Author(s): Janani Priya M K, Venkateswaramurthy N

Email(s): nvmurthi@gmail.com

DOI: 10.52711/2321-5836.2026.00009   

Address: Janani Priya M K, Venkateswaramurthy N*
Department of Pharmacy Practice, J.K.K. Nattraja College of Pharmacy, Kumarapalayam - 638183, Namakkal District, Tamil Nadu, India.
*Corresponding Author

Published In:   Volume - 18,      Issue - 1,     Year - 2026


ABSTRACT:
Alzheimer’s disease (AD) is a major global health challenge, characterized by accumulation of amyloid plaques and neurofibrillary tangles. On account of this, PUFA have gained a major therapeutic strategy which plays role on Alzheimer’s disease by contributing effects as neuroprotective, anti-oxidant and anti-inflammatory properties. Among this, we review the dual effects of omega-6 fatty acid in relation to AD and performed the literature survey in databases like PubMed, google scholar and found that 30 articles were addressed the effect of omega-6 fatty acid in AD. Arachidonic Acid (ARA) and Linoleic Acid (LA) are central to the brain development and function. In that ARA contributes to the generation of pro-inflammatory mediators such as COX and LOX enzymes, which is responsible for the generation of pro-inflammatory cytokines, various in vivo and invitro studies have been reported that by inhibiting specific enzyme such as LOX and COX, the release of ARA can be stopped which prevent the generation of pro-inflammatory mediators. while, in some human studies have reported that circulating the higher ARA can produce the better cognitive outcomes and significantly reduce the dementia risk. In contrast to ARA, another acid such as LA have contributed to the anti-inflammatory properties and the reduced LA level may decrease the cognitive function and its isomer Conjugated linoleic acid (CLA) have also gained interesting therapeutic role as it has effect on the reduction of Aß accumulation and tau phosphorylation, therefore it results in the uptake of anti-inflammatory cytokines and suppresses the inflammation. The derivative of LA such as Gamma Linoleic Acid (GLA) has inhibit the NF-kB which reduce the pro-inflammatory cytokines and also the MAPK signaling protect neurons from the amyloid toxicity. The balance of omega-3/omega-6 ratio (specifically AA: DHA) have been detected for the early AD biomarker. The therapeutic conclusion states that central target is not omega-6 fatty acids themselves but the metabolic pathway, future directions will focus on the metabolic pathway and which omega-6 will produce the anti-inflammatory effect and also the randomized controlled trials to establish the causal effects.


Cite this article:
Janani Priya M K, Venkateswaramurthy N. Janani Priya M K, Venkateswaramurthy N. Research Journal of Pharmacology and Pharmacodynamics. 2026;18(1):73-0. doi: 10.52711/2321-5836.2026.00009

Cite(Electronic):
Janani Priya M K, Venkateswaramurthy N. Janani Priya M K, Venkateswaramurthy N. Research Journal of Pharmacology and Pharmacodynamics. 2026;18(1):73-0. doi: 10.52711/2321-5836.2026.00009   Available on: https://www.rjppd.org/AbstractView.aspx?PID=2026-18-1-9


