Skip to main content

Advertisement

SpringerLink
Log in

The Dietary Components Carnosic Acid and Carnosol as Neuroprotective Agents: a Mechanistic View

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Carnosic acid (CA) and carnosol are the major diterpenes found in Rosmarinus officinalis (rosemary), a culinary spice. CA and carnosol account for over 90 % of its anti-oxidant activity in rosemary leaves. The diterpenes exert anti-oxidant, anti-inflammatory, and anti-carcinogenic activities, and present neuroprotective effects in both in vitro and in vivo experimental models. In some cases, CA exerted protective effects upon neuronal cells more intensely than resveratrol or sulforaphane. Therefore, CA and carnosol demonstrate a potential pharmacological role for rosemary diterpenes in ameliorating mammalian brain redox status, among other parameters, as for instance the modulation of neuroinflammation. The aim of this review is to discuss the biological effects of CA and carnosol on neuronal and glial cells with focus on the mechanism of action of such diterpenes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Reference

  1. Birtić S, Dussort P, Pierre FX, Bily AC, Roller M (2015) Carnosic acid. Phytochemistry 115:9–19. doi:10.1016/j.phytochem.2014.12.026

    Article  PubMed  Google Scholar 

  2. Aruoma OI, Halliwell B, Aeschbach R, Löligers J (1992) Antioxidant and pro-oxidant properties of active rosemary constituents: carnosol and carnosic acid. Xenobiotica 22(2):257–268

    Article  CAS  PubMed  Google Scholar 

  3. Kuzmenko AI, Morozova RP, Nikolenko IA, Donchenko GV, Richheimer SL, Bailey DT (1999) Chemiluminescence determination of the in vivo and in vitro antioxidant activity of RoseOx and carnosic acid. J Photochem Photobiol, B 48(1):63–67. doi:10.1016/S1011-1344(99)00011-1

    Article  CAS  Google Scholar 

  4. Erkan N, Ayranci G, Ayranci E (2008) Antioxidant activities of rosemary (Rosmarinus officinalis L.) extract, blackseed (Nigella sativa L.) essential oil, carnosic acid, rosmarinic acid and sesamol. Food Chem 110(1):76–82. doi:10.1016/j.foodchem.2008.01.058

    Article  CAS  PubMed  Google Scholar 

  5. Park JA, Kim S, Lee SY, Kim CS, Kim do K, Kim SJ, Chun HS (2008) Beneficial effects of carnosic acid on dieldrin-induced dopaminergic neuronal cell death. Neuroreport 19(13):1301–1304. doi:10.1097/WNR.0b013e32830abc1f

    Article  CAS  PubMed  Google Scholar 

  6. Lian KC, Chuang JJ, Hsieh CW, Wung BS, Huang GD, Jian TY, Sun YW (2010) Toxicol Appl Pharmacol 245(1):21–35. doi:10.1016/j.taap.2010.01.003

    Article  CAS  PubMed  Google Scholar 

  7. Mengoni ES, Vichera G, Rigano LA, Rodriguez-Puebla ML, Galliano SR, Cafferata EE, Pivetta OH, Moreno S, Vojnov AA (2011) Suppression of COX-2, IL-1β and TNF-α expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia 82(3):414–421. doi:10.1016/j.fitote.2010.11.023

    Article  CAS  PubMed  Google Scholar 

  8. Yanagitai M, Itoh S, Kitagawa T, Takenouchi T, Kitani H, Satoh T (2012) Carnosic acid, a pro-electrophilic compound, inhibits LPS-induced activation of microglia. Biochem Biophys Res Commun 418(1):22–26. doi:10.1016/j.bbrc.2011.12.087

    Article  CAS  PubMed  Google Scholar 

  9. Satoh T, McKercher SR, Lipton SA (2013) Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs. Free Radic Biol Med 65:645–657. doi:10.1016/j.freeradbiomed.2013.07.022

    Article  CAS  PubMed  Google Scholar 

  10. Pérez-Fons L, Garzón MT, Micol V (2010) Relationship between the antioxidant capacity and effect of rosemary (Rosmarinus officinalis L.) polyphenols on membrane phospholipid order. J Agric Food Chem 58(1):161–171. doi:10.1021/jf9026487

