PHYTOCHEMICAL PROFILE AND NEUROPROTECTIVE POTENTIAL OF ROSMARINUS OFFICINALIS L. FROM NILGIRIS IN ALZHEIMER’S DISEASE MANAGEMENT
DOI:
https://doi.org/10.22159/ajpcr.2025v18i6.54338Keywords:
Rosmarinus officinalis L, Alzheimer's disease, Neuroprotection, Phytochemicals, Biomarkers, Cognitive enhancementAbstract
The current review discusses the possibility of using Rosmarinus officinalis L. (rosemary) from the Nilgiris district as a plant that can be used as biomarkers for the quantification and treatment of Alzheimer's disease (AD). Specific geographic and climatic conditions, prevalent in the Nilgiris, make such cultivations unique and replete with high levels of Rosmarinus acid, carnosic acid, luteolin, and 1,8-cineole. These compounds exhibit multimodal neuroprotective effects against AD pathology through antioxidant and anti-inflammatory actions, amyloid-β and tau pathology modification, as well as enhancement of cholinergic function. The preclinical studies concerning the treatment of AD were quite important to its consequences on neuroprotection, cognitive improvement, inhibition of amyloid-β aggregation, and reduction of tau hyperphosphorylation. This paper also highlights the possibility that such compounds could be used as biomarkers to quantify AD because they can be measured in biological fluids and can have associations related to mechanisms behind AD. However, challenges ahead are standardization of rosemary extracts and improvement in their bioavailability along with penetration across the blood-brain barrier and all this in well-designed clinical trials. Future Research Future research would include the development of standardized cultivation and processing protocols to improve the bioavailability of the extract; large-scale clinical trials on AD patients; and combination of the therapy with existing AD drugs, not forgetting personalized approaches to medicine.
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References
World Health Organization. Dementia Fact Sheet. Switzerland: World Health Organization; 2021.
Jack CR Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018, PMID: 29653606, PMCID: PMC5958625
Hampel H, O’Bryant SE, Molinuevo JL, Zetterberg H, Masters CL, Lista S, et al. Blood-based biomarkers for Alzheimer disease: Mapping the road to the clinic. Nat Rev Neurol. 2018 Nov;14(11):639- 652. doi: 10.1038/s41582-018-0079-7, PMID: 30297701, PMCID: PMC6211654
Habtemariam S. The therapeutic potential of rosemary (Rosmarinus officinalis) diterpenes for Alzheimer’s disease. Evid Based Complement Alternat Med. 2016;2016:2680409. doi: 10.1155/2016/2680409, Epub 2016 Jan 28, PMID: 26941822, PMCID: PMC4749867
Andrade JM, Faustino C, Garcia C, Ladeiras D, Reis CP, Rijo P. Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity. Future Sci OA. 2018 Feb 1;4(4):FSO283. doi: 10.4155/fsoa-2017-0124, PMID: 29682318, PMCID: PMC5905578
Murugesan M, Senthil Kumar R, Kumaran KS, Saravanan D. Phytochemical screening and antimicrobial activity of medicinal plants from Nilgiris, Tamil Nadu, India. Int J Pharma Sci Rev Res. 2012;13(2):81-84.
Palanisamy UD, Kuppusamy UR, Nagappan A, Pandian SK. Rapid in vitro propagation of Rosmarinus officinalis L. using different explants. J Med Plants Res. 2014;8(39):1486-1493.
Napoli E, Giovino A, Carrubba A, Ilardi V, Ruberto G. Rosmarinus officinalis L. As a source of phenolic compounds: In vitro cultivated plant versus wild-grown. Chem Biodiversity. 2020;17(5):e2000149.
Rajan S, Ranjitha Kumari BD, Basha A, Sudhakar R, Ramesh M. Phytodiversity in Nilgiri biosphere reserve. Int J Appl Pure Sci Agric. 2016;2(11):75-82.
Kumar PB, Rajamanickam GV, Jebakumar S, Ganesh N. Geological and geomorphological characteristics of Nilgiris district, Tamil Nadu. J Earth Syst Sci. 2018;127(8):1-15.
Ramasamy SM, Selvakumar R, Saravanavel J. Geomorphology and landform evolution of the Nilgiri Hills, a part of the Western Ghats, Southern India. In: Landscapes and Landforms of India. Cham: Springer; 2019. p. 235-246.
