Alzheimer’s Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms

Abduljawad, Asaad A.; Elawad, Mohammed Ahmed; Elkhalifa, Modawy Elnour Modawy; Ahmed, Alshebli; Hamdoon, Alashary Adam Eisa; Salim, Liga Hasan Mohammed; Ashraf, Muhammad; Ayaz, Muhammad; Hassan, Syed Shams ul; Bungau, Simona

doi:10.3390/molecules27206804

Cited by 63Medicinal Plants and NeuroprotectionAlzheimer's disease research and treatmentsNatural product bioactivities and synthesis

Alzheimer’s Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms

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Abduljawad, Asaad A., Elawad, Mohammed Ahmed, Elkhalifa, Modawy Elnour Modawy, Ahmed, Alshebli, Hamdoon, Alashary Adam Eisa, Salim, Liga Hasan Mohammed, Ashraf, Muhammad, Ayaz, Muhammad +2 more·2022·Molecules

DOI 10.3390/molecules27206804PMC PMC9608803

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Abstract

Saponins are triterpenoid or steroidal glycosides and are an important group of naturally occurring compounds of plant origin. They exhibit diverse pharmacological potentials including radical scavenging, as well as neuroprotective, anti-diabetic and anti-inflammatory activities, owing to their diverse chemical scaffolds. Saponins consist of an aglycone part (non-sugar) and a glycone part (sugar) and have at least one glycosidic (C–O sugar bond) linkage present between the glycone and aglycone mostly at C-3. On the basis of the aglycone part, saponins are classified into triterpenoid glycosides, steroid glycosides and alkaloid glycosides. Saponins exhibit neuroprotective activities against various disorders of the central nervous system (CNS) including stroke, Alzheimer’s disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD). They mediate their therapeutic effects by modulation of various pathological targets. This study highlights various neuroprotective mechanisms of saponins including free radical scavenging, modulation of neuroprotective signaling pathways, activation of neurotrophic factors, modulation of neurotransmitters, inhibition of BACE1 enzyme and tau hyper-phosphorylation. The study concludes that saponins have considerable efficacy against various pathological targets of neurological disorders, especially AD, and might be an important source of leads against neurodegenerative disorders.

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The blood-brain barrier (BBB) is an important impediment to the development of AD medications because it prevents potential drug candidates from entering the brain parenchyma.
“An important impediment to the development of AD medications is the blood–brain barrier (BBB), which prevents potential drug candidates from entering the brain parenchyma.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [194]
The indicated BBB penetration values are inconsistent with the physicochemical characteristics of monoclonal antibodies (solanezumab, aducanumab, bapineuzumab) or gamma-secretase inhibitors (semagacestat, tarenflurbil).
“The indicated BBB penetration values are inconsistent with the physicochemical characteristics of monoclonal antibodies (solanezumab, aducanumab, bapineuzumab) or gamma-secretase inhibitors (semagacestat, tarenflurbil) [193,194,195].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [194]
Candidates for BBB penetration are characterized by molecular weight less than 450 Daltons, polar surface area less than 90 Å2, and hydrogen bond donor number less than 3.
“A molecular weight less than 450 Daltons, a polar surface area less than 90 Å2, and a hydrogen bond donor number less than 3 are characteristics of candidates for BBB penetration.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [194]
For a medicine to penetrate the BBB, its physicochemical properties-polar surface area, molecular weight, and lipophilicity as assessed by hydrogen bonding ability-are essential.
“For a medicine to penetrate the blood–brain barrier, its physicochemical properties—such as its polar surface area, molecular weight, and lipophilicity as assessed by hydrogen bonding ability—are essential.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [194]
The BBB is impermeable to 98% of small molecules and around 100% of large molecules in relevant quantities.
“The BBB is impermeable to 98% of small molecules and around 100% of large molecules in relevant quantities.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [194]

