Skip to main content
SpringerLink
Log in
Book cover

Natural Bio-active Compounds pp 1–24Cite as

Secondary Metabolites from Rosemary (Rosmarinus officinalis L.): Structure, Biochemistry and Therapeutic Implications Against Neurodegenerative Diseases

  • Chapter
  • First Online:

Abstract

Rosemary (Rosmarinus officinalis L.), the representative of Lamiaceae family is known for its various medicinal uses that are accompanied by their hallmark secondary metabolites, i.e., carnosol, carnosic acid and rosmarinic acid (mostly the polyphenolic diterpenes). In the age of medicines and methodologies, when we are floating through the advancements and achievements, we are being hijacked by various diseases leading to increased number of young deaths. Neurological disorders are one of them and characterized by any impairment in the nervous system, brain or spinal cord. The majority of young and aged people around the globe are manifested by neurological disorders, i.e., stroke, epilepsy, dementia, Alzheimer’s disease (AD), Parkinson’s disease (PD) and migraine. A large number of therapeutic approaches mend the symptoms in early stages of these disorders, but with the span of time, patients become progressively more disabled as they may suffer from drug-associated adverse effects. Emphasizing on the urgent need of alternative therapeutic regimens, natural products are encouraged worldwide in terms of safety and to minimize the aforesaid loss. In this order, the current chapter summarizes the protective role of R. officinalis L. and its bio-active metabolites against various neurological disorders via targeting amyloid-beta (A-β) aggregation, neuronal cell death, acetylcholinesterase (AChE), neuroinflammation, β-secretase (BACE-1) activity, mitochondrial redox status, etc. Based on the multifunctional nature due to effective bio-active secondary metabolites, R. officinalis can be a terrific alternative therapeutic source against many neurodegenerative diseases.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Alkam T, Nitta A, Mizoguchi H, Itoh A, Nabeshima T (2007) A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by A beta (25–35). Behav Brain Res 180:139–145

    Article  CAS  PubMed  Google Scholar 

  • Al-Sereiti MR, Abu-Amer KM, Sen P (1999) Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. Indian J Exp Biol 37:124–130

    CAS  PubMed  Google Scholar 

  • Alvi SS, Ansari IA, Khan MS (2015) Pleiotropic role of lycopene in protecting various risk factors mediated atherosclerosis. Ann Phytomed 4:54–60

    CAS  Google Scholar 

  • Alvi SS, Iqbal D, Ahmad S, Khan MS (2016) Molecular rationale delineating the role of lycopene as a potent HMG-CoA reductase inhibitor: in vitro and in silico study. Nat Prod Res 30:2111–2114. https://doi.org/10.1080/14786419.2015.1108977

    Article  CAS  PubMed  Google Scholar 

  • Alvi SS, Ansari IA, Ahmad MK, Iqbal J, Khan MS (2017a) Lycopene amends LPS induced oxidative stress and hypertriglyceridemia via modulating PCSK-9 expression and Apo-CIII mediated lipoprotein lipase activity. Biomed Pharmacother 96:1082–1093

    Article  CAS  PubMed  Google Scholar 

  • Alvi SS, Ansari IA, Khan I, Iqbal J, Khan MS (2017b) Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia. Free Rad Biol Med 108:394–403

    Article  CAS  Google Scholar 

  • Aumeeruddy-Elalfi Z, Gurib-Fakim A, Mahomoodally MF (2015) Antimicrobial, antibiotic potentiating activity and phytochemical profile of essential oils from exotic and endemic medicinal plants of Mauritius. Ind Crop Prod 71:197–204

    Article  CAS  Google Scholar 

  • Aumeeruddy-Elalfi Z, Gurib-Fakim A, Mahomoodally MF (2016) Chemical composition, antimicrobial and antibiotic potentiating activity of essential oils from 10 tropical medicinal plants from Mauritius. J Herb Med 6:88–95

    Article  Google Scholar 

  • 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 13:39–44

    CAS  PubMed  PubMed Central  Google Scholar 

  • Backhouse N, Rosales L, Apablaza C, Goïty L, Erazo S, Negrete R, Theodoluz C, Rodríguez J, Delporte C (2008) Analgesic, anti-inflammatory and antioxidant properties of Buddleja globosa, Buddlejaceae. J Ethnopharmacol 116:263–269

    Article  CAS  PubMed  Google Scholar 

  • Baig MH, Ahmad K, Rabbani G, Choi I (2018) Use of peptides for the management of Alzheimer’s disease: diagnosis and inhibition. Front Aging Neurosci 10:21. https://doi.org/10.3389/fnagi.2018.00021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bakirel T, Bakırel U, Keleş OÜ, Ülgen SG, Yardibi H (2008) In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits. J Ethnopharmacol 116:64–73

