592:692–702. 2018. View Article : Google Scholar : PubMed/NCBI
5	de Oliveira RB, Gravina FS, Lim R, Brichta AM, Callister RJ and van Helden DF: Heterogeneous responses to antioxidants in noradrenergic neurons of the Locus coeruleus indicate differing susceptibility to free radical content. Oxid Med Cell Longev. 2012:8202852012. View Article : Google Scholar : PubMed/NCBI
6	Daulatzai MA: Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease. J Neurosci Res. 95:943–972. 2017. View Article : Google Scholar
7	Nesi G, Sestito S, Digiacomo M and Rapposelli S: Oxidative stress, mitochondrial abnormalities and proteins deposition: Multitarget approaches in Alzheimer's disease. Curr Top Med Chemy. 17:3062–3079. 2017.
8	Tyagi N, Ovechkin AV, Lominadze D, Moshal KS and Tyagi SC: Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomocysteinemia. J Cell Biochem. 98:1150–1162. 2006. View Article : Google Scholar : PubMed/NCBI
9	Liu X, Wang J, Lu C, Zhu C, Qian B, Li Z, Liu C, Shao J and Yan J: The role of lysosomes in BDE 47-mediated activation of mitochondrial apoptotic pathway in HepG2 cells. Chemosphere. 124:10–21. 2015. View Article : Google Scholar
10	Luo P, Fei F, Zhang L, Qu Y and Fei Z: The role of glutamate receptors in traumatic brain injury: Implications for postsynaptic density in pathophysiology. Brain Res Bull. 85:313–320. 2011. View Article : Google Scholar : PubMed/NCBI
11	Dinkova-Kostova AT and Abramov AY: The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med. 88:179–188. 2015. View Article : Google Scholar : PubMed/NCBI
12	Joshi G, Gan KA, Johnson DA and Johnson JA: Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiol Aging. 36:664–679. 2015. View Article : Google Scholar
13	McDade E and Bateman RJ: Stop alzheimer's before it starts. Nature. 547:153–155. 2017. View Article : Google Scholar : PubMed/NCBI
14	Querfurth HW and LaFerla FM: Alzheimer's Disease. N Engl J Med. 362:329–344. 2010. View Article : Google Scholar : PubMed/NCBI
15	Jesky R and Hailong C: Are herbal compounds the next frontier for alleviating learning and memory impairments? An integrative look at memory, dementia and the promising therapeutics of traditional Chinese medicines. Phytother Res. 25:1105–1118. 2011. View Article : Google Scholar : PubMed/NCBI
16	Man SC, Chan KW, Lu JH, Durairajan SS, Liu LF and Li M: Systematic review on the efficacy and safety of herbal medicines for vascular dementia. Evid Based Complement Alternat Med. 2012:4262152012. View Article : Google Scholar : PubMed/NCBI
17	Zhang Y, Wang J, Wang C, Li Z, Liu X, Zhang J, Lu J and Wang D: Pharmacological basis for the use of evodiamine in alzheimer's disease: Antioxidation and antiapoptosis. Int J Mol Sci. 19:pii: E1527. 2018.
18	Hu S, Wang D, Zhang J, Du M, Cheng Y, Liu Y, Zhang N, Wang D and Wu Y: Mitochondria related pathway is essential for polysaccharides purified from Sparassis crispa mediated neuro-protection against glutamate-induced toxicity in differentiated PC12 cells. Int J Mol Sci. 17:pii: E133. 2016. View Article : Google Scholar
19	An S, Lu W, Zhang Y, Yuan Q and Wang D: Pharmacological basis for use of Armillaria mellea polysaccharides in Alzheimer's disease: Antiapoptosis and antioxidation. Oxid Med Cell Longev. 2017:41845622017. View Article : Google Scholar :
20	Du Q, Li L and Jerz G: Purification of astilbin and isoastilbin in the extract of Smilax glabra rhizome by high-speed counter-current chromatography. J Chromatogr A. 1077:98–101. 2005. View Article : Google Scholar : PubMed/NCBI
21	Zhou X, Xu Q, Li JX and Chen T: Structural revision of two flavanonol glycosides from Smilax glabra. Planta Med. 75:654–655. 2009. View Article : Google Scholar : PubMed/NCBI
22	Lu CL, Zhu W, Wang M, Xu XJ and Lu CJ: Antioxidant and anti-inflammatory activities of phenolic-enriched extracts of Smilax glabra. Evid Based Complement Alternat Med. 2014:9104382014. View Article : Google Scholar : PubMed/NCBI
23	Wang D, Li S, Chen J, Liu L and Zhu X: The effects of astilbin on cognitive impairments in a transgenic mouse model of Alzheimer's disease. Cell Mol Neurobiol. 37:695–706. 2017. View Article : Google Scholar