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Asiaticoside: Attenuation of neurotoxicity induced by MPTP in a rat model of Parkinsonism via maintaining redox balance and up-regulating the ratio of Bcl-2/Bax
Xu, C.-L., Wang, Q.-Z., Sun, L.-M., Li, X.-M., Deng, J.-M., Li, L.-F., Zhang, J., Xu, R., & Ma, S.-P. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.09.014 · Cited by 85 · cited 1× · see citing works
“ginseng Ginsenoside Rc HD Ca2+ signaling pathway [124]”
Background
EXPRESSION OF CONCERN: Ginsenosides protect striatal neurons in a cellular model of Huntington's disease
Wu, J., Jeong, H. K., Bulin, S. E., Kwon, S. W., Park, J. H., & Борисович, Б. И. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22017 · Cited by 85 · cited 1× · see citing works
“ginseng Ginsenoside Rb3 Neurite growth Antioxidant, GABA receptor, neurite outgrowth enhancing [123]”
Background
Neuroprotective effects of madecassoside in early stage of Parkinson's disease induced by MPTP in rats
Xu, C.-L., Qu, R., Zhang, J., Li, L.-F., & Ma, S.-P. (2013) · Fitoterapia · doi:10.1016/j.fitote.2013.07.009 · Cited by 84 · cited 1× · see citing works
“Hence it attenuates the MPTP-elevated levels of iron, reduces the expression of DMT1 and increases the expression of FP1 in the SN [102].”
Background
Two decades of new drug discovery and development for Alzheimer's disease
Liu, Z., Zhang, A., Sun, H. J., Han, Y., Kong, L. D., & Wang, X. (2017) · RSC Advances · doi:10.1039/c6ra26737h · Cited by 83 · cited 1× · see citing works
“The symptoms of AD are not confined to the loss of memory and cognition, but it also associated with some noncognitive characteristics such as depression, inability to perform routine daily activities and behavioral disturbances [3,4].”
Background
Four-kilobase sequence of the mouse CNP gene directs spatial and temporal expression of lacZ in transgenic mice
Gravel, M., Polo, A. D., Valera, P. B., & Braun, P. E. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19980815)53:4 · Cited by 82 · see citing works
Lawsonia Inermis Markedly Improves Cognitive Functions in Animal Models and Modulate Oxidative Stress Markers in the Brain
Mir, N. T., Saleem, U., Anwar, F., Ahmad, B., Ullah, I., Hira, S., Ismail, T., Ali, T., & Ayaz, M. (2019) · Medicina · doi:10.3390/medicina55050192 · Cited by 82 · cited 1× · see citing works
“These neurotransmitters have a significant role in mood and memory, and include serotonin, acetylcholine, norepinephrine and glutamate; all of these are implicated in the pathology of AD [34].”
BackgroundSelf-citation
Modifiable Risk Factors for Alzheimer Disease and Related Dementias Among Adults Aged ≥45 Years — United States, 2019
Omura, J. D., McGuire, L. C., Patel, R., Baumgart, M., Lamb, R., Jeffers, E. M., Olivari, B. S., Croft, J. B., Thomas, C. W., & Hacker, K. A. (2022) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm7120a2 · Cited by 82 · cited 1× · see citing works
“The prevalence of AD is found to be higher among women as compared to men [17].”
Background
Protective effect of panaxatriol saponins extracted from Panax notoginseng against MPTP-induced neurotoxicity in vivo
Luo, F., Wang, S., Qi, L., Song, J., Lv, T., & Bai, J. (2010) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2010.10.017 · Cited by 81 · cited 2× · see citing works
“9 Dipsacus asper Akebia saponin D AD mitogen-activated protein kinase (MAPK) anti- apoptosis [99]”
Background
MgFe‐LDH Nanoparticles: A Promising Leukemia Inhibitory Factor Replacement for Self‐Renewal and Pluripotency Maintenance in Cultured Mouse Embryonic Stem Cells
He, X., Zhu, Y., Yang, L., Wang, Z., Wang, Z., Feng, J., Wen, X., Cheng, L., & Zhu, R. (2021) · Advanced Science · doi:10.1002/advs.202003535 · Cited by 81 · cited 1× · see citing works
“The tubers of Dioscorea villosa (wild yam) have saponin dioscin in abundance, which upon hydrolysis, gives diosgenin, a steroidal aglycone, which is used as a precursor for steroid synthesis, including pregnenolone, progesterone and cortisone commercially [87,88].”
Background
Rg1 reduces nigral iron levels of MPTP-treated C57BL6 mice by regulating certain iron transport proteins
Wang, J., Xu, H., Yang, H., Du, X., Jiang, H. F., & Xie, J. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2008.10.003 · Cited by 79 · cited 1× · see citing works
“Ginsenoside Re helps in the dopaminergic neuron protection from MPTP-induced apoptosis via the expression of Bcl mRNA, elevating Bcl-2 protein (an apoptotic protein) levels, lowering the Bax protein (a pro-apoptotic protein) levels, the expression of Bax mRNA and inhibiting the activation of caspase-3 in the PD mouse…”
Background
Cell Cycle Events in Neurons
Zhu, X., Raina, A. K., & Smith, M. A. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65127-9 · Cited by 77 · cited 1× · see citing works
“This oxidation process in neurons causes various problems including non-recoverable DNA damage and upregulation of pro-inflammatory cytokines [37,38].”
Background
Protective Effects of Ginsenoside Rd on PC12 Cells against Hydrogen Peroxide
Ye, R., Han, J., Kong, X., Zhao, L., Cao, R. Y., Rao, Z., & Zhao, G. (2008) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.31.1923 · Cited by 77 · see citing works
Sarsasapogenin: A steroidal saponin from Asparagus racemosus as multi target directed ligand in Alzheimer’s disease
Kashyap, P., Kalaivani, M., Niranjan, M., Trikha, S., & Kumar, S. (2019) · Steroids · doi:10.1016/j.steroids.2019.108529 · Cited by 77 · see citing works
A Perspective on Inflammation in Alzheimer's Disease
Rogers, J., & Shen, Y. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb05571.x · Cited by 74 · cited 1× · see citing works
“The hypothesis is supported by epidemiological evidences, whereby it was observed that patients using anti-inflammatory agents for the management of chronic inflammatory diseases such as arthritis have a lower prevalence of AD [41].”
Result
Neurite outgrowth induced by spicatoside A, a steroidal saponin, via the tyrosine kinase A receptor pathway
Hur, J., Lee, P., Moon, E., Kang, I., Kim, S., Oh, M. S., & Kim, S. Y. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.08.016 · Cited by 74 · cited 4× · see citing works
“Ginsenosides enhance the antioxidant potentials as well as upregulate the neuronal plasticity-associated proteins such as BDNF, p-CREB, PSD-95, phospho-calcium–calmodulin-dependent kinase II, phosphor-N-methyl-D-aspartate receptor 1, phosphor-PKA catalytic β subunit and PKCγ subunit in the hippocampus regions, which m…”
BackgroundInfluential
Intrinsic Regulation of Brain Inflammatory Responses
Galea, E., Heneka, M. T., Russo, C. D., & Feinstein, D. L. (2003) · Cellular and Molecular Neurobiology · doi:10.1023/a:1025084415833 · Cited by 74 · cited 1× · see citing works
“Though the role of APOE gene polymorphisms, especially in APOEe4 carriers, is suggested to be involved, its exact mechanism remains unclear [51,52].”
Background
Role of microglia in plaque formation in senile dementia of the Alzheimer type
Rozemüller, A. J. M., Eikelenboom, P., & Stam, F. C. (1986) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02899034 · Cited by 72 · cited 1× · see citing works
“During the early stages of AD, the role of oxidative stress is very crucial, since it is linked temporally to the development of NFTs and amyloid plaques [39].”
Background
Protective effects of ginsenoside Rd against okadaic acid-induced neurotoxicity in vivo and in vitro
Li, L., Liu, J., Yan, X., Qin, K., Shi, M., Tian, L., Zhu, Y., Kang, T., & Zhao, G. (2011) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2011.08.068 · Cited by 70 · cited 1× · see citing works
“immunoreactivity, as well as the expression of proenkephalin genes induced by methamphetamine in mouse striatum [130].”
Background
Impact of behavioral and psychological symptoms of Alzheimer’s disease on caregiver outcomes
Pinyopornpanish, K., Soontornpun, A., Wongpakaran, T., Wongpakaran, N., Tanprawate, S., Pinyopornpanish, K., Nadsasarn, A., & Pinyopornpanish, M. (2022) · Scientific Reports · doi:10.1038/s41598-022-18470-8 · Cited by 70 · cited 1× · see citing works
“It is observed that the rate of health service utilization among AD patients is very high and patients go through more falls and accidents as compared to age-matched controls [5,6].”
Background
Ginsenoside Rg1 protects neurons from hypoxic–ischemic injury possibly by inhibiting Ca2+ influx through NMDA receptors and L-type voltage-dependent Ca2+ channels
Zhang, Y., Fan, X., Li, X., Peng, L., Wang, G., Ke, K., & Jiang, Z. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.12.037 · Cited by 67 · cited 1× · see citing works