    Article  PubMed  Google Scholar 

  • Barbosa LN, da Silva PI, Andrade BF, Alves FC, Albano M, de Souza MD, Doyama JT, Rall VL, Júnior AF (2015) In vitro antibacterial and chemical properties of essential oils including native plants from Brazil against pathogenic and resistant bacteria. J Oleo Sci 64:289–298

    Article  CAS  PubMed  Google Scholar 

  • Barres BA, Barde Y (2000) Neuronal and glial cell biology. Curr Opin Neurobiol 10:642–648

    Article  CAS  PubMed  Google Scholar 

  • Barreto HM, Silva Filho EC, Lima ED, Coutinho HD, Morais-Braga MF, Tavares CC, Tintino SR, Rego JV, de Abreu AP, Lustosa MD, Oliveira RW (2014) Chemical composition and possible use as adjuvant of the antibiotic therapy of the essential oil of Rosmarinus officinalis L. Ind Crops Prod 59:290–294

    Article  CAS  Google Scholar 

  • Begum A, Sandhya S, Ali SS, Vinod KR, Reddy S, Banji D (2013) An in-depth review on the medicinal flora Rosmarinus officinalis (Lamiaceae). Acta Sci Pol Technol Aliment 12:61–73

    CAS  PubMed  Google Scholar 

  • Benincá JP, Dalmarco JB, Pizzolatti MG, Fröde TS (2011) Analysis of the anti-inflammatory properties of Rosmarinus officinalis L. in mice. Food Chem 124:468–475

    Article  CAS  Google Scholar 

  • Bernardes WA, Lucarini R, Tozatti MG, Souza MG, Andrade Silva ML, da Silva Filho AA, Martins CH, Miller Crotti AE, Pauletti PM, Groppo M, Cunha WR (2010) Antimicrobial activity of Rosmarinus officinalis against oral pathogens: relevance of carnosic acid and carnosol. Chem Biodivers 7:1835–1840

    Article  CAS  PubMed  Google Scholar 

  • Borrás LI, Arráez-Román D, Herrero M, Ibáñez E, Segura-Carretero A, Fernández-Gutiérrez A (2011) Comparison of different extraction procedures for the comprehensive characterization of bioactive phenolic compounds in Rosmarinus officinalis by reversed-phase high-performance liquid chromatography with diode array detection coupled to electrospray time. J Chromatogr A 1218:7682–7690

    Article  CAS  Google Scholar 

  • Bozin B, Mimica-Dukic N, Samojlik I, Jovin E (2007) Antimicrobial and antioxidant properties of rosemary and sage (Rosmarinus officinalis L. and Salvia officinalis L., Lamiaceae) essential oils. J Agric Food Chem 55:7879–7885

    Article  CAS  PubMed  Google Scholar 

  • Brown GC, Bal-Price A (2003) Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol Neurobiol 27:325–355

    Article  CAS  PubMed  Google Scholar 

  • 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 25:1893–1901

    Article  CAS  PubMed  Google Scholar 

  • Chen WW, Zhang X, Huang WJ (2016) Role of neuroinflammation in neurodegenerative diseases. Mol Med Rep 13:3391–3396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng YS, Liao TY, Lin C, Shen HC, Wang YH, Chang CW, Liu RS, Chen RP, Tu PH (2017) An intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice. EMBO Mol Med 9:703–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi HR, Choi JS, Han YN, Bae SJ, Chung HY (2002) Peroxynitrite scavenging activity of herb extracts. Phytother Res 16:364–367

    Article  CAS  PubMed  Google Scholar 

  • Chovatiya R, Medzhitov R (2014) Stress, inflammation, and defense of homeostasis. Mol Cell 54:281–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • da Rosa JS, Facchin BM, Bastos J, Siqueira MA, Micke GA, Dalmarco EM, Pizzolatti MG, Fröde TS (2013) Systemic administration of Rosmarinus officinalis attenuates the inflammatory response induced by carrageenan in the mouse model of pleurisy. Planta Med 79:1605–1614

    Article  PubMed  Google Scholar 

  • de Oliveira MR (2015) The dietary components carnosic acid and carnosol as neuroprotective agents: a mechanistic view. Mol Neurobiol 53:6155–6168

    Article  PubMed  CAS  Google Scholar 

  • Del Baño MJ, Benavente-García O, Lorente J, Martín-Gil R, Acevedo C, Alcaraz M (2006) Radioprotective−antimutagenic effects of rosemary phenolics against chromosomal damage induced in human lymphocytes by γ-rays. J Agric Food Chem 54:2064–2068

    Article  PubMed  CAS  Google Scholar 

  • 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 66:196–202

    Article  CAS  PubMed  Google Scholar 

  • Doughari JH (2012) Phytochemicals: extraction methods, basic structures and mode of action as potential chemotherapeutic agents. In: Rao V (ed) Phytochemicals – a global perspective of their role in nutrition and health. InTech, Rijeka, pp 1–32

