Natural Products and Bioprospecting    2022, Vol. 12 Issue (5) : 34-34     DOI: 10.1007/s13659-022-00354-z
ORIGINAL ARTICLES |
Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease
Sheena E.B.Tyler1, Luke D.K.Tyler2
1 John Ray Research Field Station, Cheshire, UK;
2 School of Natural Sciences, Bangor University, Gwynedd, UK
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Abstract  Alzheimer’s disease (AD) is progressive and ultimately fatal, with current drugs failing to reverse and cure it. This study aimed to find plant species which may provide therapeutic bioactivities targeted to causal agents proposed to be driving AD. A novel toolkit methodology was employed, whereby clinical symptoms were translated into categories recognized in ethnomedicine. These categories were applied to find plant species with therapeutic effects, mined from ethnomedical surveys. Survey locations were mapped to assess how this data is at risk. Bioactivities were found of therapeutic relevance to 15 hypothesised causal bases for AD. 107 species with an ethnological report of memory improvement demonstrated therapeutic activity for all these 15 causal bases. The majority of the surveys were found to reside within biodiversity hotspots (centres of high biodiversity under threat), with loss of traditional knowledge the most common threat. Our findings suggest that the documented plants provide a large resource of AD therapeutic potential. In demonstrating bioactivities targeted to these causal bases, such plants may have the capacity to reduce or reverse AD, with promise as drug leads to target multiple AD hallmarks. However, there is a need to preserve ethnomedical knowledge, and the habitats on which this knowledge depends.
Keywords Medicinal plants      Alzheimer’s      Causal basis      Ethnomedicine      Traditional knowledge     
Corresponding Authors: Sheena E.B.Tyler,E-mail:s.tyler@johnray.org.uk     E-mail: s.tyler@johnray.org.uk
Issue Date: 12 October 2022
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Sheena E.B.Tyler,Luke D.K.Tyler. Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease[J]. Natural Products and Bioprospecting, 2022, 12(5): 34-34.
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http://npb.kib.ac.cn/EN/10.1007/s13659-022-00354-z     OR     http://npb.kib.ac.cn/EN/Y2022/V12/I5/34
1. Nichols E, Szoeke CE, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology. 2019;18(1):88–106.
2. Yiannopoulou KG, Anastasiou AI, Zachariou V, Pelidou SH. Reasons for failed trials of disease-modifying treatments for Alzheimer disease and their contribution in recent research. Biomedicines. 2019;7(4):97.
3. Breijyeh Z, Karaman R. Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules. 2020;25(24):5789.
4. Dekker FA, Rüdiger SGD. The mitochondrial Hsp90 TRAP1 and Alzheimer’s disease. Front Mol Biosci. 2021;8: 697913.
5. Lin P, Sun J, Cheng Q, Yang Y, Cordato D, Gao J. The development of pharmacological therapies for Alzheimer’s disease. Neurol Ther. 2021;10(2):609–26.
6. Collins AE, Saleh TM, Kalisch BE. Naturally occurring antioxidant therapy in Alzheimer’s disease. Antioxidants (Basel). 2022;11(2):213.
7. Fouka M, Mavroeidi P, Tsaka G, Xilouri M. In search of effective treatments targeting α-synuclein toxicity in synucleinopathies: pros and cons. Front Cell Dev Biol. 2020;8:894.
8. Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014;6(4):37.
9. McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, et al. Memantine for dementia. Cochrane Database Syst Rev. 2019;3:CD003154.
10. Vander Zanden CM, Chi EY. Passive immunotherapies targeting amyloid beta and tau oligomers in Alzheimer’s disease. J Pharm Sci. 2020;109(1):68–73.
11. Mullard A. Landmark Alzheimer’s drug approval confounds research community. Nature. 2021;594(7863):309–10.
12. Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012;75(3):311–35.
13. Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020;83(3):770–803.
14. Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv. 2015;33(8):1582–614.
15. Fabricant DS, Farnsworth NR. The value of plants used in traditional medicine for drug discovery. Environ Health Perspect. 2001;109(Suppl 1):69–75.
16. Houghton PJ. Synergy and polyvalence: paradigms to explain the activity of herbal products. Eval Herbal Med Products. 2009;85:94.
17. Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT, Taskforce INPS. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov. 2021;20(3):200–16.
18. Ostwald A, Tulloch VJ, Kyne PM, Bax NJ, Dunstan PK, Ferreira LC, et al. Mapping threats to species: method matters. Mar Policy. 2021;131: 104614.
19. Myers N, Mittermeier RA, Mittermeier CG, da Fonseca GA, Kent J. Biodiversity hotspots for conservation priorities. Nature. 2000;403(6772):853–8.
20. Mittermeier RA, Turner WR, Larsen FW, Brooks TM, Gascon C. Global biodiversity conservation: the critical role of hotspots. Biodiversity hotspots: Springer; 2011. p. 3–22.
21. Habel JC, Rasche L, Schneider UA, Engler JO, Schmid E, Rödder D, et al. Final countdown for biodiversity hotspots. Conserv Lett. 2019;12(6): e12668.
22. Mecocci P, Boccardi V, Cecchetti R, Bastiani P, Scamosci M, Ruggiero C, et al. A long journey into aging, brain aging, and Alzheimer’s disease following the oxidative stress tracks. J Alzheimers Dis. 2018;62(3):1319–35.
23. Du X, Wang X, Geng M. Alzheimer’s disease hypothesis and related therapies. Transl Neurodegener. 2018;7:2.
24. Liu PP, Xie Y, Meng XY, Kang JS. History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct Target Ther. 2019;4:29.
25. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8(6):595–608.
26. Hampel H, Hardy J, Blennow K, Chen C, Perry G, Kim SH, et al. The amyloid-β pathway in Alzheimer’s disease. Mol Psychiatry. 2021;26(10):5481–503.
27. Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741.
28. Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984;120(3):885–90.
29. Glenner GG. Amyloid beta protein and the basis for Alzheimer’s disease. Prog Clin Biol Res. 1989;317:857–68.
30. Beyreuther K, s CL. Amyloid precursor protein (APP) and beta A4 amyloid in the etiology of Alzheimer’s disease: precursor-product relationships in the derangement of neuronal function. Brain Pathol. 1991;1(4):241–51.
31. Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184–5.
32. Golde TE. Alzheimer’s disease–the journey of a healthy brain into organ failure. Mol Neurodegener. 2022;17(1):1–19.
33. Cline EN, Bicca MA, Viola KL, Klein WL. The amyloid-β oligomer hypothesis: beginning of the third decade. J Alzheimers Dis. 2018;64(s1):S567–610.
34. Ferreira ST, Lourenco MV, Oliveira MM, De Felice FG. Soluble amyloid-b oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease. Front Cell Neurosci. 2015;9:191.
35. Avgerinos KI, Ferrucci L, Kapogiannis D. Effects of monoclonal antibodies against amyloid-β on clinical and biomarker outcomes and adverse event risks: a systematic review and meta-analysis of phase III RCTs in Alzheimer’s disease. Ageing Res Rev. 2021;68: 101339.
36. Spires-Jones TL. Alzheimer’s research-breakthrough or breakdown? Brain Commun. 2021;3(4):fcab217.
37. Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85(16):1383–91.
38. Peng Y, Sun J, Hon S, Nylander AN, Xia W, Feng Y, et al. L-3-nbutylphthalide improves cognitive impairment and reduces amyloid-β in a transgenic model of Alzheimer’s disease. J Neurosci. 2010;30(24):8180–9.
39. Bihaqi SW, Singh AP, Tiwari M. Supplementation of Convolvulus pluricaulis attenuates scopolamine-induced increased tau and Amyloid precursor protein (AβPP) in rat brain. Indian J Pharmacol. 2012;44(5):593.
40. Durairajan SSK, Liu L-F, Lu J-H, Chen L-L, Yuan Q, Chung SK, et al. Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer’s disease transgenic mouse model. Neurobiol Aging. 2012;33(12):2903–19.
41. Yaghmaei P, Azarfar K, Dezfulian M, Ebrahim-Habibi A. Silymarin effect on amyloid-β plaque accumulation and gene of APP in an Alzheimer’s disease rat model. DARU J Pharm Sci. 2014;22(1):1–7.
42. Justin Thenmozhi A, Dhivyabharathi M, William Raja TR, Manivasagam T, Essa MM. Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminum chloride induced rat model of Alzheimer’s disease. Nutr Neurosci. 2016;19(6):269–78.