“ginseng Ginsenoside Rg2 Stroke Anti-apoptosis [115,116]”
Tumour necrosis factor-α gene polymorphisms and Alzheimer's disease
Culpan, D., MacGowan, S. H., Ford, J. M., Nicoll, J. A. R., Griffin, W. S. T., Dewar, D., Cairns, N. J., Hughes, A., Kehoe, P. G., & Wilcock, G. K. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00854-1 · Cited by 67 · cited 1× · see citing works
“For instance, the presence of polymorphic genes encoding IL-1 and TNFα were reported to cause excessive activation of microglia among AD patients [49,50].”
Background
Pharmacological treatment of Alzheimer’s Disease
Bianchetti, A., Ranieri, P., Margiotta, A., & Trabucchi, M. (2006) · Aging Clinical and Experimental Research · doi:10.1007/bf03327433 · Cited by 66 · see citing works
In vitro cholinesterase enzymes inhibitory potential and in silico molecular docking studies of biogenic metal oxides nanoparticles
Khalil, A. T., Ayaz, M., Ovais, M., Wadood, A., Ali, M., Shinwari, Z. K., & Mâaza, M. (2018) · Inorganic and Nano-Metal Chemistry · doi:10.1080/24701556.2019.1569686 · Cited by 66 · cited 1× · see citing works
“Only four antiAD agents are clinically approved, which include galanthamine (Reminyls®), donepezil (Aricept®), tacrine (Cognex®) and rivastigmine (Exelon®) [55,56].”
BackgroundSelf-citation
Akebia saponin D, a saponin component from Dipsacus asper Wall, protects PC 12 cells against amyloid‐β induced cytotoxicity
Zhou, Y., Yang, Z., Xu, L., Li, P., & Hu, Y. (2009) · Cell Biology International · doi:10.1016/j.cellbi.2009.06.028 · Cited by 65 · cited 2× · see citing works
“For instance, the presence of polymorphic genes encoding IL-1 and TNFα were reported to cause excessive activation of microglia among AD patients [49,50].”
Background
Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties
Hassan, S. S. U., Muhammad, I., Abbas, S. Q., Hassan, M., Majid, M., Jin, H., & BUNGAU, S. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111432 · Cited by 65 · see citing works
Self-citation
Brain Atrophy in Normal Ageing and Alzheimer's Disease
Förstl, H., Zerfaß, R., Geiger-Kabisch, C., Sattel, H. C., Besthorn, C., & Hentschel, F. (1995) · The British Journal of Psychiatry · doi:10.1192/bjp.167.6.739 · Cited by 64 · cited 4× · see citing works
“In the entorhinal cortex, which links the hippocampus (involved in the formation of memory) with the cerebral cortex, the AD symptoms start initially [19].”
BackgroundInfluential
Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N‐methyl‐ D ‐aspartate receptors composed of an NR1/NR2B subunit assembly
Gu, B., Nakamichi, N., Zhang, W., Nakamura, Y., Kambe, Y., Fukumori, R., Takuma, K., Yamada, K., Takarada, T., Taniura, H., et al. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22021 · Cited by 63 · see citing works
Dammarane-Type Saponins from Panax japonicus and Their Neurite Outgrowth Activity in SK-N-SH Cells
Zou, K., Zhu, S., Meselhy, M. R., Tohda, C., Cai, S., & Komatsu, K. (2002) · Journal of Natural Products · doi:10.1021/np0201117 · Cited by 61 · see citing works
The Economic Cost of Alzheimer's Disease and Related Dementias to the California Medicaid Program (“Medi-Cal”) in 1995
Menzin, J., Lang, K., Friedman, M., Neumann, P. G., & Cummings, J. L. (1999) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-199911000-00005 · Cited by 60 · see citing works
Possible mechanisms of the protection of ginsenoside Re against MPTP-induced apoptosis in substantia nigra neurons of Parkinson's disease mouse model
Xu, B., Liu, C., Gao, X., Zhang, W., Wang, S., & Cao, Y.-L. (2004) · Journal of Asian Natural Products Research · doi:10.1080/10286020410001690172 · Cited by 58 · cited 1× · see citing works
“MPTP is commonly used for the development of PD in experimental models, via suppressing the over-expression of cyclooxygenase-2, enhancing the tyrosine hydroxylase and suppressing mitochondria-mediated apoptosis [100].”
Method
Localization of mRNAs for trkB isoforms and p75 in rat retinal ganglion cells
SUZUKI, D. A., Nomura, S., Morii, E., Fukuda, Y., & Kosaka, J. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19981001)54:1 · Cited by 57 · see citing works
Induction of NGF synthesis in astrocytes by onjisaponins of Polygala tenuifolia, constituents of Kampo (Japanese herbal) medicine, Ninjin-Yoei-To
Yabe, T., Tuchida, H., Kiyohara, H., Takeda, T., & Yamada, H. (2003) · Phytomedicine · doi:10.1078/094471103321659799 · Cited by 56 · see citing works
20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons
Lee, E.-Y., Kim, S., Chung, K. C., Choo, M., Kim, D., Nam, G., & Rhim, H. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.02.038 · Cited by 55 · see citing works
Aerosol Delivery of Curcumin Reduced Amyloid-β Deposition and Improved Cognitive Performance in a Transgenic Model of Alzheimer’s Disease
McClure, R., Ong, H., Janve, V., Barton, S., Zhu, M., Li, B., Dawes, M., Jerome, W. G., Anderson, A., Massion, P., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160289 · Cited by 54 · see citing works
Neuroprotective potential of Malva neglecta is mediated via down-regulation of cholinesterase and modulation of oxidative stress markers
Saleem, U., Akhtar, R., Anwar, F., Shah, M. A., Chaudary, Z., Ayaz, M., & Ahmad, B. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00683-x · Cited by 53 · cited 1× · see citing works
“As this is a permanent reaction, when the reactive species are attached to certain biological molecules, this alters them both structurally and functionally [35,36] and causes genetic mutations.”
BackgroundSelf-citation
Comparative Study of Korean White, Red, and Black Ginseng Extract on Cholinesterase Inhibitory Activity and Cholinergic Function
Lee, M.-R., Yun, B.-S., In, O.-H., & Sung, C. K. (2011) · Journal of Ginseng Research · doi:10.5142/jgr.2011.35.4.421 · Cited by 50 · cited 2× · see citing works
“23 Platycodon grandiflorum Platycodin D Stroke NF-κB, COX-2 [121]”
Background
Contributions and Challenges of Public Health Social Work Practice during the Initial 2020 COVID-19 Outbreak in China
He, L., Mu, L., Jean, J. A., Zhang, L., Wu, H., Zhou, T. J., & Bu, H. (2022) · The British Journal of Social Work · doi:10.1093/bjsw/bcac077 · Cited by 49 · see citing works
Protective effect of ginsenoside Rb1 onβ-amyloid protein(1-42)-induced neurotoxicity in cortical neurons
Qian, Y., Han, H., Hu, X., & Shi, L.-L. (2009) · Neurological Research · doi:10.1179/174313209x385572 · Cited by 47 · see citing works
Neuroprotective Studies on Polygonum hydropiper L. Essential Oils Using Transgenic Animal Models
Tong, X., Li, X., Ayaz, M., Ullah, F., Sadiq, A., Ovais, M., Shahid, M. M., Khayrullin, M., & Ali, H. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.580069 · Cited by 44 · cited 1× · see citing works
“Excessive amount of free radicals readily attack various biological molecules, including neurons, and also cause mutations [25].”
BackgroundSelf-citation
Platycodin D and 2″-o-acetyl-polygalacin D2 isolated from Platycodon grandiflorum protect ischemia/reperfusion injury in the gerbil hippocampus
Choi, J. H., Yoo, K., Park, O. K., Lee, C. H., Won, M., Hwang, I. K., Ryu, S. Y., Kim, Y. S., Yi, J., Bae, Y., et al. (2009) · Brain Research · doi:10.1016/j.brainres.2009.05.005 · Cited by 43 · see citing works
Enhancing Therapeutic Efficacy of Donepezil by Combined Therapy: A Comprehensive Review
Rong, X., Jiang, L., Qu, M., Hassan, S. S. U., & Liu, Z. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666201023144836 · Cited by 43 · cited 2× · see citing works
“As this longer β1–42 rapidly forms the amyloid fibrils as compared to Aβ1–40, shifting of the cleavage site may cause the deposition of amyloid without enhancing the overall quantity of produced Aβ [29].”
BackgroundSelf-citation
Akebia saponin D attenuates ibotenic acid-induced cognitive deficits and pro-apoptotic response in rats: Involvement of MAPK signal pathway
Yu, X., Wang, L., Ma, L., You, R., Cui, R., Ji, D., Wu, Y., Zhang, C., Yang, Z., & Ji, H. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.02.014 · Cited by 42 · cited 4× · see citing works
“In the cultured cortical neurons, ginsenoside Rb1 attenuates Aβ-induced toxicity in a dose-dependent manner [98].”
BackgroundInfluential
Progress with Treatments for Alzheimer’s Disease
Levey, A. I. (2021) · New England Journal of Medicine · doi:10.1056/nejme2103722 · Cited by 41 · cited 1× · see citing works
“Alzheimer’s disease (AD) is a highly prevalent neurological disorder of old age and associated with behavioral and cognitive complications [1,2].”
Background
A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer's disease
Hayes, A. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.030866 · Cited by 38 · cited 1× · see citing works
