Herbal Medicine for the Mind: Traditionally Used Medicinal Plants for Memory Loss from the Indian Subcontinent

Abstract

Memory loss is a symptom of several neurological disorders, including dementia and Alzheimer’s disease (AD). It can significantly impact individuals, their loved ones, and society as a whole. Current pharmaceutical interventions have shown some improvement in individuals’ quality of life, but more needs to be done to reduce the burden of memory loss and AD. This paper investigates herbal remedies for memory loss, with a particular focus on the mechanisms underlying their effects. By consulting several South Asian printed books, numerous traditionally used medicinal plants with memory-enhancing properties were identified. A review of published studies showed that many of these plants have reported properties related to memory enhancement and the treatment of AD. Some of the relevant mechanistic actions reported for these plants include acetylcholinesterase inhibition, anti-inflammatory activity, antioxidant effects, and neuroprotective properties. There is also evidence that some plants exhibit a combination of different mechanisms, making them especially promising as therapeutic agents for memory loss. Our review shows the existence and potential of medicinal plants in addressing memory loss. Additionally, some reports provide a scientific basis for the use of these plants in conditions characterized by memory decline, such as AD. This study underscores the importance of further research to evaluate the efficacy of traditionally used medicinal plants in the management of memory loss.

Keywords

Acetylcholinesterase / Alzheimer’s disease / Herbs / Memory / Plants / South Asia / Traditional medicines

References

[1] O’Neil-Pirozzi TM, Cappon DB, Pascual-Leone A. Adherence to cognitive and physical exercise engagement: a challenge to successful dementia risk reduction and prevention efforts. Front Dement 2023;2:1254986. doi:10.3389/frdem.2023.1254986, PMID:39081974.

[2] Fasouli ES, Katsantoni E. Age-associated myeloid malignancies - the role of STAT3 and STAT5 in myelodysplastic syndrome and acute myeloid leukemia. FEBS Lett 2024; 598(22):2809-2828. doi: 10.1002/1873-3468.14985, PMID:39048534.

[3] Ozceylan O, Sezgin-Bayindir Z. Current Overview on the Use of Nanosized Drug Delivery Systems in the Treatment of Neurodegenerative Diseases. ACS Omega 2024; 9(33):35223-35242. doi:10.1021/ acsomega.4c01774, PMID:39184484.

[4] Ibrahim N, Nadian I, Noor DR, Fadilah F. Prediction of Translational Regulation by Network Interaction in Synaptic Plasticity Induced with Centella asiatica. ScientificWorldJournal 2023; 2023:4199614. doi:10.1155/2023/4199614, PMID:37440991.

[5] Voglhuber J, Ljubojevic-Holzer S, Abdellatif M, Sedej S. Targeting Cardiovascular Risk Factors Through Dietary Adaptations and Caloric Restriction Mimetics. Front Nutr 2021;8:758058. doi:10.3389/ fnut.2021.758058, PMID:34660673.

[6] Ung CY, Correia C, Li H, Adams CM, Westendorf JJ, Zhu S. Multiorgan locked-state model of chronic diseases and systems pharmacology opportunities. Drug Discov Today 2024; 29(1):103825. doi:10.1016/j.drudis.2023.103825, PMID:37967790.

[7] Almeaqli MT, Alaidaa Y, Alnajjar FM, Al Shararh AS, Alharbi DS, Almslmani YI, et al. Therapeutic Effects of Arctiin on Alzheimer’s Disease-like Model in Rats by Reducing Oxidative Stress, Inflammasomes and Fibrosis. Curr Alzheimer Res 2024; 21(4):276-288. doi:10.2 174/0115672050333388240801043509, PMID:39136502.

[8] Knight F, Ridge D, Loveday C, Weidner W, Roeser J, Halton C, et al. A Role-Needs Framework: Rethinking Support for Informal Caregivers for Alzheimer’s Across the Global South and Global North. Int J Geriatr Psychiatry 2024; 39(9):e6141. doi:10.1002/gps.6141, PMID:39289861.

[9] Pehlivanlar E, Çakir DA, Sanajou S, Tezel Yalçin H, Baydar T, Erkekoğlu P, et al. Synthesis and characterization of new hexahydroquinoline derivatives and evaluation of their cytotoxicity, intracellular ROS production, and inhibitory effects on inflammatory mediators. Turk J Chem 2024; 48(4):659-675. doi:10.55730/1300-0527.3686, PMID:39296790.

[10] Tayarani-Najaran Z, Dehghanpour Farashah M, Emami SA, Ramazani E, Shahraki N, Hadipour E. Protective effects of betanin, a novel acetylcholinesterase inhibitor, against H(2) O(2)-induced apoptosis in PC12 cells. Mol Biol Rep 2024; 51(1):986. doi:10.1007/s11033-024- 09923-6, PMID:39283367.

[11] Hong CT, Lee HH, Chung CC, Chiu WT, Lee TY, Chen DY, et al. Poststroke Cognitive Impairment: A Longitudinal Follow-Up and Pre/Poststroke Mini-Mental State Examination Comparison. Curr Alzheimer Res 2022; 19(10):716-723. doi:10.2174/1567205019666220802151 945, PMID:35927922.

[12] Sivasinprasasn S, Tocharus J, Mahatheeranont S, Nakrat S, Tocharus C. Anthocyanin-Rich Fraction of Black Rice Bran Extract Protects against Amyloid β-Induced Oxidative Stress, Endoplasmic Reticulum Stress, and Neuronal Apoptosis in SK-N-SH Cells. Pharmaceuticals (Basel) 2024; 17(8):1039. doi:10.3390/ph17081039, PMID:39204144.

