Giza, Egypt
Giza, Egypt
Giza, Egypt
Giza, Egypt
Giza, Egypt
VAC 4.3.3 Пищевые системы
VAC 1.5.6 Биотехнология
UDK 66 Химическая технология. Химическая промышленность. Пищевая промышленность. Металлургия. Родственные отрасли
Neurodegenerative disorder leads to a progressive memory loss that has only limited known medications. The use of ashwagandha, probiotics, or their combination may improve cholinergic activity, consequently providing therapeutic potency against amnesia and neuroplasticity disorders. We aimed to explore the modulatory benefits of ashwagandha extract and probiotics against induced behavioral and neurochemical retardations. Acid curd (Karish) cheese samples were supplemented with ashwagandha extract and/or probiotics and subjected to chemical, microbiological, rheological, sensorial, and biological investigations by standard techniques. The supplementation of Karish cheese with ashwagandha never deteriorated its chemical composition or rheological parameters. On the contrary, it exerted high antioxidant and phenolic potentials. Also, ashwagandha extract performed antimicrobial action against the tested pathogenic bacteria and showed better prebiotic effects with Lactobacillus plantarum. The biological study revealed that treating dementia-modeled rats with Karish cheese supplemented with ashwagandha and/or probiotics resulted in a detectable improvement in the behavioral and neurochemical measurements. However, the cheese supplemented with a formula of ashwagandha and probiotics had the greatest regenerating effect. The supplementation of Karish cheese with ashwagandha and/or probiotics exhibited a modulatory efficiency against experimentally induced behavioral and neurochemical disorders.
Ashwagandha, Karish cheese, Lactobacillus plantarum, probiotic, therapeutic effect, dementia, rats
1. Salama HH, Kholif AMM, Fouad MT, Koç GÇ. Properties of novel ultra-filtrated soft cheese supplemented with sumac extract. Egyptian Journal of Chemistry. 2022;65(6):219–231. https://doi.org/10.21608/ejchem.2021.99475.4627
2. Al-Moghazy M, El-sayed HS, Salama HH, Nada AA. Edible packaging coating of encapsulated thyme essential oil in liposomal chitosan emulsions to improve the shelf life of Karish cheese. Food Bioscience. 2021;43. https://doi.org/10.1016/j.fbio.2021.101230
3. Saper Al Garory NH, Abdul-Abbas SJ, Al-Hashimi AG. The role of fermented dairy products in human health. Revis Bionatura. 2023;8(2). https://doi.org/10.21931/RB/CSS/2023.08.02.66
4. Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396(10248):413–446. https://doi.org/10.1016/S0140-6736(20)30367-6
5. Kim H, Osuka Y, Kojima N, Sasai H, Nakamura K, Oba C, et al. Inverse association between cheese consumption and lower cognitive function in japanese community-dwelling older adults based on a cross-sectional study. Nutrients. 2023;15(14). https://doi.org/10.3390/nu15143181
6. Ni J, Nishi SK, Babio N, Martínez‐González MA, Corella D, Castañer O, et al. Dairy product consumption and changes in cognitive performance: two‐year analysis of the PREDIMED‐plus cohort. Molecular Nutrition and Food Research. 2022;66(14). https://doi.org/10.1002/mnfr.202101058
7. McDade E, Llibre-Guerra JJ, Holtzman DM, Morris JC, Bateman RJ. The informed road map to prevention of Alzheimer disease: A call to arms. Molecular Neurodegeneration. 2021;16. https://doi.org/10.1186/s13024-021-00467-y
8. O’Donnell H. A review of primary, secondary, and tertiary prevention strategies for Alzheimer’s Disease. Undergraduate Journal of Public Health. 2023;7. https://doi.org/10.3998/ujph.3946
9. Frisoni GB, Altomare D, Ribaldi F, Villain N, Brayne C, Mukadam N, et al. Dementia prevention in memory clinics: Recommendations from the European task force for brain health services. The Lancet Regional Health – Europe. 2023;26. https://doi.org/10.1016/j.lanepe.2022.100576
10. Khalil HMA, Salama HH, Al-Mokaddem AK, Aljuaydi SH, Edris AE. Edible dairy formula fortified with coconut oil for neuroprotection against aluminium chloride-induced Alzheimer’s disease in rats. Journal of Functional Foods. 2020;75. https://doi.org/10.1016/j.jff.2020.104296
