Trans-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta Aggregation in LPS-Induced Neuroinflammation Mouse Model
- 36 Downloads
Trans-cinnamaldehyde (CNM) has recently drawn attention due to its potent anti-inflammatory and antioxidant properties. The current study explored the memory enhancing effects of CNM against lipopolysaccharide (LPS)-induced neuroinflammation in mice. CNM and curcumin (a reference antioxidant) were administered at a dose of 50 mg/kg i.p. 3 h after a single LPS injection (0.8 mg/kg, i.p.) and continued daily for 7 days. Our results displayed that CNM and curcumin significantly ameliorated the LPS-induced impairment of learning and memory, neuroinflammation, oxidative stress and neuronal apoptosis. Memory functions and locomotor activity were assessed by Morris water maze, object recognition test and open field test. Both CNM and curcumin activated the nuclear factor erythroid 2 related factor 2 (Nrf2) and restored levels of downstream antioxidant enzymes superoxide dismutase and glutathione-S-transferase (GST) in the hippocampus. They also attenuated LPS-induced increase in hippocampal contents of interleukin-1β (IL-1β), malondialdehyde and caspase-3. Immunohistochemistry results showed that both CNM and curcumin reduced Aβ1–42 protein accumulation in brain of mice. Remarkably CNM’s effect on IL-1β was less pronounced than curcumin; however it showed higher GST activity and more potent anti-apoptotic and anti-amylodogenic effect. We conclude that, CNM produces its memory enhancing effects through modulation of Nrf2 antioxidant defense in hippocampus, inhibition of neuroinflammation, apoptosis and amyloid protein burden.
KeywordsTrans-cinnamaldehyde Neuroinflammation Nrf2 Curcumin LPS Amyloid beta
The authors are grateful for Dr. Nouran Elshehaby who generously provided the Aβ1–42 antibody and Dr. Asmaa Khairy who helped with immunohistochemistry analysis.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
Informed consent was obtained from all individual participants included in the study.
- 4.Chen X, Guo C, Kong J (2012) Oxidative stress in neurodegenerative diseases. Neural Regen Res 7:376–385. https://doi.org/10.3969/j.issn.1673-5374.2012.05.009 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Maher A, El-sayed NS, Breitinger H, Zakaria M (2014) Overexpression of NMDAR2B in an inflammatory model of Alzheimer’s disease: modulation by NOS inhibitors. Brain Res Bull 109:109–116. https://doi.org/10.1016/j.brainresbull.2014.10.007 CrossRefPubMedGoogle Scholar
- 12.Chen YF, Wang YW, Huang WS et al (2016) Trans-cinnamaldehyde, an essential oil in cinnamon powder, ameliorates cerebral ischemia-induced brain injury via inhibition of neuroinflammation through attenuation of iNOS, COX-2 expression and NFκ-B signaling pathway. NeuroMolecular Med 18:322–333. https://doi.org/10.1007/s12017-016-8395-9 CrossRefPubMedGoogle Scholar
- 15.Larasati YA, Meiyanto E (2018) Revealing the potency of cinnamon as an anti-cancer and chemopreventive agent. Indones J Cancer Chemoprev 9:47–62. https://doi.org/10.14499/indonesianjcanchemoprev9iss1pp47-62 CrossRefGoogle Scholar
- 17.Zhang L, Zhang Z, Fu Y et al (2016) Trans-cinnamaldehyde improves memory impairment by blocking microglial activation through the destabilization of iNOS mRNA in mice challenged with lipopolysaccharide. Neuropharmacology 110:503–518. https://doi.org/10.1016/j.neuropharm.2016.08.013 CrossRefPubMedGoogle Scholar
- 21.Zhong W, Qian K, Xiong J et al (2016) Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling. Biomed Pharmacother 83:302–313. https://doi.org/10.1016/j.biopha.2016.06.036 CrossRefGoogle Scholar
- 23.Roghani M, Mehraein F, Zamani M et al (2017) The effects of aqueous cinnamon bark extract and cinnamaldehyde on neurons of substantia nigra and behavioral impairment in a mouse model of Parkinson’s disease. J basic Clin Pathophysiol 5:27–32. https://doi.org/10.22070/JBCP.2017.2222.1072 CrossRefGoogle Scholar
- 31.Asaoka K (1984) Affinity purification and characterization of glutathione S-transferases from bovine liver. J Biochem 95:685–696. https://doi.org/10.1093/oxfordjournals.jbchem.a134658 CrossRefPubMedGoogle Scholar
- 33.Mo C, Wang L, Zhang J et al (2014) The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. Antioxid Redox Signal 20:574–588. https://doi.org/10.1089/ars.2012.5116 CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Sies H, Berndt C, Jones DP (2017) Oxidative stress. Annu Rev Biochem 86:715–748. https://doi.org/10.1146/annurev-biochem-061516-045037 CrossRefGoogle Scholar
- 42.Dai W, Wang H, Fang J et al (2018) Curcumin provides neuroprotection in model of traumatic brain injury via the Nrf2-ARE signaling pathway. Brain Res Bull 140:65–71. https://doi.org/10.1016/j.brainresbull.2018.03.020 CrossRefPubMedGoogle Scholar
- 43.González-Reyes S, Guzmán-Beltrán S, Medina-Campos ON, Pedraza-Chaverri J (2013) Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin-induced toxicity in primary cultures of cerebellar granule neurons of rats. Oxid Med Cell Longev. https://doi.org/10.1155/2013/801418 CrossRefPubMedPubMedCentralGoogle Scholar