[13] Pathak C, Kabra UD. A comprehensive review of multi-target directed ligands in the treatment of Alzheimer’s disease. Bioorg Chem 2024;144:107152. doi:10.1016/j.bioorg.2024.107152, PMID:38290187.

[14] A P, Agrawal M, Ahmed H, Yadav A, Gupta U, et al. Dethe MR, Nose-tobrain drug delivery for the treatment of Alzheimer’s disease: current advancements and challenges. Expert Opin Drug Deliv 2022; 19(1):87-102. doi:10.1080/17425247.2022.2029845, PMID:35040728.

[15] Mohamed IE, Osman EE, Saeed A, Ming LC, Goh KW, Razi P, et al. Plant extracts as emerging modulators of neuroinflammation and immune receptors in Alzheimer’s pathogenesis. Heliyon 2024; 10(16):e35943. doi:10.1016/j.heliyon.2024.e35943, PMID:39229544.

[16] Ghayur MN. Traditional Chinese medicine research and education in Canada. J Altern Complement Med 2009; 15(6):689-694. doi:10.1089/acm.2008.0552, PMID:19500004.

[17] Ghayur MN, Janssen LJ. A natural way to cardiovascular health. Nat Rev Cardiol 2010; 7(3):1-2. doi:10.1038/nrcardio.2009.131-c1, PMID:20213930.

[18] Ghayur MN. Natural products breaking through. Pharmacog Mag 2006; 2(5):1-2.

[19] Azhar I, Usmanghani K. Essential Oils. Karachi: Research Institute of Indusyunic Medicine; 2002.

[20] Azhar I, Mazhar F. Spices as Medicine. Karachi: Research Institute of Indusyunic Medicine; 2003.

[21] Baqar SR. Medicinal and Poisonous Plants of Pakistan. Karachi: Printas; 1989.

[22] Gilani AH. Constipation and its treatment with natural drugs used in Pakistan. In: CapassoF,Mascolo N (eds). Natural Drugs and the Digestive Tract. Roma: EMSI; 1992:117-121.

[23] Kapoor LD. Handbook of Ayurvedic Medicinal Plants. Boca Raton: CRC Press; 1990.

[24] Memon MIA, Shahani NM. Survey and domestication of wild medicinal plants distribution in Sindh Province of Pakistan, Annual Research Report, Department of Plant Breeding and Genetics. Tandojam: Sindh Agriculture University Press; 1986.

[25] Nadkarni KM. Indian Materia Medica. Bombay: Popular Prakashan; 1976.

[26] Pakistan Forest Institute (PFI). A Note on the Plants of Medicinal Value in Pakistan. Islamabad: Printing Corporation of Pakistan Press; 1984.

[27] Rahman A, Said HM, Ahmad VU.Pakistan Encyclopedia Planta Medica Vol 1. Karachi: Hamdard Foundation Press; 1986.

[28] Said HM. Hamdard Pharmacopoeia of Eastern Medicine. 2nd ed. Karachi: Hamdard Foundation of Pakistan; 1970.

[29] Said HM. Diseases of the liver: Greco-Arab Concepts. Karachi: Hamdard Foundation Press; 1982.

[30] Said HM, Ahmad VU, Rahman A.Pakistan Encyclopedia Planta Medica Vol 2. Karachi: Hamdard Foundation Press; 1986.

[31] Said HM.Medicinal Herbal Vol 1. Karachi: Hamdard Foundation Pakistan; 1996.

[32] Shinwari ZK, Khan AA, Nakaike T. Medicinal and Other Useful Plants of District Swat Pakistan. Peshawar: Al-Aziz Communications; 2003.

[33] Usmanghani K, Saeed A, Alam MT. Indusyunic medicine. Karachi: B.C.C. & T. Press; 1997.

[34] Zaman MB, Khan MS. Hundred Drug Plants of West Pakistan/ Islamabad: Printing Corporation of Pakistan Press; 1970.

[35] Naskar R, Ghosh A, Bhattacharya R, Chakraborty S. A critical appraisal of geroprotective activities of flavonoids in terms of their bio-accessibility and polypharmacology. Neurochem Int 2024;180:105859. doi:10.1016/j.neuint.2024.105859, PMID:39265701.

[36] Zhu H, Liu J, Zhou J, Jin Y, Zhao Q, Jiang X, et al. Notopterygium incisum roots extract (NRE) alleviates neuroinflammation pathology in Alzheimer’s disease through TLR4-NF-κB pathway. J Ethnopharmacol 2024;335:118651. doi:10.1016/j.jep.2024.118651, PMID:39094757.

[37] Li XX, Yang P, Zhang YH, Song W, Wang XM, Li J. Research progress on mechanisms of ligustilide in treatment of nervous system diseases. Zhongguo Zhong Yao Za Zhi 2024; 49(9):2290-2298. doi:10.19540/j. cnki.cjcmm.20240221.601, PMID:38812129.

[38] Tan TYC, Lim XY, Norahmad NA, Chanthira Kumar H, Teh BP, Lai NM, et al. Neurological Applications of Celery (Apium graveolens): A Scoping Review. Molecules 2023; 28(15):5824. doi:10.3390/mol ecules28155824, PMID:37570794.

