Curcumin Attenuates Lipopolysaccharide-Induced Neuroinflammation and Memory Deficiency by Inhibiting Microglia Activation in Mice Hippocampus
Full Text



How to Cite

Iteire, K., Uwejigho, R., & Okonofua, G. (2022). Curcumin Attenuates Lipopolysaccharide-Induced Neuroinflammation and Memory Deficiency by Inhibiting Microglia Activation in Mice Hippocampus. Galician Medical Journal, 29(4), E202245.


Background. Curcumin has a variety of properties, including antioxidant and anti-inflammatory ones, and has demonstrated some protective prospects on neurological conditions.

Aim: This study explored the neuroprotective ability of curcumin in lipopolysaccharide-induced neuroinflammation in an animal model.

Methods. A total of thirty-two adult male mice were randomly assigned to four groups (A, B, C, and D, n=8): Group A (Control) received distilled water; Group B was administered lipopolysaccharide (LPS) only to induce neuroinflammation for seven days; Group C was treated with both LPS and curcumin simultaneously for fourteen days; Group D received only curcumin for fourteen days. After appropriate exposure to the mice, their cognitive abilities were assessed using the Y-maze and novel object recognition tests. At the termination of the administration period, the mice were sacrificed, and the hippocampi were dissected for histology and immunostaining using GFAP and Iba1. Statistical analysis for the data generated was done with GraphPad prism. Tests of significance were with one-way ANOVA and Tukey tests for post-hoc.

Results. Curcumin significantly (p < 0.05) increased object recognition, mean alternation, and markedly restored neuronal distortion caused by LPS toxicity in the CA3 region and the dentate gyrus of the hippocampus of Group C animals as compared to Group B. In addition, curcumin significantly down-regulated Iba1 expression and GFAP cell activities of both the CA3 region and the dentate gyrus.

Conclusions. Curcumin showed a promising role in attenuating LPS-induced neuroinflammation in the brain by inhibiting microglial activation and improving memory of neurotoxic mice.
Full Text


Kocaadam B, Şanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Critical Reviews in Food Science and Nutrition. 2015;57(13):2889–2895. Available from:

Gao F, Shen J, Zhao L, Hao Q, Yang Y. Curcumin alleviates lipopolysaccharide (LPS)-activated neuroinflammation via modulation of miR-199b-5p/IκB Kinase β (IKKβ)/Nuclear Factor Kappa B (NF-κB) pathway in microglia. Medical Science Monitor. 2019;25:9801–9810. Available from:

Bellaver B, Souza DG, Bobermin LD, Souza DO, Gonçalves C-A, Quincozes-Santos A. Resveratrol protects hippocampal astrocytes against LPS-induced neurotoxicity through HO-1, p38 and ERK pathways. Neurochemical Research. 2015;40(8):1600–1608. Available from:

Chen C-J, Ou Y-C, Lin S-Y, Raung S-L, Liao S-L, Lai C-Y, et al. Glial activation involvement in neuronal death by Japanese encephalitis virus infection. Journal of General Virology. 2009;91(4):1028–1037. Available from:

Cunningham C. Microglia and neurodegeneration: the role of systemic inflammation. Glia. 2012;61(1):71–90. Available from:

Fakhoury M. Microglia and astrocytes in Alzheimer’s disease: implications for therapy. Current Neuropharmacology. 2018;16(5):508–518. Available from:

Rostalski H, Leskelä S, Huber N, Katisko K, Cajanus A, Solje E, et al. Astrocytes and microglia as potential contributors to the pathogenesis of C9orf72 repeat expansion-associated FTLD and ALS. Frontiers in Neuroscience. 2019;13:486. Available from:

Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, et al. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Scientific Reports. 2019;9(1):5790. Available from:

Khan MS, Ali T, Abid MN, Jo MH, Khan A, Kim MW, et al. Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and hippocampus of the adult rat brain. Neurochemistry International. 2017;108:343–354. Available from:

Duthey B, Tanna S. Background paper 6.11: Alzheimer disease and other dementias. A Public Health Approach to Innovation. 2013.