REFERENCES: 
1.    World Health Organization. (2025, March 31). Dementia. WHO. https://www.who.int/news-room/fact-sheets/detail/dementia.
2.    Chávez-Castillo M. Gotera MP, Duran P. Díaz MP. Nava M. Cano C. et al. Neuroprotective Role of Omega-3 Fatty Acids: Fighting Alzheimer’s Disease. Molecules.2025;30(15):3057. https://doi.org/10.3390/molecules30153057.
3.    Stefaniak O. Dobrzyńska M. Drzymała-Czyż S. Przysławski J. Diet in the Prevention of Alzheimer’s Disease: Current Knowledge and Future Research Requirements.Nutrients.2022;14(21):4564. https://doi.org/10.3390/nu14214564.
4.    Savitha P. Saravana Kumar S.2. Effect of Omega-3 Fatty acids on Memory – Review. Research J. Pharm. and Tech.2014;7(6):715-18.
5.    Sushmita V. Patil, Vaishnavi K. Patil, Paresh A. Patil. Review on Herbal medicines of Alzheimer’s Disease. Asian J. Res. Pharm. Sci. 2020; 10(3):171-77. 10.5958/2231-5659.2020.00033.8.
6.    Rohan R. Vakhariya. Swati S. Talokar.V. R. Salunkhe, C.S. Magdum. Cognitive Disorders and its Herbal Remedies. Res. J. Pharmacognosy and Phytochem. 2017; 9(1): 42-6. 10.5958/0975-4385.2017.00007.3.
7.    Pramod Shridhar Salve. Aditya Ashok Pohankar. Steffi George. Jay Rajendra Gadge. Alzheimer’s Disease: A Study on Natural and Herbal Treatment. Research Journal of Pharmacy and Technology.2025;18(2):898-6. 10.52711/0974-360X.2025.00132.
8.    Vivek Kumar Sharma. Current Therapeutic Strategies for Alzheimer’s disease: A Lost Direction or A Hope Remains. Research J. Pharmacology and Pharmacodynamics. 2010; 2(3): 215-20.
9.    De Oliveira Otto MC. Wu JHY. Thacker EL. Lai HTM.Lemaitre RN. Padhye N. et al. Circulating Omega-3 and Omega-6 Fatty Acids, Cognitive Decline, and Dementia in Older Adults. Journal of Alzheimer’s Disease. 2023;95(3):965–79. https://doi.org/10.3233/JAD-230083.
10.    Loef M, & WH. The omega-6/omega-3 ratio and dementia or cognitive decline: a systematic review on human studies and biological evidence. J Nutr Gerontol Geriatr. 2013;32(1):1–23. https://doi.org/10.1080/21551197.2012.752335.
11.    Galeano P. de Ceglia M. Mastrogiovanni M. Campanelli L. Medina-Vera D. Campolo N. et al. The Effect of Fat Intake with Increased Omega-6-to-Omega-3 Polyunsaturated Fatty Acid Ratio in Animal Models of Early and Late Alzheimer’s Disease-like Pathogenesis. Int J Mol Sci. 2023 ;24(23):17009. https://doi.org/10.3390/ijms242317009.
12.    Abdullah, L. Evans, J. E. Emmerich, T. Crynen, G. Shackleton. Keegan A. P. Luis, C Tai, L. LaDu. M. J., Mullan, M. Crawford, F., & Bachmeier C., et.al. APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer's Disease. Aging.2017;9(3):964-85. https://doi.org/10.18632/aging.101203
13.    Ma QL. Zhu C. Morselli M. Su T. Pelligrini M. Lu Z.et al. The Novel Omega-6 Fatty Acid Docosapentaenoic Acid Positively Modulates Brain Innate Immune Response for Resolving Neuroinflammation at Early and Late Stages of Humanized APOE-Based Alzheimer’s Disease Models. Front Immunol. 2020;11(1):558036. . https://doi.org/10.3389/fimmu.2020.55803. 
14.    Fujita Y. Kano K. Kishino S. Nagao T. Shen X. Sato C. et al. Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model. Sci Rep. 2021;11(1):9749. https://doi.org/10.1038/s41598-021-88870-9.