    Google Scholar 

  • Drachman DA (2014) The amyloid hypothesis, time to move on: amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimers Dement 10:372–380

    Article  PubMed  Google Scholar 

  • Faixová Z, Faix S (2008) Biological effects of rosemary (Rosmarinus officinalis L.) essential oil. Folia Vet 52:135–139

    Google Scholar 

  • Felicidade I, Lima JD, Pesarini JR, Monreal AC, Mantovani MS, Ribeiro LR, Oliveira RJ (2014) Mutagenic and antimutagenic effects of aqueous extract of rosemary (Rosmarinus officinalis L.) on meristematic cells of Allium cepa. Genet Mol Res 13:9986–9996

    Article  CAS  PubMed  Google Scholar 

  • Funke SA, Willbold D (2012) Peptides for therapy and diagnosis of Alzheimer’s disease. Curr Pharm Des 18:755–767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genova ML, Bianchi C, Lenaz G (2005) Supercomplex organization of the mitochondrial respiratory chain and the role of the coenzyme Q pool: pathophysiological implications. Biofactors 25:5–20

    Article  CAS  PubMed  Google Scholar 

  • González-Vallinas M, Molina S, Vicente G, de la Cueva A, Vargas T, Santoyo S, García-Risco MR, Fornari T, Reglero G, de Molina AR (2013) Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells. Pharmacol Res 72:61–68

    Article  PubMed  CAS  Google Scholar 

  • González-Vallinas M, Molina S, Vicente G, Zarza V, Martín-Hernández R, García-Risco MR, Fornari T, Reglero G, De Molina AR (2014) Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of rosemary diterpenes in colon and pancreatic cancer. PLoS One 9:e98556. https://doi.org/10.1371/journal.pone.0098556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • González-Vallinas M, Reglero G, Ramírez de Molina A (2015) Rosemary (Rosmarinus officinalis L.) extract as a potential complementary agent in anticancer therapy. J Nutr Cancer 67:1221–1229

    Google Scholar 

  • Gouveia AR, Alves M, Silva JA, Saraiva C (2016) The antimicrobial effect of rosemary and thyme essential oils against Listeria monocytogenes in sous vide cook-chill beef during storage. Procedia Food Sci 7:173–176

    Article  Google Scholar 

  • Grundman M, Dibernardo A, Raghavan N, Krams M, Yuen E (2013) 2012: a watershed year for Alzheimer’s disease research. J Nutr Health Aging 17:51–53

    Article  CAS  PubMed  Google Scholar 

  • Gutiérrez R, Alvarado JL, Presno M, Pérez-Veyna O, Serrano CJ, Yahuaca P (2010) Oxidative stress modulation by Rosmarinus officinalis in CCl4-induced liver cirrhosis. Phytother Res 24:595–601

    Article  PubMed  CAS  Google Scholar 

  • Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid b-peptide. Nat Rev Mol Cell Biol 8:101–112

    Article  CAS  PubMed  Google Scholar 

  • Habtemariam S (2016) The therapeutic potential of rosemary (Rosmarinus officinalis) diterpenes for Alzheimer’s disease. Evid-Based Complement Alternat Med 2016:2680409. https://doi.org/10.1155/2016/2680409

    Article  PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  • Haraguchi H, Saito T, Okamura N, Yagi A (1995) Inhibition of lipid peroxidation and superoxide generation by diterpenoids from Rosmarinus officinalis. Planta Med 61:333–336

    Article  CAS  PubMed  Google Scholar 

  • Harkat-Madouri L, Asma B, Madani K, Said ZB, Rigou P, Grenier D, Allalou H, Remini H, Adjaoud A, Boulekbache-Makhlouf L (2015) Chemical composition, antibacterial and antioxidant activities of essential oil of Eucalyptus globulus from Algeria. Ind Crops Prod 78:148–153

    Article  CAS  Google Scholar 

  • Hasler G, Fromm S, Carlson PJ, Luckenbaugh DA, Waldeck T, Geraci M, Roiser JP, Neumeister A, Meyers N, Charney DS, Drevets WC (2008) Neural response to catecholamine depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects. Arch Gen Psychiatry 65:521–531

    Article  PubMed  PubMed Central  Google Scholar 

  • Herrup K (2015) The case for rejecting the amyloid cascade hypothesis. Nat Neurosci 18:794–799

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Weng Z, Chu CT, Zhang L, Cao G, Gao Y, Signore A, Zhu J, Hastings T, Greenamyre JT, Chen J (2011) Peroxiredoxin-2 protects against 6-hydroxydopamine-induced dopaminergic neurodegeneration via attenuation of the apoptosis signal-regulating kinase (ASK1) signaling cascade. J Neurosci 31:247–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang MT, Ho CT, Wang ZY, Ferraro T, Lou YR, Stauber K, Ma W, Georgiadis C, Laskin JD, Conney AH (1994) Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res 54:701–708