[39] Zhang JN, Pei ZD, Wang WY, Zhao MY, Pei WH, Zhang H, et al. Integration of High-Resolution LC-Q-TOF Mass Spectrometry and Multidimensional Chemical-Biological Analysis to Detect Nanomolar-Level Acetylcholinesterase Inhibitors from Different Parts of Zanthoxylum nitidum. J Agric Food Chem 2024; 72(31):17328-17342. doi:10.1021/acs.jafc.4c00866, PMID:39045647.

[40] Guo J, Liu S, Guo Y, Bai L, Ho CT, Bai N. Chemical characterization, multivariate analysis and comparison of biological activities of different parts of Fraxinus mandshurica. Biomed Chromatogr 2024; 38(6):e5861. doi:10.1002/bmc.5861, PMID:38501361.

[41] Rauf A, Ibrahim M, Alomar TS, AlMasoud N, Khalil AA, Khan M, et al. Hypoglycemic, anti-inflammatory, and neuroprotective potentials of crude methanolic extract from Acacia nilotica L. - results of an in vitro study. Food Sci Nutr 2024; 12(5):3483-3491. doi:10.1002/fsn3.4017, PMID:38726429.

[42] Vivekanandhan P, Alharbi SA, Ansari MJ. Toxicity, biochemical and molecular docking studies of Acacia nilotica L., essential oils against insect pests. Toxicon 2024;243:107737. doi:10.1016/j.toxicon. 2024.107737, PMID:38677379.

[43] Eldeen IM, Van Heerden FR, Van Staden J. In vitro biological activities of niloticane, a new bioactive cassane diterpene from the bark of Acacia nilotica subsp. kraussiana. J Ethnopharmacol 2010; 128(3):555-560. doi:10.1016/j.jep.2010.01.057, PMID:20138134.

[44] Cao Y, Li M, Gu L, Zhao X, Zhou A, Miao Y, et al. Chinese traditional formula Kaixin San suppressed ferroptosis of hippocampal neurons and cardiomyocytes in mice with paradoxical sleep deprivation. J Ethnopharmacol 2023;304:116034. doi:10.1016/j.jep.2022.116034, PMID:36529245.

[45] Venkatesan K. Author Correction: Anti-amnesic and anti-cholinesterase activities of α-asarone against scopolamine-induced memory impairments in rats. Eur Rev Med Pharmacol Sci 2023; 27(8):3218. doi:10.26355/eurrev_202304_32182, PMID:37140272.

[46] Esfandiari E, Ghanadian M, Rashidi B, Mokhtarian A, Vatankhah AM. The Effects of Acorus calamus L. in Preventing Memory Loss, Anxiety, and Oxidative Stress on Lipopolysaccharide-induced Neuroinflammation Rat Models. Int J Prev Med 2018;9:85. doi:10.4103/ijpvm. IJPVM_75_18, PMID:30450168.

[47] Sundaramahalingam M, Ramasundaram S, Rathinasamy SD, Natarajan RP, Somasundaram T. Role of Acorus calamus and alpha-asarone on hippocampal dependent memory in noise stress exposed rats. Pak J Biol Sci 2013; 16(16):770-778. doi:10.3923/pjbs.2013.770.778, PMID:24498829.

[48] Reddy S, Rao G, Shetty B, Hn G. Effects of Acorus calamus Rhizome Extract on the Neuromodulatory System in Restraint Stress Male Rats. Turk Neurosurg 2015; 25(3):425-431. doi:10.5137/1019-5149.JTN.11405-14.1, PMID:26037183.

[49] Oh MH, Houghton PJ, Whang WK, Cho JH. Screening of Korean herbal medicines used to improve cognitive function for anti-cholinesterase activity. Phytomedicine 2004; 11(6):544-548. doi:10.1016/j.phymed.2004.03.001, PMID:15500267.

[50] Pradeep S, Jain AS, Dharmashekara C, Prasad SK, Akshatha N, Pruthvish R, et al. Synthesis, Computational Pharmacokinetics Report, Conceptual DFT-Based Calculations and Anti-Acetylcholinesterase Activity of Hydroxyapatite Nanoparticles Derived From Acorus Calamus Plant Extract. Front Chem 2021;9:741037. doi:10.3389/ fchem.2021.741037, PMID:34692640.

[51] Mukherjee PK, Kumar V, Mal M, Houghton PJ. In vitro acetylcholinesterase inhibitory activity of the essential oil from Acorus calamus and its main constituents. Planta Med 2007; 73(3):283-285. doi: 10.1055/s-2007-967114, PMID:17286241.

[52] Malik R, Kalra S, Pooja, Singh G, Meenu, Gahlot V, et al. Antioxidative and neuroprotective potential of Acorus calamus linn. and Cordia dichotoma G. Forst. In Alzheimer’s type dementia in rodent. Brain Res 2024;1822:148616. doi:10.1016/j.brainres.2023.148616, PMID:37793605.

[53] Mikami M, Takuya O, Yoshino Y, Nakamura S, Ito K, Kojima H, et al. Acorus calamus extract and its component α-asarone attenuate murine hippocampal neuronal cell death induced by l-glutamate and tunicamycin. Biosci Biotechnol Biochem 2021; 85(3):493-501. doi:10.1093/bbb/zbaa071, PMID:33589895.

[54] Désiré GNS, Simplice FH, Guillaume CW, Kamal FZ, Parfait B, Hermann TDS, et al. Cashew (Anacardium occidentale) Extract: Possible Effects on Hypothalamic-Pituitary-Adrenal (HPA) Axis in Modulating Chronic Stress. Brain Sci 2023; 13(11):1561. doi:10.3390/brainsci13111561, PMID:38002521.

