Sharadendu Bali¹* and Muhammad Arif Khan²

¹MS (General Surgery), PhD (Biochemistry); Professor, General Surgery, TMMC, TMU, Moradabad, UP, India
²Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara 18000, Dir (L), KPK, Pakistan

*Corresponding Author: Sharadendu Bali, MS (General Surgery), PhD (Biochemistry); Professor, General Surgery, TMMC, TMU, Moradabad, UP, India.

Received: March 26, 2025; Published: April 15, 2025

Abstract

Citrus limon (C. Limon), commonly known as lemon, represents one of the most significant crops in fruit production. Its unique tangy flavor lends itself to diverse culinary and beverage applications, including use in desserts, ice creams, beverages, and as a quintessential cooking ingredient. This review aims to synthesize the existing literature on the neuroprotective effects of phytochemicals present in lemon pickle, a traditional condiment made from Citrus limon. We extracted data from published studies that examine a wide array of phytochemicals found in lemon, including nobiletin, hesperidin, hesperetin, naringin, naringenin, rutin, heptamethoxyflavone (HMF), tangeretin (TGN), quercetin, limonene, eriodictyol, isoimperatorin (IMP), apigenin, luteolin, and vitamin C. This review focuses on in-vitro, animal, and human clinical studies exploring the impact of these phytochemicals on neurodegenerative diseases. Our findings showed that Phytochemicals found in lemon pickle demonstrate multi-targeted mechanisms that have the potential to ameliorate various aspects of neurodegenerative diseases. These include decreasing oxidative stress, anti-neuroinflammatory effects, modulation of multiple signaling pathways, and protection against neurotoxicity. In human clinical trials, consumption of citrus phytochemicals was associated with improvements in cognitive performance and other biomarkers, although the underlying mechanisms were not consistently specified. In conclusion, lemon pickle emerges as a promising dietary inclusion that offers a plethora of neuroprotective phytochemicals. Their collective intake through lemon pickle consumption could offer a simple strategy for reducing the risk of neurodegenerative diseases and improving brain health.

 Keywords: Neuroprotective; Lemon Pickle; Citrus limon; Citrus Phytochemicals; Neurodegenerative Diseases; Cognitive Function; Nimbu Achar; Neurotherapeutic Spices