    CAS  PubMed  Google Scholar 

  • Hussain AI, Anwar F, Chatha SA, Jabbar A, Mahboob S, Nigam PS (2010) Rosmarinus officinalis essential oil: antiproliferative, antioxidant and antibacterial activities: Braz. J Microbiol 41:1070–1078

    CAS  Google Scholar 

  • Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the aminoterminal Neh2 domain. Genes Dev 13:76–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarrott B, Williams SJ (2015) Chronic brain inflammation: the neurochemical basis for drugs to reduce inflammation. Neurochem Res 41:523–533

    Article  PubMed  CAS  Google Scholar 

  • Jia Z, Misra BR, Zhu H, Li Y, Misra HP (2009) Upregulation of cellular glutathione by 3H-1,2-dithiole-3-thione as a possible treatment strategy for protecting against acrolein-induced neurocytotoxicity. Neurotoxicology 30:1–9

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Jindal A, Soyal D, Sancheti G, Goyal PK (2006) Radioprotective potential of Rosemarinus officinalis against lethal effects of gamma radiation: a preliminary study. J Environ Pathol Toxicol Oncol 25:633–642

    Article  PubMed  Google Scholar 

  • Jordán MJ, Lax V, Rota MC, Lorán S, Sotomayor JA (2012) Relevance of carnosic acid, carnosol, and rosmarinic acid concentrations in the in vitro antioxidant and antimicrobial activities of Rosmarinus officinalis (L.) methanolic extracts. J Agric Food Chem 60:9603–9608

    Article  PubMed  CAS  Google Scholar 

  • Kar S, Palit S, Ball WB, Das PK (2012) Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis 17:735–747

    Article  CAS  PubMed  Google Scholar 

  • Khan I, Ahmad W, Karim N, Ahmad M, Khan M, Tariq SA, Sultana N, Shah R, Khan A, Abdelhalim A (2016) Antidiabetic activity and histopathological analysis of carnosol isolated from Artemisia indica Linn. in streptozotocin-induced diabetic rats. Med Chem Res 26:335–343

    Article  CAS  Google Scholar 

  • Kim HG, Ju MS, Kim DH, Hong J, Cho SH, Cho KH, Park W, Lee EH, Kim SY, Oh MS (2010a) Protective effects of Chunghyuldan against ROS-mediated neuronal cell death in models of Parkinson’s disease. Basic Clin Pharmacol Toxicol 107:958–964

    Article  CAS  PubMed  Google Scholar 

  • Kim SY, Park E, Park JA, Choi BS, Kim S, Jeong G, Kim CS, Kim DK, Kim SJ, Chun HS (2010b) The plant phenolic diterpene carnosol suppresses sodium nitroprusside-induced toxicity in C6 glial cells. J Agric Food Chem 58:1543–1550

    Article  CAS  PubMed  Google Scholar 

  • 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 26:1620–1622

    Article  CAS  PubMed  Google Scholar 

  • Kwon SH, Lee HK, Kim JA, Hong SI, Kim HC, Jo TH, Park YI, Lee CK, Kim YB, Lee SY, Jang CG (2010) Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via antiacetylcholinesterase and anti-oxidative activities in mice. Eur J Pharmacol 649:210–217

    Article  CAS  PubMed  Google Scholar 

  • Lee CH, Hwang DS, Kim HG, Oh H, Park H, Cho JH, Lee JM, Jang JB, Lee KS, Oh MS (2010) Protective effect of Cyperi rhizoma against 6-hydroxydopamine-induced neuronal damage. J Med Food 13:564–571

    Article  CAS  PubMed  Google Scholar 

  • Li XL, Liu JX, Li P, Zheng YQ (2014) Protective effect of rosmarinic acid on hypoxia/reoxygenation injury in cardiomyocytes. China J Chinese Materia Med 39:1897–1901

    CAS  Google Scholar 

  • Li H, Chen C, Cao X (2015) Essential oils-oriented chiral esters as potential pesticides: asymmetric syntheses, characterization and bio-evolution. Ind Crops Prod 76:432–436

    Article  CAS  Google Scholar 

  • Li CZ, Grajales S, Shuang S, Dong C, Nair M (2017) b-amyloid biomarker detection for Alzheimer’s disease. J Anal Test 1:15. https://doi.org/10.1007/s41664-017-0014-8

    Article  Google Scholar 

  • Lo AH, Liang YC, Lin-Shiau SY, Ho CT, Lin JK (2002) Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages. Carcinogenesis 23:983–991

    Article  CAS  PubMed  Google Scholar 

  • Lovkova MY, Buzuk GN, Sokolova SM, Kliment’eva NI (2001) Chemical features of medicinal plants. Appl Biochem Microbiol 37:229–237

    Article  CAS  Google Scholar 

  • Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830:3143–3153

    Article  CAS  PubMed  Google Scholar 

  • 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—Nrf-2 activators and GSK-3 inhibitors. Inflammopharmacology 20:127–150