    Article  PubMed  Google Scholar 

  11. Maruoka H, Sasaya H, Sugihara K, Shimoke K, Ikeuchi T (2011) Low-molecular-weight compounds having neurotrophic activity in cultured PC12 cells and neurons. J Biochem 150(5):473–475. doi:10.1093/jb/mvr113

    Article  CAS  PubMed  Google Scholar 

  12. Wijeratne SS, Cuppett SL (2007) Potential of rosemary (Rosemarinus officinalis L.) diterpenes in preventing lipid hydroperoxide-mediated oxidative stress in Caco-2 cells. J Agric Food Chem 55(4):1193–1199. doi:10.1021/jf063089m

    Article  CAS  PubMed  Google Scholar 

  13. Haraguchi H, Saito T, Okamura N, Yagi A (1995) Inhibition of lipid peroxidation and superoxide generation by diterpenoids from Rosmarinus officinalis. Planta Med 61(4):333–336. doi:10.1055/s-2006-958094

    Article  CAS  PubMed  Google Scholar 

  14. Johnson JJ (2011) Carnosol: a promising anti-cancer and anti-inflammatory agent. Cancer Lett 305(1):1–7. doi:10.1016/j.canlet.2011.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Visanji JM, Thompson DG, Padfield PJ (2006) Induction of G2/M phase cell cycle arrest by carnosol and carnosic acid is associated with alteration of cyclin A and cyclin B1 levels. Cancer Lett 237(1):130–136. doi:10.1016/j.canlet.2005.05.045

    Article  CAS  PubMed  Google Scholar 

  16. Poeckel D, Greiner C, Verhoff M, Rau O, Tausch L, Hörnig C, Steinhilber D, Schubert-Zsilavecz M, Werz O (2008) Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes. Biochem Pharmacol 76(1):91–97. doi:10.1016/j.bcp.2008.04.013

    Article  CAS  PubMed  Google Scholar 

  17. Johnson JJ, Syed DN, Suh Y, Heren CR, Saleem M, Siddiqui IA, Mukhtar H (2010) Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention. Cancer Prev Res (Phila) 3(9):1112–1123. doi:10.1158/1940-6207

    Article  CAS  Google Scholar 

  18. Fawcett JR, Bordayo EZ, Jackson K, Liu H, Peterson J, Svitak A, Frey WH 2nd (2002) Inactivation of the human brain muscarinic acetylcholine receptor by oxidative damage catalyzed by a low molecular weight endogenous inhibitor from Alzheimer’s brain is prevented by pyrophosphate analogs, bioflavonoids and other antioxidants. Brain Res 950(1-2):10–20. doi:10.1016/S0006-8993(02)02981-5

    Article  CAS  PubMed  Google Scholar 

  19. Tamaki Y, Tabuchi T, Takahashi T, Kosaka K, Satoh T (2010) Activated glutathione metabolism participates in protective effects of carnosic acid against oxidative stress in neuronal HT22 cells. Planta Med 76(7):683–688. doi:10.1055/s-0029-1240622

    Article  CAS  PubMed  Google Scholar 

  20. del Baño MJ, Lorente J, Castillo J, Benavente-García O, del Río JA, Ortuño A, Quirin KW, Gerard D (2003) Phenolic diterpenes, flavones, and rosmarinic acid distribution during the development of leaves, flowers, stems, and roots of Rosmarinus officinalis. Antioxidant activity. J Agric Food Chem 51(15):4247–4253. doi:10.1021/jf0300745

    Article  PubMed  Google Scholar 

  21. Luis JC, Johnson CB (2005) Seasonal variations of rosmarinic and carnosic acids in rosemary extracts. Analysis of their in vitro antiradical activity. Span J Agric Res 3(1):106–112

    Article  Google Scholar 

  22. Satoh T, Kosaka K, Itoh K, Kobayashi A, Yamamoto M, Shimojo Y, Kitajima C, Cui J, Kamins J, Okamoto S, Izumi M, Shirasawa T, Lipton AS (2008) Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1. J Neurochem 104(4):1116–1131. doi:10.1111/j.1471-4159.2007.05039.x