References

1. Klimek-Szczykutowicz, M., et al. “Citrus limon (Lemon) Phenomenon-A Review of the Chemistry, Pharmacological Properties, Applications in the Modern Pharmaceutical, Food, and Cosmetics Industries, and Biotechnological Studies”. Plants (Basel, Switzerland)1 (2020): 119.
2. Magalhães D., et al. “Functional Ingredients and Additives from Lemon by-Products and Their Applications in Food Preservation: A Review”. Foods (Basel, Switzerland)5 (2020): 1095.
3. Klimek-Szczykutowicz M., et al. “Citrus limon (Lemon) Phenomenon-A Review of the Chemistry, Pharmacological Properties, Applications in the Modern Pharmaceutical, Food, and Cosmetics Industries, and Biotechnological Studies”. Plants (Basel, Switzerland)1 (2020): 119.
4. Makni M., et al. “Citrus limon from Tunisia: Phytochemical and Physicochemical Properties and Biological Activities”. Biomed Research International 2018 (2018): 6251546.
5. Jishan Khan., et al. “Identification of potential phytochemicals from <i>Citrus Limon</i> against main protease of SARS-CoV-2: molecular docking, molecular dynamic simulations and quantum computations”. Journal of Biomolecular Structure and Dynamics (2021).
6. Zaib S., et al. “Neurodegenerative diseases: their onset, epidemiology, causes and treatment”. Chemistry Select20 (2023): e202300225.
7. Finder VH. “Alzheimer's disease: a general introduction and pathomechanism”. Journal of Alzheimer's Diseases3 (2010): S5-S19.
8. https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years
9. Kumar A., et al. “Alzheimer Disease”. In: StatPearls. Treasure Island (FL): StatPearls Publishing (2024).
10. Jagadeesan A J., et al. “Current trends in etiology, prognosis and therapeutic aspects of Parkinson's disease: a review”. Acta bio-medica: Atenei Parmensis3 (2017): 249-262.
11. Zarei S., et al. “A comprehensive review of amyotrophic lateral sclerosis”. Surgical Neurology International 6 (2015): 171.
12. Noguchi-Shinohara M and Ono K. “The Mechanisms of the Roles of α-Synuclein, Amyloid-β, and Tau Protein in the Lewy Body Diseases: Pathogenesis, Early Detection, and Therapeutics”. International Journal of Molecular Sciences12 (2023): 10215.
13. Barmaki H., et al. “Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease”. Frontiers in Aging Neuroscience 15 (2023): 1281338.
14. Ghemrawi R and Khair M. “Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases”. International Journal of Molecular Sciences17 (2020): 6127.
15. Almikhlafi MA., et al. “Mitochondrial Medicine: A Promising Therapeutic Option Against Various Neurodegenerative Disorders”. Current Neuropharmacology5 (2023): 1165-1183.
16. Lewerenz J and Maher P. “Chronic Glutamate Toxicity in Neurodegenerative Diseases-What is the Evidence?”. Frontiers in Neuroscience 9 (2015): 469.
17. Scarian E., et al. “New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases”. International Journal of Molecular Sciences5 (2024): 2698.
18. Riaz A., et al. “Memory boosting effect of Citrus limon, Pomegranate and their combinations”. Pakistan Journal of Pharmaceutical Sciences 6 (2014): 1837-1840.
19. Falls N., et al. “Amelioration of neurodegeneration and cognitive impairment by Lemon oil in experimental model of Stressed mice”. Biomedicine and Pharmacotherapy = Biomedecine and Pharmacotherapie 106 (2018): 575-583.
20. Liu C., et al. “Extraction and isolation of acetylcholinesterase inhibitors from Citrus limon peel using an in vitro method”. Journal of Separation Science8 (2020): 1531-1543.
21. Nakajima A and Ohizumi Y. “Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer's Disease and Parkinson's Disease”. International Journal of Molecular Sciences14 (2019): 3380.
22. Lee J H., et al. “Nobiletin attenuates neurotoxic mitochondrial calcium overload through K+ influx and ΔΨm across mitochondrial inner membrane”. The Korean Journal of Physiology and Pharmacology3 (2023): 311-319.
23. Su JD., et al. “3',4'-didemethylnobiletin induces phase II detoxification gene expression and modulates PI3K/Akt signaling in PC12 cells”. Free Radical Biology and Medicine1 (2024): 126-141.
24. Lu YH., et al. “Protective effects of the citrus flavanones to PC12 cells against cytotoxicity induced by hydrogen peroxide”. Neuroscience Letters1 (2010): 6-11.
25. Leem E., et al. “Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson’s disease”. Journal of Nutritional Biochemistry 25 (2014): 801-806.
26. Emran TB., et al. “Naringin and Naringenin Polyphenols in Neurological Diseases: Understandings from a Therapeutic Viewpoint”. Life (Basel, Switzerland)1 (2022): 99.