15.    Youn K. Lee S. Jun M. Gamma-linolenic acid ameliorates Aβ-induced neuroinflammation through NF-κB and MAPK signalling pathways. J Funct Foods. 2018; 42:30–7. https://doi.org/10.1016/j.jff.2017.12.065.
16.    Kalyanam Bharathi, Flavio J D Souza, Chandana C, Vishwanath B A. Molecular Targets of Alzheimer’s Disease Treatment. Research Journal of Pharmacology and Pharmacodynamics.2025;17(2):121-0. 10.52711/2321-5836.2025.00020.
17.    Shatabdi Choudhury, Chitra Vellapandian. Alzheimer’s Disease Pathophysiology and its Implications. Research J. Pharm. and Tech. 2019; 12(4):2045-2048. 10.5958/0974-360X.2019.00338.X.
18.    Jeennor S. Cheawchanlertfa P. Suttiwattanakul S. Panchanawaporn S. Chutrakul C. Laoteng K. et.al. The codon-optimized ∆< sup>6</sup> -desaturase gene of Pythium sp. as an empowering tool for engineering n3/n6 polyunsaturated fatty acid biosynthesis. BMC Biotechnol. 2015 ;15(1):82. https://doi.org/10.1186/s12896-015-0200-6.
19.    Alarcon-Gil J. Sierra-Magro A. Morales-Garcia JA. Sanz-SanCristobal M. Alonso-Gil S. Cortes-Canteli M. et al. Neuroprotective and Anti-Inflammatory Effects of Linoleic Acid in Models of Parkinson’s Disease. The Implication of Lipid Droplets and Lipophagy. Cells. 2022 ;11(15):2297. https://doi.org/10.3390/cells11152297.
20.    Porcedda C. Manca C. Carta G. Piras F. Banni S. Sogos V.et al. Anti-neuroinflammatory effects of conjugated linoleic acid isomers, c9,t11 and t10, c12, on activated BV-2 microglial cells. Front Cell Neurosci. 2024; 18:1442786. https://doi.org/10.3389/fncel.2024.1442786.
21.    Sadybekov, A. V. Duro. M. V. Wang, S. Ebright B. Dikeman. D. Hugo. C., Yassine, H. N. et.al. Development of Potent, Selective cPLA2 Inhibitors for Targeting Neuroinflammation in Alzheimer’s Disease and Other Neurodegenerative Disorders. bioRxiv. 2025;2025–03. https://doi.org/10.3389/fncel.2024.1442786.
22.    Lin D. Gold A. Kaye S. Atkinson JR. Tol M. Sas A.et al. Arachidonic Acid Mobilization and Peroxidation Promote Microglial Dysfunction in Aβ Pathology. Journal of Neuroscience. 2024 ;44(31): https://doi.org/10.1523/JNEUROSCI.0202-24.2024.
23.    Stephenson DT. Lemere CA. Selkoe DJ. Clemens JA. Cytosolic Phospholipase A 2 (cPLA 2) Immunoreactivity Is Elevated in Alzheimer’s Disease Brain. Neurobiology of disease. 1996;3(1):51-3. https://doi.org/10.1006/nbdi.1996.0005.
24.    Chen CT. Trepanier MO. Hopperton KE. Domenichiello AF. Masoodi M. Bazinet RP. Inhibiting mitochondrial β-oxidation selectively reduces levels of nonenzymatic oxidative polyunsaturated fatty acid metabolites in the brain. Journal of Cerebral Blood Flow and Metabolism. 2014;34(3):376–9. https://doi.org/10.1038/jcbfm.2013.221.
25.    Lowry JR. Marshall N. Wenzel TJ. Murray TE. Klegeris A. The dietary fatty acids α-linolenic acid (ALA) and linoleic acid (LA) selectively inhibit microglial nitric oxide production. Molecular and Cellular Neuroscience. 2020; 109:103569. https://doi.org/10.1016/j.mcn.2020.103569.
26.    Amick KA. Mahapatra G. Gao Z. Dewitt A. Craft S. Jain M. et al. Plasma glycocholic acid and linoleic acid identified as potential mediators of mitochondrial bioenergetics in Alzheimer’s dementia. Front Aging Neurosci. 2022; 14:954090. https://doi.org/10.3389/fnagi.2022.954090.