    Article  CAS  PubMed  Google Scholar 

  23. Romo Vaquero M, García Villalba R, Larrosa M, Yáñez-Gascón MJ, Fromentin E, Flanagan J, Roller M, Tomás-Barberán FA, Espín JC, García-Conesa MT (2013) Bioavailability of the major bioactive diterpenoids in a rosemary extract: metabolic profile in the intestine, liver, plasma, and brain of Zucker rats. Mol Nutr Food Res 57(10):1834–1846. doi:10.1002/mnfr.201300052

    CAS  PubMed  Google Scholar 

  24. Doolaege EH, Raes K, De Vos F, Verhé R, De Smet S (2011) Absorption, distribution and elimination of carnosic acid, a natural antioxidant from Rosmarinus officinalis, in rats. Plant Foods Hum Nutr 66(2):196–202. doi:10.1007/s11130-011-0233-5

    Article  CAS  PubMed  Google Scholar 

  25. Satoh T, Izumi M, Inukai Y, Tsutsumi Y, Nakayama N, Kosaka K, Shimojo Y, Kitajima C, Itoh K, Yokoi T, Shirasawa T (2008) Carnosic acid protects neuronal HT22 Cells through activation of the antioxidant-responsive element in free carboxylic acid- and catechol hydroxyl moieties-dependent manners. Neurosci Lett 434(3):260–265. doi:10.1016/j.neulet.2008.01.079

    Article  CAS  PubMed  Google Scholar 

  26. Talalay P (2000) Chemoprotection against cancer by induction of phase 2 enzymes. Biofactors 12(1-4):5–11

    Article  CAS  PubMed  Google Scholar 

  27. Itoh K, Tong KI, Yamamoto M (2004) Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med 36(10):1208–1213. doi:10.1016/j.freeradbiomed.2004.02.075

    Article  CAS  PubMed  Google Scholar 

  28. Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, Ohtsuji M, Kang MI, Kobayashi A, Yokoyama S, Yamamoto M (2006) Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell 21(5):689–700. doi:10.1016/j.molcel.2006.01.013

    Article  CAS  PubMed  Google Scholar 

  29. Kraft AD, Johnson DA, Johnson JA (2004) Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci 24(5):1101–1112. doi:10.1523/JNEUROSCI.3817-03.2004

    Article  CAS  PubMed  Google Scholar 

  30. Hong F, Freeman ML, Liebler DC (2005) Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol 18(12):1917–1926. doi:10.1021/tx0502138

    Article  CAS  PubMed  Google Scholar 

  31. Chen JH, Ou HP, Lin CY, Lin FJ, Wu CR, Chang SW, Tsai CW (2012) Carnosic acid prevents 6-hydroxydopamine-induced cell death in SH-SY5Y cells via mediation of glutathione synthesis. Chem Res Toxicol 25(9):1893–1901. doi:10.1021/tx300171u

    Article  CAS  PubMed  Google Scholar 

  32. Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830(5):3143–3153. doi:10.1016/j.bbagen.2012.09.008

    Article  CAS  PubMed  Google Scholar 

  33. Lu SC (2009) Regulation of glutathione synthesis. Mol Aspects Med 30(1-2):42–59. doi:10.1016/j.mam.2008.05.005

    Article  CAS  PubMed  Google Scholar 

  34. Lin CY, Chen JH, Fu RH, Tsai CW (2014) Induction of Pi form of glutathione S-transferase by carnosic acid is mediated through PI3K/Akt/NF-κB pathway and protects against neurotoxicity. Chem Res Toxicol 27(11):1958–1966. doi:10.1021/tx5003063

    Article  CAS  PubMed  Google Scholar 

  35. Salminen A, Hyttinen JM, Kaarniranta K (2011) AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl) 89(7):667–676. doi:10.1007/s00109-011-0748-0