43. Ma H, Johnson SL, Liu W, DaSilva NA, Meschwitz S, Dain JA, et al. Evaluation of polyphenol anthocyanin-enriched extracts of blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry for free radical scavenging, reactive carbonyl species trapping, anti-glycation, anti-β-amyloid aggregation, and microglial neuroprotective effects. Int J Mol Sci. 2018;19(2):461.
44. Ogunruku OO, Oboh G, Passamonti S, Tramer F, Boligon AA. Capsicum annuum var. grossum (Bell Pepper) Inhibits β-Secretase Activity and β-Amyloid1–40 Aggregation. J Med Food. 2017;20(2):124–30.
45. Briffa M, Ghio S, Neuner J, Gauci AJ, Cacciottolo R, Marchal C, et al. Extracts from two ubiquitous Mediterranean plants ameliorate cellular and animal models of neurodegenerative proteinopathies. Neurosci Lett. 2017;638:12–20.
46. Kleinrichert K, Alappat B. Comparative analysis of antioxidant and anti-amyloidogenic properties of various polyphenol rich phytoceutical extracts. Antioxidants. 2019;8(1):13.
47. Shin SJ, Jeong Y, Jeon SG, Kim S, Lee S-K, Choi HS, et al. Uncaria rhynchophylla ameliorates amyloid beta deposition and amyloid beta-mediated pathology in 5XFAD mice. Neurochem Int. 2018;121:114–24.
48. Lee J-E, Kim M-S, Park S-Y. Effect of natural antioxidants on the aggregation and disaggregation of beta-amyloid. Trop J Pharm Res. 2017;16(11):2629–35.
49. Ishigaki Y, Tanaka H, Akama H, Ogara T, Uwai K, Tokuraku K. A microliter-scale high-throughput screening system with quantum-dot nanoprobes for amyloid-β aggregation inhibitors. PLoS ONE. 2013;8(8): e72992.
50. Kashyap P, Muthusamy K, Niranjan M, Trikha S, Kumar S. Sarsasapogenin: a steroidal saponin from Asparagus racemosus as multi target directed ligand in Alzheimer’s disease. Steroids. 2020;153: 108529.
51. Zhao L, Wang J-L, Liu R, Li X-X, Li J-F, Zhang L. Neuroprotective, antiamyloidogenic and neurotrophic effects of apigenin in an Alzheimer’s disease mouse model. Molecules. 2013;18(8):9949–65.
52. Pakdeepak K, Chokchaisiri R, Tocharus J, Jearjaroen P, Tocharus C, Suksamrarn A. 5, 6, 7, 4’-Tetramethoxyflavanone protects against neuronal degeneration induced by dexamethasone by attenuating amyloidogenesis in mice. EXCLI J. 2020;19:16.
53. Mahaman YAR, Huang F, Wu M, Wang Y, Wei Z, Bao J, et al. Moringa oleifera alleviates homocysteine-induced Alzheimer’s disease-like pathology and cognitive impairments. J Alzheimers Dis. 2018;63(3):1141–59.
54. Du Y, Qu J, Zhang W, Bai M, Zhou Q, Zhang Z, et al. Morin reverses neuropathological and cognitive impairments in APPswe/PS1dE9 mice by targeting multiple pathogenic mechanisms. Neuropharmacology. 2016;108:1–13.
55. Boubakri A, Leri M, Bucciantini M, Najjaa H, Ben Arfa A, Stefani M, et al. Allium roseum L. extract inhibits amyloid beta aggregation and toxicity involved in Alzheimer’s disease. PLoS ONE. 2020;15(9):e0223815.
56. Malishev R, Shaham-Niv S, Nandi S, Kolusheva S, Gazit E, Jelinek R. Bacoside-A, an Indian traditional-medicine substance, inhibits β-amyloid cytotoxicity, fibrillation, and membrane interactions. ACS Chem Neurosci. 2017;8(4):884–91.
57. Morshedi D, Kesejini TS, Aliakbari F, Karami-Osboo R, Shakibaei M, Marvian AT, et al. Identification and characterization of a compound from Cuminum cyminum essential oil with antifibrilation and cytotoxic effect. Res Pharm Sci. 2014;9(6):431.
58. Dhouafli Z, Rigacci S, Leri M, Bucciantini M, Mahjoub B, Tounsi MS, et al. Screening for amyloid-β aggregation inhibitor and neuronal toxicity of eight Tunisian medicinal plants. Ind Crops Prod. 2018;111:823–33.
59. Wang Q, Yu X, Patal K, Hu R, Chuang S, Zhang G, et al. Tanshinones inhibit amyloid aggregation by amyloid-β peptide, disaggregate amyloid fibrils, and protect cultured cells. ACS Chem Neurosci. 2013;4(6):1004–15.
60. McLaurin J, Kierstead ME, Brown ME, Hawkes CA, Lambermon MH, Phinney AL, et al. Cyclohexanehexol inhibitors of Aβ aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nat Med. 2006;12(7):801–8.
61. Weinberg RP, Koledova VV, Shin H, Park JH, Tan YA, Sinskey AJ, et al. Oil palm phenolics inhibit the in vitro aggregation of β-amyloid peptide into oligomeric complexes. Int J Alzheimer’s Dis. 2018;2018:1.
62. Wang Y, Xia Z, Xu J-R, Wang Y-X, Hou L-N, Qiu Y, et al. α-Mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates β-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation. Neuropharmacology. 2012;62(2):871–81.
63. Diomede L, Rigacci S, Romeo M, Stefani M, Salmona M. Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit. PLoS ONE. 2013;8(3):e58893.
64. Hamaguchi T, Ono K, Murase A, Yamada M. Phenolic compounds prevent Alzheimer’s pathology through different effects on the amyloid-β aggregation pathway. Am J Pathol. 2009;175(6):2557–65.
65. Snow AD, Castillo GM, Nguyen BP, Choi PY, Cummings JA, Cam J, et al. The Amazon rain forest plant Uncaria tomentosa (cat’s claw) and its specific proanthocyanidin constituents are potent inhibitors and reducers of both brain plaques and tangles. Sci Rep. 2019;9(1):1–28.
66. Du W-J, Guo J-J, Gao M-T, Hu S-Q, Dong X-Y, Han Y-F, et al. Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity. Sci Rep. 2015;5(1):1–10.
67. Ladiwala ARA, Lin JC, Bale SS, Marcelino-Cruz AM, Bhattacharya M, Dordick JS, et al. Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Aβ into off-pathway conformers. J Biol Chem. 2010;285(31):24228–37.
68. Sehgal N, Gupta A, Valli RK, Joshi SD, Mills JT, Hamel E, et al. Withania somnifera reverses Alzheimer’s disease pathology by enhancing lowdensity lipoprotein receptor-related protein in liver. Proc Natl Acad Sci U S A. 2012;109(9):3510–5.
69. Fan Y, Wang N, Rocchi A, Zhang W, Vassar R, Zhou Y, et al. Identification of natural products with neuronal and metabolic benefits through autophagy induction. Autophagy. 2017;13(1):41–56.
70. Chen F, Eckman EA, Eckman CB. Reductions in levels of the Alzheimer’s amyloid beta peptide after oral administration of ginsenosides. FASEB J. 2006;20(8):1269–71.
71. Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, et al. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci. 2005;25(38):8807–14.
72. Dhanasekaran M, Holcomb LA, Hitt AR, Tharakan B, Porter JW, Young KA, et al. Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer’s disease animal model. Phytother Res. 2009;23(1):14–9.
73. Shytle RD, Tan J, Bickford PC, Rezai-Zadeh K, Hou L, Zeng J, et al. Optimized turmeric extract reduces β-Amyloid and phosphorylated Tau protein burden in Alzheimer’s transgenic mice. Curr Alzheimer Res. 2012;9(4):500–6.
74. Xing Z, He Z, Wang S, Yan Y, Zhu H, Gao Y, et al. Ameliorative effects and possible molecular mechanisms of action of fibrauretine from Fibraurea recisa Pierre on d-galactose/AlCl 3-mediated Alzheimer’s disease. RSC Adv. 2018;8(55):31646–57.
75. Zhu Y, Bickford PC, Sanberg P, Giunta B, Tan J. Blueberry opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activation protein kinase. Rejuvenation Res. 2008;11(5):891–901.