    Article  CAS  PubMed  Google Scholar 

  • Makino T, Ono T, Liu N, Nakamura T, Muso E, Honda G (2002) Suppressive effects of rosmarinic acid on mesangio proliferative glomerulonephritis in rats. Nephron 92:898–904

    Article  CAS  PubMed  Google Scholar 

  • 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 14:941–947

    Article  CAS  PubMed  Google Scholar 

  • Manoharan S, VasanthaSelvan M, Silvan S, Baskaran N, Singh AK, Kumar VV (2010) Carnosic acid: a potent chemopreventive agent against oral carcinogenesis. Chem Biol Interact 188:616–622

    Article  CAS  PubMed  Google Scholar 

  • Martin HL, Teismann P (2009) Glutathione: a review on its role and significance in Parkinson’s disease. FASEB J 23:3263–3272

    Article  CAS  PubMed  Google Scholar 

  • 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 279:8919–8929

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Cheng A (2006) Neurohormetic phytochemicals: low dose toxins that induce adaptive neuronal stress responses. Trends Neurosci 29:632–639

    Article  CAS  PubMed  Google Scholar 

  • Mena NP, Urrutia PJ, Lourido F, Carrasco CM, Núñez MT (2015) Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders. Mitochondrion 21:92–105

    Article  CAS  PubMed  Google Scholar 

  • Menting KW, Claassen JAHR (2014) β-Secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease. Front Aging Neurosci 6:165. https://doi.org/10.3389/fnagi.2014.00165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller DM, Singh IN, Wang JA, Hall ED (2013) Administration of the Nrf2-ARE activators sulforaphane and carnosic acid attenuates 4-hydroxy-2-nonenal-induced mitochondrial dysfunction ex vivo. Free Radic Biol Med 57:1–9. https://doi.org/10.1016/j.freeradbiomed.2012.12.011

    Article  CAS  PubMed  Google Scholar 

  • Miraj S (2016) An evidence-based review on herbal remedies of Rosmarinus officinalis. Der Pharma Lett 8:426–436

    CAS  Google Scholar 

  • Moi P, Chan K, Asunis I, Cao A, Kan YW (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A 91:9926–9930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moreira PI, Carvalho C, Zhu X, Smith MA, Perry G (2010) Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology. Biochim Biophys Acta 1802:2–10

    Article  CAS  PubMed  Google Scholar 

  • Morris G, Anderson G, Dean O, Berk M, Galecki P, Martin-Subero M, Maes M (2014) The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol 50:1059–1084

    Article  CAS  PubMed  Google Scholar 

  • Naemura A, Ura M, Yamashita T, Arai R, Yamamoto J (2008) Long-term intake of rosemary and common thyme herbs inhibits experimental thrombosis without prolongation of bleeding time. Thromb Res 122:517–522

    Article  CAS  PubMed  Google Scholar 

  • Naoi M, Maruyama W, Shamoto-Nagai M, Yi H, Akao Y, Tanaka M (2005) Oxidative stress in mitochondria: decision to survival and death of neurons in neurodegenerative disorders. Mol Neurobiol 31:81–93

    Article  CAS  PubMed  Google Scholar 

  • Nobile V, Michelotti A, Cestone E, Caturla N, Castillo J, Benavente-García O, Pérez-Sánchez A, Micol V (2016) Skin photoprotective and antiageing effects of a combination of rosemary (Rosmarinus officinalis) and grapefruit (Citrus paradisi) polyphenols. Food Nutr Res 60:31871. https://doi.org/10.3402/fnr.v60.31871

    Article  PubMed  Google Scholar 

  • Orhan I, Aslan S, Kartal M, Şener B, Başer KH (2008) Inhibitory effect of Turkish Rosmarinus officinalis L. on acetylcholinesterase and butyrylcholinesterase enzymes. Food Chem 108:663–668

    Article  CAS  PubMed  Google Scholar 

  • Ozarowski M, Mikolajczak PL, Bogacz A, Gryszczynska A, Kujawska M, Jodynis-Liebert J, Piasecka A, Napieczynska H, Szulc M, Kujawski R, Bartkowiak-Wieczorek J (2013) Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain. Fitoterapia 91:261–271

    Article  CAS  PubMed  Google Scholar 

  • Papa S, Martino PL, Capitanio G, Gaballo A, De Rasmo D, Signorile A, Petruzzella V (2012) The oxidative phosphorylation system in mammalian mitochondria. Adv Exp Med Biol 942:3–37

    Article  CAS  PubMed  Google Scholar 

  • Park JA, Kim S, Lee SY, Kim CS, Kim DK, Kim SJ, Chun HS (2008) Beneficial effects of carnosic acid on dieldrin-induced dopaminergic neuronal cell death. Neuroreport 19:1301–1304