    Article  CAS  Google Scholar 

  36. Castro-Caldas M, Carvalho AN, Rodrigues E, Henderson C, Wolf CR, Gama MJ (2012) Glutathione S-transferase pi mediates MPTP-induced c-Jun N-terminal kinase activation in the nigrostriatal pathway. Mol Neurobiol 45(3):466–477. doi:10.1007/s12035-012-8266-9

    Article  CAS  PubMed  Google Scholar 

  37. Carvalho AN, Marques C, Rodrigues E, Henderson CJ, Wolf CR, Pereira P, Gama MJ (2013) Ubiquitin-proteasome system impairment and MPTP-induced oxidative stress in the brain of C57BL/6 wild-type and GSTP knockout mice. Mol Neurobiol 47(2):662–672. doi:10.1007/s12035-012-8368-4

    Article  CAS  PubMed  Google Scholar 

  38. Hou CW, Lin YT, Chen YL, Wang YH, Chou JL, Ping LY, Jeng KC (2012) Neuroprotective effects of carnosic acid on neuronal cells under ischemic and hypoxic stress. Nutr Neurosci 15(6):257–263. doi:10.1179/1476830512Y.0000000021

    Article  CAS  PubMed  Google Scholar 

  39. Jiang J, Borisenko GG, Osipov A, Martin I, Chen R, Shvedova AA, Sorokin A, Tyurina YY, Potapovich A, Tyurin VA, Graham SH, Kagan VE (2004) Arachidonic acid-induced carbon-centered radicals and phospholipid peroxidation in cyclo-oxygenase-2-transfected PC12 cells. J Neurochem 90(5):1036–1049. doi:10.1111/j.1471-4159.2004.02577.x

    Article  CAS  PubMed  Google Scholar 

  40. Nakanishi M, Rosenberg DW (2013) Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol 35(2):123–137. doi:10.1007/s00281-012-0342-8

    Article  CAS  PubMed  Google Scholar 

  41. Trebino CE, Stock JL, Gibbons CP et al (2003) Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase. Proc Natl Acad Sci U S A 100(15):9044–9049. doi:10.1073/pnas.1332766100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kalinski P (2012) Regulation of immune responses by prostaglandin E2. J Immunol 188(1):21–28. doi:10.4049/jimmunol.1101029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wu CR, Tsai CW, Chang SW, Lin CY, Huang LC, Tsai CW (2015) Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson’s disease: involvement of antioxidative enzymes induction. Chem Biol Interact 225:40–46. doi:10.1016/j.cbi.2014.11.011

    Article  CAS  PubMed  Google Scholar 

  44. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658. doi:10.1111/j.1471-4159.2006.03907.x

    Article  CAS  PubMed  Google Scholar 

  45. Itoh K, Ye P, Matsumiya T, Tanji K, Ozaki T (2015) Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria. J Clin Biochem Nutr 56(2):91–97. doi:10.3164/jcbn.14-134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Elomri A, Han J, Ben Abdrabbah M, Isoda H (2012) Down regulation effect of Rosmarinus officinalis polyphenols on cellular stress proteins in rat pheochromocytoma PC12 cells. Cytotechnology 64(3):231–240. doi:10.1007/s10616-011-9352-y

    Article  Google Scholar 

  47. Luo W, Sun W, Taldone T, Rodina A, Chiosis G (2010) Heat shock protein 90 in neurodegenerative diseases. Mol Neurodegener 5:24. doi:10.1186/1750-1326-5-24

    Article  PubMed  PubMed Central  Google Scholar 

  48. Zhao L, Rosales C, Seburn K, Ron D, Ackerman SL (2010) Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjögren syndrome. Hum Mol Genet 19(1):25–35. doi:10.1093/hmg/ddp464

    Article  CAS  PubMed  Google Scholar 

  49. Kimura N, Shimada N, Ishijima Y, Fukuda M, Takagi Y, Ishikawa N (2003) Nucleoside diphosphate kinases in mammalian signal transduction systems: recent development and perspective. J Bioenerg Biomembr 35(1):41–47

    Article  CAS  PubMed  Google Scholar 

  50. El Omri A, Han J, Yamada P, Kawada K, Ben Abdrabbah M, Isoda H (2010) Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2. J Ethnopharmacol 131(2):451–458. doi:10.1016/j.jep.2010.07.006