[55] Oyagbemi AA, Adebayo AK, Adebiyi OE, Adigun KO, Folarin OR, Esan OO, et al. Leaf extract of Anacardium occidentale ameliorates biomarkers of neuroinflammation, memory loss, and neurobehavioral deficit in N(ω)-nitro-L-arginine methyl ester (L-NAME) treated rats. Biomarkers 2023; 28(3):263-272. doi:10.1080/1354750X.2022.2164354, PMID:36632742.

[56] Srichomphu P, Wattanathorn J, Thukham-Mee W, Muchimapura S. Anxiety, Insomnia, and Memory Impairment in Metabolic Syndrome Rats Are Alleviated by the Novel Functional Ingredients from Anacardium occidentale. Antioxidants (Basel) 2022; 11(11):2203. doi:10.3390/antiox11112203, PMID:36358575.

[57] Bini KKN, Kobenan KC, Kouakou M, Kouadio IS, Zengin G, Jekő J, et al. Phytochemical profiling, antioxidant activities, enzymatic activities and insecticidal potential of aqueous extracts of four plants on the larvae of Helicoverpa armigera (Lepidoptera: Noctuidae), the main pest of cotton plant in Ivory Coast. Arch Insect Biochem Physiol 2023; 113(3):e22017. doi:10.1002/arch.22017, PMID:37185885.

[58] Morais SM, Silva KA, Araujo H, Vieira IG, Alves DR, Fontenelle RO, et al. Anacardic Acid Constituents from Cashew Nut Shell Liquid: NMR Characterization and the Effect of Unsaturation on Its Biological Activities. Pharmaceuticals (Basel) 2017; 10(1):31. doi:10.3390/ph10010031, PMID:28300791.

[59] Stasiuk M, Janiszewska A, Kozubek A. Phenolic lipids affect the activity and conformation of acetylcholinesterase from Electrophorus electricus (Electric eel). Nutrients 2014; 6(5):1823-1831. doi:10.3390/nu6051823, PMID:24787269.

[60] de Paula AA, Martins JB, dos Santos ML, Nascente Lde C, Romeiro LA, Areas TF, et al. New potential AChE inhibitor candidates. Eur J Med Chem 2009; 44(9):3754-3759. doi:10.1016/j.ejmech.2009.03.045, PMID:19446931.

[61] De Lima SG, Feitosa CM, Citó AM, Moita Neto JM, Lopes JA, Leite AS, et al. Effects of immature cashew nut-shell liquid (Anacardium occidentale) against oxidative damage in Saccharomyces cerevisiae and inhibition of acetylcholinesterase activity. Genet Mol Res 2008; 7(3):806-818. doi:10.4238/vol7-3gmr473, PMID:18949700.

[62] Stasiuk M, Bartosiewicz D, Kozubek A. Inhibitory effect of some natural and semisynthetic phenolic lipids upon acetylcholinesterase activity. Food Chem 2008; 108(3):996-1001. doi:10.1016/j.foodchem.2007.12.011, PMID:26065763.

[63] Faldu KG, Patel SS, Shah JS. Celastrus paniculatus oil ameliorates NFKB mediated neuroinflammation and synaptic plasticity in the scopolamine- induced cognitive impairment rat model. Metab Brain Dis 2023; 38(4):1405-1419. doi:10.1007/s11011-023-01186-7, PMID:368 09523.

[64] Arya A, Kaushik D, Almeer R, Bungau SG, Sayed AA, Abdel-Daim MM, et al. Application of Green Technologies in Design-Based Extraction of Celastrus paniculatus (Jyotishmati) Seeds, SEM, GC-MS Analysis, and Evaluation for Memory Enhancing Potential. Front Nutr 2022;9:871183. doi:10.3389/fnut.2022.871183, PMID:35662919.

[65] Malik J, Karan M, Dogra R. Ameliorating effect of Celastrus paniculatus standardized extract and its fractions on 3-nitropropionic acid induced neuronal damage in rats: possible antioxidant mechanism. Pharm Biol 2017; 55(1):980-990. doi:10.1080/13880209.2017.12859 45, PMID:28164735.

[66] Bhagya V, Christofer T, Shankaranarayana Rao BS. Neuroprotective effect of Celastrus paniculatus on chronic stress-induced cognitive impairment. Indian J Pharmacol 2016; 48(6):687-693. doi:10.4103/0253-7613.194853, PMID:28066108.

[67] Raut SB, Parekar RR, Jadhav KS, Rege NN. Marathe PA, Effect of Jyotiṣmatī seed oil on spatial and fear memory using scopolamine induced amnesia in mice. Anc Sci Life 2015; 34(3):130-133. doi:10.4103/0257-7941.157149, PMID:26120226.

[68] Bhanumathy M, Harish MS, Shivaprasad HN, Sushma G. Nootropic activity of Celastrus paniculatus seed. Pharm Biol 2010; 48(3):324-327. doi:10.3109/13880200903127391, PMID:20645820.

[69] Godkar PB, Gordon RK, Ravindran A, Doctor BP. Celastrus pan iculatus seed oil and organic extracts attenuate hydrogen peroxide- and glutamate-induced injury in embryonic rat forebrain neuronal cells. Phytomedicine 2006; 13(1-2):29-36. doi:10.1016/j.phymed.2003.11.011, PMID:16360930.