    Article  CAS  PubMed  Google Scholar 

  • Park SE, Kim S, Sapkota K, Kim SJ (2010) Neuroprotective effect of Rosmarinus officinalis extract on human dopaminergic cell line, SH-SY5Y. Cell Mol Neurobiol 30:759–767

    Article  PubMed  Google Scholar 

  • Peng CH, Su JD, Chyau CC, Sung TY, Ho SS, Peng CC, Peng RY (2007) Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects. Biosci Biotechnol Biochem 71:2223–2232

    Article  CAS  PubMed  Google Scholar 

  • Perez-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 58:161–171

    Article  CAS  PubMed  Google Scholar 

  • Perry NS, Houghton PJ, Theobald A, Jenner P, Perry EK (2000) In vitro inhibition of erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 52:895–902

    Article  CAS  PubMed  Google Scholar 

  • Perry NS, Bollen C, Perry EK, Ballard C (2003) Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 75:651–659

    Article  CAS  PubMed  Google Scholar 

  • Petiwala SM, Johnson JJ (2015) Diterpenes from rosemary (Rosmarinus officinalis): defining their potential for anti-cancer activity. Cancer Lett 367:93–102

    Article  CAS  PubMed  Google Scholar 

  • Posadas SJ, Caz V, Largo C, De la Gandara B, Matallanas B, Reglero G, De Miguel E (2009) Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats. Exp Gerontol 44:383–389

    Article  CAS  PubMed  Google Scholar 

  • Pun PB, Lu J, Kan EM, Moochhala S (2010) Gases in the mitochondria. Mitochondrion 10:83–93

    Article  CAS  PubMed  Google Scholar 

  • Qiao S, Li W, Tsubouchi R, Haneda M, Murakami K, Takeuchi F, Nisimoto Y, Yoshino M (2005) Rosmarinic acid inhibits the formation of reactive oxygen and nitrogen species in RAW264.7 macrophages. Free Rad Res 39:995–1003

    Article  CAS  Google Scholar 

  • Rahimifard M, Navaei-Nigjeh M, Mahroui N, Mirzaei S, Siahpoosh Z (2014) Improvement in the function of isolated rat pancreatic islets through reduction of oxidative stress using traditional Iranian medicine. Cell J 16:147–163

    PubMed  PubMed Central  Google Scholar 

  • Raschetti R, Albanese E, Vanacore N, Maggini M (2007) Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Med 4:1818–1828

    Article  CAS  Google Scholar 

  • Rašković A, Milanović I, Pavlović N, Ćebović T, Vukmirović S, Mikov M (2014) Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential. BMC Compl Altern Med 14:225. https://doi.org/10.1186/1472-6882-14-225

    Article  Google Scholar 

  • Samuelsson G, Bohlin L (2001) Drugs of natural origin: a treatise of pharmacognosy, 6th edn. Swedish Pharmaceutical Press, Stockholm

    Google Scholar 

  • Santos FA, Rao VSN (2000) Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytother Res 14:240–244

    Article  CAS  PubMed  Google Scholar 

  • Santoyo S, Cavero S, Jaime L, Ibanez E, Senorans FJ, Reglero G (2005) Chemical composition and antimicrobial activity of Rosmarinus officinalis L. essential oil obtained via supercritical fluid extraction. J Food Prot 68:790–795

    Article  CAS  PubMed  Google Scholar 

  • Satoh T, Kosaka K, Itoh K, Kobayashi A, Yamamoto M, Shimojo Y, Kitajima C, Cui J, Kamins J, Okamoto SI, Izumi M (2008a) 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 104:1116–1131

    Article  CAS  PubMed  Google Scholar 

  • Satoh T, Izumi M, Inukai Y, Tsutsumi Y, Nakayama N, Kosaka K, Shimojo Y, Kitajima C, Itoh K, Yokoi T, Shirasawa T (2008b) 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 434:260–265

    Article  CAS  PubMed  Google Scholar 

  • Satoh T, McKercher SR, Lipton SA (2013) Nrf2/ARE mediated antioxidant actions of pro-electrophilic drugs. Free Rad Biol Med 65:645–657

    Article  CAS  PubMed  Google Scholar 

  • Satyal P, Jones TH, Lopez EM, McFeeters RL, Ali NA, Mansi I, Al-kaf AG, Setzer WN (2017) Chemotypic characterization and biological activity of Rosmarinus officinalis. Foods 6:20. https://doi.org/10.3390/foods6030020

    Article  CAS  PubMed Central  Google Scholar 

  • Savelev S, Okello E, Perry NS, Wilkins RM, Perry EK (2003) Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharma Biochem Behav 75:661–668

    Article  CAS  Google Scholar 

  • Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM (2008) Amyloid-ß protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14:837–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimojo Y, Kosaka K, Noda Y, Shimizu T, Shirasawa T (2010) Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis. J Neurosci Res 88:896–904

