Curcumin Alleviates β Amyloid-Induced Neurotoxicity in HT22 Cells via Upregulating SOD2
Curcumin protects neuronal cells exposed to β amyloid (Aβ); the mechanism, however, is still obscure. The aim of this study is to determine whether the type 2 superoxide dismutase (SOD2) mediates curcumin-induced protective effects in Aβ-treated neuronal cells. In this study, the HT22 neuronal cells were exposed to Aβ to imitate neuronal injury in Alzheimer’s disease (AD). After 24-h treatment, 10 μM Aβ decreased cell viability and mitochondrial functions, including mitochondrial complex activities and mitochondrial membrane potential (MMP), and also downregulated anti-oxidants SOD2, glutathione (GSH), and catalase (CAT) levels (P < 0.05), meanwhile, increased lactic dehydrogenase (LDH) release, apoptosis level, intracellular reactive oxygen species (ROS) and mitochondrial superoxide accumulation (P < 0.05). And, co-administration of 1 μM curcumin significantly reduced the Aβ-induced cell injury and oxidative damage above (P < 0.05). Downregulating SOD2 by using small interfering RNA (siRNA), however, significantly abolished the curcumin-induced protective and anti-oxidative effects in HT22 cells (P < 0.05); the scramble (SC)-siRNA did not cause marked effects on the curcumin-induced protective effects (P > 0.05). These findings showed that curcumin can alleviate Aβ-induced injury in neuronal cells, and SOD2 protein may mediate the neuroprotective effects.
KeywordsCurcumin β amyloid SOD2 Alzheimer’s disease Neuroprotection
This work was supported by the National Nature Science Foundation of China (61773130), Natural Science Foundation of Guangdong Province, China (2016A030313613), and the Science and Technology Program of Guangzhou, China (201707010027).
Compliance with Ethical Standards
All procedures were approved by the Ethics Committee of the General Hospital of Southern Theatre of PLA.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Alberdi E, Sánchez-Gómez MV, Ruiz A, Cavaliere F, Ortiz-Sanz C, Quintela-López T, Capetillo-Zarate E, Solé-Domènech S, Matute C (2018) Mangiferin and morin attenuate oxidative stress, mitochondrial dysfunction, and neurocytotoxicity, induced by amyloid beta oligomers. Oxidative Med Cell Longev 2018:2856063. https://doi.org/10.1155/2018/2856063 CrossRefGoogle Scholar
- Anstey KJ, Peters R, Clare L, Lautenschlager NT, Dodge HH, Barnes DE, Shahar S, Brodaty H, Rees G (2017) Joining forces to prevent dementia: the international research network on dementia prevention (IRNDP). Int Psychogeriatr 29:1757–1760. https://doi.org/10.1017/S1041610217001685 CrossRefGoogle Scholar
- Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC, Dominantly Inherited Alzheimer Network (2012) Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367(9):795–804. https://doi.org/10.1056/NEJMoa1202753 CrossRefGoogle Scholar
- Chan KY, Wang W, Wu JJ, Liu L, Theodoratou E, Car J, Middleton L, Russ TC, Deary IJ, Campbell H, Wang W, Rudan I, Global Health Epidemiology Reference Group (GHERG) (2013) Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990-2010: a systematic review and analysis. Lancet 381:2016–2023. https://doi.org/10.1016/S0140-6736(13)60221-4 CrossRefGoogle Scholar
- Chuang KA, Li MH, Lin NH, Chang CH, Lu IH, Pan IH, Takahashi T, Perng MD, Wen SF (2017) Rhinacanthin C alleviates amyloid-β fibrils’ toxicity on neurons and attenuates neuroinflammation triggered by LPS, amyloid-β, and interferon-γ in glial cells. Oxidative Med Cell Longev 2017:5414297. https://doi.org/10.1155/2017/5414297 Google Scholar
- Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, Vellas B, Sur C, Mukai Y, Voss T, Furtek C, Mahoney E, Harper Mozley L, Vandenberghe R, Mo Y, Michelson D (2018) Randomized trial of verubecestat for mild-to-moderate Alzheimer’s disease. N Engl J Med 378:1691–1703. https://doi.org/10.1056/NEJMoa1706441 CrossRefGoogle Scholar
- Fiala M, Liu PT, Espinosa-Jeffrey A, Rosenthal MJ, Bernard G, Ringman JM, Sayre J, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J (2007) Innate immunity and transcription of MGAT-III and toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc Natl Acad Sci U S A 104:12849–11254. https://doi.org/10.1073/pnas.0701267104 CrossRefGoogle Scholar
- Han Z, Chen YR, Jones CI 3rd, Meenakshisundaram G, Zweier JL, Alevriadou BR (2007) Shear-induced reactive nitrogen species inhibit mitochondrial respiratory complex activities in cultured vascular endothelial cells. Am J Physiol Cell Physiol 292:C1103–C1112. https://doi.org/10.1152/ajpcell.00389.2006 CrossRefGoogle Scholar
- Joshi D, Mittal DK, Shukla S, Srivastav SK, Dixit VA (2017) Curcuma longa Linn. Extract and curcumin protect CYP 2E1 enzymatic activity against mercuric chloride-induced hepatotoxicity and oxidative stress: a protective approach. Exp Toxicol Pathol 69:373–382. https://doi.org/10.1016/j.etp.2017.02.009 CrossRefGoogle Scholar
- Ma L, Niu W, Yang S, Tian J, Luan H, Cao M, Xi W, Tu W, Jia J, Lv J (2018) Inhibition of mitochondrial permeability transition pore opening contributes to cannabinoid type 1 receptor agonist ACEA-induced neuroprotection. Neuropharmacology 135:211–222. https://doi.org/10.1016/j.neuropharm.2018.03.024 CrossRefGoogle Scholar
- Reddy PH, Manczak M, Yin X, Grady MC, Mitchell A, Tonk S, Kuruva CS, Bhatti JS, Kandimalla R, Vijayan M, Kumar S, Wang R, Pradeepkiran JA, Ogunmokun G, Thamarai K, Quesada K, Boles A, Reddy AP (2018) Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J Alzheimers Dis 61:843–866. https://doi.org/10.3233/JAD-170512 CrossRefGoogle Scholar
- Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM (2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280:5892–5901. https://doi.org/10.1074/jbc.M404751200 CrossRefGoogle Scholar
- Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY, Chan EWL (2018) Piper sarmentosum Roxb. Confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells. J Ethnopharmacol 217:187–194. https://doi.org/10.1016/j.jep.2018.02.025 CrossRefGoogle Scholar