27.    Youn K. Lee S. Jun M. Gamma-linolenic acid ameliorates Aβ-induced neuroinflammation through NF-κB and MAPK signalling pathways. J Funct Foods. 2018; 42:30–7.  https://doi.org/10.1016/j.jff.2017.12.065.  
28.    M. Vijey Aanandhi. Niventhi.A, Rujaswini.T, Hemalatha C.N, Praveen.D. A Comprehensive Review on the Role of Tau Proteins in Alzheimer’s Pathology. Research J. Pharm. and Tech 2018; 11(2):788-90. 10.5958/0974-360X.2018.00149.X.
29.    Rahul P. Pol.N. S. Naikwade, R. J. Dias. Targeting Aβ protein in Alzheimer’s Disease. Research J. Pharm. and Tech.2020; 13(2):1004-08. 10.5958/0974-360X.2020.00186.9.
30.    Dhinakaran S, Tamilanban T, Chitra V. Targets for Alzheimer’s Disease. Research J. Pharm. and Tech. 2019; 12(6):3073-77. 10.5958/0974-360X.2019.00521.3.
31.    Wang S. Li B. Solomon V. Fonteh A. Rapoport SI. Bennett DA et al. Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4. Mol Neurodegener. 2022;17(1):42. https://doi.org/10.1186/s13024-022-00549-5.
32.    Di Meco A. Lauretti E. Vagnozzi AN. Praticò D. Zileuton restores memory impairments and reverses amyloid and tau pathology in aged Alzheimer’s disease mice. Neurobiol Aging. 2014;35(11):2458–64. https://doi.org/10.1016/j.neurobiolaging.2014.05.016 
33.    Wang Y. Guan PP. Yu X. Guo YS. Zhang YJ. Wang ZY. et al. COX-2 metabolic products, the prostaglandin I 2 and F 2α, mediate the effects of TNF-α and Zn 2+ in stimulating the phosphorylation of Tau.Oncotarget.2017;8(59):99296-11. https://doi.org/10.18632/oncotarget.21853.
34.    Sanchez-Mejia RO. Newman JW. Toh S. Yu GQ. Zhou Y. Halabisky B.et al. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease. Nat Neurosci. 2008 11(11):1311–8. https://doi.org/10.1038/nn.2213
35.    Park YS, JHJ, LKH, HTR, & PYS. Prolyl endopeptidase inhibitory activity of unsaturated fatty acids. J Agric Food Chem. 2006;54(4):1238–42. https://doi.org/10.1021/jf052521h.
36.    Snowden SG. Ebshiana AA. Hye A. A Y. Pletnikova O. O’Brien R. et al. Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study. PLoS Med. 2017;14(3). https://doi.org/10.1371/journal.pmed.1002266.
37.    Esselun C. Dieter F. Sus N. Frank J. Eckert GP. Walnut Oil Reduces Aβ Levels and Increases Neurite Length in a Cellular Model of Early Alzheimer Disease. Nutrients. 2022 ;14(9):1694. https://doi.org/10.3390/nu14091694. 
38.    Al-Okbi SY. Mohammed SE. Al-Siedy ESK. Ali NA. Fish oil and primrose oil suppress the progression of alzheimer’s like disease induced by aluminum in rats. J Oleo Sci. 2020;69(7):771–82. https://doi.org/10.5650/jos.ess20015.
39.    Binyamin O. Nitzan K. Frid K. Ungar Y. Rosenmann H. Gabizon R. Brain targeting of 9c,11t-Conjugated Linoleic Acid, a natural calpain inhibitor, preserves memory and reduces Aβ and P25 accumulation in 5XFAD mice. Sci Rep. 2019;9(1).18437. https://doi.org/10.1038/s41598-019-54971-9.
40.    Khan SA. Haider A. Mahmood W. Roome T. Abbas G. Gamma-linolenic acid ameliorated glycation-induced memory impairment in rats. Pharm Biol. 2017;55(1):1817–23. https://doi.org/10.1080/13880209.2017.1331363.
41.    Fonteh AN. Cipolla M. Chiang AJ. Edminster SP. Arakaki X. Harrington MG. Polyunsaturated Fatty Acid Composition of Cerebrospinal Fluid Fractions Shows Their Contribution to Cognitive Resilience of a Pre-symptomatic Alzheimer’s Disease Cohort. Front Physiol. 2020; 11:83. https://doi.org/10.3389/fphys.2020.00083.