11. El-Sayed HS, Salama HH, Edris AE. Survival of Lactobacillus helveticus CNRZ32 in spray dried functional yogurt powder during processing and storage. Journal of the Saudi Society of Agricultural Sciences. 2020;19(7):461–467. https://doi.org/10.1016/j.jssas.2020.08.003
12. Mikulska P, Malinowska M, Ignacyk M, Szustowski P, Nowak J, Pesta K, et al. Ashwagandha (Withania somnifera) – Current research on the health-promoting activities: A narrative review. Pharmaceutics. 2023;15(4). https://doi.org/10.3390/pharmaceutics15041057
13. Hosny EN, El-Gizawy MM, Sawie HG, Abdel-Wahhab KG, Khadrawy YA. Neuroprotective effect of ashwagandha extract against the neurochemical changes induced in rat model of hypothyroidism. Journal of Dietary Supplements. 2021;18(1):72–91. https://doi.org/10.1080/19390211.2020.1713959
14. Polumackanycz M, Petropoulos SA, Śledziński T, Goyke E, Konopacka A, Plenis A, et al. Withania somnifera L.: Phenolic compounds composition and biological activity of commercial samples and its aqueous and hydromethanolic extracts. Antioxidants. 2023;12(3). https://doi.org/10.3390/antiox12030550
15. Verma N, Gupta SK, Tiwari S, Mishra AK. Safety of ashwagandha root extract: A randomized, placebo-controlled, study in healthy volunteers. Complementary Therapies in Medicine. 2021;57. https://doi.org/10.1016/j.ctim.2020.102642
16. Elhadidy ME, Sawie HG, Meguid NA, Khadrawy YA. Protective effect of ashwagandha (Withania somnifera) against neurotoxicity induced by aluminum chloride in rats. Asian Pacific Journal of Tropical Biomedicine. 2018;8(1):59–66. https://doi.org/10.4103/2221-1691.221139
17. Ajgaonkar A, Jain M, Debnath K. Efficacy and safety of ashwagandha (Withania somnifera) root extract for improvement of sexual health in healthy women: A prospective, randomized, placebo-controlled study. Cureus. 2022;14(10). https://doi.org/10.7759/cureus.30787
18. Marotta A, Sarno E, Del Casale A, Pane M, Mogna L, Amoruso A, et al. Effects of probiotics on cognitive reactivity, mood, and sleep quality. Frontiers in Psychiatry. 2019;10. https://doi.org/10.3389/fpsyt.2019.00164
19. Asan-Ozusaglam M, Celik I. White pitahaya as a natural additive: potential usage in cosmetic industry. Foods and Raw Materials. 2023;11(1):57–63. https://doi.org/10.21603/2308-4057-2023-1-552
20. Irokanulo EO, Yadung Q-EM, Orotayo DE, Nwonuma CO, Alonge OS. In vitro probiotic evaluation of yeasts from coconut and raffia juices. Food Processing: Techniques and Technology. 2023;53(4):672–679. https://doi.org/10.21603/2074-9414-2023-4-2467
21. Akhgarjand C, Vahabi Z, Shab-Bidar S, Etesam F, Djafarian K. Effects of probiotic supplements on cognition, anxiety, and physical activity in subjects with mild and moderate Alzheimer’s disease: A randomized, double-blind, and placebo-controlled study. Frontiers in Aging Neuroscience. 2022;14. https://doi.org/10.3389/fnagi.2022.1032494
22. Liu N, Yang D, Sun J, Li Y. Probiotic supplements are effective in people with cognitive impairment: A meta-analysis of randomized controlled trials. Nutrition Reviews. 2023;81(9):1091–1104. https://doi.org/10.1093/nutrit/nuac113
23. Huang H-J, Chen J-L, Liao J-F, Chen Y-H, Chieu M-W, Ke Y-Y, et al. Lactobacillus plantarum PS128 prevents cognitive dysfunction in Alzheimer’s disease mice by modulating propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis. BMC Complementary Medicine and Therapies. 2021;21. https://doi.org/10.1186/s12906-021-03426-8
24. Mustafa MA, Ashry M, Salama HH, Abdelhamid SM, Hassan LK, Abdel-Wahhab KG. Ameliorative role of ashwagandha/probiotics fortified yogurt against AlCl3 toxicity in rats. International Journal of Dairy Science. 2020;15(4):169–181. https://doi.org/10.3923/ijds.2020.169.181
25. Salama HH, El-Said MM, Abdelhamid SM, Abozed SS, Mounier MM. Effect of fortification with sage loaded liposome on the chemical, physical, microbiological properties and cytotoxicity of yoghurt. Egyptian Journal of Chemistry. 2020;63(10):3879–3890. https://doi.org/10.21608/EJCHEM.2020.27321.2572