Erkkinen MG, Kim M-O, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harbor Perspectives in Biology. 2017;10(4):a033118. Available from:

Rajmohan R, Reddy PH. Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. Journal of Alzheimer’s Disease. 2017;57(4):975–999. Available from:

Husain M, Mehta MA. Cognitive enhancement by drugs in health and disease. Trends in Cognitive Sciences. 2011;15(1):28–36. Available from:

National Research Council. Guide for the Care and Use of Laboratory Animals. 8th Edition. 2011.

Raduolovic K, Mak’Anyengo R, Kaya B, Steinert A, Niess JH. Injections of lipopolysaccharide into mice to mimic entrance of microbial-derived products after intestinal barrier breach. Journal of Visualized Experiments. 2018;(135):e57610. Available from:

Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong J-S, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007;55(5):453–462. Available from:

Qin L, Liu Y, Hong J-S, Crews FT. NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration. Glia. 2013;61(6):855–868. Available from:

Bossù P, Cutuli D, Palladino I, Caporali P, Angelucci F, Laricchiuta D, et al. A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18. Journal of Neuroinflammation. 2012;9(1):101. Available from:

Gasparotto J, Ribeiro CT, Bortolin RC, Somensi N, Rabelo TK, Kunzler A, et al. Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA–induced dopaminergic denervation. Scientific Reports. 2017;7(1):8795. Available from:

Momeni S, Segerström L, Roman E. Supplier-dependent differences in intermittent voluntary alcohol intake and response to naltrexone in Wistar rats. Frontiers in Neuroscience. 2015;9:424. Available from:

Reyaz N, Tayyab M, Khan SA, Siddique T. Correlation of glial fibrillary acidic protein (GFAP) with grading of the neuroglial tumours. J Coll Physicians Surg Pak. 2005;15(8):472-475. Available from:

Ohsawa K, Imai Y, Sasaki Y, Kohsaka S. Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity. Journal of Neurochemistry. 2004;88(4):844–856. Available from:

Pluta R, Furmaga-Jabłońska W, Januszewski S, Czuczwar SJ. Post-ischemic brain neurodegeneration in the form of Alzheimer’s disease proteinopathy: possible therapeutic role of curcumin. Nutrients. 2022;14(2):248. Available from:

Hou J, Xue J, Lee M, Sun M, Zhao X, Zheng Y, et al. Compound K is able to ameliorate the impaired cognitive function and hippocampal neurogenesis following chemotherapy treatment. Biochemical and Biophysical Research Communications. 2013;436(1):104–109. Available from:

Liu P, Zou L, Jiao Q, Chi T, Ji X, Qi Y, et al. Xanthoceraside attenuates learning and memory deficits via improving insulin signaling in STZ-induced AD rats. Neuroscience Letters. 2013;543:115–120. Available from:

Iwai T, Jin K, Ohnuki T, Sasaki-Hamada S, Nakamura M, Saitoh A, et al. Glucagon-like peptide-2-induced memory improvement and anxiolytic effects in mice. Neuropeptides. 2015;49:7–14. Available from:

Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Archives of General Psychiatry. 2001;58(5):445–452. Available from:

Prieur E, Jadavji N. Assessing spatial working memory using the spontaneous alternation Y-maze test in aged male mice. BIO-PROTOCOL. 2019;9(3):e3162. Available from:

Rehman SU, Ali T, Alam SI, Ullah R, Zeb A, Lee KW, et al. Ferulic acid rescues LPS-induced neurotoxicity via modulation of the TLR4 receptor in the mouse hippocampus. Molecular Neurobiology. 2018;56(4):2774–2790. Available from:

Lynnette R. Ferguson, Martin Philpott. Cancer prevention by dietary bioactive components that target the immune response. Current Cancer Drug Targets. 2007;7(5):459–464. Available from:

Nouri Z, Fakhri S, El-Senduny FF, Sanadgol N, Abd-ElGhani GE, Farzaei MH, et al. On the neuroprotective effects of naringenin: pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective. Biomolecules. 2019;9(11):690. Available from:

Nava Catorce M, Gevorkian G. LPS-induced murine neuroinflammation model: main features and suitability for pre-clinical assessment of nutraceuticals. Current Neuropharmacology. 2016;14(2):155–164. Available from:

Hadizadeh-Bazaz M, Vaezi G, khaksari M, Hojati V. Curcumin attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against methamphetamine neurotoxicity in male Wistar rats: histological and biochemical changes. NeuroToxicology. 2021;84:208–217. Available from:

Graeber MB, Li W, Rodriguez ML. Role of microglia in CNS inflammation. FEBS Letters. 2011;585(23):3798–3805. Available from:

Liu B, Hong J-S. Role of Microglia in Inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. Journal of Pharmacology and Experimental Therapeutics. 2003;304(1):1–7. Available from:

González-Granillo AE, Gnecco D, Díaz A, Garcés-Ramírez L, de la Cruz F, Juarez I, et al. Curcumin induces cortico-hippocampal neuronal reshaping and memory improvements in aged mice. Journal of Chemical Neuroanatomy. 2022;121:102091. Available from:

Han Y, Chen R, Lin Q, Liu Y, Ge W, Cao H, et al. Curcumin improves memory deficits by inhibiting HMGB1‐RAGE/TLR4‐NF‐κB signalling pathway in APPswe/PS1dE9 transgenic mice hippocampus. Journal of Cellular and Molecular Medicine. 2021;25(18):8947–8956. Available from:

Iteire KA, Sowole AT, Ogunlade B. Exposure to pyrethroids induces behavioral impairments, neurofibrillary tangles and tau pathology in Alzheimer’s type neurodegeneration in adult Wistar rats. Drug and Chemical Toxicology. 2020;45(2):839–849. Available from:

Noh H, Jeon J, Seo H. Systemic injection of LPS induces region-specific neuroinflammation and mitochondrial dysfunction in normal mouse brain. Neurochemistry International. 2014;69:35–40. Available from:

Sorrenti V, Contarini G, Sut S, Dall’Acqua S, Confortin F, Pagetta A, et al. Curcumin Prevents acute neuroinflammation and long-term memory impairment induced by systemic lipopolysaccharide in mice. Frontiers in Pharmacology. 2018;9:183. Available from:

Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. In: Aggarwal BB, Surh YJ, Shishodia S, eds. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Boston: Springer; 2007. Available from:

Liu Z-J, Liu W, Liu L, Xiao C, Wang Y, Jiao J-S. Curcumin protects neuron against cerebral ischemia-induced inflammation through improving PPAR-gamma function. Evidence-Based Complementary and Alternative Medicine. 2013;2013:470975. Available from:

Yi L-T, Dong S-Q, Wang S-S, Chen M, Li C-F, Geng D, et al. Curcumin attenuates cognitive impairment by enhancing autophagy in chemotherapy. Neurobiology of Disease. 2020;136:104715. Available from:

Wu S, Guo T, Qi W, Li Y, Gu J, Liu C, et al. Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood‑brain barrier. Experimental and Therapeutic Medicine. 2021;22(1):783. Available from:

Kelly Á, Vereker E, Nolan Y, Brady M, Barry C, Loscher CE, et al. Activation of p38 plays a pivotal role in the inhibitory effect of lipopolysaccharide and Interleukin-1β on long term potentiation in rat dentate gyrus. Journal of Biological Chemistry. 2003;278(21):19453–19462. Available from:

Kelley KW, O’Connor JC, Lawson MA, Dantzer R, Rodriguez-Zas SL, McCusker RH. Aging leads to prolonged duration of inflammation-induced depression-like behavior caused by Bacillus Calmette-Guérin. Brain, Behavior, and Immunity. 2013;32:63–69. Available from:

Zager A, Brandão WN, Margatho RO, Peron JP, Tufik S, Andersen ML, et al. The wake-promoting drug modafinil prevents motor impairment in sickness behavior induced by LPS in mice: role for dopaminergic D1 receptor. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018;81:468–476. Available from:

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.