[70] Godkar PB, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus seed water soluble extracts protect against glutamate toxicity in neuronal cultures from rat forebrain. J Ethnopharmacol 2004; 93(2-3):213-219. doi:10.1016/j.jep.2004.03.051, PMID:15234755.

[71] Kumar MH, Gupta YK. Antioxidant property of Celastrus paniculatus willd.: a possible mechanism in enhancing cognition. Phytomedicine 2002; 9(4):302-311. doi:10.1078/0944-7113-00136, PMID:12120811.

[72] Gattu M, Boss KL, Terry AV Jr, Buccafusco JJ. Reversal of scopolamineinduced deficits in navigational memory performance by the seed oil of Celastrus paniculatus. Pharmacol Biochem Behav 1997;57(4):793-799. doi: 10.1016/s0091-3057(96)00391-7, PMID:9259008.

[73] Nalini K, Karanth KS, Rao A, Aroor AR. Effects of Celastrus paniculatus on passive avoidance performance and biogenic amine turnover in albino rats. J Ethnopharmacol 1995;47(2):101-108. doi: 10.1016/0378-8741(95)01264-e, PMID:7500635.

[74] Chakrabarty M, Bhat P, Kumari S, D’Souza A, Bairy KL, Chaturvedi A, et al. Cortico-hippocampal salvage in chronic aluminium induced neurodegeneration by Celastrus paniculatus seed oil: Neurobehavioural, biochemical, histological study. J Pharmacol Pharmacother 2012; 3(2):161-171. doi:10.4103/0976-500X.95520, PMID:22629092.

[75] Brinza I, Boiangiu RS, Cioanca O, Hancianu M, Dumitru G, Hritcu L, et al. Direct Evidence for Using Coriandrum sativum var. microcarpum Essential Oil to Ameliorate Scopolamine-Induced Memory Impairment and Brain Oxidative Stress in the Zebrafish Model. Antioxidants (Basel) 2023; 12(8):1534. doi:10.3390/antiox12081534, PMID:37627529.

[76] Munni YA, Dash R, Mitra S, Dash N, Shima M, Moon IS. Mechanistic study of Coriandrum sativum on neuritogenesis and synaptogenesis based on computationally guided in vitro analyses. J Ethnopharmacol 2023;306:116165. doi:10.1016/j.jep.2023.116165, PMID:36641106.

[77] Mima Y, Izumo N, Chen JR, Yang SC, Furukawa M, Watanabe Y. Effects of Coriandrum sativum Seed Extract on Aging-Induced Memory Impairment in Samp8 Mice. Nutrients 2020; 12(2):455. doi:10.3390/ nu12020455, PMID:32054079.

[78] Velaga MK, Yallapragada PR, Williams D, Rajanna S, Bettaiya R. Hydroalcoholic seed extract of Coriandrum sativum (Coriander) alleviates lead-induced oxidative stress in different regions of rat brain. Biol Trace Elem Res 2014; 159(1-3):351-363. doi:10.1007/s12011- 014-9989-4, PMID:24793421.

[79] Cioanca O, Hritcu L, Mihasan M, Hancianu M. Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloid β(1- 42) rat model of Alzheimer’s disease. Physiol Behav 2013; 120:193-202. doi:10.1016/j.physbeh.2013.08.006, PMID:23958472.

[80] Mani V, Parle M, Ramasamy K, Abdul Majeed AB. Reversal of memory deficits by Coriandrum sativum leaves in mice. J Sci Food Agric 2011; 91(1):186-192. doi:10.1002/jsfa.4171, PMID:20848667.

[81] Hajlaoui H, Arraouadi S, Noumi E, Aouadi K, Adnan M, Khan MA, et al. Antimicrobial, Antioxidant, Anti-Acetylcholinesterase, Antidiabetic, and Pharmacokinetic Properties of Carum carvi L. and Coriandrum sativum L. Essential Oils Alone and in Combination. Molecules 2021; 26(12):3625. doi:10.3390/molecules26123625, PMID:34199316.

[82] Jongwachirachai P, Ruankham W, Apiraksattayakul S, Intharakham S, Prachayasittikul V, Suwanjang W, et al. Neuroprotective Properties of Coriander-Derived Compounds on Neuronal Cell Damage under Oxidative Stress-Induced SH-SY5Y Neuroblastoma and in Silico ADMET Analysis. Neurochem Res 2024; 49(12):3308-3325. doi:10.1007/ s11064-024-04239-0, PMID:39298035.

[83] Liu QF, Jeong H, Lee JH, Hong YK, Oh Y, Kim YM, et al. Coriandrum sativum Suppresses Aβ42-Induced ROS Increases, Glial Cell Proliferation, and ERK Activation. Am J Chin Med 2016; 44(7):1325-1347. doi:10.1142/S0192415X16500749, PMID:27776428.

[84] Pavithra Mettupalayam Kaliyannan Sundaramoorthy, Kilavan Packiam K. In vitro enzyme inhibitory and cytotoxic studies with Evolvulus alsinoides (Linn.) Linn. Leaf extract: a plant from Ayurveda recognized as Dasapushpam for the management of Alzheimer’s disease and diabetes mellitus. BMC Complement Med Ther 2020; 20(1):129. doi:10.1186/s12906-020-02922-7, PMID:32345272.

[85] Sethiya NK, Nahata A, Singh PK, Mishra SH. Neuropharmacological evaluation on four traditional herbs used as nervine tonic and commonly available as Shankhpushpi in India. J Ayurveda Integr Med 2019; 10(1):25-31. doi:10.1016/j.jaim.2017.08.012, PMID:29530454.