26. Official methods of analysis of AOAC International. 19th ed. Gaithersburg: AOAC International; 2012.
27. Guide for the care and use of agricultural animals in research and teaching. Champaign: Federation of Animal Science Societies; 2010.
28. Tepe B, Donmez E, Unlu M, Candan F, Daferera D, Vardar-Unlu G, et al. Antimicrobial and antioxidative activities of the essential oils and methanol extracts of Salvia cryptantha (Montbret et Aucher ex Benth.) and Salvia multicaulis (Vahl). Food Chemistry. 2004;84(4):519–525. https://doi.org/10.1016/S0308-8146(03)00267-X
29. Lourens-Hattingh A, Viljoen BC. Yogurt as probiotic carrier food. International Dairy Journal. 2001;11(1–2):1–17. https://doi.org/10.1016/S0958-6946(01)00036-X
30. El-Shenawy M, Fouad MT, Hassan LK, Seleet FL, El-Aziz MA. A probiotic beverage made from tiger-nut extract and milk permeate. Pakistan Journal of Biological Sciences. 2019;22(4):180–187. https://doi.org/10.3923/pjbs.2019.180.187
31. Morgese MG, Trabace L. Monoaminergic system modulation in depression and Alzheimer’s disease: A new standpoint? Frontiers in Pharmacology. 2019;10. https://doi.org/10.3389/fphar.2019.00483
32. Chien C-Y, Chien Y-J, Lin Y-H, Lin Y-H, Chan S-T, Hu W-C, et al. Supplementation of Lactobacillus plantarum (TCI227) prevented potassium-oxonate-induced hyperuricemia in rats. Nutrients 2022;14(22). https://doi.org/10.3390/nu14224832
33. Gould TD, Dao DT, Kovacsics CE. The open field test. In: Gould TD, editor. Mood and anxiety related phenotypes in mice: Characterization using behavioral tests. Totowa: Humana Press; 2009. pP. 1–20. https://doi.org/10.1007/978-1-60761-303-9_1
34. Hliňák Z, Krejčı́ I. Oxiracetam prevents the MK-801 induced amnesia for the elevated plus-maze in mice. Behavioural Brain Research. 2000;117(1–2):147–151. https://doi.org/10.1016/S0166-4328(00)00298-9
35. Gümüş HG, Agyemang AA, Romantsik O, Sandgren R, Karlsson H, Gram M, et al. Behavioral testing and litter effects in the rabbit. Behavioural Brain Research. 2018;353:236–241. https://doi.org/10.1016/j.bbr.2018.02.032
36. Wright RL, Lightner EN, Harman JS, Meijer OC, Conrad CD. Attenuating corticosterone levels on the day of memory assessment prevents chronic stress-induced impairments in spatial memory. European Journal of Neuroscience. 2006;24(2):595–605. https://doi.org/10.1111/j.1460-9568.2006.04948.x
37. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 1961;7(2):88–90. https://doi.org/10.1016/0006-2952(61)90145-9
38. Kim C, Speisky MB, Kharouba SN. Rapid and sensitive method for measuring norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites in rat brain by high-performance liquid chromatography: Differential effect of probenecid, haloperidol and yohimbine on the concentrations. Journal of Chromatography. 1987;386:25–35. https://doi.org/10.1016/S0021-9673(01)94581-9
39. Munir N, Mahmood Z, Shahid M, Afzal MN, Jahangir M, Ali Shah SM, et al. Withania somnifera chemical constituents’ in vitro antioxidant potential and their response on spermatozoa parameters. Dose-Response. 2022;20(1). https://doi.org/10.1177/15593258221074936
40. Ali MA, Kamal MM, Rahman MH, Siddiqui MN, Haque MA, Saha KK, et al. Functional dairy products as a source of bioactive peptides and probiotics: current trends and future prospectives. Journal of Food Science and Technology. 2022;59(4):1263–1279. https://doi.org/10.1007/s13197-021-05091-8
41. Wang Y, Wu J, Lv M, Shao Z, Hungwe M, Wang J, et al. Metabolism characteristics of lactic acid bacteria and the expanding applications in food industry. Frontiers in Bioengineering and Biotechnology. 2021;9. https://doi.org/10.3389/fbioe.2021.612285
42. Balajirao KN, Akhre T, Hingane LD. Ashwagandha as antibacterial. International Journal of Innovative Research in Technology. 2021;8(7):350–355.