    CAS  PubMed  Google Scholar 

  • Sies H (2015) Oxidative stress: a concept in redox biology and medicine. Redox Biol 4:180–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song JX, Shaw PC, Sze CW, Tong Y, Yao XS, Ng TB, Zhang YB (2010) Chrysotoxine, a novel bibenzyl compound, inhibits 6-hydroxydopamine induced apoptosis in SH-SY5Y cells via mitochondria protection and NF-kappaB modulation. Neurochem Int 57:676–689

    Article  CAS  PubMed  Google Scholar 

  • Sotelo-Félix JI, Martinez-Fong D, De la Torre PM (2002) Protective effect of carnosol on CCl4-induced acute liver damage in rats. Eur J Gastroenterol Hepatol 14:1001–1006

    Article  PubMed  Google Scholar 

  • Soyal D, Jindal A, Singh I, Goyal PK (2007) Protective capacity of rosemary extract against radiation induced hepatic injury in mice. Iran J Radiat Res 4:161–168

    Google Scholar 

  • Sperner-Unterweger B, Kohl C, Fuchs D (2014) Immune changes and neurotransmitters: possible interactions in depression. Prog Neuropsy Biol Psychiat 48:268–276

    Article  CAS  Google Scholar 

  • Stephenson J, Nutma E, van der Valk P, Amor S (2018) Inflammation in CNS neurodegenerative diseases. Immunology 154:204–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takaki I, Bersani-Amado LE, Vendruscolo A, Sartoretto SM, Diniz SP, Bersani-Amado CA, Cuman RK (2008) Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models. J Med Food 11:741–746

    Article  CAS  PubMed  Google Scholar 

  • 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 76:683–688

    Article  CAS  PubMed  Google Scholar 

  • Teixeira B, Marques A, Ramos C, Serrano C, Matos O, Neng NR, Nogueira JM, Saraiva JA, Nunes ML (2013) Chemical composition and bioactivity of different oregano (Origanum vulgare) extracts and essential oil. J Sci Food Agric 93:2707–2714

    Article  CAS  PubMed  Google Scholar 

  • Tian LL, Zhou Z, Zhang Q, Sun YN, Li CR, Cheng CH, Zhong ZY, Wang SQ (2007) Protective effect of (±) isoborneol against 6-OHDA-induced apoptosis in SH-SY5Y cells. Cell Physiol Biochem 20:1019–1032

    Article  CAS  PubMed  Google Scholar 

  • Tu Z, Moss-Pierce T, Ford P et al (2013) Rosemary (Rosmarinus officinalis L.) extract regulates glucose and lipid metabolism by activating AMPK and PPAR pathways in HepG2 cells. J Agric Food Chem 61:2803–2810

    Article  CAS  PubMed  Google Scholar 

  • Ulbricht C, Abrams TR, Brigham A, Ceurvels J, Clubb J, Curtiss W, Kirkwood CD, Giese N, Hoehn K, Iovin R, Isaac R (2010) An evidence-based systematic review of rosemary (Rosmarinus officinalis) by the Natural Standard Research Collaboration. J Diet Suppl 7:351–413

    Article  PubMed  Google Scholar 

  • Vali S, Mythri RB, Jagatha B, Padiadpu J, Ramanujan KS, Andersen JK, Gorin F, Bharath MM (2007) Integrating glutathione metabolism and mitochondrial dysfunction with implications for Parkinson’s disease: a dynamic model. Neuroscience 149:917–930

    Article  CAS  PubMed  Google Scholar 

  • Van Itallie TB (2015) Biomarkers, ketone bodies and the prevention of Alzheimer’s disease. Metabolism 64:S51–S57

    Article  CAS  Google Scholar 

  • Vaquero MR, Garcia 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 57:1834–1846

    Google Scholar 

  • Venditti P, Di Stefano L, Di Meo S (2013) Mitochondrial metabolism of reactive oxygen species. Mitochondrion 13:71–82. https://doi.org/10.1016/j.mito.2013.01.008

    Article  CAS  PubMed  Google Scholar 

  • Verma R, Nehru B (2009) Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson’s disease. Neurochem Int 55:369–375

    Article  CAS  PubMed  Google Scholar 

  • 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 40:186–192

    PubMed  Google Scholar 

  • Villareal MO, Ikeya A, Sasaki K, Arfa AB, Neffati M, Isoda H (2017) Anti-stress and neuronal cell differentiation induction effects of Rosmarinus officinalis L. essential oil. BMC Compl Altern Med 17:549. https://doi.org/10.1186/s12906-017-2060-1

    Article  CAS  Google Scholar 

  • Viuda-Martos M, El Gendy A-N, Sendra E et al (2010a) Chemical composition and antioxidant and antilisteria activities of essential oils obtained from some egyptian plants. J Agric Food Chem 58:9063–9070