“The inflammatory hypothesis in AD also suggests that polymorphisms in the genes regulating the inflammatory process cause sporadic AD [48].”
Background
Saponins and flavonoids from Bacopa floribunda plant extract exhibit antioxidant and anti-inflammatory effects on amyloid beta 1-42-induced Alzheimer's disease in BALB/c mice
Oyeleke, M. B., & Owoyele, B. V. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.114997 · Cited by 38 · cited 5× · see citing works
“8 Astragalus membranaceus Astragaloside IV PD, Stroke Antioxidant, tumor interleukin-1β (IL-1β), necrosis factor α (TNFα), Nuclear factor kappa B (NF-κB), Ca2+ influx, regeneration of the neural network [74]”
BackgroundInfluential
SAPONINS*
Hostettmann, K., & Marston, A. (2005) · Elsevier eBooks · doi:10.1016/b0-12-369397-7/00548-3 · Cited by 37 · see citing works
Photoclick Reaction Constructs Glutathione-Responsive Theranostic System for Anti-Tuberculosis
Zheng, J., Long, X., Chen, H., Ji, Z., Shu, B., Yue, R., Liao, Y., Ma, S., Qiao, K., Liu, Y., et al. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.845179 · Cited by 34 · cited 1× · see citing works
“The total saponin content of Dipsacus asper has also been reported to offer protection against Aβ-induced neuronal toxicity [97].”
Background
Natural Products for Chronic Diseases: A Ray of Hope
Hassan, S. S. U., Abdel‐Daim, M. M., Behl, T., & BUNGAU, S. G. (2022) · Molecules · doi:10.3390/molecules27175573 · Cited by 32 · cited 1× · see citing works
“Initially, the presence of immune system cells and antigens around the Aβ aggregates and tau proteins in AD patients brain signals the involvement of inflammatory process in the pathogenesis of AD [40].”
BackgroundSelf-citation
Kalopanaxsaponins A and B Isolated from Kalopanax pictus Ameliorate Memory Deficits in Mice
Joh, E., Lee, I., & Kim, D. (2011) · Phytotherapy Research · doi:10.1002/ptr.3596 · Cited by 30 · cited 1× · see citing works
“5 Polygala tenuifolia Onjisaponin F AD Nerve growth factor (NGF), Choline Acetyltransferase (ChAT) [108]”
Background
Protective effects of xanthoceraside on learning and memory impairment induced by Aβ25–35in mice
Chi, T., Wang, L.-H., Qu, C., Yang, B.-Z., Ji, X., Wáng, Y., Okuyama, T., Okada, Y., & Zou, L. (2009) · Journal of Asian Natural Products Research · doi:10.1080/10286020903337832 · Cited by 30 · see citing works
Gypenoside TN-2 ameliorates scopolamine-induced learning deficit in mice
Hong, S.-W., Yang, J.-H., Joh, E., Kim, H. J., & Kim, D. (2011) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2011.02.002 · Cited by 28 · cited 1× · see citing works
“Madecassosides have been reported to exhibit neuroprotective activity in MPTP-induced Parkinsonism models and could retrieve the DA (dopamine) depletion and enhance the Bcl-2/Bax ratio and BDNF protein expression [103].”
Background
Steroidal glycoalkaloid content of potato, tomato and their somatic hybrids
Roddick, J. G., & Melchers, G. (1985) · Theoretical and Applied Genetics · doi:10.1007/bf00252292 · Cited by 28 · cited 1× · see citing works
“The tubers of Dioscorea villosa (wild yam) have saponin dioscin in abundance, which upon hydrolysis, gives diosgenin, a steroidal aglycone, which is used as a precursor for steroid synthesis, including pregnenolone, progesterone and cortisone commercially [87,88].”
Background
Unravelling the potential neuroprotective facets of erythropoietin for the treatment of Alzheimer’s disease
Kaur, D., Behl, T., Sehgal, A., Singh, S., Sharma, N., Badavath, V. N., Hassan, S. S. U., Hasan, M. M., Bhatia, S., Al-Harassi, A., et al. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00820-6 · Cited by 28 · cited 1× · see citing works
“The positions of these mutations proposed that it may contribute to the development of AD by changing the processing of βAPP in such a manner which is amyloidogenic [29,30].”
BackgroundSelf-citation
Ginsenosides attenuate kainic acid-induced synaptosomal oxidative stress via stimulation of adenosine A2A receptors in rat hippocampus
Shin, E., Koh, Y. H., Kim, A., Nah, S.-Y., JEONG, J., CHAE, J., KIM, S., YEN, T., Yoon, H., & KIM, W. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.08.038 · Cited by 26 · see citing works
Cognition-Enhancing and Neuroprotective Effects of Hederacolchiside-E from Pulsatilla koreana
Han, C.-K., Choi, W. W., & Oh, K.-B. (2007) · Planta Medica · doi:10.1055/s-2007-981530 · Cited by 25 · cited 1× · see citing works
“These results shows that ginseng, as well as the purified ginsenosides, might show similar useful effects [95].”
Background
Neuroprotective Effects of Green Tea Seed Isolated Saponin Due to the Amelioration of Tauopathy and Alleviation of Neuroinflammation: A Therapeutic Approach to Alzheimer’s Disease
Khan, M. I., Khan, M. Z., Shin, J. H., Shin, T. S., Lee, Y. B., Kim, M. Y., & Kim, J. D. (2022) · Molecules · doi:10.3390/molecules27072079 · Cited by 22 · cited 4× · see citing works
“The saponin inhibited amyloid beta (Aβ42) fibrillization up to 68% at a 40 μM concentration [76].”
BackgroundMethodInfluential
Rosmarinus officinalis and Methylphenidate Exposure Improves Cognition and Depression and Regulates Anxiety-Like Behavior in AlCl3-Induced Mouse Model of Alzheimer’s Disease
Malik, N., Amber, S., & Zahid, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.943163 · Cited by 22 · cited 2× · see citing works
“The thread of a neuropil consists of small-sized curly and dystrophic neurites that are scattered in neuropils and holding some abnormal filaments [31,32].”
Background
Ginsenosides attenuate methamphetamine-induced behavioral side effects in mice via activation of adenosine A2A receptors: possible involvements of the striatal reduction in AP-1 DNA binding activity and proenkephalin gene expression
Shin, E., Nabeshima, T., Suh, H., Jhoo, W., Oh, K., Lim, Y. K., Kim, D. S., Choi, K. H., & Kim, H. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.08.018 · Cited by 21 · see citing works
Challenges in Alzheimer’s Disease Drug Discovery and Development: The Role of Modeling, Simulation, and Open Data
Conrado, D. J., Duvvuri, S., Geerts, H., Burton, J., Biesdorf, C., Ahamadi, M., Macha, S., Hather, G., Francisco Morales, J., Podichetty, J., et al. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1782 · Cited by 21 · see citing works
Phytochemicals-based Therapeutics against Alzheimer's Disease: An Update
Ayaz, M., Nawaz, A., Naz, F., Ullah, F., Sadiq, A., & Islam, Z. U. (2022) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026622666220815104305 · Cited by 21 · cited 3× · see citing works
“Currently available AD agents are associated with severe side effects and have limited efficacy [5].”
BackgroundSelf-citation
The effects of the total saponin of Dipsacus asperoides on the damage of cultured neurons induced by beta-amyloid protein 25-35
Qian, Y., Liu, Y. U., Hu, H., Ren, H.-M., Chen, X., & Xu, J. (2002) · Anatomical Science International · doi:10.1046/j.0022-7722.2002.00029.x · Cited by 20 · cited 1× · see citing works
“Hederacolchiside-E, which is an oleanolic glycoside when given orally at 30 and 60 mg kg−1 doses, shows an increase in the step-through latency time as efficiently as tacrine given at a 30 mg kg−1 oral dose using the passive avoidance paradigm [96].”
Method
Investigation of Natural Compounds for Therapeutic Potential in Streptozotocin-induced Diabetic Neuroinflammation and Neuropathic Pain
Faheem, M., Khan, A., Shah, F. A., & Li, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1019033 · Cited by 20 · see citing works
Bioactive Complex Triterpenoid Saponins from the Leguminosae Family
Parente, J. P., & da Silva, B. P. (2009) · Natural Product Communications · doi:10.1177/1934578x0900400131 · Cited by 11 · cited 1× · see citing works
“Various plant families synthesize and store saponins [78,80,81].”
Background
Editorial: Current Trends in Medicinal Plant Research and Neurodegenerative Disorders
Ayaz, M., Ali, T., Sadiq, A., Ullah, F., & Naseer, M. I. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.922373 · Cited by 10 · see citing works
Self-citation
Understanding the genetic, molecular, and cellular basis of ageing as the biggest risk factor of Alzheimer's disease
Yadav, M., Pandey, P., & Sharma, P. (2022) · European Journal of Biological Research · doi:10.5281/zenodo.6323798 · Cited by 3 · see citing works
Current Trends in Medicinal Plant Research and Neurodegenerative Disorders
(2022) · Frontiers research topics · doi:10.3389/978-2-88976-633-8 · Cited by 2 · see citing works
Untitled work
Cann, S. A. H., Netten, J. P. V., & Netten, C. V. (2000) · Pure Amsterdam UMC · doi:10.1002/1531-8249(200003)47:3