43. Khanchandani N, Shah P, Kalwani T, Ardeshna A, Dharajiya D. Antibacterial and antifungal activity of ashwagandha (Withania somnifera L.): A review. Journal of Drug Delivery and Therapeutics. 2019;9(5-s):154–161. https://doi.org/10.22270/jddt.v9i5-s.3573
44. Kumar A, Kumar SPJ, Chintagunta AD, Agarwal DK, Pal G, Singh AN, et al. Biocontrol potential of Pseudomonas stutzeri endophyte from Withania somnifera (ashwagandha) seed extract against pathogenic Fusarium oxysporum and Rhizoctonia solani. Archives of Phytopathology and Plant Protection. 2022;55(1):1–18. https://doi.org/10.1080/03235408.2021.1983384
45. Reddy YM, Kumar SPJ, Saritha K V, Gopal P, Reddy TM, Simal-Gandara J. Phytochemical profiling of methanolic fruit extract of Gardenia latifolia Ait. by LC-MS/MS analysis and evaluation of its antioxidant and antimicrobial activity. Plants. 2021;10(3). https://doi.org/10.3390/plants10030545
46. Turrini F, Donno D, Beccaro GL, Pittaluga A, Grilli M, Zunin P, et al. Bud-derivatives, a novel source of polyphenols and how different extraction processes affect their composition. Foods. 2020;9(10). https://doi.org/10.3390/foods9101343
47. Momin JK, Prajapati JB. Effect of selected medicinal herbs on viability and acid production of lactic dairy starters. Emergent Life Sciences Research. 2019;5(2):35–42. https://doi.org/10.31783/elsr.2019.523542
48. Peterson CT. Dysfunction of the microbiota-gut-brain axis in neurodegenerative disease: The promise of therapeutic modulation with prebiotics, medicinal herbs, probiotics, and synbiotics. Journal of Evidence-Based Integrative Medicine. 2020;25:1–19. https://doi.org/10.1177/2515690X20957225
49. Zahran HA, Mabrouk AMM, Salama HH. Evaluation of yoghurt fortified with encapsulated echium oil rich in stearidonic acid as a low-fat dairy food. Egyptian Journal of Chemistry. 2022;65(4):29–41. https://doi.org/10.21608/ejchem.2021.99859.4642
50. Mehanna NM, Elwahsh NAA, El-Deeb AM, Nasser AA. Impact of using eggshells powder as a natural source of calcium on composition and quality of bio-karish cheese. Current Science International. 2020;9(4):607–616. https://doi.org/10.36632/csi/2020.9.4.53
51. Delgado FJ, Rodríguez-Pinilla J, Márquez G, Roa I, Ramírez R. Physicochemical, proteolysis and texture changes during the storage of a mature soft cheese treated by high-pressure hydrostatic. European Food Research and Technology. 2015;240:1167–1176. https://doi.org/10.1007/s00217-015-2420-3
52. Alamdar Husain S, David J, Ibrahim M, Nayeem Ali M, Chandra D, Srivastava P. Studies on chemical properties and nutritive value of dairy dessert (sandesh) incorporated with ashwagandha (Withania somnifera) and tulsi (Ocimum sanctum). Journal of Pharma Research. 2015;4(8):281–283.
53. Carvajal MA, Alaniz AJ, Gutierrez-Gomez C, Vergara PM, Sejian V, Bozinovic F. Increasing importance of heat stress for cattle farming under future global climate scenarios. Science of The Total Environment. 2021;801. https://doi.org/10.1016/j.scitotenv.2021.149661
54. Khatoon N, Gupta RK. Probiotics beverages of sweet lime and sugarcane juices and its physiochemical, microbiological & shelf-life studies. Journal of Pharmacognosy and Phytochemistry. 2015;4(3):25–34.