[86] Mehla J, Pahuja M, Agarwal A, Gupta YK. Dethe SM, Amelioration of intracerebroventricular streptozotocin induced cognitive impairment by Evolvulus alsinoides in rats: in vitro and in vivo evidence. Neurochem Int 2012; 61(7):1052-1064. doi:10.1016/j.neuint.2012.07.022, PMID:22892278.

[87] Auddy B, Ferreira M, Blasina F, Lafon L, Arredondo F, Dajas F, et al. Screening of antioxidant activity of three Indian medicinal plants, traditionally used for the management of neurodegenerative diseases. J Ethnopharmacol 2003;84(2-3):131-138. doi:10.1016/s0378-8741(02)00322-7, PMID:12648805.

[88] Nithya K, Siddaraman R, Sheelajoice PP, Rajarathinam M, Chandra VB. Nootropic activity of methanolic extract from Evolvulus alsinoides Linn. in mice with scopolamine-induced amnesia. Bioinformation 2023; 19(12):1212-1216. doi:10.6026/973206300191212, PMID:38250536.

[89] Yadav MK, Singh SK, Singh M, Mishra SS, Singh AK, Tripathi JS, et al. Neuroprotective Activity of Evolvulus alsinoides & Centella asiatica Ethanolic Extracts in Scopolamine-Induced Amnesia in Swiss Albino Mice. Open Access Maced J Med Sci 2019; 7(7):1059-1066. doi:10.3889/oamjms.2019.247, PMID:31049081.

[90] Nahata A, Patil UK, Dixit VK. Effect of Evolvulus alsinoides Linn. on learning behavior and memory enhancement activity in rodents. Phytother Res 2010; 24(4):486-493. doi:10.1002/ptr.2932, PMID:19610035.

[91] Siripurapu KB, Gupta P, Bhatia G, Maurya R, Nath C, Palit G. Adaptogenic and anti-amnesic properties of Evolvulus alsinoides in rodents. Pharmacol Biochem Behav 2005; 81(3):424-432. doi:10.1016/j.pbb.2005.03.003, PMID:15899513.

[92] Gupta A, Raj H, Karchuli MS, Upmanyu N. Comparative evaluation of ethanolic extracts of Bacopa monnieri, Evolvulus alsinoides, Tinospora cordifolia and their combinations on cognitive functions in rats. Curr Aging Sci 2013; 6(3):239-243. doi:10.2174/18746098112059990036, PMID:23866011.

[93] Malik J, Karan M, Vasisht K. Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi. Pharm Biol 2011; 49(12):1234-1242. doi:10.3109/13880209.2011.584539, PMID:21846173.

[94] Shah J, Goyal R. Investigation of neuropsychopharmacological effects of a polyherbal formulation on the learning and memory process in rats. J Young Pharm 2011; 3(2):119-124. doi:10.4103/0975- 1483.80296, PMID:21731356.

[95] Baek HI, Ha KC, Park YK, Kim TY, Park SJ. Efficacy and Safety of Panax ginseng Sprout Extract in Subjective Memory Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients 2024; 16(12):1952. doi:10.3390/nu16121952, PMID:38931306.

[96] Cho YY, Park JH, Lee JH, Chung S. Ginsenosides Decrease β-Amyloid Production via Potentiating Capacitative Calcium Entry. Biomol Ther (Seoul) 2024; 32(3):301-308. doi:10.4062/biomolther.2023. 172, PMID:38586949.

[97] Afshan H, Khatoon H, Aziz A, Arefa M, Khaliq SA, Alam N. Memory and cognition enhancing effects of combination of Melissa officinalis and Panax ginseng. Pak J Pharm Sci 2023;36(5 Special):1609-1618. PMID:38008959.

[98] She L, Tang H, Zeng Y, Li L, Xiong L, Sun J, et al. Ginsenoside RK 3 promotes neurogenesis in Alzheimer’s disease through activation of the CREB/BDNF pathway. J Ethnopharmacol 2024;321:117462. doi:10.1016/j.jep.2023.117462, PMID:37981117.

[99] Wang X, Shi YJ, Niu TY, Chen TT, Li HB, Wu SH, et al. Neuroprotective effect of 20 (S) - Protopanaxadiol (PPD) attenuates NLRP3 inflammasome- mediated microglial pyroptosis in vascular dementia rats. Neurosci Lett 2023;814:137439. doi:10.1016/j.neulet.2023.137439, PMID:37579868.

[100] Murata K, Iida D, Ueno Y, Samukawa K, Ishizaka T, Kotake T, et al. Novel polyacetylene derivatives and their inhibitory activities on acetylcholinesterase obtained from Panax ginseng roots. J Nat Med 2017; 71(1):114-122. doi:10.1007/s11418-016-1036-7, PMID:27568312.

[101] Althobaiti NA, Menaa F, Dalzell JJ, Albalawi AE, Ismail H, Alghuthay mi MA, et al. Ethnomedicinal Plants with Protective Effects against Beta-Amyloid Peptide (Aβ)1-42 Indicate Therapeutic Potential in a New In Vivo Model of Alzheimer’s Disease. Antioxidants (Basel) 2022; 11(10):1865. doi:10.3390/antiox11101865, PMID:36290588.