    Article  PubMed  Google Scholar 

  51. Kosaka K, Mimura J, Itoh K, Satoh T, Shimojo Y, Kitajima C, Maruyama A, Yamamoto M, Shirasawa T (2010) Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h cells

  52. Vaka SR, Murthy SN, Repka MA, Nagy T (2011) Upregulation of endogenous neurotrophin levels in the brain by intranasal administration of carnosic acid. J Pharm Sci 100(8):3139–3145. doi:10.1002/jps.22528

    Article  CAS  PubMed  Google Scholar 

  53. Davis JB (1996) Oxidative mechanisms in beta-amyloid cytotoxicity. Neurodegeneration 5(4):441–444

    Article  CAS  PubMed  Google Scholar 

  54. Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23(1):134–147. doi:10.1016/S0891-5849(96)00629-6

    Article  CAS  PubMed  Google Scholar 

  55. Gupta A, Iadecola C (2015) Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease. Front Aging Neurosci 7:115. doi:10.3389/fnagi.2015.00115

    Article  PubMed  PubMed Central  Google Scholar 

  56. Salminen A, Haapasalo A, Kauppinen A, Kaarniranta K, Soininen H, Hiltunen M (2015) Impaired mitochondrial energy metabolism in Alzheimer’s disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape. Prog Neurobiol 131:1–20. doi:10.1016/j.pneurobio.2015.05.001

    Article  CAS  PubMed  Google Scholar 

  57. Meng P, Yoshida H, Matsumiya T (2013) Carnosic acid suppresses the production of amyloid-β 1-42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells. Neurosci Res 75(2):94–102. doi:10.1016/j.neures.2012.11.007

    Article  CAS  PubMed  Google Scholar 

  58. Martin D, Rojo AI, Salinas M, Diaz R, Gallardo G, Alam J, De Galarreta CM, Cuadrado A (2004) Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 279(10):8919–8929. doi:10.1074/jbc.M309660200

    Article  CAS  PubMed  Google Scholar 

  59. Kosaka K, Yokoi T (2003) Carnosic acid, a component of rosemary (Rosmarinus officinalis L.), promotes synthesis of nerve growth factor in T98G human glioblastoma cells. Biol Pharm Bull 26(11):1620–1622. doi:10.1248/bpb.26.1620

    Article  CAS  PubMed  Google Scholar 

  60. Mimura J, Kosaka K, Maruyama A, Satoh T, Harada N, Yoshida H, Satoh K, Yamamoto M, Itoh K (2011) Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes. J Biochem 150(2):209–217. doi:10.1093/jb/mvr065

    Article  CAS  PubMed  Google Scholar 

  61. Vigé X, Costa E, Wise BC (1991) Mechanism of nerve growth factor mRNA regulation by interleukin-1 and basic fibroblast growth factor in primary cultures of rat astrocytes. Mol Pharmacol 40(2):186–192

    PubMed  Google Scholar 

  62. Friedman WJ, Thakur S, Seidman L, Rabson AB (1996) Regulation of nerve growth factor mRNA by interleukin-1 in rat hippocampal astrocytes is mediated by NFkappaB. J Biol Chem 271(49):31115–31120. doi:10.1074/jbc.271.49.31115

    Article  CAS  PubMed  Google Scholar 

  63. Galve-Roperh I, Malpartida JM, Haro A, Brachet P, Díaz-Laviada I (1997) Regulation of nerve growth factor secretion and mRNA expression by bacterial lipopolysaccharide in primary cultures of rat astrocytes. J Neurosci Res 49(5):569–575

    Article  CAS  PubMed  Google Scholar 

  64. Sofroniew MV, Howe CL, Mobley WC (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24:1217–1281. doi:10.1146/annurev.neuro.24.1.1217

    Article  CAS  PubMed  Google Scholar 

  65. Maes M, Fišar Z, Medina M, Scapagnini G, Nowak G, Berk M (2012) New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology 20(3):127–150. doi:10.1007/s10787-011-0111-7