55. Mirzaei-Alamouti H, Moradi S, Shahalizadeh Z, Razavian M, Amanlou H, Harkinezhad T, et al. Both monensin and plant extract alter ruminal fermentation in sheep but only monensin affects the expression of genes involved in acid-base transport of the ruminal epithelium. Animal Feed Science and Technology. 2016;219:132–143. https://doi.org/10.1016/j.anifeedsci.2016.06.009
56. Bakirci I. The effects of some herbs on the activities of thermophilic dairy cultures. Nahrung. 1999;43(5):333–335.
57. Verma KC. Ashwagandha (Withania somnifera Dunal): Wonder medicinal plant. Agricultural Reviews. 2010;31(4):292–297.
58. Callaway TR, Wright ADG, Brikis O, Edrington TS, Nisbet DJ. Evaluation of bacterial diversity in the rumen and feces of cattle. In: Nelson KE, editor. Encyclopedia of metagenomics. New York: Springer-Verlag; 2014. pp. 171–176.
59. Ruan J, Yao Y. Behavioral tests in rodent models of stroke. Brain Hemorrhages. 2020;1(4):171–184. https://doi.org/10.1016/j.hest.2020.09.001
60. Chen X, Zhang M, Ahmed M, Surapaneni KM, Veeraraghavan VP, Arulselvan P. Neuroprotective effects of ononin against the aluminium chloride-induced Alzheimer’s disease in rats. Saudi Journal of Biological Sciences. 2021;28(8):4232–4239. https://doi.org/10.1016/j.sjbs.2021.06.031
61. Reddy DS, Kulkarni SK. Possible role of nitric oxide in the nootropic and antiamnesic effects of neurosteroids on aging- and dizocilpine-induced learning impairment. Brain Research. 1998;799(2):215–229. https://doi.org/10.1016/S0006-8993(98)00419-3
62. Zhang S-Y, Chen S-Q, Zhang J-Y, Chen C-H, Xiang X-J, Cai H-R, et al. The effects of bilateral prostriata lesions on spatial learning and memory in the rat. Frontiers in Behavioral Neuroscience. 2022;16. https://doi.org/10.3389/fnbeh.2022.1010321
63. Cinalli DA, Cohen SJ, Guthrie K, Stackman RW. Object recognition memory: Distinct yet complementary roles of the mouse CA1 and perirhinal cortex. Frontiers in Molecular Neuroscience. 2020;13. https://doi.org/10.3389/fnmol.2020.527543
64. Halverson T, Alagiakrishnan K. Gut microbes in neurocognitive and mental health disorders. Annals of Medicine. 2020;52(8):423–443. https://doi.org/10.1080/07853890.2020.1808239
65. Socała K, Doboszewska U, Szopa A, Serefko A, Włodarczyk M, Zielińska A, et al. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacological Research. 2021;172. https://doi.org/10.1016/j.phrs.2021.105840
66. Mindus C, Ellis J, van Staaveren N, Harlander-Matauschek A. Lactobacillus-based probiotics reduce the adverse effects of stress in rodents: A meta-analysis. Frontiers in Behavioral Neuroscience. 2021;15. https://doi.org/10.3389/fnbeh.2021.642757
67. Xiao J, Wang T, Xu Y, Gu X, Li D, Niu K, et al. Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats. Translational Psychiatry. 2020;10. https://doi.org/10.1038/s41398-020-0719-8
68. Webberley TS, Masetti G, Bevan RJ, Kerry-Smith J, Jack AA, Michael DR, et al. The impact of probiotic supplementation on cognitive, pathological and metabolic markers in a transgenic mouse model of Alzheimer’s disease. Frontiers in Neuroscience. 2022;16. https://doi.org/10.3389/fnins.2022.843105
69. Hassan HM, Elnagar MR, Abdelrazik E, Mahdi MR, Hamza E, Elattar EM, 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. 2022;16. https://doi.org/10.3389/fnana.2022.1012422
70. Skalny AV, Aschner M, Jiang Y, Gluhcheva YG, Tizabi Y, Lobinski R, et al. Molecular mechanisms of aluminum neurotoxicity: Update on adverse effects and therapeutic strategies. Advances in Neurotoxicology. 2021;5:1–34. https://doi.org/10.1016/bs.ant.2020.12.001
71. Mold MJ, O’Farrell A, Morris B, Exley C. Aluminum and tau in neurofibrillary tangles in familial Alzheimer’s disease. Journal of Alzheimer’s Disease Reports. 2021;5(1).