76. Wang LS, Tao X, Liu XM, Zhou YF, Zhang MD, Liao YH, et al. Cajaninstilbene Acid Ameliorates Cognitive Impairment Induced by Intrahippocampal Injection of Amyloid-β. Front Pharmacol. 2019;10:1084.
77. Hyung SJ, DeToma AS, Brender JR, Lee S, Vivekanandan S, Kochi A, et al. Insights into antiamyloidogenic properties of the green tea extract (-)-epigallocatechin-3-gallate toward metal-associated amyloid-β species. Proc Natl Acad Sci U S A. 2013;110(10):3743–8.
78. Gulisano W, Maugeri D, Baltrons MA, Fà M, Amato A, Palmeri A, et al. Role of amyloid-β and tau proteins in Alzheimer’s disease: confuting the amyloid cascade. J Alzheimers Dis. 2018;64(s1):S611–31.
79. Kametani F, Hasegawa M. Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer’s disease. Front Neurosci. 2018;12:25.
80. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR. Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol. 1999;58(4):376–88.
81. Erten-Lyons D, Woltjer R, Dodge H, Nixon R, Vorobik R, Calvert J, et al. Factors associated with resistance to dementia despite high Alzheimer disease pathology. Neurology. 2009;72(4):354–60.
82. Chételat G, La Joie R, Villain N, Perrotin A, de La Sayette V, Eustache F, et al. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer’s disease. Neuroimage Clin. 2013;2:356–65.
83. Kim J, Chakrabarty P, Hanna A, March A, Dickson DW, Borchelt DR, et al. Normal cognition in transgenic BRI2-Aβ mice. Mol Neurodegener. 2013;8(1):1–12.
84. Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci. 2015;18(6):794–9.
85. Medina M, Avila J. The role of extracellular Tau in the spreading of neurofibrillary pathology. Front Cell Neurosci. 2014;8:113.
86. Wang Y, Mandelkow E. Tau in physiology and pathology. Nat Rev Neurosci. 2016;17(1):22–35.
87. Marcucci V, Kleiman J. Biomarkers and their implications in Alzheimer’s disease: a literature review. Explor Res Hypothesis Med. 2021.
88. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, et al. Dendritic function of tau mediates amyloid-β toxicity in Alzheimer’s disease mouse models. Cell. 2010;142(3):387–97.
89. Gong C-X, Liu F, Grundke-Iqbal I, Iqbal K. Impaired brain glucose metabolism leads to Alzheimer neurofibrillary degeneration through a decrease in tau O-GlcNAcylation. J Alzheimers Dis. 2006;9(1):1–12.
90. Peng Y, Hu Y, Xu S, Li P, Li J, Lu L, et al. L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AβPP/PS1-Alzheimer’s transgenic mice. J Alzheimers Dis. 2012;29(2):379–91.
91. Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces β-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res. 2008;1214:177–87.
92. George RC, Lew J, Graves DJ. Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer’s disease pathogenesis. J Alzheimers Dis. 2013;36(1):21–40.
93. Chen J, Deng X, Liu N, Li M, Liu B, Fu Q, et al. Quercetin attenuates tau hyperphosphorylation and improves cognitive disorder via suppression of ER stress in a manner dependent on AMPK pathway. J Funct Foods. 2016;22:463–76.
94. Ye S, Wang T-T, Cai B, Wang Y, Li J, Zhan J-X, et al. Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase IV protein levels in Alzheimer’s disease model rats. Neural Regen Res. 2017;12(9):1479.
95. Monti MC, Margarucci L, Riccio R, Casapullo A. Modulation of tau protein fibrillization by oleocanthal. J Nat Prod. 2012;75(9):1584–8.
96. Nguyen DK, Dai TTX. Study on tau-aggregation inhibitors in Alzheimer’s disease of methanol extracts of several medicinal plants collected in the Mekong Delta, Vietnam. Sci Technol Dev J-Nat Sci. 2017;1(T2):21–8.
97. Cornejo A, Aguilar Sandoval F, Caballero L, Machuca L, Muñoz P, Caballero J, et al. Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease. J Enzyme Inhib Med Chem. 2017;32(1):945–53.
98. Radenahmad N, Saleh F, Sawangjaroen K, Vongvatcharanon U, Subhadhirasakul P, Rundorn W, et al. Young coconut juice, a potential therapeutic agent that could significantly reduce some pathologies associated with Alzheimer’s disease: novel findings. Br J Nutr. 2011;105(5):738–46.
99. Kim G-H, Lim K, Yang HS, Lee J-K, Kim Y, Park S-K, et al. Improvement in neurogenesis and memory function by administration of Passiflora incarnata L. extract applied to sleep disorder in rodent models. J Chem Neuroanatomy. 2019;98:27–40.
100. Ahmadi M, Taherianfard M, Shomali T. Zataria multiflora could improve hippocampal tau protein and TNFα levels and cognitive behavior defects in a rat model of Alzheimer’s disease. Avicenna J Phytomed. 2019;9(5):465.
101. Corpas R, Griñán-Ferré C, Rodríguez-Farré E, Pallàs M, Sanfeliu C. Resveratrol induces brain resilience against Alzheimer neurodegeneration through proteostasis enhancement. Mol Neurobiol. 2019;56(2):1502–16.
102. Jones JR, Lebar MD, Jinwal UK, Abisambra JF, Koren J III, Blair L, et al. The diarylheptanoid (+)-a R, 11 S-myricanol and two flavones from bayberry (Myrica cerifera) destabilize the microtubule-associated protein Tau. J Nat Prod. 2011;74(1):38–44.
103. Peng Y, Tao H, Wang S, Xiao J, Wang Y, Su H. Dietary intervention with edible medicinal plants and derived products for prevention of Alzheimer’s disease: a compendium of time-tested strategy. J Funct Foods. 2021;81: 104463.
104. Small SA, Duff K. Linking Aβ and tau in late-onset Alzheimer’s disease: a dual pathway hypothesis. Neuron. 2008;60(4):534–42.
105. Roda AR, Serra-Mir G, Montoliu-Gaya L, Tiessler L, Villegas S. Amyloidbeta peptide and tau protein crosstalk in Alzheimer’s disease. Neural Regen Res. 2022;17(8):1666–74.
106. Hernández F, Diaz-Hernández M, Avila J, Lucas JJ. Testing the ubiquitin– proteasome hypothesis of neurodegeneration in vivo. Trends Neurosci. 2004;27(2):66–9.
107. Hartl FU. Molecular chaperones in cellular protein folding. Nature. 1996;381(6583):571–80.
108. Ciechanover A, Kwon YT. Protein quality control by molecular chaperones in neurodegeneration. Front Neurosci. 2017;11:185.
109. Hommen F, Bilican S, Vilchez D. Protein clearance strategies for disease intervention. J Neural Transm (Vienna). 2021;129:141.
110. Ciechanover A. The ubiquitin-proteasome proteolytic pathway. Cell. 1994;79(1):13–21.
111. de Vrij FM, Fischer DF, van Leeuwen FW, Hol E. Protein quality control in Alzheimer’s disease by the ubiquitin proteasome system. Prog Neurobiol. 2004;74(5):249–70.
112. Hegde AN, Smith SG, Duke LM, Pourquoi A, Vaz S. Perturbations of Ubiquitin-Proteasome-Mediated Proteolysis in Aging and Alzheimer’s Disease. Front Aging Neurosci. 2019;11:324.
113. Boland B, Yu WH, Corti O, Mollereau B, Henriques A, Bezard E, et al. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2018;17(9):660–88.
114. Schmidt MF, Gan ZY, Komander D, Dewson G. Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities. Cell Death Differ. 2021;28(2):570–90.
115. Le Guerroué F, Youle RJ. Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective. Cell Death Differ. 2021;28(2):439–54.
116. Moghaddam MG, Ahmad FBH, Samzadeh-Kermani A. Biological activity of betulinic acid: a review. 2012.
117. Huang L, Ho P, Chen C-H. Activation and inhibition of the proteasome by betulinic acid and its derivatives. FEBS Lett. 2007;581(25):4955–9.
118. Yagishita Y, Fahey JW, Dinkova-Kostova AT, Kensler TW. Broccoli or sulforaphane: is it the source or dose that matters? Molecules. 2019;24(19):3593.
119. Liu Y, Hettinger CL, Zhang D, Rezvani K, Wang X, Wang H. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington’s disease. J Neurochem. 2014;129(3):539–47.