[102] Ayoub IM, George MY, Menze ET, Mahmoud M, Botros M, Essam M, et al. Insights into the neuroprotective effects of Salvia officinalis L. and Salvia microphylla Kunth in the memory impairment rat model. Food Funct 2022; 13(4):2253-2268. doi:10.1039/d1fo02988f, PMID:35137748.

[103] Babault N, Noureddine A, Amiez N, Guillemet D, Cometti C. Acute Effects of Salvia Supplementation on Cognitive Function in Athletes During a Fatiguing Cycling Exercise: A Randomized Cross-Over, Placebo- Controlled, and Double-Blind Study. Front Nutr 2021;8:771518. doi:10.3389/fnut.2021.771518, PMID:34926550.

[104] Wightman EL, Jackson PA, Spittlehouse B, Heffernan T, Guillemet D, Kennedy DO. The Acute and Chronic Cognitive Effects of a Sage Extract: A Randomized, Placebo Controlled Study in Healthy Humans. Nutrients 2021; 13(1):218. doi:10.3390/nu13010218, PMID:33466627.

[105] Perry NSL, Menzies R, Hodgson F, Wedgewood P, Howes MR, Brooker HJ, et al. A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age. Phytomedicine 2018; 39:42-48. doi:10.1016/j.phymed.2017.08.015, PMID:29433682.

[106] Kennedy DO, Dodd FL, Robertson BC, Okello EJ, Reay JL, Scholey AB, et al. Monoterpenoid extract of sage (Salvia lavandulaefolia) with cholinesterase inhibiting properties improves cognitive performance and mood in healthy adults. J Psychopharmacol 2011; 25(8):1088-1100. doi:10.1177/0269881110385594, PMID:20937617.

[107] Scholey AB, Tildesley NT, Ballard CG, Wesnes KA, Tasker A, Perry EK, et al. An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers. Psychopharmacology (Berl) 2008; 198(1):127-139. doi:10.1007/s00213- 008-1101-3, PMID:18350281.

[108] Chiang N, Ray S, Lomax J, Goertzen S, Komarnytsky S, Ho CT, et al. Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.). Int J Mol Sci 2021; 22(14):7382. doi:10.3390/ijms22147382, PMID:34299002.

[109] Dinel AL, Lucas C, Guillemet D, Layé S, Pallet V, Joffre C. Chronic Supplementation with a Mix of Salvia officinalis and Salvia lavandulaefolia Improves Morris Water Maze Learning in Normal Adult C57Bl/6J Mice. Nutrients 2020; 12(6):1777. doi:10.3390/nu12061777, PMID:325 49250.

[110] Hasanein P, Felehgari Z, Emamjomeh A. Preventive effects of Salvia officinalis L. against learning and memory deficit induced by diabetes in rats: Possible hypoglycaemic and antioxidant mechanisms. Neurosci Lett 2016; 622:72-77. doi:10.1016/j.neulet.2016.04.045, PMID:27113201.

[111] Smach MA, Hafsa J, Charfeddine B, Dridi H, Limem K. Effects of sage extract on memory performance in mice and acetylcholinesterase activity. Ann Pharm Fr 2015; 73(4):281-288. doi:10.1016/j.pharma. 2015.03.005, PMID:25934446.

[112] Eidi M, Eidi A, Bahar M. Effects of Salvia officinalis L. (sage) leaves on memory retention and its interaction with the cholinergic system in rats. Nutrition 2006; 22(3):321-326. doi:10.1016/j.nut.2005.06.010, PMID:16500558.

[113] Leonard M, Dickerson B, Estes L, Gonzalez DE, Jenkins V, Johnson S, et al. Acute and Repeated Ashwagandha Supplementation Improves Markers of Cognitive Function and Mood. Nutrients 2024; 16(12):1813. doi:10.3390/nu16121813, PMID:38931168.

[114] Abomosallam M, Hendam BM, Abdallah AA, Refaat R, El-Hak HNG. Neuroprotective effect of Withania somnifera leaves extract nanoemulsion against penconazole-induced neurotoxicity in albino rats via modulating TGF-β1/Smad2 signaling pathway. Inflammopharmacology 2024; 32(3):1903-1928. doi:10.1007/s10787-024-01461-8, PMID:38630361.

[115] Borgonetti V, Galeotti N. L.) L.) Novel Combination of Choline with Withania somnifera ( Dunal, and Bacopa monnieri ( Wetts Reduced Oxidative Stress in Microglia Cells, Promoting Neuroprotection. Int J Mol Sci 2023; 24(18):14038. doi:10.3390/ijms241814038, PMID:37762339.

[116] Al-Dmour RH, Al-Tawarah NM, Mwafi N, Alkhataybeh BM, Khleifat KM, Tarawneh A, et al. Enhancement of hippocampal-dependent spatial memory by Ashwagandha (Withania somnifera) characterized by activation of NMDA receptors against monosodium glutamate-induced neurotoxicity in rats. Int J Neurosci 2024; 134(11):1220-1228. doi:10.1080/00207454.2023.2255372, PMID:37659008.

[117] Costa G, Serra M, Maccioni R, Casu MA, Kasture SB, Acquas E, et al. Withania somnifera influences MDMA-induced hyperthermic, cognitive, neurotoxic and neuroinflammatory effects in mice. Biomed Pharmacother 2023;161:114475. doi:10.1016/j.biopha.2023.114475, PMID: 36905810.

[118] Xing D, Yoo C, Gonzalez D, Jenkins V, Nottingham K, Dickerson B, et al. Effects of Acute Ashwagandha Ingestion on Cognitive Function. Int J Environ Res Public Health 2022; 19(19):11852. doi:10.3390/ijerph191911852, PMID:36231152.