72. Abbas F, Eladl MA, El-Sherbiny M, Abozied N, Nabil A, Mahmoud SM, et al. Celastrol and thymoquinone alleviate aluminum chloride-induced neurotoxicity: Behavioral psychomotor performance, neurotransmitter level, oxidative-inflammatory markers, and BDNF expression in rat brain. Biomedicine and Pharmacotherapy. 2022;151. https://doi.org/10.1016/j.biopha.2022.113072
73. Elmorsy E, Elsharkawy E, Alhumaydhi FA, Salama M. The protective effect of Indian Catechu methanolic extract against aluminum chloride-induced neurotoxicity, A rodent model of Alzheimer’s disease. Heliyon. 2021;7(2). https://doi.org/10.1016/j.heliyon.2021.e06269
74. Elshamy S, Abdel Motaal A, Abdel-Halim M, Medhat D, Handoussa H. Potential neuroprotective activity of Mentha longifolia L. in aluminum chloride-induced rat model of Alzheimer’s disease. Journal of Food Biochemistry. 2021;45(4). https://doi.org/10.1111/jfbc.13644
75. Kasem NRA, Mannaa FA, Abdel-Wahhab KG, Mourad HH, Gomaa HF. Preventive efficiency of Chelidonium majus ethanolic extract against aflatoxin B1 induced neurochemical deteriorations in rats. Pakistan Journal of Biological Sciences. 2022;25(3):234–244. https://doi.org/10.3923/pjbs.2022.234.244
76. Igbokwe IO, Igwenagu E, Igbokwe NA. Aluminium toxicosis: a review of toxic actions and effects. Interdisciplinary Toxicology. 2019;12(2):45–70. https://doi.org/10.2478/intox-2019-0007
77. Makhdoomi S, Mahboobian MM, Haddadi R, Komaki A, Mohammadi M. Silibinin-loaded nanostructured lipid carriers (NLCs) ameliorated cognitive deficits and oxidative damages in aluminum chloride-induced neurotoxicity in male mice. Toxicology. 2022;477. https://doi.org/10.1016/j.tox.2022.153260
78. Ott DB, Hartwig A, Stillman MJ. Competition between Al3+ and Fe3+ binding to human transferrin and toxicological implications: structural investigations using ultra-high resolution ESI MS and CD spectroscopy. Metallomics. 2019;11(5):968–981. https://doi.org/10.1039/C8MT00308D
79. De Nicolo B, Cataldi-Stagetti E, Diquigiovanni C, Bonora E. Calcium and reactive oxygen species signaling interplays in cardiac physiology and pathologies. Antioxidants. 2023;12(2). https://doi.org/10.3390/antiox12020353
80. Ramos-González EJ, Bitzer-Quintero OK, Ortiz G, Hernández-Cruz JJ, Ramírez-Jirano LJ. Relationship between inflammation and oxidative stress and its effect on multiple sclerosis. Neurología. 2021. https://doi.org/10.1016/j.nrl.2021.10.003
81. Antoniadou F, Papamitsou T, Kavvadas D, Kapoukranidou D, Sioga A, Papaliagkas V. Toxic environmental factors and their association with the development of dementia: A mini review on heavy metals and ambient particulate matter. Materia Socio-Medica. 2020;32(4):299–306. https://doi.org/10.5455/msm.2020.32.299-306
82. Hybertson BM, Gao B, McCord JM. Effects of the phytochemical combination PB123 on Nrf2 activation, gene expression, and the cholesterol pathway in HepG2 cells. OBM Integrative and Complimentary Medicine. 2022;7(1). https://doi.org/10.21926/obm.icm.2201002
83. Bashir A, Nabi M, Tabassum N, Afzal S, Ayoub M. An updated review on phytochemistry and molecular targets of Withania somnifera (L.) Dunal (Ashwagandha). Frontiers in Pharmacology. 2023;14. https://doi.org/10.3389/fphar.2023.1049334
84. Wongtrakul J, Thongtan T, Kumrapich B, Saisawang C, Ketterman AJ. Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model. Heliyon. 2021;7(10). https://doi.org/10.1016/j.heliyon.2021.e08172