120. Park HS, Hwang ES, Choi GY, Kim HB, Park KS, Sul JY, et al. Sulforaphane enhances long-term potentiation and ameliorate scopolamineinduced memory impairment. Physiol Behav. 2021;238: 113467.
121. Park H-M, Kim J-A, Kwak M-K. Protection against amyloid beta cytotoxicity by sulforaphane: role of the proteasome. Arch Pharmacal Res. 2009;32(1):109–15.
122. Di Meco A, Curtis ME, Lauretti E, Praticò D. Autophagy dysfunction in Alzheimer’s disease: mechanistic insights and new therapeutic opportunities. Biol Psychiat. 2020;87(9):797–807.
123. Yim WW, Mizushima N. Lysosome biology in autophagy. Cell Discov. 2020;6:6.
124. Ramesh N, Pandey UB. Autophagy dysregulation in ALS: when protein aggregates get out of hand. Front Mol Neurosci. 2017;10:263.
125. Limanaqi F, Biagioni F, Gambardella S, Familiari P, Frati A, Fornai F. Promiscuous roles of autophagy and proteasome in neurodegenerative proteinopathies. Int J Mol Sci. 2020;21(8):3028.
126. Uddin M, Stachowiak A, Mamun AA, Tzvetkov NT, Takeda S, Atanasov AG, et al. Autophagy and Alzheimer’s disease: from molecular mechanisms to therapeutic implications. Front Aging Neurosci. 2018;10:4.
127. Watanabe Y, Taguchi K, Tanaka M. Ubiquitin, autophagy and neurodegenerative diseases. Cells. 2020;9(9):2022.
128. Konings E, Timmers S, Boekschoten MV, Goossens GH, Jocken JW, Afman LA, et al. The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene patterns in obese men. Int J Obes (Lond). 2014;38(3):470–3.
129. Park D, Jeong H, Lee MN, Koh A, Kwon O, Yang YR, et al. Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition. Sci Rep. 2016;6(1):1–11.
130. Fan X, Wang J, Hou J, Lin C, Bensoussan A, Chang D, et al. Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway. J Transl Med. 2015;13:92.
131. Fan D, Liu L, Wu Z, Cao M. Combating Neurodegenerative diseases with the plant alkaloid berberine: molecular mechanisms and therapeutic potential. Curr Neuropharmacol. 2019;17(6):563–79.
132. Zhang S, Yu Z, Xia J, Zhang X, Liu K, Sik A, et al. Anti-Parkinson’s disease activity of phenolic acids from Eucommia ulmoides Oliver leaf extracts and their autophagy activation mechanism. Food Funct. 2020;11(2):1425–40.
133. Velagapudi R, Lepiarz I, El-Bakoush A, Katola FO, Bhatia H, Fiebich BL, et al. Induction of autophagy and activation of SIRT-1 deacetylation mechanisms mediate neuroprotection by the pomegranate metabolite urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells. Mol Nutr Food Res. 2019;63(10):1801237.
134. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol. 2006;147(S1):S232–40.
135. Sochocka M, Diniz BS, Leszek J. Inflammatory response in the CNS: friend or foe? Mol Neurobiol. 2017;54(10):8071–89.
136. Shastri A, Bonifati DM, Kishore U. Innate immunity and neuroinflammation. Mediators Inflamm. 2013;2013: 342931.
137. Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308(5726):1314–8.
138. Mariani MM, Kielian T. Microglia in infectious diseases of the central nervous system. J Neuroimmune Pharmacol. 2009;4(4):448–61.
139. Biber K, Owens T, Boddeke E. What is microglia neurotoxicity (Not)? Glia. 2014;62(6):841–54.
140. Perry VH, Holmes C. Microglial priming in neurodegenerative disease. Nat Rev Neurol. 2014;10(4):217–24.
141. Hickman S, Izzy S, Sen P, Morsett L, El Khoury J. Microglia in neurodegeneration. Nat Neurosci. 2018;21(10):1359–69.
142. Kim SK, Nabekura J, Koizumi S. Astrocyte-mediated synapse remodeling in the pathological brain. Glia. 2017;65(11):1719–27.
143. Alberini CM, Cruz E, Descalzi G, Bessières B, Gao V. Astrocyte glycogen and lactate: new insights into learning and memory mechanisms. Glia. 2018;66(6):1244–62.
144. Sofroniew MV. Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci. 2015;16(5):249–63.
145. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119(1):7–35.
146. Zhao J, O’Connor T, Vassar R. The contribution of activated astrocytes to Aβ production: implications for Alzheimer’s disease pathogenesis. J Neuroinflammation. 2011;8(1):1–17.
147. Garwood C, Pooler A, Atherton J, Hanger D, Noble W. Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture. Cell Death Dis. 2011;2(6):e167.
148. Gorshkov K, Aguisanda F, Thorne N, Zheng W. Astrocytes as targets for drug discovery. Drug Discovery Today. 2018;23(3):673–80.
149. Griffin WST, Barger SW. Neuroinflammatory cytokines—the common thread in Alzheimer’s pathogenesis. US neurology. 2010;6(2):19. Tyler and Tyler Natural Products and Bioprospecting (2022) 12:34 Page 30 of 37
150. Albaret G, Sifré E, Floch P, Laye S, Aubert A, Dubus P, et al. Alzheimer’s disease and helicobacter pylori infection: inflammation from stomach to brain? J Alzheimers Dis. 2020;73(2):801–9.
151. Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17(3):157–72.
152. McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol. 2013;126(4):479–97.
153. in’t Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med. 2001;345(21):1515–21.
154. Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology. 2008;70(19):1672–7.
155. Nichols MR, St-Pierre MK, Wendeln AC, Makoni NJ, Gouwens LK, Garrad EC, et al. Inflammatory mechanisms in neurodegeneration. J Neurochem. 2019;149(5):562–81.
156. Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, et al. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Arch Neurol. 2004;61(5):668–72.
157. Alcolea D, Martínez-Lage P, Sánchez-Juan P, Olazarán J, Antúnez C, Izagirre A, et al. Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology. 2015;85(7):626–33.
158. Streit WJ, Braak H, Xue QS, Bechmann I. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease. Acta Neuropathol. 2009;118(4):475–85.
159. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405.
160. Lue L-F, Brachova L, Civin WH, Rogers J. Inflammation, Aβ deposition, and neurofibrillary tangle formation as correlates of Alzheimer’s disease neurodegeneration. J Neuropathol Exp Neurol. 1996;55(10):1083–8.
161. Kim N, Martinez CC, Jang DS, Lee JK, Oh MS. Anti-neuroinflammatory effect of Iresine celosia on lipopolysaccharide-stimulated microglial cells and mouse. Biomed Pharmacother. 2019;111:1359–66.
162. Deng L-L, Yuan D, Zhou Z-Y, Wan J-Z, Zhang C-C, Liu C-Q, et al. Saponins from Panax japonicus attenuate age-related neuroinflammation via regulation of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways. Neural Regen Res. 2017;12(11):1877.
163. Njan AA, Adenuga FO, Ajayi AM, Sotunde O, Ologe MO, Olaoye SO, et al. Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus. Heliyon. 2020;6(5): e04011.
164. Dutta K, Patel P, Rahimian R, Phaneuf D, Julien JP. Withania somnifera reverses transactive response DNA binding protein 43 proteinopathy in a mouse model of amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Neurotherapeutics. 2017;14(2):447–62.
165. Moon M, Kim HG, Choi JG, Oh H, Lee PK, Ha SK, et al. 6-Shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia. Biochem Biophys Res Commun. 2014;449(1):8–13.
166. Li C, Zhang C, Zhou H, Feng Y, Tang F, Hoi MP, et al. Inhibitory effects of betulinic acid on LPS-induced neuroinflammation involve M2 microglial polarization via CaMKKβ-dependent AMPK activation. Front Mol Neurosci. 2018;11:98.
167. Ma J, Ren Q, Dong B, Shi Z, Zhang J, Jin D-Q, et al. NO inhibitory constituents as potential anti-neuroinflammatory agents for AD from Blumea balsamifera. Bioorg Chem. 2018;76:449–57.
168. Choi WJ, Kim SK, Park HK, Sohn UD, Kim W. Anti-inflammatory and anti-superbacterial properties of sulforaphane from shepherd’s purse. Korean J Physiol Pharmacol. 2014;18(1):33–9.