    Article  CAS  PubMed  Google Scholar 

  66. Martín-de-Saavedra MD, Budni J, Cunha MP et al (2013) Nrf2 participates in depressive disorders through an anti-inflammatory mechanism. Psychoneuroendocrinology 38(10):2010–2022. doi:10.1016/j.psyneuen.2013.03.020

    Article  PubMed  Google Scholar 

  67. Bakunina N, Pariante CM, Zunszain PA (2015) Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology 144(3):365–373. doi:10.1111/imm.12443

    Article  CAS  PubMed Central  Google Scholar 

  68. Yoshida H, Mimura J, Imaizumi T, Matsumiya T, Ishikawa A, Metoki N, Tanji K, Ota K, Hayakari R, Kosaka K, Itoh K, Satoh K (2011) Edaravone and carnosic acid synergistically enhance the expression of nerve growth factor in human astrocytes under hypoxia/reoxygenation. Neurosci Res 69(4):291–298. doi:10.1016/j.neures.2010.12.016

    Article  CAS  PubMed  Google Scholar 

  69. Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N (2006) Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev 12(1):9–20. doi:10.1111/j.1527-3458.2006.00009.x

    Article  CAS  PubMed  Google Scholar 

  70. Higashi Y (2009) Edaravone for the treatment of acute cerebral infarction: role of endothelium-derived nitric oxide and oxidative stress. Expert Opin Pharmacother 10(2):323–331. doi:10.1517/14656560802636888

    Article  CAS  PubMed  Google Scholar 

  71. Mattson MP, Cheng A (2006) Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci 29(11):632–639. doi:10.1016/j.tins.2006.09.001

    Article  CAS  PubMed  Google Scholar 

  72. Foresti R, Bains SK, Pitchumony TS, de Castro Brás LE, Drago F, Dubois-Randé JL, Bucolo C, Motterlini R (2013) Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells. Pharmacol Res 76:132–148. doi:10.1016/j.phrs.2013.07.010

    Article  CAS  PubMed  Google Scholar 

  73. Sperner-Unterweger B, Kohl C, Fuchs D (2014) Immune changes and neurotransmitters: possible interactions in depression? Prog Neuropsychopharmacol Biol Psychiatry 48:268–276. doi:10.1016/j.pnpbp.2012.10.006

    Article  CAS  PubMed  Google Scholar 

  74. Cederbaum AI, Lu Y, Wang X, Wu D (2015) Synergistic toxic interactions between CYP2E1, LPS/TNFα, and JNK/p38 MAP kinase and their implications in alcohol-induced liver injury. Adv Exp Med Biol 815:145–172. doi:10.1007/978-3-319-09614-8_9

    Article  CAS  PubMed  Google Scholar 

  75. Yoshida H, Meng P, Matsumiya T et al (2014) Carnosic acid suppresses the production of amyloid-β 1-42 and 1-43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells. Neurosci Res 79:83–93. doi:10.1016/j.neures.2013.11.004

    Article  CAS  PubMed  Google Scholar 

  76. Mangoura D, Sakellaridis N, Jones J, Vernadakis A (1989) Early and late passage C-6 glial cell growth: similarities with primary glial cells in culture. Neurochem Res 14(10):941–947

    Article  CAS  PubMed  Google Scholar 

  77. Kim SY, Park E, Park JA et al (2010) The plant phenolic diterpene carnosol suppresses sodium nitroprusside-induced toxicity in c6 glial cells. J Agric Food Chem 58(3):1543–1550. doi:10.1021/jf903294x

    Article  CAS  PubMed  Google Scholar 

  78. Vincent VA, Tilders FJ, Van Dam AM (1998) Production, regulation and role of nitric oxide in glial cells. Mediators Inflamm 7(4):239–255. doi:10.1080/09629359890929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Barres BA, Barde Y (2000) Neuronal and glial cell biology. Curr Opin Neurobiol 10(5):642–648. doi:10.1016/S0959-4388(00)00134-3