27. Vafeiadou K., et al. “The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury”. Archives of Biochemistry and Biophysics1 (2009): 100-109.
28. Hwang S L and Yen GC. “Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells”. Journal of Agricultural and Food Chemistry3 (2008): 859-864.
29. Kim J., et al. “Benefits of hesperidin in central nervous system disorders: a review”. Anatomy and Cell Biology 4 (2019): 369-377.
30. Joshi S., et al. “Therapeutic Potential and Clinical Evidence of Hesperidin as Neuroprotective Agent”. Central Nervous System Agents in Medicinal Chemistry1 (2022): 5-14.
31. Babylon L., et al. “Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease”. Antioxidants (Basel, Switzerland)7 (2021): 1003.
32. Jo S H., et al. “Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways”. Archives of Pharmacal Research8 (2019): 695-703.
33. Vauzour D., et al. “Activation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons”. Journal of Neurochemistry4 (2021): 1355-1367.
34. Scoditti E. “Neuroinflammation and Neurodegeneration: The Promising Protective Role of the Citrus Flavanone Hesperetin”. Nutrients 12.8 (2007): 2336.
35. Evans J A., et al. “Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases”. Nutrients 11 (2022): 2228.
36. Liu W., et al. “Protective effects of apigenin against 1-methyl-4-phenylpyridinium ion induced neurotoxicity in PC12 cells. International Journal of Molecular Medicine3 (2015): 739-746.
37. Wu PS., et al. “Luteolin and Apigenin Attenuate 4-Hydroxy-2-Nonenal-Mediated Cell Death through Modulation of UPR, Nrf2-ARE and MAPK Pathways in PC12 Cells”. PloS one6 (2015): e0130599.
38. Ashrafizadeh M., et al. “Tangeretin: a mechanistic review of its pharmacological and therapeutic effects. Journal of Basic and Clinical Physiology and Pharmacology4 (2020).
39. Shu Z., et al. “Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells”. International Immunopharmacology2 (2014): 275-282.
40. Bureau G., et al. “Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation”. Journal of Neuroscience Research2 (2008): 403-410.
41. Matsuzaki K and Ohizumi Y. “Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders”. Nutrients1 (2021): 145.
42. Yu X L., et al. “Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress”. Food and function10 (2015): 3296-3306.
43. Na JY., et al. “Rutin alleviates prion peptide-induced cell death through inhibiting apoptotic pathway activation in dopaminergic neuronal cells”. Cellular and Molecular Neurobiology7 (2014): 1071-1079.
44. He P., et al. “Eriodictyol alleviates lipopolysaccharide-triggered oxidative stress and synaptic dysfunctions in BV-2 microglial cells and mouse brain”. Journal of Cellular Biochemistry 9 (2019): 14756-14770.
45. Morelli S., et al. “Neuroprotective effect of didymin on hydrogen peroxide-induced injury in the neuronal membrane system”. Cells, Tissues, Organs2-3 (2014): 184-200.
46. Nakajima A and Ohizumi Y. “Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer's Disease and Parkinson's Disease”. International Journal of Molecular Sciences14 (2019): 3380.
47. Mileykovskaya E., et al. “Nobiletin: Targeting the Circadian Network to Promote Bioenergetics and Healthy Aging”. Biokhimiia 85.12 (2020): 1554-1559.
48. Nagase H., et al. “Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities”. Biochemical and Biophysical Research Communications4 (2005): 1330-1336.
49. Kang J., et al. “Nobiletin improves emotional and novelty recognition memory but not spatial referential memory”. Journal Of Natural Medicines1 (2017): 181-189.
50. Ghasemi-Tarie R., et al. “Nobiletin prevents amyloid β1-40-induced cognitive impairment via inhibition of neuroinflammation and oxidative/nitrosative stress”. Metabolic Brain Disease5 (2022): 1337-1349.
51. Amarsanaa K., et al. “Nobiletin Exhibits Neuroprotective Effects against Mitochondrial Complex I Inhibition via Regulating Apoptotic Signaling”. Experimental Neurobiology1 (2021): 73-86.
52. Lee D., et al. “Hesperidin Improves Memory Function by Enhancing Neurogenesis in a Mouse Model of Alzheimer's Disease”. Nutrients 15 (2022): 3125.
53. Justin Thenmozhi A., et al. “Hesperidin ameliorates cognitive dysfunction, oxidative stress and apoptosis against aluminium chloride induced rat model of Alzheimer's disease”. Nutritional Neuroscience6 (2017): 360-368.
54. Cirmi S., et al. “Neurodegenerative Diseases: Might Citrus Flavonoids Play a Protective Role?”. Molecules (Basel, Switzerland)10 (2016): 1312.