169. Li R, Huang YG, Fang D, Le WD. (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res. 2004;78(5):723–31.
170. Lim H-S, Kim YJ, Kim B-Y, Park G, Jeong S-J. The anti-neuroinflammatory activity of tectorigenin pretreatment via downregulated NF-κB and ERK/JNK pathways in BV-2 microglial and microglia inactivation in mice with lipopolysaccharide. Front Pharmacol. 2018;9:462.
171. Grossi C, Rigacci S, Ambrosini S, Ed Dami T, Luccarini I, Traini C, et al. The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology. PLoS ONE. 2013;8(8):e71702.
172. Simonyi A, Chen Z, Jiang J, Zong Y, Chuang DY, Gu Z, et al. Inhibition of microglial activation by elderberry extracts and its phenolic components. Life Sci. 2015;128:30–8.
173. Alkuwari A, Al Naemi M, Vito P, Stilo R, Ahmed T, Al NH. Biolog
174. Lim HJ, Dong G-Z, Lee HJ, Ryu J-H. In vitro neuroprotective activity of sesquiterpenoids from the flower buds of Tussilago farfara. J Enzyme Inhibition Med Chem. 2015;30(5):852–6.
175. Meyer P-F, Tremblay-Mercier J, Leoutsakos J, Madjar C, Lafaille-Maignan M-É, Sava and tissue-specific subnetworks. Mol Biosyst. 2009;5(5):422–43.
340. Liu J-L, Fan Y-G, Yang Z-S, Wang Z-Y, Guo C. Iron and Alzheimer’s disease: from pathogenesis to therapeutic implications. Front Neurosci. 2018;12:632.
341. Huat TJ, Camats-Perna J, Newcombe EA, Valmas N, Kitazawa M, Medeiros R. Metal toxicity links to Alzheimer’s disease and neuroinflammation. J Mol Biol. 2019;431(9):1843–68.
342. Bush AI. The metal theory of Alzheimer’s disease. J Alzheimers Dis. 2013;33(Suppl 1):S277–81.
343. Lippi SLP, Neely CLC, Amaya AL. Trace concentrations, heavy implications: influences of biometals on major brain pathologies of Alzheimer’s disease. Int J Biochem Cell Biol. 2022;143: 106136.
344. Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron. 2001;30(3):665–76.
345. Zhang Y, He M-l. Deferoxamine enhances alternative activation of microglia and inhibits amyloid beta deposits in APP/PS1 mice. Brain Res. 2017;1677:86–92.
346. Benoit SL, Maier RJ. The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation. Sci Rep. 2021;11(1):1–11.
347. Bjørklund G, Mutter J, Aaseth J. Metal chelators and neurotoxicity: lead, mercury, and arsenic. Arch Toxicol. 2017;91(12):3787–97.
348. Roemhild K, von Maltzahn F, Weiskirchen R, Knüchel R, von Stillfried S, Lammers T. Iron metabolism: pathophysiology and pharmacology. Trends Pharmacol Sci. 2021;42(8):640–56.
349. Fasae KD, Abolaji AO, Faloye TR, Odunsi AY, Oyetayo BO, Enya JI, et al. Metallobiology and therapeutic chelation of biometals (copper, zinc and iron) in Alzheimer’s disease: limitations, and current and future perspectives. J Trace Elem Med Biol. 2021;67: 126779.
350. Yeo D, Choi TG, Kim SS. Metal ions-mediated oxidative stress in Alzheimer’s disease and chelation therapy. Reactive Oxygen Species: IntechOpen; 2021.
351. Amadi CN, Offor SJ, Frazzoli C, Orisakwe OE. Natural antidotes and management of metal toxicity. Environ Sci Pollut Res. 2019;26(18):18032–52.
352. Lima TG, Benevides FLN, Esmeraldo FL, Farias IS, Dourado DXC, Fontenele EGP, et al. Treatment of iron overload syndrome: a general review. Rev Assoc Med Bras. 2019;65:1216–22.
353. Hegde ML, Bharathi P, Suram A, Venugopal C, Jagannathan R, Poddar P, et al. Challenges associated with metal chelation therapy in Alzheimer’s disease. J Alzheimers Dis. 2009;17(3):457–68.
354. El-Shanshory M, Hablas NM, Aboonq MS, Fakhreldin AR, Attia M, Arafa W, et al. Nigella sativa improves anemia, enhances immunity and relieves iron overload-induced oxidative stress as a novel promising treatment in children having beta-thalassemia major. J Herbal Med. 2019;16: 100245.
355. Moayedi B, Gharagozloo M, Esmaeil N, Maracy MR, Hoorfar H, Jalaeikar M. A randomized double-blind, placebo-controlled study of therapeutic effects of silymarin in β-thalassemia major patients receiving desferrioxamine. Eur J Haematol. 2013;90(3):202–9.
356. Darvishi Khezri H, Salehifar E, Kosaryan M, Aliasgharian A, Jalali H, Hadian Amree A. Potential effects of silymarin and its flavonolignan components in patients with β-Thalassemia major: a comprehensive review in 2015. Adv Pharmacol Sci. 2016;2016.
357. Jetsrisuparb AJ, Komwilaisak P, Wiangnon S. Green tea consumption prevented iron overload: a case report of thalassemia intermedia. J Hematol Transfusion Med. 2014;24(4):389–94.
358. Sarkar R, Hazra B, Mandal N. Amelioration of iron overload-induced liver toxicity by a potent antioxidant and iron chelator, Emblica officinalis Gaertn. Toxicol Ind Health. 2015;31(7):656–69.
359. Tirgar P, Desai T. Investigation into iron chelating activity of Triticum aestivum (wheat grass) in iron-dextran induce iron overload model of thalassaemia. J Pharm Res. 2011;4(9):3066–9.
360. Lakey-Beitia J, Burillo AM, La Penna G, Hegde ML, Rao K. Polyphenols as potential metal chelation compounds against Alzheimer’s disease. J Alzheimers Dis. 2021;82(s1):S335–57.
361. Ashok A, Rai NK, Tripathi S, Bandyopadhyay S. Exposure to As-, Cd-, and Pb-mixture induces Aβ, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats. Toxicol Sci. 2015;143(1):64–80.
362. Wisessaowapak C, Visitnonthachai D, Watcharasit P, Satayavivad J. Prolonged arsenic exposure increases tau phosphorylation in differentiated SH-SY5Y cells: the contribution of GSK3 and ERK1/2. Environ Toxicol Pharmacol. 2021;84: 103626.
363. Kianoush S, Balali-Mood M, Mousavi SR, Moradi V, Sadeghi M, Dadpour B, et al. Comparison of therapeutic effects of garlic and d-Penicillamine in patients with chronic occupational lead poisoning. Basic Clin Pharmacol Toxicol. 2012;110(5):476–81.
364. Roy M, Sinha D, Mukherjee S, Biswas J. Curcumin prevents DNA damage and enhances the repair potential in a chronically arsenicexposed human population in West Bengal, India. Eur J Cancer Prev. 2011;20(2):123–31.
365. Muthumani M, Prabu SM. Silibinin potentially protects arsenicinduced oxidative hepatic dysfunction in rats. Toxicol Mech Methods. 2012;22(4):277–88.
366. Desai V, Ganatra T, Joshi U, Desai T, Tirgar P. An investigation into the heavy metal chelating potential of ananas comosus fruit in arsenic intoxicated rats. J Pharm Res. 2012;5(8):4084–7.
367. Reddy YA, Chalamaiah M, Ramesh B, Balaji G, Indira P. Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats. J Food Sci Technol. 2014;51(5):908–14.
368. Velaga MK, Daughtry LK, Jones AC, Yallapragada PR, Rajanna S, Rajanna B. Attenuation of lead-induced oxidative stress in rat brain, liver, kidney and blood of male Wistar rats by Moringa oleifera seed powder. J Environ Pathol Toxicol Oncol. 2014;33(4):323.
369. El-Boshy M, Ashshi A, Gaith M, Qusty N, Bokhary T, AlTaweel N, et al. Studies on the protective effect of the artichoke (Cynara scolymus) leaf extract against cadmium toxicity-induced oxidative stress, hepatorenal damage, and immunosuppressive and hematological disorders in rats. Environ Sci Pollut Res. 2017;24(13):12372–83.