[119] Gopukumar K, Thanawala S, Somepalli V, Rao TSS, Thamatam VB, Chauhan S. Efficacy and Safety of Ashwagandha Root Extract on Cognitive Functions in Healthy, Stressed Adults: A Randomized, Double- Blind, Placebo-Controlled Study. Evid Based Complement Alternat Med 2021; 2021:8254344. doi:10.1155/2021/8254344, PMID:348 58513.

[120] Choudhary MI, et al.Nawaz SA, ul-Haq Z, Lodhi MA, Ghayur MN, Jalil S, Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun 2005; 334(1):276-287. doi:10.1016/j.bbrc.2005.06.086, PMID:161 08094.

[121] Ghayur MN, Gilani AH, Ahmed T, Khalid A, Nawaz SA, Agbedahunsi JM, et al. Muscarinic, Ca(++) antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia. J Pharm Pharmacol 2008; 60(10):1375-1383. doi:10.1211/jpp/60.10.0014, PMID:18812031.

[122] Luciano TF, Teodoro de Souza C, de Oliveira J, Muller AP. Reversal of high-fat diet-induced cognitive impairment and oxidative stress in the brain through Zingiber officinale supplementation. Metab Brain Dis 2024; 39(8):1495-1503. doi:10.1007/s11011-024-01406-8, PMID:39120852.

[123] Yang C, Zhao M, Chen Y, Song J, Wang D, Zou M, et al. Dietary bitter ginger-derived zerumbone improved memory performance during aging through inhibition of the PERK/CHOP-dependent endoplasmic reticulum stress pathway. Food Funct 2024; 15(18):9070-9084. doi:10.1039/d4fo00402g, PMID:39078275.

[124] Wang J, Akbari A, Chardahcherik M, Wu J. Ginger (Zingiber Officinale Roscoe) ameliorates ethanol-induced cognitive impairment by modulating NMDA and GABA-A receptors in rat hippocampus. Metab Brain Dis 2024; 39(1):67-76. doi:10.1007/s11011-023-01301-8, PMID:37966694.

[125] da Rosa N, de Medeiros FD, de Oliveira J, Laurentino AOM, Peretti EM, Machado RS, et al. 6-Shogaol improves behavior and memory in Wistar rats prenatally exposed to lipopolysaccharide. Int J Dev Neurosci 2022; 82(1):39-49. doi:10.1002/jdn.10157, PMID:34755374.

[126] Marefati N, Abdi T, Beheshti F, Vafaee F, Mahmoudabady M, Hosseini M. Zingiber officinale (Ginger) hydroalcoholic extract improved avoidance memory in rat model of streptozotocin-induced diabetes by regulating brain oxidative stress. Horm Mol Biol Clin Investig 2021; 43(1):15-26. doi:10.1515/hmbci-2021-0033, PMID:34679261.

[127] Zhao X, Hu Q, Wang X, Li C, Chen X, Zhao D, et al. Dual-target inhibitors based on acetylcholinesterase: Novel agents for Alzheimer’s disease. Eur J Med Chem 2024;279:116810. doi:10.1016/j.ejmech.2024.116810, PMID:39243456.

[128] Jaqua EE, Tran MN, Hanna M. Alzheimer Disease: Treatment of Cognitive and Functional Symptoms. Am Fam Physician 2024; 110(3):281-293. PMID:39283851.

[129] Rafe MR, Saha P, Bello ST. Targeting NMDA receptors with an antagonist is a promising therapeutic strategy for treating neurological disorders. Behav Brain Res 2024;472:115173. doi:10.1016/j. bbr.2024.115173, PMID:39097148.

[130] Thakral S, Yadav A, Singh V, Kumar M, Kumar P, Narang R, et al. Alzheimer’s disease: Molecular aspects and treatment opportunities using herbal drugs. Ageing Res Rev 2023;88:101960. doi:10.1016/j. arr.2023.101960, PMID:37224884.

[131] Daraban BS, Popa AS, Stan MS. Latest Perspectives on Alzheimer’s Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant- Based Drug Delivery Systems. Molecules 2024; 29(17):4056. doi:10.3390/molecules29174056, PMID:39274904.

[132] Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest 2017; 127(10):3577-3587. doi:10.1172/JCI90609, PMID:28872464.

[133] Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol 2021; 17(3):157-172. doi:10.1038/s41582-020-00435-y, PMID:333 18676.

[134] Tofighi N, Asle-Rousta M, Rahnema M, Amini R. Protective effect of alpha-linoleic acid on Aβ-induced oxidative stress, neuroinflammation, and memory impairment by alteration of α7 nAChR and NMDAR gene expression in the hippocampus of rats. Neurotoxicology 2021; 85:245-253. doi:10.1016/j.neuro.2021.06.002, PMID:34111468.

[135] Miller VM, Lawrence DA, Mondal TK, Seegal RF. Reduced glutathione is highly expressed in white matter and neurons in the unperturbed mouse brain—implications for oxidative stress associated with neurodegeneration. Brain Res 2009; 1276:22-30. doi:10.1016/j.brainres.2009.04.029, PMID:19393633.

[136] Locke A. Using the Values of Integrative Medicine to Create the Future of Healthcare. Glob Adv Integr Med Health 2024; 13:27536130241253607. doi:10.1177/27536130241253607, PMID: 38751850.