Muthukumarasamy R, Anbazhagan S, Rajendran C, Vennila C, Ramesh T. Rainfall variability and its impact on crop productivity in the Nilgiris, Tamil Nadu. J Agrometeorol. 2019;21(3):275-281. 13. Kumar R, Sharma S, Kumari A, Singh D. Cultivation practices and processing of rosemary (Rosmarinus officinalis L.) under subtropical conditions. J Appl Res Med Aromatic Plants. 2019;12:30-37.
Ravindran PN, Babu KN, Shiva KN. Rosemary. In: Handbook of Herbs and Spices. Cambridge: Wood head Publishing; 2020. p. 512-533.
Jiang Y, Liu H, Zhang Y, Wang Q. Effect of cutting height on the growth and essential oil yield of rosemary (Rosmarinus officinalis L.). Ind Crops Products. 2019;134:109-114.
Ramakrishna A, Dhanalakshmi R, Suryanarayana V, Gopikrishna P, Sridevi S. Influence of altitude on the phytochemical profile and antioxidant activity of rosemary (Rosmarinus officinalis L.) grown in different regions of India. Ind Crops Products. 2021;162:113284.
Verma RS, Padalia RC, Chauhan A. Chemical composition of rosemary (Rosmarinus officinalis L.) oils from different altitudes of western Himalaya. J Essential Oil Res. 2018;30(5):379-387.
Habtemariam S. The therapeutic potential of rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer’s disease. Evid Based Complement Alternat Med. 2016;2016:2680409. doi: 10.1155/2016/2680409, Epub 2016 Jan 28, PMID: 26941822, PMCID: PMC4749867
Kumar S, Yadav A, Bhandari P, Singh B. Comparative evaluation of antioxidant potential of rosemary (Rosmarinus officinalis L.) extracts from different geographical locations in India. J Food Sci Technol. 2019;56(9):4232-4241.
Trivellini A, Lucchesini M, Maggini R, Guidi L, Ferrante A, Vernieri P, et al. Rosemary (Rosmarinus officinalis L.) as a source of phenolic compounds: In vitro cultivated plant versus wild-grown. J Sci Food Agric. 2016;96(2):614-624.
Andrade JM, Faustino C, Garcia C, Ladeiras D, Reis CP, Rijo P. Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity. Future Sci OA. 2018 Feb 1;4(4):FSO283. doi: 10.4155/fsoa-2017-0124, PMID: 29682318, PMCID: PMC5905578
Hase T, Shimizu T, Takahashi Y, Yokoi T, Honda T, Yamato M. Rosmarinic acid in health and disease: Pharmacological activities and molecular mechanisms of action. Int J Mol Sci. 2019;20(5):1071.
Alagawany M, Abd El-Hack ME, Farag MR, Gopi M, Karthik K, Malik YS, et al. Rosmarinic acid: Modes of action, medicinal values and health benefits. Anim Health Res Rev. 2017 Dec;18(2):167-176. doi: 10.1017/S1466252317000081, Epub 2017 Nov 7, PMID: 29110743
Sahu S, Chidambaram S, Tyagi R, Singh S, Sharma S. Rosmarinic acid attenuates cognitive deficits and neurodegeneration in an aluminum-induced rat model of Alzheimer’s disease. Neurotoxicity Res. 2020;38(2):478-490.
Luo C, Liu Y, Wang Y, Fan Y, Zhang H. Rosmarinic acid ameliorates memory deficits in a rat model of Alzheimer’s disease by modulating the cholinergic system. Neurochem Res. 2020;45(4):825-834.
Habtemariam S. Molecular pharmacology of rosmarinic and salvianolic acids: Potential seeds for Alzheimer’s and vascular dementia drugs. Int J Mol Sci. 2018 Feb 3;19(2):458. doi: 10.3390/ijms19020458, PMID: 29401682, PMCID: PMC5855680
Bahri S, Hammami I, Mahmoudi H, Ben Salem I, Gdoura R, Elleuch M. Neuroprotective effect of carnosic acid against cognitive impairment induced by chronic stress in rats. J Appl Pharma Sci. 2016;6(11):117- 124.
Satoh T, Izumi M, Inukai Y, Tsutsumi Y, Nakayama N, Kosaka K, et al. 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. 2008 Apr 4;434(3):260-265. doi: 10.1016/j.neulet.2008.01.079, Epub 2008 Feb 13, PMID: 18329808
Meng P, Tang Y, Zhang L, Li W, Zhou J. Carnosic acid attenuates memory deficits and neuronal damage in a rat model of Alzheimer’s disease. J Mol Neurosci. 2019;67(4):557-564.