370. Singh T, Goel RK. Neuroprotective effect of Allium cepa L. in aluminium chloride induced neurotoxicity. Neurotoxicology. 2015;49:1–7.
371. Jakkala LK, Ali SA. Amelioration of the toxic effects of aluminium induced neurodegenerative changes in brain of albino rats by aloe vera. J Global Biosci. 2015;4(8):3171–7.
372. Tito A, Carola A, Bimonte M, Barbulova A, Arciello S, de Laurentiis F, et al. A tomato stem cell extract, containing antioxidant compounds and metal chelating factors, protects skin cells from heavy metal-induced damages. Int J Cosmet Sci. 2011;33(6):543–52.
373. Abib RT, Peres KC, Barbosa AM, Peres TV, Bernardes A, Zimmermann LM, Quincozes-Santos A, Fiedler HD, Leal RB, Farina M, Gottfried C. Epigallocatechin- 3-gallate protects rat brain mitochondria against cadmiuminduced damage. Food and chemical toxicology. 2011;49(10):2618–23.
374. Susan A, Rajendran K, Sathyasivam K, Krishnan UM. An overview of plant-based interventions to ameliorate arsenic toxicity. Biomed Pharmacother. 2019;109:838–52.
375. Brookmeyer R, Evans DA, Hebert L, Langa KM, Heeringa SG, Plassman BL, et al. National estimates of the prevalence of Alzheimer’s disease in the United States. Alzheimers Dement. 2011;7(1):61–73.
376. Kantarci K, Lowe VJ, Lesnick TG, Tosakulwong N, Bailey KR, Fields JA, et al. Early postmenopausal transdermal 17β-estradiol therapy and amyloid-β deposition. J Alzheimers Dis. 2016;53(2):547–56.
377. Rossetti MF, Cambiasso MJ, Holschbach MA, Cabrera R. Oestrogens and progestagens: synthesis and action in the brain. J Neuroendocrinol. 2016;28(7).
378. Uddin M, Rahman M, Jakaria M, Hossain M, Islam A, Ahmed M, et al. Estrogen signaling in Alzheimer’s disease: molecular insights and therapeutic targets for Alzheimer’s dementia. Mol Neurobiol. 2020;57(6):2654–70.
379. Henderson VW. Alzheimer’s disease: review of hormone therapy trials and implications for treatment and prevention after menopause. J Steroid Biochem Mol Biol. 2014;142:99–106.
380. Henderson VW, Ala T, Sainani KL, Bernstein AL, Stephenson BS, Rosen AC, et al. Raloxifene for women with Alzheimer disease: a randomized controlled pilot trial. Neurology. 2015;85(22):1937–44.
381. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity. Brain Res. 2011;1379:188–98.
382. Rocca W, Bower J, Maraganore D, Ahlskog J, Grossardt B, De Andrade M, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology. 2007;69(11):1074–83.
383. Hodis HN, Sarrel P. Menopausal hormone therapy and breast cancer: what is the evidence from randomized trials? Climacteric. 2018;21(6):521–8.
384. Deli T, Orosz M, Jakab A. Hormone replacement therapy in cancer survivors —review of the literature. Pathol Oncol Res. 2020;26(1):63–78.
385. de Villiers TJ, Hall JE, Pinkerton JV, Pérez SC, Rees M, Yang C, et al. Revised global consensus statement on menopausal hormone therapy. Maturitas. 2016;91:153–5.
386. Cassidy A. Committee on Toxicity draft report on phyto-oestrogens and health–review of proposed health effects of phyto-oestrogen exposure and recommendations for future research. Nutr Bull. 2003;28(2):205–13.
387. Kuhnle GG, Dell’Aquila C, Aspinall SM, Runswick SA, Joosen AM, Mulligan AA, et al. Phytoestrogen content of fruits and vegetables commonly consumed in the UK based on LC–MS and 13C-labelled standards. Food Chem. 2009;116(2):542–54.
388. Lima SMRR, Bernardo BFA, Yamada SS, Reis BF, da Silva GMD, Galvão MAL. Effects of Glycine max (L.) Merr. soy isoflavone vaginal gel on epithelium morphology and estrogen receptor in postmenopausal women: a 12-week, randomized, double-blind, placebocontrolled trial. Maturitas. 2014;78(3):205–11.
389. Soni M, Rahardjo TBW, Soekardi R, Sulistyowati Y, Yesufu-Udechuku A, Irsan A, et al. Phytoestrogens and cognitive function: a review. Maturitas. 2014;77(3):209–20.
390. Henderson VW, St John JA, Hodis HN, Kono N, McCleary CA, Franke AA, et al. Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology. 2012;78(23):1841–8.
391. Casini ML, Marelli G, Papaleo E, Ferrari A, D’Ambrosio F, Unfer V. Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: a randomized, double-blind, crossover, placebo-controlled study. Fertil Steril. 2006;85(4):972–8.
392. Thorp AA, Sinn N, Buckley JD, Coates AM, Howe PR. Soya isoflavone supplementation enhances spatial working memory in men. Br J Nutr. 2009;102(9):1348–54.
393. Fournier L, Ryan-Borchers T, Robison L, Wiediger M, Park J, Chew B, et al. The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women. J Nutr Health Aging. 2007;11(2):155.
394. Reinli K, Block G. Phytoestrogen content of foods–a compendium of literature values. Nutr Cancer. 1996;26(2):123–48.
395. Pan M, Li Z, Yeung V, Xu R-J. Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene of BDNF, TrkB receptor and synaptic factors in ovariectomized rats. Nutr Metab. 2010;7(1):1–11.
396. Lee M-R, Kim B, Lee Y, Park S-Y, Shim J-H, Chung B-H, et al. Ameliorative effects of Pueraria lobata extract on postmenopausal symptoms through promoting estrogenic activity and bone markers in ovariectomized rats. Evid-Based Complement Altern Med. 2021;2021:1.
397. Jdidi H, Ghorbel Koubaa F, Aoiadni N, Elleuch A, Makni-Ayadi F, El Feki A. Effect of Medicago sativa compared to 17β-oestradiol on osteoporosis in ovariectomized mice. Arch Physiol Biochem. 2020:1–8.
398. Bianchi VE, Bresciani E, Meanti R, Rizzi L, Omeljaniuk RJ, Torsello A. The role of androgens in women’s health and wellbeing. Pharmacol Res. 2021;171: 105758.
399. Raber J. Androgens, apoE, and Alzheimer’s disease. Sci Aging Knowl Environ. 2004;2004(11):re2.
400. Ajani EO, Usman LA. Tamarindus indica fruit pulp restores reproductive function in sodium fluoride administered rats. FASEB J. 2020;34(S1):1.
401. Itzhaki RF, Lathe R, Balin BJ, Ball MJ, Bearer EL, Braak H, et al. Microbes and Alzheimer’s disease. J Alzheimers Dis. 2016;51(4):979–84.
402. Wozniak MA, Frost AL, Preston CM, Itzhaki RF. Antivirals reduce the formation of key Alzheimer’s disease molecules in cell cultures acutely infected with herpes simplex virus type 1. PLoS ONE. 2011;6(10): e25152.
403. Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR. Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology. 2016;87(22):2324–32.
404. Zhao YL, Gou ZP, Shang JH, Li WY, Kuang Y, Li MY, et al. Anti-microbial effects in vitro and in vivo of Alstonia scholaris. Nat Prod Bioprospect. 2021;11(1):127–35.
405. Khan MR, Omoloso AD, Kihara M. Antibacterial activity of Alstonia scholaris and Leea tetramera. Fitoterapia. 2003;74(7–8):736–40.
406. Shoeib A, Zarouk A, El-Esnawy N. Screening of antiviral activity of some terrestrial leaf plants against acyclovir-resistant HSV type-1 in cell culture. Aust J Basic Appl Sci. 2011;5(10):75–92.
407. Xu HX, Wan M, Loh BN, Kon OL, Chow PW, Sim KY. Screening of traditional medicines for their inhibitory activity against HIV-1 protease. Phytother Res. 1996;10(3):207–10.
408. Ajibesin KK, Essien EE, Adesanya SA. Antibacterial constituents of the leaves of Dacryodes edulis. Afr J Pharm Pharmacol. 2011;5(15):1782–6.
409. Fakoya A, Owojuyigbe O, Fakoya S, Adeoye S. Possible antimicrobial activity of Morinda lucida stem bark, leaf and root extracts. Afr J Biotechnol. 2014;13(3):471.