    Article  CAS  PubMed  Google Scholar 

  80. Jaronczyk K, Bui L, Soong JM, McLaughlin BE, Marks GS, Brien JF, Nakatsu K (2004) The source of heme for vascular heme oxygenase II: de novo heme biosynthesis in rat aorta. Can J Physiol Pharmacol 82(4):218–224

    Article  CAS  PubMed  Google Scholar 

  81. Wegiel B, Otterbein LE (2012) Go green: the anti-inflammatory effects of biliverdin reductase. Front Pharmacol 3:47. doi:10.3389/fphar.2012.00047

    Article  PubMed  PubMed Central  Google Scholar 

  82. Cheng L, Li F, Ma R, Hu X (2015) Forsythiaside inhibits cigarette smoke-induced lung inflammation by activation of Nrf2 and inhibition of NF-κB. Int Immunopharmacol 28(1):494–499. doi:10.1016/j.intimp.2015.07.011

    Article  CAS  PubMed  Google Scholar 

  83. Choudhury S, Ghosh S, Gupta P, Mukherjee S, Chattopadhyay S (2015) Inflammation-induced ROS generation causes pancreatic cell death through modulation of Nrf2-NF-κB and SAPK/JNK pathway. Free Radic Res 20:1–41. doi:10.3109/10715762.2015.1075016

    Google Scholar 

  84. Jarrott B, Williams SJ (2015) Chronic brain inflammation: the neurochemical basis for drugs to reduce inflammation. Neurochem Res. doi:10.1007/s11064-015-1661-7

    PubMed  Google Scholar 

  85. Azad N, Rasoolijazi H, Joghataie MT, Soleimani S (2011) Neuroprotective effects of carnosic acid in an experimental model of Alzheimer’s disease in rats. Cell J 13(1):39–44

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Machado DG, Bettio LE, Cunha MP, Capra JC, Dalmarco JB, Pizzolatti MG, Rodrigues AL (2009) Antidepressant-like effect of the extract of Rosmarinus officinalis in mice: involvement of the monoaminergic system. Prog Neuropsychopharmacol Biol Psychiatry 33(4):642–650. doi:10.1016/j.pnpbp.2009.03.004

    Article  CAS  PubMed  Google Scholar 

  87. Machado DG, Cunha MP, Neis VB et al (2013) Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L. Food Chem 136(2):999–1005. doi:10.1016/j.foodchem.2012.09.028

    Article  CAS  PubMed  Google Scholar 

  88. Machado DG, Cunha MP, Neis VB et al (2012) Rosmarinus officinalis L. hydroalcoholic extract, similar to fluoxetine, reverses depressive-like behavior without altering learning deficit in olfactory bulbectomized mice. J Ethnopharmacol 143(1):158–169. doi:10.1016/j.jep.2012.06.017

    Article  CAS  PubMed  Google Scholar 

  89. Chen Y, Wang H, Zhang R, Wang H, Peng Z, Sun R, Tan Q (2012) Microinjection of sanguinarine into the ventrolateral orbital cortex inhibits Mkp-1 and exerts an antidepressant-like effect in rats. Neurosci Lett 506(2):327–331. doi:10.1016/j.neulet.2011.11.038

    Article  CAS  PubMed  Google Scholar 

  90. Zanella CA, Treichel H, Cansian RL, Roman SS (2012) The effects of acute administration of the hydroalcoholic extract of rosemary (Rosmarinus officinalis L.) (Lamiaceae) in animal models of memory. Braz J Pharm Sci 48(3):389–397. doi:10.1590/S1984-82502012000300005

    Article  Google Scholar 

Download references

Acknowledgments

None.

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Química, Departamento de Química (DQ), Instituto de Ciências Exatas e da Terra (ICET), Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiabá, MT, Brazil

    Marcos Roberto de Oliveira

Authors
  1. Marcos Roberto de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcos Roberto de Oliveira.

Ethics declarations

Conflict of Interest Statement

None.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(XLSX 12 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Oliveira, M.R. The Dietary Components Carnosic Acid and Carnosol as Neuroprotective Agents: a Mechanistic View. Mol Neurobiol 53, 6155–6168 (2016). https://doi.org/10.1007/s12035-015-9519-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-015-9519-1

Keywords

Search

Navigation