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[85]Hostettmann K. Marston A. Saponins Cambridge University Press Cambridge, UK 2005
[91]Hostettmann K. Marston A. Chemistry and Pharmacology of Natural Products Cambridge University Press Cambridge, UK 1995 Volume 548

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Green Synthesis of Silver Nanoparticles from Allium cepa L. Peel Extract, Their Antioxidant, Antipathogenic, and Anticholinesterase Activity
Baran, M. F., Keskin, C., Baran, A., Hatipoğlu, A., Yıldıztekin, M., Küçükaydın, S., Kurt, K., Hoşgören, H., Sarker, M. M. R., Sufianov, A. A., et al. (2023) · Molecules · doi:10.3390/molecules28052310 · Cited by 153 · see citing works
“Numerous research has been carried out demonstrating the potential of plant-based synthetic metallic nanoparticles as anticholinesterase drugs [17].”
Background
Antiaging effects of dietary supplements and natural products
Gao, L., Liu, X., Luo, X., Lou, X., Li, P., Li, X., & Liu, X. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1192714 · Cited by 60 · see citing works
“Rb1, Rb2, Rc, and Rd have more glycosyl groups on C-3 and C-20 than rare ginsenosides, including F2, Rg3, Rh2, and C-K (Hou et al., 2021; Abduljawad et al., 2022).”
Background
Effect of nutrition in Alzheimer’s disease: A systematic review
Lou, I. X., Ali, K., & Chen, Q. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1147177 · Cited by 58 · see citing works
“Following a healthy dietary pattern, a high intake of plant-based foods, probiotics, nuts, and omega-3 polyunsaturated fatty acids and a low intake of saturated fats, animal-based proteins, and refined sugars can decrease the risk of neurocognitive impairment (Pistollato et al., 2018; Abduljawad et al., 2022).”
Background
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56 · see citing works
Applications of Extracellular Vesicles in Nervous System Disorders: An Overview of Recent Advances
Khan, S. U., Khan, M. I., Khan, M. U., Khan, N. M., BUNGAU, S. G., & Hassan, S. S. U. (2022) · Bioengineering · doi:10.3390/bioengineering10010051 · Cited by 33 · see citing works
Self-citation
Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?
Ailioaie, L. M., Ailioaie, C., & Litscher, G. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15030916 · Cited by 37 · see citing works
A mechanistic review of pharmacological activities of homeopathic medicine licorice against neural diseases
Zulfugarova, P., Zivari‐Ghader, T., Maharramova, S., Ahmadian, E., Eftekhari, A., Khalilov, R. I., Türksoy, V. A., Rosic, G. L., & Selaković, D. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1148258 · Cited by 30 · see citing works
Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune–Neuroinflammation Mechanism
Weaver, D. F. (2023) · Brain Sciences · doi:10.3390/brainsci14010041 · Cited by 31 · see citing works
“The Mediterranean diet, the related MIND diet (which incorporates constituents designed to lower blood pressure) and other healthful dietary regimens are associated with cognitive benefits in studies and a decreased probability of AD [53–56].”
Therapeutic Candidates for Alzheimer’s Disease: Saponins
Zhang, R., Zeng, M., Zhang, X., Zheng, Y., Lv, N., Wang, L., Gan, J., Li, Y., Jiang, X., & Yang, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310505 · Cited by 28 · see citing works
“Sapo ins possess multiple bio ctivities, such as re uction of amyloid beta (Aβ) deposition [22], inhibition of tau pr tein pho phoryl tion [23], antioxidation [24], antiapoptosis [25], and anti-i flammati n [26].”
Background
Polyphenol-enriched Desmodium elegans DC. ameliorate scopolamine-induced amnesia in animal model of Alzheimer’s disease: In Vitro, In Vivo and In Silico approaches
Mahnashi, M. H., Ashraf, M., Alhasaniah, A. H., Ullah, H., Zeb, A., Ghufran, M., Fahad, S., Ayaz, M., & Daglia, M. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115144 · Cited by 25 · see citing works
Self-citation
In silico molecular docking and dynamic simulation of anti-cholinesterase compounds from the extract of Catunaregam spinosa for possible treatment of Alzheimer's disease
Thandivel, S., Poovarasan, R., Tamizharasan, G., Abisek, A., Khute, S., Kareti, S. R., & Subash, P. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27880 · Cited by 24 · see citing works
“AD is a neurodegenerative disorder affecting memory, thinking, and behaviour, causing language difficulties, disorientation, mood changes, and personality changes in individuals [1].”
Background
From Molecules to Medicines: The Role of AI-Driven Drug Discovery Against Alzheimer’s Disease and Other Neurological Disorders
Alghamdi, M. A. (2025) · Pharmaceuticals · doi:10.3390/ph18071041 · Cited by 22 · see citing works
“AD is a degenerative disease of the nervous system among the elderly population, which drastically affects patients’ thinking, memory, and behavior [44].”
Exploring the Potential Therapeutic Approach Using Ginsenosides for the Management of Neurodegenerative Disorders
Manju, & Bharadvaja, N. (2023) · Molecular Biotechnology · doi:10.1007/s12033-023-00783-2 · Cited by 17 · see citing works
“Indian ginseng or ashwa-gandha India, the middle east, and some parts of Africa Rh1, Rg3 Used in Ayurvedic medicine to improve vitality, reduce stress and boost the immune system [20] the brain [23].”
Quantitative-HPLC-DAD polyphenols analysis, anxiolytic and cognition enhancing potentials of Sorbaria tomentosa Lindl. Rehder
Mahnashi, M. H., Ayaz, M., Alqahtani, Y. S., Alyami, B. A., Shahid, M. M., Alqahtani, O. S., Kabrah, S. M., Zeb, A., Ullah, F., & Sadiq, A. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116786 · Cited by 17 · see citing works
Self-citation
Phytochemical regulation of CaMKII in Alzheimer’s disease: A review of molecular mechanisms and therapeutic potential
Lin, Z., & Sun, M. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107790 · Cited by 14 · see citing works
Different Effects of Cyclical Ketogenic vs. Nutritionally Balanced Reduction Diet on Serum Concentrations of Myokines in Healthy Young Males Undergoing Combined Resistance/Aerobic Training
Kysel, P., Haluzíková, D., Pleyerová, I., Řezníčková, K., Laňková, I., Lacinová, Z., Havrlantová, T., Mráz, M., Kasperová, B. J., Kovarova, V., et al. (2023) · Nutrients · doi:10.3390/nu15071720 · Cited by 14 · see citing works
Mapping new pharmacological interventions for cognitive function in Alzheimer’s disease: a systematic review of randomized clinical trials
Lou, I. X., Chen, J., Ali, K., Shaikh, A. L., & Chen, Q. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1190604 · Cited by 13 · see citing works
“Various nutrients and nutraceuticals have been linked to improvements in cognition and other psychological aspects related to AD (Guzman-Martinez et al., 2021; Abduljawad et al., 2022; Mahnashi et al., 2022; Xu Lou et al., 2023) Some examples include Gingko Biloba (Liao et al.”
Background
Synthesis and Characterization of Amoxicillin‐Functionalized Ag/ AgCl Nanoparticles: A Promising Multifunctional Platform for Next‐Generation Nanomedicine
Laouini, S. E., Bouafia, A., Azzi, M., Laib, I., Fellah, M., Abdullah, M. M. S., Al‐Lohedan, H. A., & Abdullah, J. A. A. (2025) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.35661 · Cited by 12 · see citing works
Phytochemical analysis, radical scavenging and glioblastoma U87 cells toxicity studies of stem bark of buckthorn (Rhamnus pentapomica R. Parker)
Rehman, Y. U., Iqbal, A., Ali, G., Alotaibi, G., Ahmed, A., & Ayaz, M. (2024) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-023-04309-w · Cited by 11 · see citing works