410. Zhang H-J, Rumschlag-Booms E, Guan Y-F, Wang D-Y, Liu K-L, Li W-F, et al. Potent inhibitor of drug-resistant HIV-1 strains identified from the medicinal plant Justicia gendarussa. J Nat Prod. 2017;80(6):1798–807.
411. Adamson CS, Chibale K, Goss RJM, Jaspars M, Newman DJ, Dorrington RA. Antiviral drug discovery: preparing for the next pandemic. Chem Soc Rev. 2021;50(6):3647–55.
412. Notka F, Meier G, Wagner R. Concerted inhibitory activities of Phyllanthus amarus on HIV replication in vitro and ex vivo. Antiviral Res. 2004;64(2):93–102.
413. Yang Z, Wang Y, Zheng Z, Zhao S, Zhao J, Lin Q, et al. Antiviral activity of Isatis indigotica root-derived clemastanin B against human and avian influenza A and B viruses in vitro. Int J Mol Med. 2013;31(4):867–73.
414. Kumaki Y, Wandersee MK, Smith AJ, Zhou Y, Simmons G, Nelson NM, et al. Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin. Antiviral Res. 2011;90(1):22–32.
415. Abreu CM, Price SL, Shirk EN, Cunha RD, Pianowski LF, Clements JE, et al. Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTR. PLoS ONE. 2014;9(5): e97257.
416. Itzhaki RF, Golde TE, Heneka MT, Readhead B. Do infections have a role in the pathogenesis of Alzheimer disease? Nat Rev Neurol. 2020;16(4):193–7.
417. Mouhajir F, Hudson J, Rejdali M, Towers G. Multiple antiviral activities of endemic medicinal plants used by Berber peoples of Morocco. Pharm Biol. 2001;39(5):364–74.
418. Haidari M, Ali M, Casscells SW III, Madjid M. Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir. Phytomedicine. 2009;16(12):1127–36.
419. Neurath AR, Strick N, Li Y-Y, Debnath AK. Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide. BMC Infect Dis. 2004;4(1):1–12.
420. Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333.
421. Kapadia SP, Pudakalkatti PS, Shivanaikar S. Detection of antimicrobial activity of banana peel (Musa paradisiaca L.) on Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans: an in vitro study. Contemp Clin Dent. 2015;6(4):496.
422. Carrol DH, Chassagne F, Dettweiler M, Quave CL. Antibacterial activity of plant species used for oral health against Porphyromonas gingivalis. PLoS ONE. 2020;15(10): e0239316.
423. Bairamian D, Sha S, Rolhion N, Sokol H, Dorothée G, Lemere CA, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease. Mol Neurodegener. 2022;17(1):19.
424. Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017;7(1):13537.
425. Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017;49:60–8.
426. Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy K, Frisoni G, et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep. 2017;7(1):1–15.
427. Kowalski K, Mulak A. Brain-gut-microbiota axis in Alzheimer’s disease. J Neurogastroenterol Motil. 2019;25(1):48–60.
428. Kim CS, Cha L, Sim M, Jung S, Chun WY, Baik HW, et al. Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial. J Gerontol A Biol Sci Med Sci. 2021;76(1):32–40.
429. Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasuti C, et al. Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep. 2017;7(1):2426.
430. Bonfili L, Cuccioloni M, Gong C, Cecarini V, Spina M, Zheng Y, et al. Gut microbiota modulation in Alzheimer’s disease: focus on lipid metabolism. Clin Nutr. 2022;41(3):698–708.
431. Singh A, D’Amico D, Andreux PA, Dunngalvin G, Kern T, Blanco-Bose W, et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr. 2021;76:297.
432. Eid HM, Wright ML, Anil Kumar NV, Qawasmeh A, Hassan STS, Mocan A, et al. Significance of microbiota in obesity and metabolic diseases and the modulatory potential by medicinal plant and food ingredients. Front Pharmacol. 2017;8:387.
433. Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, et al. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. 2020;69(7):1218–28.
434. Izadi M, Ali TA, Pourkarimi E. Over fifty years of life, death, and cannibalism: a historical recollection of apoptosis and autophagy. Int J Mol Sci. 2021;22(22):12366.
435. Su JH, Anderson AJ, Cummings BJ, Cotman CW. Immunohistochemical evidence for apoptosis in Alzheimer’s disease. NeuroReport. 1994;5(18):2529–33.
436. Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC. Neuronal cell death. Physiol Rev. 2018;98(2):813–80.
437. Mattson MP, Arumugam TV. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab. 2018;27(6):1176–99.
438. Liu RM. Aging, cellular senescence, and Alzheimer’s disease. Int J Mol Sci. 2022;23(4):1989.
439. Gómez-Estrada H, Díaz-Castillo F, Franco-Ospina L, Mercado-Camargo J, Guzmán-Ledezma J, Medina JD, et al. Folk medicine in the northern coast of Colombia: an overview. J Ethnobiol Ethnomed. 2011;7:27.
440. Upasani MS, Upasani SV, Beldar VG, Beldar CG, Gujarathi PP. Infrequent use of medicinal plants from India in snakebite treatment. Integr Med Res. 2018;7(1):9–26.
441. Mehta P, Bisht K, Sekar KC. Diversity of threatened medicinal plants of Indian Himalayan Region. Plant Biosyst Int J Dealing Aspects Plant Biol. 2021;155(6):1121–32.
442. Pedrollo CT, Kinupp VF, Shepard G, Heinrich M. Medicinal plants at Rio Jauaperi, Brazilian Amazon: ethnobotanical survey and environmental conservation. J Ethnopharmacol. 2016;186:111–24.
443. Rai PK, Lalramnghinglova H. Ethnomedicinal plant resources of Mizoram, India: implication of traditional knowledge in health care system. Ethnobotanical Leaflets. 2010;2010(3):6.
444. Pieroni A, Sõukand R. The disappearing wild food and medicinal plant knowledge in a few mountain villages of North-Eastern Albania. J Appl Botany Food Qual. 2017;90.
445. Bhattarai S, Chaudhary RP, Taylor RS. Ethnomedicinal plants used by the people of Manang district, central Nepal. J Ethnobiol Ethnomed. 2006;2:41.
446. Sharma J, Gairola S, Gaur RD, Painuli RM, Siddiqi TO. Ethnomedicinal plants used for treating epilepsy by indigenous communities of sub-Himalayan region of Uttarakhand, India. J Ethnopharmacol. 2013;150(1):353–70.
447. Getaneh S, Girma Z. An ethnobotanical study of medicinal plants in Debre Libanos Wereda, Central Ethiopia. Afr J Plant Sci. 2014;8(7):366–79.
448. Singh YN. Traditional medicine in Fiji: some herbal folk cures used by Fiji Indians. J Ethnopharmacol. 1986;15(1):57–88.
449. Longuefosse JL, Nossin E. Medical ethnobotany survey in Martinique. J Ethnopharmacol. 1996;53(3):117–42.
450. Malawani A, Nuneza O, Uy M, Senarath W. Ethnobotanical survey of the medicinal plants used by the Maranois in Pualas, Lanao del Sur. Philippines BEPLS. 2017;6(6):45–53.
451. Motti R, Motti P. An ethnobotanical survey of useful plants in the agro Nocerino Sarnese (Campania, southern Italy). Hum Ecol. 2017;45(6):865–78.
452. Gazzaneo LRS, De Lucena RFP, de Albuquerque UP. Knowledge and use of medicinal plants by local specialists in a region of Atlantic Forest in the state of Pernambuco (Northeastern Brazil). J Ethnobiol Ethnomed. 2005;1(1):1–8.
453. Lulekal E, Kelbessa E, Bekele T, Yineger H. An ethnobotanical study of medicinal plants in Mana Angetu district, southeastern Ethiopia. J Ethnobiol Ethnomed. 2008;4:10.
454. Polat R, Satıl F. An ethnobotanical survey of medicinal plants in Edremit Gulf (Balıkesir-Turkey). J Ethnopharmacol. 2012;139(2):626–41.
455. Bussmann RW, Sharon D. Traditional medicinal plant use in Northern Peru: tracking two thousand years of healing culture. J Ethnobiol Ethnomed. 2006;2:47.