Wu CR, Chen HY, Liao JW, Lin IH, Chang YC. Carnosic acid ameliorates cognitive deficits and attenuates oxidative stress in APP/ PS1 transgenic mice. Neurochem Res. 2021;46(4):897-908.
Nabavi SF, Braidy N, Gortzi O, Sobarzo-Sanchez E, Daglia M, Skalicka- Woźniak K, et al. Luteolin as an anti-inflammatory and neuroprotective agent: A brief review. Brain Res Bull. 2015 Oct;119(Pt A):1-11. doi: 10.1016/j.brainresbull.2015.09.002, Epub 2015 Sep 8, PMID: 26361743
Gu JX, Cheng XJ, Luo X, Yang X, Pang YP, Zhang XF, et al. Luteolin ameliorates cognitive impairments by suppressing the expression of inflammatory cytokines and enhancing synapse-associated proteins GAP-43 and SYN levels in streptozotocin-induced diabetic rats. Neurochem Res. 2018 Oct;43(10):1905-1913. doi: 10.1007/s11064- 018-2608-6, Epub 2018 Aug 7, PMID: 30088237
Porres-Martínez M, Ruiz-Navas E, Cañete-Rodríguez A, Vera F, Sanchez-Munoz L, Galindo-Cardiel I. Memory enhancing effects of Spanish sage (Salvia lavandulaefolia) essential oil: Involvement of the olfactory system. Behav Brain Res. 2016;306:212-220.
Seol GH, Kim SS, Kim E, Hong JH, Kim HS. Inhalation of 1,8-cineole increases spontaneous body temperature in mice. J Cardiovasc Pharmacol. 2019;73(5):307-312.
FDA-NIH Biomarker Working Group. BEST Biomarkers, Endpoints, and other Tools Resource. Bethesda, MD: National Institutes of Health; 2016.
Cummings J. The role of biomarkers in Alzheimer’s disease drug development. Adv Exp Med Biol. 2019;1118:29-61. doi: 10.1007/978- 3-030-05542-4-2, PMID: 30747416, PMCID: PMC6750734
Hampel H, O’Bryant SE, Durrleman S, Younesi E, Rojkova K, Escott- Price V, et al. A precision medicine initiative for Alzheimer’s disease: The road ahead to biomarker-guided integrative disease modeling. Climacteric. 2017 Apr;20(2):107-118. doi: 10.1080/13697137.2017.1287866, Epub 2017 Feb 9, PMID: 28286989
Joachim E, Reich M, Bednarski P, Schubert-Zsilavecz M, Wurglics M. Comparison of the absorption, distribution, metabolism, and excretion of carnosic acid, carnosol, and rosmarinic acid in rats. J Agricu Food Chem. 2019;67(44):12323-12334.
Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement (N Y). 2018 Sep 6;4:575-590. doi: 10.1016/j. trci.2018.06.014, PMID: 30406177, PMCID: PMC6214864
Borrás-Linares I, Pérez-Sánchez A, Lozano-Sánchez J, Barrajón- Catalán E, Arráez-Román D, Cifuentes A, et al. A bioguided identification of the active compounds that contribute to the antiproliferative/cytotoxic effects of rosemary extract on colon cancer cells. Food Chem Toxicol. 2015 Jun;80:215-222. doi: 10.1016/j. fct.2015.03.013, Epub 2015 Mar 20, PMID: 25801906
Sahu S, Chidambaram S, Tyagi R, Singh S, Sharma S. Rosmarinic acid attenuates cognitive deficits and neurodegeneration in an aluminum-induced rat model of Alzheimer’s disease. Neurotox Res. 2021;39(2):379-94
Xu B, Wang Y, Wang H, Zhang Z, Zhao X, Wang J. Luteolin rescues cognitive impairments by modulating the amyloid-β-induced oxidative stress and neuroinflammation. Behav Brain Res. 2020;383:112515.
Moss M, Cook J, Wesnes K, Duckett P. Inhalation of rosemary essential oil improves cognitive performance in healthy adults. Ther Adv Psychopharmacol. 2018;8(12):305-13.
Hasanein P, Mahtaj AK. Ameliorative effect of rosmarinic acid on scopolamine-induced memory impairment in rats. Neurosci Lett. 2015;585:23-27.doi: 10.1016/j.neulet.2014.11.027
Meng P, Tang Y, Zhang L, Li W, Zhou J. Carnosic acid attenuates memory deficits and neuronal damage in a rat model of Alzheimer’s disease. J Neurol Sci. 2018;393:79-87.