“Oxidative stress is a warning that a cell’s capacity for antioxidant defence is being overwhelmed by the destructive generation of reactive oxygen and nitrogen species (RONS) [10].”
BackgroundSelf-citation
The roles of natural triterpenoid saponins against Alzheimer's disease
Zhou, J., Li, H., Zhou, Y. J., Li, X., Yang, Z., Tohda, C., Komatsu, K., Piao, X., & Ge, Y. (2023) · Phytotherapy Research · doi:10.1002/ptr.7967 · Cited by 9 · see citing works
“Natural triterpenoid saponins (TS), found in medicinal plants such as ginseng, Panax notoginseng , wild jujube, Siberian ginseng, and American ginseng (Abduljawad et al., 2022), have been demonstrated significant neuroprotective effects in attenuating nervous system disorders including AD.”
Background
Phytochemicals-based β-amyloid cleaving enzyme-1 and MAO-B inhibitors for the treatment of Alzheimer’s disease: molecular simulations-based predictions
Mahnashi, M. H., Ayaz, M., Ghufran, M., Almazni, I. A., Alqahtani, O. S., Alyami, B. A., Alqahtani, Y. S., Khan, H. A., Sadiq, A., & Waqas, M. S. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2265494 · Cited by 7 · see citing works
“Beta secretase/BACE1, a membrane-bound aspartyl-prote-ase enzyme, is implicated in the catalytic processing of the amyloid precursor protein (APP) to form amyloidogenic plaques known as A b (Abduljawad et al., 2022; Moussa-Pacha et al., 2020).”
Self-citation
In-depth LC-MS and in-vitro studies of a triterpenoid saponin capilliposide-A metabolism modulation in gut microbiota of mice
Zhao, H., Hu, X., Guan, S., Cai, J., Li, X., Fang, J., Lin, B., Zhu, W., Tian, J., Jin, J., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1361643 · Cited by 7 · see citing works
Exploring the potential mechanism of Polygonatum sibiricum for Alzheimer’s disease based on network pharmacology and molecular docking: An observational study
Luo, L., Pan, Y., Chen, F., & Zhang, Z. (2024) · Medicine · doi:10.1097/md.0000000000040726 · Cited by 6 · see citing works
Macroalgae Polysaccharides Enhance Brain Health by Mitigating Scopolamine-induced Oxidative Stress and Inflammation Via Nrf-2/TLR4/NF-kB Pathways
Shah, Z., Iqbal, A., Badshah, S. L., Mir, M. A., Sohni, S., Ullah, H., Shah, S. A., Bashir, N., Ayaz, M., & Daglia, M. (2025) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-025-10230-5 · Cited by 6 · see citing works
“Scientific exploration of natural resources including marine organisms, herbal products, and their derived secondary metabolites represent valuable alternative sources for the discovery of new drugs against human diseases (Abduljawad et al. 2022).”
Self-citation
Phytochemical based on nanoparticles for neurodegenerative alzheimer disease management: Update review
Youssef, B., Ibrahim, E. A., Moselhy, S. S., ElShebiney, S. A., & ELabd, W. K. (2025) · Discover Nano · doi:10.1186/s11671-025-04356-x · Cited by 7 · see citing works
Hyperglycemia-associated Alzheimer’s-like symptoms and other behavioral effects attenuated by Plumeria obtusa L. Extract in alloxan-induced diabetic rats
Naz, S., Imran, I., Farooq, M. A., Shah, S. A. H., Ajmal, I., Zahra, Z., Aslam, A., Sarwar, M. I., Shah, J., & Aleem, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1077570 · Cited by 6 · see citing works
Antineuroinflammatory Potential of Uvaol Transformation Products by Three Fungal Species
Wang, J., We, L., Lu, J., Zhu, M., Wu, Y., Pan, W., Fan, B., Song, Y., Wang, W., & Chen, G. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c09088 · Cited by 6 · see citing works
Saponins: A class of bioactive natural products with wide applications in human health
da Silva, R. M. G., Kacew, S., & Granero, F. O. (2024) · Studies in natural products chemistry · doi:10.1016/b978-0-443-15756-1.00013-6 · Cited by 5 · see citing works
Synergistic activity of nootropic herbs as potent therapeutics for Alzheimer's disease: A cheminformatics, pharmacokinetics, and system pharmacology approach
Bosco, R. B. D., Christyraj, J. R. S. S., & Yesudhason, B. V. (2024) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823241307019 · Cited by 5 · see citing works
Identification of stigmasterol derived AChE inhibitors for Alzheimer’s disease using high throughput virtual screening and molecular dynamics simulations
Rahman, M. O., Ahmed, S. S., Alqahtani, A. S., Rehman, M. T., Sultana, N., Bouhrim, M., Ali, M. A., & Lee, J. (2025) · Scientific Reports · doi:10.1038/s41598-025-20527-3 · Cited by 4 · see citing works
Eco-friendly synthesis of silver nanoparticles from the leaf blades extract of seagrass Thalassia hemprichii: Multifunctional agents for biomedical and environmental applications
Eranhottu, S., Cherian, T., Mohanraju, R., Devi, N. S., Sanal, J., Varghese, L. S., Ambili, P., Thomas, M., Fahmeeda Parveen, P. S., & Peijnenburg, W. J. G. M. (2025) · Journal of Genetic Engineering and Biotechnology · doi:10.1016/j.jgeb.2025.100600 · Cited by 4 · see citing works
“16 16 – 18 Noble-metal nanomaterials have remarkable chemical and physical qualities that enable unique interactions with the environment.”
Contradictory dual role of antinutrients in nutrient inhibition and anti-aging: A comprehensive review on health benefits, processing techniques, and dietary strategies
Karabulut, G., Günal‐Köroğlu, D., Yılmaz, H., Erskine, E., & Çapanoğlu, E. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102929 · Cited by 4 · see citing works
Mechanistic insights into Aβ42 aggregation inhibition by bacoside A and withanolide A: An in silico and in vitro approach
Srivastava, S., Deep, S., & Khare, S. K. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.144315 · Cited by 4 · see citing works
Formulating Treatment to Cure Alzheimer’s Dementia: Approach #2
Fessel, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063524 · Cited by 5 · see citing works
“…by saponins, which provide neuroprotective mechanisms, including those of free radical scavenging, the modulation of neuroprotective signaling pathways, the activation of neurotrophic factors, the modulation of neurotransmitters, the inhibition of BACE1 enzyme, and tau hyperphosphorylation [63].”
Background
Carrier-free antitumor nanomedicines based on plant-derived compounds: From conceptual innovation to therapeutic potential
Han, Q., Wang, J., Long, L., Wang, N., & Xiao, J. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.115364 · Cited by 3 · see citing works
Dengzhan Shengmai capsule ameliorates cognitive impairment via inhibiting ER stress in APP/PS1 mice
Ma, H., Zheng, J., Qiu, Y.-H., Su, S., Lu, F.-M., Wu, G., Zhang, S., & Cai, Y. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.119016 · Cited by 2 · see citing works
Nanoparticle-Based Biomarkers for Neurological Disorders
Kiran, N. S., Yashaswini, C., Chatterjee, A., Ali, N., & Prajapati, B. G. (2025) · Nanotechnology in the life sciences · doi:10.1007/978-3-031-80185-3_6 · Cited by 3 · see citing works
Green Approach for the Purification of the Bioactive Compound Saponin from the Root Extract of Argemone mexicana and the Evaluation of Antioxidant, Antimicrobial, Anti-inflammatory and Anticancer Activities
Basha, E. K., & Dhamodaran, V. (2025) · Biomedical Materials & Devices · doi:10.1007/s44174-025-00291-8 · Cited by 2 · see citing works
“This lowers inflammation and speeds up healing in a number of inflammatory conditions [22].”
Nutrition and Neuroinflammation
Na’Allah, A., Asuku, A. O., AbdulRazaq, A., Ambali, O. A., Oyeleke, M. B., & Odetayo, A. F. (2025) · Nutritional neurosciences · doi:10.1007/978-981-95-1983-5_3 · Cited by 2 · see citing works