456. Lee C, Kim S-Y, Eum S, Paik J-H, Bach TT, Darshetkar AM, et al. Ethnobotanical study on medicinal plants used by local Van Kieu ethnic people of Bac Huong Hoa nature reserve, Vietnam. J Ethnopharmacol. 2019;231:283–94.
457. Ji H, Shengji P, Chunlin L. An ethnobotanical study of medicinal plants used by the Lisu people in Nujiang, northwest Yunnan, China. Econ Bot. 2004;58(1):S253–64.
458. Malan DF, Neuba DF, Kouakou KL. Medicinal plants and traditional healing practices in Ehotile people, around the Aby Lagoon (eastern littoral of Côte d’Ivoire). J Ethnobiol Ethnomed. 2015;11:21.
459. Voeks RA, Leony A. Forgetting the forest: assessing medicinal plant erosion in eastern Brazil. Econ Bot. 2004;58(1):S294–306.
460. Nankaya J, Gichuki N, Lukhoba C, Balslev H. Sustainability of the loita Maasai childrens’ ethnomedicinal knowledge. Sustainability. 2019;11(19):5530.
461. Begossi A, Hanazaki N, Tamashiro JY. Medicinal plants in the Atlantic Forest (Brazil): knowledge, use, and conservation. Hum Ecol. 2002;30(3):281–99.
462. Joly LG, Guerra S, Séptimo R, Solís PN, Correa M, Gupta M, et al. Ethnobotanical inventory of medicinal plants used by the Guaymi Indians in western Panama. Part I. J Ethnopharmacol. 1987;20(2):145–71.
463. Au DT, Wu J, Jiang Z, Chen H, Lu G, Zhao Z. Ethnobotanical study of medicinal plants used by Hakka in Guangdong, China. J Ethnopharmacol. 2008;117(1):41–50.
464. Chander MP, Kartick C, Gangadhar J, Vijayachari P. Ethno medicine and healthcare practices among Nicobarese of Car Nicobar—an indigenous tribe of Andaman and Nicobar Islands. J Ethnopharmacol. 2014;158:18–24.
465. Kassam K-A. Viewing change through the prism of indigenous human ecology: findings from the Afghan and Tajik Pamirs. Hum Ecol. 2009;37(6):677–90.
466. Pawera L, Verner V, Termote C, Sodombekov I, Kandakov A, Karabaev N, et al. Medical ethnobotany of herbal practitioners in the Turkestan Range, southwestern Kyrgyzstan. Acta Societatis Botanicorum Poloniae. 2016;85(1).
467. Chakraborty P. Herbal genomics as tools for dissecting new metabolic pathways of unexplored medicinal plants and drug discovery. Biochimie open. 2018;6:9–16.
468. Roychoudhury A, Bhowmik R. State-of-the-art technologies for improving the quality of medicinal and aromatic plants. In: Aftab T, Hakeem KR, editors. Medicinal and aromatic plants. Cham: Springer; 2021. p. 593–627.
469. Espinosa-Leal CA, Puente-Garza CA, García-Lara S. In vitro plant tissue culture: means for production of biological active compounds. Planta. 2018;248(1):1–18.
470. Hanafy AS, Dietrich D, Fricker G, Lamprecht A. Blood-brain barrier models: rationale for selection. Adv Drug Deliv Rev. 2021;176: 113859.
471. Hajal C, Le Roi B, Kamm RD, Maoz BM. Biology and models of the blood–brain barrier. Annu Rev Biomed Eng. 2021;23:359–84.
472. Kim HN. Engineered models for studying blood-brain-barrier-associated brain physiology and pathology. 2021.
473. Adriani G, Ma D, Pavesi A, Kamm RD, Goh EL. A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood–brain barrier. Lab Chip. 2017;17(3):448–59.
474. Fernandes DC, Reis RL, Oliveira JM. Advances in 3D neural, vascular and neurovascular models for drug testing and regenerative medicine. Drug Discovery Today. 2021;26(3):754–68.
475. Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE. beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci. 1992;12(2):376–89.
476. Abdul HM, Sama MA, Furman JL, Mathis DM, Beckett TL, Weidner AM, et al. Cognitive decline in Alzheimer’s disease is associated with selective changes in calcineurin/NFAT signaling. J Neurosci. 2009;29(41):12957–69.
477. Berridge MJ. Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia. Prion. 2013;7(1):2–13.
478. Tong BC, Wu AJ, Li M, Cheung KH. Calcium signaling in Alzheimer’s disease & therapies. Biochim Biophys Acta Mol Cell Res. 2018;1865(11 Pt B):1745–60.
479. Karpurapu M, Lee YG, Qian Z, Wen J, Ballinger MN, Rusu L, et al. Inhibition of nuclear factor of activated T cells (NFAT) c3 activation attenuates acute lung injury and pulmonary edema in murine models of sepsis. Oncotarget. 2018;9(12):10606.
480. Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature. 2018;560(7717):185–91.
481. Bacyinski A, Xu M, Wang W, Hu J. The paravascular pathway for brain waste clearance: current understanding, significance and controversy. Front Neuroanat. 2017;11:101.
482. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4(147):147.
483. Ishida K, Yamada K, Nishiyama R, Hashimoto T, Nishida I, Abe Y, et al. Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration. J Exp Med. 2022;219(3): e20211275.
484. Wheat J, Currie G, Kiat H, Bone K. Improving lymphatic drainage with herbal preparations: a potentially novel approach to management of lymphedema. Aust J Med Herbalism. 2009;21(3):66–70.
485. Ruggiero MA, Gordon DP, Orrell TM, Bailly N, Bourgoin T, Brusca RC, et al. A higher level classification of all living organisms. PLoS ONE. 2015;10(4): e0119248.
486. Xiang S, Liu F, Lin J, Chen H, Huang C, Chen L, et al. Fucoxanthin inhibits β-amyloid assembly and attenuates β-amyloid oligomer-induced cognitive impairments. J Agric Food Chem. 2017;65(20):4092–102.
487. Olasehinde TA, Olaniran AO, Okoh AI. Macroalgae as a valuable source of naturally occurring bioactive compounds for the treatment of Alzheimer’s disease. Mar Drugs. 2019;17(11):609.
488. Ogawa Y, Kaneko Y, Sato T, Shimizu S, Kanetaka H, Hanyu H. Sarcopenia and muscle functions at various stages of Alzheimer disease. Front Neurol. 2018;9:710.
489. Salvadori L, Mandrone M, Manenti T, Ercolani C, Cornioli L, Lianza M, et al. Identification of Withania somnifera-Silybum marianum-Trigonella foenum-graecum Formulation as a Nutritional Supplement to Contrast Muscle Atrophy and Sarcopenia. Nutrients. 2021;13(1):49.
490. Sethy R, Kullu B. Micropropagation of ethnomedicinal plant Calotropis sp. and enhanced production of stigol. Plant Cell Tissue Organ Cult (PCTOC). 2022;149:147.
491. Sharma N, Acharya S, Kumar K, Singh N, Chaurasia O. Hydroponics as an advanced technique for vegetable production: an overview. J Soil Water Conserv. 2018;17(4):364–71.
492. Maggini R, Kiferle C, Pardossi A. Hydroponic production of medicinal plants. Medicinal plants: antioxidant properties, traditional uses and conservation strategies. Hauppauge: Nova Science Publishers Inc; 2014. p. 91–116.
493. Nwafor I, Nwafor C, Manduna I. Constraints to cultivation of medicinal plants by smallholder farmers in South Africa. Horticulturae. 2021;7(12):531.
494. Sambo P, Nicoletto C, Giro A, Pii Y, Valentinuzzi F, Mimmo T, et al. Hydroponic solutions for soilless production systems: issues and opportunities in a smart agriculture perspective. Front Plant Sci. 2019;10:923.
495. Izquierdo J. editor Simplified hydroponics: a tool for food security in Latin America and the Caribbean. Int Conf Exhib Soil Cult: ICESC. 2005;2005:742.
496. Carrasco G, Manríquez P, Galleguillos F, Fuentes-Peñailillo F, Urrestarazu M, editors. Evolution of soilless culture in Chile. III International Symposium on Soilless Culture and Hydroponics: Innovation and Advanced Technology for Circular Horticulture 1321; 2021.
497. Noe N, Lehmann J. Prelude medicinal plants. Belgian Biodiversity Platform. Database. 2012.
498. Hoffman M, Koenig K, Bunting G, Costanza WJ. Biodiversity Hotspots (version 2016.1). 2016.
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