55. Li C., et al. “Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice”. Behavioural Brain Research 281 (2015): 32-42.
56. Tejada S., et al. “Potential Anti-inflammatory Effects of Hesperidin from the Genus Citrus”. Current Medicinal Chemistry37 (2018): 4929-4945.
57. Kim J., et al. “Benefits of hesperidin in central nervous system disorders: a review. Anatomy and Cell Biology4 (2019): 369-377.
58. Joshi S., et al. “Therapeutic Potential and Clinical Evidence of Hesperidin as Neuroprotective Agent. Central Nervous System Agents in Medicinal Chemistry1 (2022): 5-14.
59. Scoditti E. “Neuroinflammation and Neurodegeneration: The Promising Protective Role of the Citrus Flavanone Hesperetin”. Nutrients8 (2020): 2336.
60. Evans J A., et al. “Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases”. Nutrients11 (2022): 2228.
61. Garabadu D and Agrawal N. “Naringin Exhibits Neuroprotection Against Rotenone-Induced Neurotoxicity in Experimental Rodents”. Neuromolecular Medicine22 (2020): 314-330.
62. Kim HD., et al. “Naringin treatment induces neuroprotective effects in a mouse model of Parkinson's disease in vivo, but not enough to restore the lesioned dopaminergic system”. Journal of Nutritional Biochemistry 28 (2016): 140-146.
63. Leem E., et al. “Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease”. Journal of Nutritional Biochemistry25 (2014): 801-806.
64. Zhu Q., et al. “A Dihydroflavonoid Naringin Extends the Lifespan of C elegans and Delays the Progression of Aging-Related Diseases in PD/AD Models via DAF-16”. Oxidative Medicine and Cellular Longevity (2020): 6069354-6069354.
65. Kumar A., et al. “Protective effect of naringin, a citrus flavonoid, against colchicine-induced cognitive dysfunction and oxidative damage in rats”. Journal of Medicinal Food 134 (2010): 976-984.
66. Hassan H M., et al. “Neuroprotective effect of naringin against cerebellar changes in Alzheimer's disease through modulation of autophagy, oxidative stress and tau expression: An experimental study”. Frontiers in Neuroanatomy 16 (2022): 1012422.
67. Poudineh M., et al. “Neuropharmaceutical Properties of Naringin Against Alzheimer's and Parkinson's Diseases: Naringin Protection Against AD and PD”. Galen Medical Journal 11 (2022): e2337.
68. Furukawa Y., et al. “Isolation and characterization of activators of ERK/MAPK from citrus plants”. International Journal of Molecular Sciences2 (2012): 1832-1845.
69. Matsuzaki K and Ohizumi Y. “Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders”. Nutrients1 (2021): 145.
70. Khan M B., et al. “Naringenin ameliorates Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular-streptozotocin in rat model”. Neurochemistry International7 (2012): 1081-1093.
71. Koda T., et al. “Rutin supplementation in the diet has protective effects against toxicant-induced hippocampal injury by suppression of microglial activation and pro-inflammatory cytokines: protective effect of rutin against toxicant-induced hippocampal injury”. Cellular and Molecular Neurobiology4 (2009): 523-531.
72. Suganya S N and Sumathi T. “Effect of rutin against a mitochondrial toxin, 3-nitropropionicacid induced biochemical, behavioral and histological alterations-a pilot study on Huntington's disease model in rats”. Metabolic Brain Disease2 (2017): 471-481.
73. Xu P X., et al. “Rutin improves spatial memory in Alzheimer's disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation”. Behavioural Brain Research 264 (2014): 173-180.
74. Ashrafizadeh M., et al. “Tangeretin: a mechanistic review of its pharmacological and therapeutic effects”. Journal of Basic and Clinical Physiology and Pharmacology4 (2020).
75. Matsuzaki K and Ohizumi Y. “Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders”. Nutrients1 (2021): 145.
76. Yang JS., et al. “Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease dementia in rats”. Inflammopharmacology 4 (2017): 471-484.
77. Sharma DR., et al. “Quercetin protects against aluminium induced oxidative stress and promotes mitochondrial biogenesis via activation of the PGC-1α signaling pathway”. Neurotoxicology 51 (2015): 116-137.
78. Zhang Y., et al. “Quercetin promotes neuronal and behavioral recovery by suppressing inflammatory response and apoptosis in a rat model of intracerebral hemorrhage”. Neurochemical Research1 (2015): 195-203.
79. Zhang X., et al. “Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice”. Neuropharmacology 108 (2016): 179-192.