Screening for dual-target enzyme inhibitors derived from Gardenia jasminoides roots, a medicinal and edible plant: investigation of their potential anti-dementia activity
Liu, X., Zhou, Y., Meng, R., Han, J., Chen, M., Bo, X., Li, S., Song, D., & Zhang, Y. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1682948 · Cited by 2 · see citing works
“However, these agents exhibit suboptimal eﬃcacy and are associated with signiﬁcant adverse eﬀects, such as hepatotoxicity (31, 32).”
Allium Macrostemon Bge. Attenuates the Cognitive Decline of Aging Mice by Enhancing BDNF / TrkB Pathway
Sheng, R., Zhao, M., Pu, K., Zhou, Y., Zeng, L., Chen, Y., Wang, P., Liu, X., & Xu, S. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.70010 · Cited by 2 · see citing works
“Studies have shown that saponins are significant neuroprotective agents, with ginsenosides, astraga-loside, sarsasapogenin, and timosaponin being among the most studied (Abduljawad et al. 2022; Yang et al. 2023; Yao, Zhang, and Wang 2023).”
Machine learning tools for the characterization of bioactive metabolites derived from different parts of Ochrosia elliptica Labill. for the management of Alzheimer's disease
Salem, M. A., Abdel-Sattar, E. A., Mandour, A. A., & El‐Shiekh, R. A. (2025) · RSC Advances · doi:10.1039/d5ra00021a · Cited by 1 · see citing works
Alzheimer’s Disease: A Study on Natural and Herbal Treatment
Salve, P. S., Pohankar, A. A., George, S., & Gadge, J. R. (2025) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2025.00132 · Cited by 1 · see citing works
Herbs Acting in the CNS
León, F., Zakid, A. A., Gupta, S., Mukhopadhyay, S., Tarawneh, A. H., Obeng, S., Cutler, S. J., & McCurdy, C. R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-95702-1.00490-5 · Cited by 1 · see citing works
Baphia longipedicellata exhibits antidiabetic, antioxidant, and hepatoprotective activities: in vitro and in vivo studies
Oladoja, F. A., Awodele, O., Oreagba, I. A., Irokosu, E. S., Oyinloye, E. O., Murtala, A. A., Ganiyu-Abideen, N. A., & Pender, G. C. (2025) · RPS Pharmacy and Pharmacology Reports · doi:10.1093/rpsppr/rqaf010 · Cited by 1 · see citing works
Neuroprotective potential of Rhus coriaria : Insights into acetylcholinesterase inhibition and amyloid-β modulation
Ahmed, A., Khan, H. R., Shen, Y., Xu, S., Zhao, Y., Lv, J., Zhu, X., Fu, X., & Li, P. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251404020 · Cited by 1 · see citing works
Self-citation
Phytoconstituents of Leaves and Roots Ethanolic Extract of Talinum paniculatum and Their Biological Activities
Susilo, S., Aini, F. N., & Permanasari, E. D. (2024) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2024.00105 · Cited by 1 · see citing works
Saponins Effect on Human Insulin Amyloid Aggregation
Mari, E., Vilasi, S., Moretti, P., Mangione, M. R., Giorgini, G., Galeazzi, R., & Ortore, M. G. (2024) · Biomolecules · doi:10.3390/biom15010040 · Cited by 1 · see citing works
“Also, even more recently, a few papers suggested the promising role of saponins against neurodegenerative diseases [18,19].”
Neurotransmitter Modulation and Cognitive Enhancement
Kumar, D., Singh, R. K., & Mishra, A. K. (2025) · Springer eBooks · doi:10.1007/978-981-95-0125-0_4 · Cited by 1 · see citing works
ASPECTOS FISIOPATOLÓGICOS QUE CIRCUNDAM A DOENÇA DE ALZHEIMER: UMA REVISÃO BIBLIOGRÁFICA DE LITERATURA
Biancardi, I. M., Carneiro, I. R., SILVA, M. L. R. D., Quincór, R. R. D. S., & Sardinha, R. M. (2023) · Congresso Brasileiro de Estudos Patológicos On-line · doi:10.51161/ii-conbesp/14165
Bioactive And Cytotoxic Potentials of the Extract Fractions of Strophanthus Hispidus on Neuroblastoma (SH-SY5Y) Cell Line Model of Alzheimer’s Disease
Akinyemi, P. A., Adebesin, O. A., Arotiba, O. M., Adewole, A. R., & Okpuzor, J. E. (2023) · Journal of applied science and environmental management · doi:10.4314/jasem.v27i11.36
“The study by Abduljawad et al. (2022) concluded that Saponins have considerable efficacy against various pathological targets of neurological disorders.”
Background
Exploring the potential mechanism of Polygonatum sibiricum for Alzheimer's disease based on network pharmacology and molecular dockingPreprint
Luo, L., Pan, Y., Chen, F., & Zhang, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-4225413/v1
Novel Galantamine-ferulicacid hybrids: A Multi-target approach to Alzheimer’s disease
Singh, S., & Kakadiya, J. (2025) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2025.00316
Nutritional profile, medicinal properties and growing businesses of Moringa oleifera: A review
Patel, D., Patel, Y. K., Vithalkar, A., & Kaiwartya, K. (2025) · International Journal of Agriculture and Food Science · doi:10.33545/2664844x.2025.v7.i7d.519
BENEFÍCIOS DE COMPOSTOS BIOATIVOS SOBRE VIAS DE SINALIZAÇÃO DA DOENÇA DE ALZHEIMER: UMA REVISÃO INTEGRATIVA
Burigo, F. E. T., & Pincerati, M. R. (2025) · Aracê. · doi:10.56238/arev7n10-295
Additional file 1 of Phytochemical analysis, radical scavenging and glioblastoma U87 cells toxicity studies of stem bark of buckthorn (Rhamnus pentapomica R. Parker)
Rehman, Y. U., Iqbal, A., Ali, G., Alotaibi, G., Ahmed, A., & Ayaz, M. (2024) · Figshare · doi:10.6084/m9.figshare.24934223
Self-citation
Differential solvent extraction, qualitative phytochemical analysis, isolation of secondary metabolites, antioxidant, enzymes inhibitory, antimicrobial, and phytotoxic potentials of Jurinea himalaica R.R.Stewart
Ullah, F., Hayat, A., Mir, M. A., Khan, M. A., Bashir, N., Mosa, O. F., Sadiq, A. M. M., & Ayaz, M. (2026) · Beni-Suef University Journal of Basic and Applied Sciences · doi:10.1186/s43088-025-00720-z
“…screening of plant-derived compounds which have the capacity to inhibit enzymes, scavenge free radicals, and affect plant growth is not only helping in the identification of new drug candidates but is also supporting efforts to find eco-friendly alternatives to synthetic agrochemicals [12–14].”
Self-citation
Saraswata Ghrita mitigates AlCl₃- and D-galactose–induced cognitive deficits in a murine Alzheimer’s-like model: In silico and in vivo insights
Badal, R., Kaur, B., Singh, H., Sharma, P., Yadav, P., Mahapatra, A., Ghildiyal, S., Patel, A. K., Kumar, L., Sharma, B., et al. (2026) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2026.111742
Dietary Saponin-Mediated Health Promotion: Unraveling the Molecular Mechanism through the PI3K/Akt Signaling Pathway
Luo, J., Luo, J., Huang, Y., Lei, Q., Wu, Y., Han, B., & Xu, B. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c17741
Role of Cereals and Pseudo-cereals in the Management of Neurodegenerative Diseases (NDDs) with a Special Reference to Alzheimer’s and Parkinson’s Disease
Chakraborty, A., & Guha, S. (2026) · Recent Progress in Nutrition · doi:10.21926/rpn.2602008
Current progress in the use of pyrazole-containing compounds for neuroprotection as a strategy to counteract neurodegeneration
Bastos, I. M., Moreira, D. R., Rebelo, S., & Silva, V. L. M. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118161
Natural products in neurodegenerative diseases: role of serine/threonine kinases
Ahmed, L. A., Ahmed, M. K., Sayed, N. S. E., & Farag, M. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44173-8.00023-1
Phytochemical profiling of Olea europaea subsp. cuspidata aerial parts using LC-DAD-QToF: cholinesterase inhibition and molecular docking insights into potential Alzheimer’s disease targets
El‐Shiekh, R. A., Mandour, A. A., Abdel-Sattar, E. A., & Ali, N. B. (2026) · Natural Product Research · doi:10.1080/14786419.2026.2727544