Recomonded Articles:

Author(s): Gautam Kumar, Ravi Kumar, Harshit Rana

DOI: 10.52711/2321-5836.2023.00007         Access: Open Access Read More

Author(s): Purnendu Panda, Banamali Das, DS Sahu, SK Meher, BK Das, MM Rao, GChD Naga Lakshmi.

DOI: 10.5958/2321-5836.2015.00011.7         Access: Open Access Read More

Author(s): Purnendu Panda, Banamali Das, DS Sahu, SK Meher, Das, GC Nanda.

DOI: Not Available         Access: Open Access Read More

Author(s): Syed Sagheer Ahmed, Chandra Prakash. K, Saba Tabassum, Noor Salma, Ahalya Devi. K H

DOI: 10.5958/2321-5836.2019.00003.X         Access: Open Access Read More

Author(s): Sudhanshu Kumar Meher, Purnendu Panda, Banmali Das, G. C. Bhuyan, Dr. K. K. Rath

DOI: 10.5958/2321-5836.2018.00023.X         Access: Open Access Read More

Author(s): T. Shekshavali, S. Roshan

DOI: 10.5958/2321-5836.2016.00031.8         Access: Open Access Read More

Author(s): VI Zalavadiya, VK Shah, DD Santani, MS Patel, JM Fosi, AK Chaudhary.

DOI: Not Available         Access: Open Access Read More

Author(s): Sachin Aglawe, Amol Gayke, Kavita Sharma, Sonali Jadhav, Sanjivani Gore, Bhagyashri Pandit, Sonali Valate, Mayuri Wagh

DOI: 10.5958/2321-5836.2020.00003.8         Access: Open Access Read More

Author(s): S. D. Kadam, S. A. Chavhan, S. A. Shinde, P. N. Sapkal

DOI: 10.5958/2321-5836.2018.00032.0         Access: Open Access Read More

Author(s): Ganesh G. Dhakad, Kaveri P. Tambe, Sangita P. Shirsat, Neha R. Jaiswal

DOI: 10.52711/2321-5836.2022.00031         Access: Open Access Read More

Author(s): Ganesh G. Dhakad, Sayali V. Ganjiwale, Shweta M. Nawghare, Abhijit V. Shrirao, N.I. Kochar, A. V. Chandewar

DOI: 10.52711/2321-5836.2023.00014         Access: Open Access Read More

Author(s): Sanjib Kumar Das, Anuradha Das, Banamali Das, Purnendu Panda, G. C. Bhuyan, Bipin Bihari Khuntia

DOI: 10.5958/2321-5836.2017.00036.2         Access: Open Access Read More

Author(s): Dipsundar Sahu, Shakti Bhushan, Debajyoti Das, Saroj Kumar Debnath, Laxmidhar Barik, Vandana Meena, Vikas Singh, Amit Kumar Dixit, PVV Prasad

DOI: 10.52711/2321-5836.2021.00015         Access: Open Access Read More

Author(s): Swapnil S. Lad, Swati U. Kolhe, Omkar A. Devade, Chetashri N. Patil, Rohit D. Nalawade, Manthan R. Rode

DOI: 10.52711/2321-5836.2023.00026         Access: Open Access Read More

Author(s): Purnendu Panda, Indu.S, Banamali Das, Krishna Rao.S, M.M. Rao

DOI: 10.52711/2321-5836.2023.00025         Access: Open Access Read More

Author(s): Upadhyay SU, Jain VC, Upadhyay UM.

DOI: 10.5958/2321-5836.2015.00021.X         Access: Open Access Read More

Author(s): S. Janet Beula, T. Rama Mohan Reddy, R. Suthakaran, K. Suneetha

DOI: 10.52711/2321-5836.2021.00013         Access: Open Access Read More

Author(s): Pallavi B. Jire, Mayuri V. Khairnar, Mayuri V. Mali, Sulbha G. Patil

DOI: 10.52711/2321-5836.2023.00024         Access: Open Access Read More

Author(s): Indranil Chanda, Smriti Rekha Chanda , Sadhan Kr Dutta.

DOI: Not Available         Access: Open Access Read More

Research Journal of Pharmacology and Pharmacodynamics (RJPPD) is an international, peer-reviewed journal....... Read more >>>

RNI: Not Available                     
DOI: 10.5958 2321-5836 

Journal Policies & Information




Recent Articles




Tags