    Article  CAS  PubMed  Google Scholar 

  • Viuda-Martos M, Ruiz Navajas Y, Sánchez Zapata E, Fernández-López J, Pérez-Álvarez JA (2010b) Antioxidant activity of essential oils of five spice plants widely used in a Mediterranean diet. Flavour Frag J 25:13–19

    Article  CAS  Google Scholar 

  • Wang X, Su B, Zheng L, Perry G, Smith MA, Zhu X (2009) The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease. J Neurochem 109:S153–S159

    Article  CAS  Google Scholar 

  • Wang W, Li N, Luo M, Zu Y, Efferth T (2012) Antibacterial activity and anticancer activity of Rosmarinus officinalis L. essential oil compared to that of its main components. Molecules 17:2704–2713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239

    Article  CAS  PubMed  Google Scholar 

  • Wilkins HM, Swerdlow RH (2016) Relationships between mitochondria and neuroinflammation: implications for Alzheimer’s disease. Curr Top Med Chem 16:849–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilmo AP, Martin P (2010) World Alzheimer report 2010. The global economic impact of dementia. Alzheimer’s Disease International, London

    Google Scholar 

  • Wortmann M (2012) Dementia: a global health priority-highlights from an ADI and World Health Organization report. Alzheimer’s Res Ther 4:40. https://doi.org/10.1186/alzrt143

    Article  Google Scholar 

  • Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134:489–492

    Article  CAS  PubMed  Google Scholar 

  • Xiang Q, Ma Y, Dong J, Shen R (2014) Carnosic acid induces apoptosis associated with mitochondrial dysfunction and Akt inactivation in HepG2 cells. Int J Food Sci Nutr 7486:76–84

    Google Scholar 

  • Yamamoto J, Yamada K, Naemura A, Yamashita T, Arai R (2005) Testing various herbs for antithrombotic effect. Nutrition 21:580–587

    Article  PubMed  Google Scholar 

  • 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 418:22–26

    Article  CAS  PubMed  Google Scholar 

  • Yoshida H, Meng P, Matsumiya T, Tanji K, Hayakari R, Xing F, Wang L, Tsuruga K, Tanaka H, Mimura J, Kosaka K (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

    Article  CAS  PubMed  Google Scholar 

  • Yu MH, Choi JH, Chae IG, Im HG, Yang SA, More K, Lee IS, Lee J (2012) Suppression of LPS-induced inflammatory activities by Rosmarinus officinalis L. Food Chem 136:1047–1054

    Article  PubMed  CAS  Google Scholar 

  • 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 48:389–397

    Article  Google Scholar 

  • Zhang Y, Adelakun TA, Qu L, Li X, Li J, Han L, Wang T (2014) New terpenoid glycosides obtained from Rosmarinus officinalis L. aerial parts. Fitoterapia 99:78–85

    Article  CAS  PubMed  Google Scholar 

  • Zhang D, Lee B, Nutter A, Song P, Dolatabadi N, Parker J, Sanz-Blasco S, Newmeyer T, Ambasudhan R, McKercher SR, Masliah E (2015) Protection of cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid. J Neurochem 133:898–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou X, Hollern D, Liao J, Andrechek E, Wang H (2013) NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and extrasynaptic receptors. Cell Death Dis 4:e560. https://doi.org/10.1038/cddis.2013.82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are highly indebted to Prof. S. W. Akhtar, chancellor, for providing us the state-of the-art research laboratory.

Author information

Authors and Affiliations

  1. IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India

    Sahir Sultan Alvi, Parvej Ahmad & M. Salman Khan

  2. Faculty of Natural Sciences, Department of Biosciences, Jamia Millia Islamia University, New Delhi, India

    Maleeha Ishrat

  3. Department of Medical Laboratory Sciences, College of Applied medical Sciences, Majmaah University, Al-Majmaah, Saudi Arabia

    Danish Iqbal

Authors
  1. Sahir Sultan Alvi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Parvej Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maleeha Ishrat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Danish Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Salman Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Salman Khan .

Editor information

Editors and Affiliations

  1. Department of Biotechnology, East West First Grade College of Science, Bengaluru, Karnataka, India

    Mallappa Kumara Swamy

  2. Department of Botany, Gandhi Faiz-e-Aam College, Shahjahanpur, Uttar Pradesh, India

    Mohd Sayeed Akhtar

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Alvi, S.S., Ahmad, P., Ishrat, M., Iqbal, D., Khan, M.S. (2019). Secondary Metabolites from Rosemary (Rosmarinus officinalis L.): Structure, Biochemistry and Therapeutic Implications Against Neurodegenerative Diseases. In: Swamy, M., Akhtar, M. (eds) Natural Bio-active Compounds. Springer, Singapore. https://doi.org/10.1007/978-981-13-7205-6_1

Download citation

Publish with us

Policies and ethics

Search

Navigation