24	Zhang X, Chen Y, Cai G, Li X and Wang D: Carnosic acid induces apoptosis of hepatocellular carcinoma cells via ROS-mediated mitochondrial pathway. Chem Biol Interact. 277:91–100. 2017. View Article : Google Scholar : PubMed/NCBI
25	Li Z, Chen X, Lu W, Zhang S, Guan X, Li Z and Wang D: Anti-oxidative stress activity is essential for Amanita caesarea mediated neuroprotection on glutamate-induced apoptotic HT22 cells and an Alzheimer's disease mouse model. Int J Mol Sci. 18:pii: E1623. 2017. View Article : Google Scholar
26	Parikh A, Kathawala K, Li J, Chen C, Shan Z, Cao X, Wang YJ, Garg S and Zhou XF: Self-nanomicellizing solid dispersion of edaravone: Part II: In vivo assessment of efficacy against behavior deficits and safety in Alzheimer's disease model. Drug Des Devel Ther. 12:2111–2128. 2018. View Article : Google Scholar : PubMed/NCBI
27	Zhao JM, Li L, Chen L, Shi Y, Li YW, Shang HX, Wu LY, Weng ZJ, Bao CH and Wu HG: Comparison of the analgesic effects between electro-acupuncture and moxibustion with visceral hypersensitivity rats in irritable bowel syndrome. World J Gastroenterol. 23:2928–2939. 2017. View Article : Google Scholar : PubMed/NCBI
28	Chun KA: Beta-amyloid imaging in dementia. Yeungnam Univ J Med. 35:1–6. 2018. View Article : Google Scholar
29	Yamini P, Ray RS and Chopra K: Vitamin D₃ attenuates cognitive deficits and neuroinflammatory responses in ICV-STZ induced sporadic Alzheimer's disease. Inflammopharmacology. 26:39–55. 2018. View Article : Google Scholar
30	Tönnies E and Trushina E: Oxidative stress, synaptic dysfunction, and Alzheimer's disease. J Alzheimers Dis. 57:1105–1121. 2017. View Article : Google Scholar
31	Koh CH, Whiteman M, Li QX, Halliwell B, Jenner AM, Wong BS, Laughton KM, Wenk M, Masters CL, Beart PM, et al: Chronic exposure to U18666A is associated with oxidative stress in cultured murine cortical neurons. J Neurochem. 98:1278–1289. 2006. View Article : Google Scholar : PubMed/NCBI
32	Circu ML and Aw TY: Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 48:749–762. 2010. View Article : Google Scholar : PubMed/NCBI
33	Resseguie EA, Staversky RJ, Brookes PS and O'Reilly MA: Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction. Redox Biol. 5:176–185. 2015. View Article : Google Scholar : PubMed/NCBI
34	Skulachev VP: Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett. 423:275–280. 1998. View Article : Google Scholar : PubMed/NCBI
35	Reubold TF and Eschenburg S: A molecular view on signal transduction by the apoptosome. Cell Signal. 24:1420–1425. 2012. View Article : Google Scholar : PubMed/NCBI
36	Allan LA and Clarke PR: Apoptosis and autophagy: Regulation of caspase-9 by phosphorylation. FEBS J. 276:6063–6073. 2009. View Article : Google Scholar : PubMed/NCBI
37	Espin R, Roca FJ, Candel S, Sepulcre MP, González-Rosa JM, Alcaraz-Pérez F, Meseguer J, Cayuela ML, Mercader N and Mulero V: TNF receptors regulate vascular homeostasis in zebrafish through a caspase-8, caspase-2 and P53 apoptotic program that bypasses caspase-3. Dis Model Mech. 6:383–396. 2013. View Article : Google Scholar :
38	Gross A and Katz SG: Non-apoptotic functions of BCL-2 family proteins. Cell Death Differ. 24:1348–1358. 2017. View Article : Google Scholar : PubMed/NCBI
39	Wang X, Wu J, Yu C, Tang Y, Liu J, Chen H, Jin B, Mei Q, Cao S and Qin D: Lychee seed saponins improve cognitive function and prevent neuronal injury via inhibiting neuronal apoptosis in a rat model of Alzheimer's disease. Nutrients. 9:pii: E105. 2017. View Article : Google Scholar
40	Tong Y, Bai L, Gong R, Chuan J, Duan X and Zhu Y: Shikonin protects PC12 cells against beta-amyloid peptide-induced cell injury through antioxidant and antiapoptotic activities. Sci Rep. 8:262018. View Article : Google Scholar
41	Lai YC, Li CC, Sung TC, Chang CW, Lan YJ and Chiang YW: The role of cardiolipin in promoting the membrane pore-forming activity of BAX oligomers. Biochim Biophys Acta Biomembr. 1861:268–280. 2019. View Article : Google Scholar
42	O'Connell MA and Hayes JD: The Keap1/Nrf2 pathway in health and disease: From the bench to the clinic. Biochem Soc Trans. 43:687–689. 2015. View Article : Google Scholar : PubMed/NCBI