80. Xia S F., et al. “Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress”. Physiology and Behavior 138 (2015): 325-331.
81. Lu J., et al. “Quercetin activates AMP-activated protein kinase by reducing PP2C expression protecting old mouse brain against high cholesterol-induced neurotoxicity”. The Journal of Pathology2 (2010): 199-212.
82. Sharma D R., et al. “Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus”. Neuroscience 324 (2016): 163-176.
83. Eddin LB., et al. “Neuroprotective Potential of Limonene and Limonene Containing Natural Products”. Molecules (Basel, Switzerland)15 (2021): 4535.
84. Li L., et al. “Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation”. Molecular Medicine (Cambridge, Mass)1 (2022): 11.
85. Rajendran P., et al. “Isoimperatorin therapeutic effect against aluminum induced neurotoxicity in albino mice”. Frontiers in Pharmacology 14 (2023): 1103940.
86. Liu R., et al. “The flavonoid apigenin protects brain neurovascular coupling against amyloid-β₂₅₋₃₅-induced toxicity in mice”. Journal of Alzheimer's Disease1 (2011): 85-100.
87. Liu Y., et al. “Luteolin protects against high fat diet-induced cognitive deficits in obesity mice. Behavioural Brain Research 267 (2014): 178-188.
88. Fu X., et al. “Protective role of luteolin against cognitive dysfunction induced by chronic cerebral hypoperfusion in rats”. Pharmacology, biochemistry, and behavior 126 (2014): 122-130.
89. De Nuccio F., et al. “Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson's Disease”. Biology11 (2021): 1155.
90. Hashimoto M., et al. “Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly”. Food and Function5 (2022): 2768-2781.
91. Yamada S., et al. “Beneficial effects of a nobiletin-rich formulated supplement of Sikwasa (C. depressa) peel on cognitive function in elderly Japanese subjects; A multicenter, randomized, double-blind, placebo-controlled study”. Food Science and Nutrition12 (2021): 6844-6853.
92. Seki Takashi., et al. “Nobiletin-rich <i>Citrus reticulata</i> peels, a kampo medicine for Alzheimer's disease: A case series”. Geriatrics and Gerontology International1 (2013): 236-238.
93. Neshatdoust S., et al. “High-flavonoid intake induces cognitive improvements linked to changes in serum brain-derived neurotrophic factor: Two randomised, controlled trials”. Nutrition and Healthy Aging1 (2016): 81-93.
94. Bazyar H., et al. “The effects of rutin flavonoid supplement on glycemic status, lipid profile, atherogenic index of plasma, brain-derived neurotrophic factor (BDNF some serum inflammatory, and oxidative stress factors in patients with type 2 diabetes mellitus: A double-blind, placebo-controlled trial”. Phytotherapy Research: PTR 1 (2023): 271-284.
95. Nakamura Y., et al. “Effect of quercetin glycosides on cognitive functions and cerebral blood flow: a randomized, double-blind, and placebo-controlled study”. European Review for Medical and Pharmacological Sciences23 (2022): 8700-8712.
96. Taliou A., et al. “An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders”. Clinical therapeutics5 (2013): 592-602.
97. De Luca P., et al. “Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study”. Cells16 (2022): 2552.
98. Igase M., et al. “Auraptene in the Peels of Citrus Kawachiensis (Kawachibankan) Contributes to the Preservation of Cognitive Function: A Randomized, Placebo-Controlled, Double-Blind Study in Healthy Volunteers”. The Journal of Prevention of Alzheimer's Disease3 (2018): 197-201.
99. Kean RJ., et al. “Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults”. The American Journal of Clinical Nutrition 3 (2015): 506-514.
100. Alharbi M H., et al. “Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males”. European Journal of Nutrition6 (2016): 2021-2029.
101. Lamport DJ., et al. “The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults”. The British Journal of Nutrition 12 (2016): 2160-2168.
102. Zhang S., et al. “Citrus consumption and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study”. The British Journal of Nutrition 8 (2017): 1174-1180.
103. Bruno A., et al. “Bergamot Polyphenolic Fraction Supplementation Improves Cognitive Functioning in Schizophrenia: Data From an 8-Week, Open-Label Pilot Study”. Journal of Clinical Psychopharmacology4 (2017): 468-471.
104. Park M., et al. “Flavonoid-Rich Orange Juice Intake and Altered Gut Microbiome in Young Adults with Depressive Symptom: A Randomized Controlled Study”. Nutrients6 (2020): 1815.
105. Chang SC., et al. “Dietary flavonoid intake and risk of incident depression in midlife and older women”. The American Journal of Clinical Nutrition3 (2016): 704-714.