Luo C, Zou L, Sun H, Peng J, Gao C, Bao L, et al. A review of the anti-inflammatory effects of rosmarinic acid on inflammatory diseases. Front Pharmacol. 2020 Feb 28;11:153. doi: 10.3389/fphar.2020.00153, PMID: 32184728, PMCID: PMC7059186
Rezai-Zadeh K, Shytle D, Bai Y, Tian J, Hou H, Mori T, et al. Luteolin as a therapeutic option for Alzheimer’s disease. J Neuroinflammation. 2017;14(1):23.
Li Y, Zhang X, Chen Y, Wang Q, Liu Z. Quality markers of traditional Chinese medicine: Concept, progress, and perspective. Engineering. 2019;5:888-94.
Seol GH, Kang P, Lee HS, Seol GH. Antioxidant activity of linalool in patients with carpal tunnel syndrome. BMC Neurol. 2016 Feb 2;16:17. doi: 10.1186/s12883-016-0541-3, PMID: 26831333, PMCID: PMC4736622
50. Gao H, Sun S, Yang Y, Wang Z, Zhang L, Li M, et al. Promising polyphenols as neuroprotective agents: Chemical and molecular mechanism. J Agric Food Chem. 2020;68(8):2254-67.
Hussain G, Zhang L, Rasul A, Anwar H, Sohail MU, Razzaq A, et al. Role of plant-derived flavonoids and their mechanism in attenuation of Alzheimer’s and Parkinson’s diseases: An update of recent data. Molecules. 2018 Apr 2;23(4):814. doi: 10.3390/molecules23040814, PMID: 29614843, PMCID: PMC6017497
Pengelly A, Snow J, Mills SY, Scholey A, Wesnes K, Butler LR. Short-term study on the effects of rosemary on cognitive function in an elderly population. J Med Food. 2012 Jan;15(1):10-7. doi: 10.1089/ jmf.2011.0005, Epub 2011 Aug 30, PMID: 21877951
Habtemariam S. The therapeutic potential of rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer’s disease. Evid Based Complement Alternat Med. 2016;2016:2680409. doi: 10.1155/2016/2680409, Epub 2016 Jan 28, PMID: 26941822, PMCID: PMC474986754. Chooluck K, Rojsanga P, Phechkrajang C, Jaturanpinyo M. Bioanalytical method validation for determination of rosmarinic acid in simulated biological media using HPLC. Int J Appl Pharma. 2021;13(2):110-113. doi:10.22159/ijap.2021v13i2.40366
Melkani I, Kumar B, Pandey NK, Singh S, Baghel DS, Sudhakar K. Therapeutic impact of nanomedicine for the treatment of neuropathic pain: Principle, prospective and future. Int J Appl Pharma. 2024;16(5):46-58. doi:10.22159/ijap.2024v16i5.50457
Begum A, Sandhya S, Anoop Kumar N, Ali SS. Evaluation of herbal hair lotion loaded with rosemary for possible hair growth in C57BL/6 mice. Adv Biomed Res. 2023 Mar 21;12:60. doi: 10.4103/abr.abr- 306-21. PMID: 37200757, PMCID: PMC10186041
Mena P, Cirlini M, Tassotti M, Herrlinger KA, Dall’Asta C, Del Rio D. Phytochemical profiling of flavonoids, phenolic acids, terpenoids, and volatile fraction of a rosemary (Rosmarinus officinalis L.) Extract. Molecules. 2016 Nov 19;21(11):1576. doi: 10.3390/molecules21111576, PMID: 27869784, PMCID: PMC6273513
Mena P, Cirlini M, Tassotti M, Herrlinger KA, Dall’Asta C, Del Rio D. Phytochemical profiling of flavonoids, phenolic acids, terpenoids, and volatile fraction of a rosemary (Rosmarinus officinalis L.) Extract. Molecules. 2016 Nov 19;21(11):1576. doi: 10.3390/molecules21111576, PMID: 27869784, PMCID: PMC6273513
Andrade JM, Faustino C, Garcia C, Ladeiras D, Reis CP, Rijo P. Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity. Future Sci OA. 2018 Feb 1;4(4):FSO283. doi: 10.4155/fsoa-2017-0124, PMID: 29682318, PMCID: PMC5905578
Syarifah AN, Suryadi H, Mun’IM A. Validation of rosmarinic acid quantification using high-performance liquid chromatography in various plants. Pharmacogn J. 2022;14(1):165-171
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Copyright (c) 2025 Dhanush V, Sukeshan M P, Suranther Krishnamoorthi, Jeevan S, Harish N, Jeyaprakash M R
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