43	Chu H, Yu H, Ren D, Zhu K and Huang H: Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-κB and Nrf-2. Int J Mol Med. 37:1669–1676. 2016. View Article : Google Scholar : PubMed/NCBI
44	Zhu L, Liu Z, Feng Z, Hao J, Shen W, Li X, Sun L, Sharman E, Wang Y, Wertz K, et al: Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells. J Nutr Biochem. 21:1089–1098. 2010. View Article : Google Scholar : PubMed/NCBI
45	Khalaj L, Nejad SC, Mohammadi M, Zadeh SS, Pour MH, Ahmadiani A, Khodagholi F, Ashabi G, Alamdary SZ and Samami E: Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus. Brain Res. 1527:117–130. 2013. View Article : Google Scholar : PubMed/NCBI
46	Kaur SJ, McKeown SR and Rashid S: Mutant SOD1 mediated pathogenesis of amyotrophic lateral sclerosis. Gene. 577:109–118. 2016. View Article : Google Scholar
47	Kansanen E, Kuosmanen SM, Leinonen H and Levonen AL: The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol. 1:45–49. 2013. View Article : Google Scholar : PubMed/NCBI
48	Qu Z, Zhang J, Yang H, Huo L, Gao J, Chen H and Gao W: Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat. Physiol Behav. 154:114–125. 2016. View Article : Google Scholar
49	Jiang T, Sun Q and Chen S: Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson's disease and Alzheimer's disease. Prog Neurobiol. 147:1–19. 2016. View Article : Google Scholar : PubMed/NCBI
50	Xu T, Niu C, Zhang X and Dong M: β-Ecdysterone protects SH-SY5Y cells against β-amyloid-induced apoptosis via c-Jun N-terminal kinase- and Akt-associated complementary pathways. Lab Invest. 98:489–499. 2018. View Article : Google Scholar : PubMed/NCBI
51	Kim DI, Lee KH, Gabr AA, Choi GE, Kim JS, Ko SH and Han HJ: Aβ-Induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis. Biochim Biophys Acta. 1863:2820–2834. 2016. View Article : Google Scholar : PubMed/NCBI
52	Leuner K, Schütt T, Kurz C, Eckert SH, Schiller C, Occhipinti A, Mai S, Jendrach M, Eckert GP, Kruse SE, et al: Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation. Antioxid Redox Signal. 16:1421–1433. 2012. View Article : Google Scholar : PubMed/NCBI
53	Fujita K, Yamafuji M, Nakabeppu Y and Noda M: Therapeutic approach to neurodegenerative diseases by medical gases: Focusing on redox signaling and related antioxidant enzymes. Oxid Med Cell Longev. 2012:3242562012. View Article : Google Scholar : PubMed/NCBI
54	Islam MT: Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res. 39:73–82. 2017. View Article : Google Scholar
55	Fei M, Jianghua W, Rujuan M, Wei Z and Qian W: The relationship of plasma Aβ levels to dementia in aging individuals with mild cognitive impairment. J Neurol Sci. 305:92–96. 2011. View Article : Google Scholar : PubMed/NCBI
56	Park SY and Ferreira A: The generation of a 17 kDa neurotoxic fragment: An alternative mechanism by which tau mediates beta-amyloid-induced neurodegeneration. J Neurosci. 25:5365–5375. 2005. View Article : Google Scholar : PubMed/NCBI
57	Reifert J, Hartung-Cranston D and Feinstein SC: Amyloid beta-mediated cell death of cultured hippocampal neurons reveals extensive Tau fragmentation without increased full-length tau phosphorylation. J Biol Chem. 286:20797–20811. 2011. View Article : Google Scholar : PubMed/NCBI
58	Bartus RT: On neurodegenerative diseases, models, and treatment strategies: Lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp Neurol. 163:495–529. 2000. View Article : Google Scholar : PubMed/NCBI
59	Ferreira-Vieira TH, Guimaraes IM, Silva FR and Ribeiro FM: Alzheimer's disease: Targeting the cholinergic system. Curr Neuropharmacol. 14:101–115. 2016. View Article : Google Scholar : PubMed/NCBI
60	Deiana S, Platt B and Riedel G: The cholinergic system and spatial learning. Behav Brain Res. 221:389–411. 2011. View Article : Google Scholar
61	Lushchekina S, Kots E, Novichkova D, Petrov K and Masson P: Role of Acetylcholinesterase in β-amyloid aggregation studied by accelerated molecular dynamics. Bionanoscience. 7:396–402. 2017. View Article : Google Scholar
62	Nitta A, Itoh A, Hasegawa T and Nabeshima T: beta-Amyloid protein-induced Alzheimer's disease animal model. Neurosci Lett. 170:63–66. 1994. View Article : Google Scholar : PubMed/NCBI