106. Uddin M S., et al. “Exploring the Effect of Phyllanthus emblica L. on Cognitive Performance, Brain Antioxidant Markers and Acetylcholinesterase Activity in Rats: Promising Natural Gift for the Mitigation of Alzheimer's Disease”. Annals of Neurosciences4 (2016): 218-229.
107. Jang H., et al. “Phyllanthus emblica L. (Indian gooseberry) extracts protect against retinal degeneration in a mouse model of amyloid beta-induced Alzheimer’s disease”. Journal of Functional Foods 37 (2017): 330-338.
108. Biswas K., et al. “In-vitro cholinesterase inhibitory activity of dry fruit extract of Phyllanthus emblica relevant to the treatment of Alzheimer’s disease”. Journal of Phytopharmacology1 (2015): 5-8.
109. Rajalakshmi S., et al. “Neuroprotective behaviour of Phyllanthus emblica (L) on human neural cell lineage (PC12) against glutamate-induced cytotoxicity”. Gene Reports 17 (2019): 100545.
110. Chen YY., et al. “Preventive Effect of Indian Gooseberry (Phyllanthus emblica L.) Fruit Extract on Cognitive Decline in High‐Fat Diet (HFD)‐Fed Rats”. Molecular Nutrition and Food Research7 (2023): 2200791.
111. Pugazhendhi A., et al. “Assessment of antioxidant, anticholinesterase and antiamyloidogenic effect of Terminalia chebula, Terminalia arjuna and its bioactive constituent 7-methyl gallic acid-an in vitro and in silico studies”. Journal of Molecular Liquids 257 (2018): 69-81.
112. Shen YC., et al. “Neuroprotective effect of Terminalia chebula extracts and ellagic acid in pc12 cells”. African Journal of Traditional, Complementary and Alternative Medicines4 (2018): 22-30.
113. Zhao L., et al. “Protective effect of Terminalia chebula Retz. extract against Aβ aggregation and Aβ-induced toxicity in Caenorhabditis elegans”. Journal of Ethnopharmacology 268 (2021): 113640.
114. Kim MS., et al. “Terminalia chebula extract prevents scopolamine-induced amnesia via cholinergic modulation and anti-oxidative effects in mice”. BMC Complementary and Alternative Medicine 18 (2018): 1-11.
115. , et al. “Terminalia chebula Retz improve memory and learning in Alzheimer's Model: (Experimental Study in Rat)”. Research Journal of Pharmacy and Technology 11.11 (2018): 4888-4891.
116. Reddy V., et al. “Neuroprotective Activity of Methanolic extract of Terminala bellerica Fruit against Aluminium Chloride and Haloperidol Induced Amnesia in Mice”. Journal of Young Pharmacists2s (2020): 87.
117. Badoni H., et al. “Anti-parkinson's activity of Emblica officinalis and Terminalia bellirica”. Journal of Critical Reviews 17 (2020).
118. Sukma M., et al. “Neuroprotective and Anti-inflammatory Effects of Three Fruits of Triphala, Emblica officinalis, Terminalia chebula and T. belerica”. (2021).
119. Abdel-Salam OME., et al. “Protective effect of hot peppers against amyloid β peptide and brain injury in AlCl3-induced Alzheimer's disease in rats”. Iranian Journal of Basic Medical Sciences3 (2023): 335-342.
120. Wang J., et al. “Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer's disease-type pathology and cognitive deficits in APP/PS1 mice”. Translational Psychiatry1 (2020): 230.
121. Sharma H., et al. “Trachyspermum ammi Bioactives Promote Neuroprotection by Inhibiting Acetylcholinesterase, Aβ-Oligomerization/Fibrilization, and Mitigating Oxidative Stress In Vitro”. Antioxidants 1 (2023): 9.
122. Timalsina B., et al. “Thymol in Trachyspermum ammi seed extract exhibits neuroprotection, learning, and memory enhancement in scopolamine‐induced Alzheimer's disease mouse model”. Phytotherapy Research 7 (2023): 2811-2826.
123. Sharma M., et al. “Neuroprotective Potential of Trachyspermum Ammi Essential Oil Against Monosodium Glutamate Induced Excitotoxicity by Reducing Accumulation of Β-Amyloid”. Journal of Biological Regulators and Homeostatic Agents 7 (2023): 3773-3781.
124. Mokhtarzadeh Bazargani M., et al. “Evaluating the effect of trachyspermum ammi (ajwain) hydro-alcoholic extract on oxidative stress markers and cholinesterase activity n brain of male rats fed by a high cholesterol diet”. Daneshvar Medicine1 (2021): 59-69.

Citation

Citation: Sharadendu Bali and Muhammad Arif Khan. “The Neurotherapeutic Attributes of Indian Citrus Pickle: A Tangy Tradition with Neuroprotective Secrets ”.Acta Scientific Medical Sciences 9.5 (2025): 89-118.

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Copyright: © 2025 Sharadendu Bali and Muhammad Arif Khan. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.