Neuroprotective effects of saponins on neurodegenerative diseases
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Fatima, K., Cho, H., Olawuyi, I. F., & Lee, W. (2026) · Nutrition Research · doi:10.1016/j.nutres.2026.09.007

Authors: Abduljawad, A. A., Elawad, M. A., Elkhalifa, M. E. M., Ahmed, A., Hamdoon, A. A. E., Salim, L. H. M., Ashraf, M., Ayaz, M., Hassan, S. S. U., & Bungau, S.
Affiliations: Umm al-Qura University (SA)
University of Khartoum (SD)
University of Malakand (PK)
Shanghai Jiao Tong University (CN)
University of Oradea (RO)
Corresponding author: Abduljawad, Asaad A.
Ayaz, Muhammad
Hassan, Syed Shams ul
Bungau, Simona
ORCID: Abduljawad, Asaad A.
Elawad, Mohammed Ahmed
Elkhalifa, Modawy Elnour Modawy
Ahmed, Alshebli
Hamdoon, Alashary Adam Eisa
Salim, Liga Hasan Mohammed
Ashraf, Muhammad
Ayaz, Muhammad
Hassan, Syed Shams ul
Bungau, Simona
Venue: Molecules
Publisher: MDPI AG
Published: 2022-10-11
Volume: 27
Issue: 20
Pages: 6804
ISSN: 1420-3049 (ISSN-L)
DOI: 10.3390/molecules27206804
PMC: PMC9608803
OpenAlex: W4304632685
Cited by: 63
References: 132
Citations by year: 2026: 7 · 2025: 24 · 2024: 14 · 2023: 16 · 2022: 2
FWCI: 3.23
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Molecules (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
Keywords: saponins, Alzheimer's disease, neurodegenerative diseases, neuroprotection, triterpenoid saponins, steroid glycosides, free radical scavenging, neurotrophic factors, neurotransmitters, BACE1 inhibition, tau hyperphosphorylation, Huntington's disease, Parkinson's disease, dietary phytochemicals
MeSH terms: Alzheimer Disease, Free Radicals, Glycosides, Humans, Nerve Growth Factors, Public Health, Saponins, Steroids, Triterpenes, Aspartic Acid Endopeptidases, Neurotransmitter Agents, Neurodegenerative Diseases, Amyloid Precursor Protein Secretases

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Alzheimer’s Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms

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