Exploration of Neuroscience

From: Phenolic compounds as anti-Alzheimer’s disease agents

Table 1. Phenolic compounds that inhibit clinical indications of Alzheimer’s disease

No.	Compound	Mechanism	IC₅₀ (μM)	IC₅₀ (µmol/µmol AChE)	Eq. Trolox (mM)	Ref.
1	Ferulic acid	Aβ-42	9.3			[43]
2	Curcumin	Aβ-42	0.2			[44]
2	Curcumin	AChE	58.08			[108]
3	Rosmarinic acid	Aβ-42	20.3			[45]
		τ-protein	7.7			[71]
		AChE	> 150			[109]
		BuChE	33.50			[109]
4	Resveratrol	Aβ-42	30.0			[46]
		AChE	1.66			[109]
		BuChE	1.56			[109]
5	3,4-Di-O-caffeoylquinic acid	Aβ-42	4.7			[48]
5	3,4-Di-O-caffeoylquinic acid	BACE1	3.3			[47]
6	3,5-Di-O-caffeoylquinic acid	Aβ-42	16.4			[48]
7	4,5-Di-O-caffeoylquinic acid	Aβ-42	0.1			[48]
8	1,4,5-Tri-O-caffeoylquinic acid	Aβ-42	2.2			[48]
9	3,4,5-Tri-O-caffeoylquinic acid	Aβ-42	0.3			[48]
10	3,4,5-Tri-O-caffeoylquinic acid methyl ester	Aβ-42	3.0			[48]
11	Caffeic acid	Aβ-42	32.8			[48]
		NO	40.0			[75]
		AChE	179.9			[75]
12	Chlorogenic acid	Aβ-42	92.9			[48]
		NO	49.6			[75]
		AChE	410			[102]
13	Acteoside	Aβ-42	11.3			[56]
		AChE	19.9			[113]
		BuChE	35.0			[113]
14	Cistanoside D	Aβ-42	> 100			[56]
15	Methylacteoside	Aβ-42	> 100			[56]
16	Oraposide	Aβ-42	8.2			[56]
17	3'''-O-methylcrenatoside	Aβ-42	28.4			[56]
18	Methyloraposide	Aβ-42	> 100			[56]
19	Isoacteoside	Aβ-42	33.5			[56]
20	Isocrenatoside	Aβ-42	27.4			[56]
21	Hydroxytyrosol	Aβ-42	92.0			[56]
22	Syringaldehyde	BACE1	34.90			[58]
22	Syringaldehyde	AChE	> 1,000			[96]
23	Benzoic acid	BACE1	309.30			[58]
24	Phthalic acid	BACE1	133.40			[58]
25	Urolithin B	BACE1	35.6			[58]
26	(+)-Usnic acid	BACE1	43.1			[58]
27	Esculetin	BACE1	7.67			[59]
		AChE	6.13			[59]
		BuChE	8.66			[59]
28	Bergenin	BACE1	> 400			[60]
29	11-O-p-hydroxybenzoylbergenin	BACE1	23.80			[60]
30	11-O-protocatechoylbergenin	BACE1	0.60			[60]
31	1,2,3-Trigalloyl glucopyranoside	BACE1	9.43			[63]
32	Acetonyl geraniin	BACE1	0.71			[63]
33	Helioscopinin A	BACE1	0.99			[63]
34	Helioscopinin B	BACE1	0.41			[63]
35	Furosin	BACE1	17.77			[63]
36	Rugosin E	BACE1	0.06			[63]
37	Euphorscopin	BACE1	2.50			[63]
38	Jolkinin	BACE1	54.93			[63]
39	1-Galloyl glucopyranose	BACE1	> 350			[63]
40	1,6-Digalloyl glucopyranose	BACE1	> 350			[63]
41	2,6-Digalloyl glucopyranose	BACE1	> 350			[63]
42	1,2,3,4,6-Pentagalloyl glucopyranose	BACE1	> 350			[63]
43	1,2,6-Trigalloyl glucopyranose	BACE1	> 350			[63]
44	2-Galloyl galactose	BACE1	> 350			[63]
45	Corilagin	BACE1	> 350			[63]
46	Elaeocarpusin	BACE1	> 350			[63]
47	Geraniin	BACE1	> 350			[63]
48	Helioscopin B	BACE1	> 350			[63]
49	1,2,6-Trigalloyl allose	BACE1	> 350			[63]
50	1,3,6-Trigalloyl allose	BACE1	> 350			[63]
51	1,2,3,6-Tetragalloyl allose	BACE1	> 350			[63]
52	Bixanin	BACE1	> 350			[63]
53	3-O-galloylshikimic acid	BACE1	> 350			[63]
54	5-Pyrogallo-O-quinic acid	BACE1	> 350			[63]
55	α-Viniferin	BACE1	> 350			[63]
56	Schizandrin	BACE1	> 350			[63]
57	Gastrodin	GSK3β	NE			[73]
58	Salidroside	GSK3β	NE			[74]
59	Methylchlorogenic acid	NO	34.9			[75]
60	(E)-1,7-diphenylhept-4-en-3-one	SET-OH/H HAT-OOH	149.8		0.28	[76]
		AChE	277.8			[76]
		BuChE	NA			[76]
61	5-hydroxy-7-(4-hydroxy -3-methoxyphenyl)-1-phenylheptan-3-one	SET-OH/H HAT-OOH	14.81		1.74	[76]
		AChE	190.7			[76]
		BuChE	252.0			[76]
62	(4Z,6E)-5-hydroxy-1,7-diphenylhepta-4,6-dien-3-one	SET-OH/H HAT-OOH	> 250		0.33	[76]
		AChE	194.5			[76]
		BuChE	NA			[76]
63	p-Hydroxycinnamic acid	SET-OH/H HAT-OOH	29.94		3.20	[76]
		AChE	68.5			[113]
		BuChE	> 100			[113]
64	p-Hydroxybenzoic acid	AChE	150.6	6.36		[77, 95]
65	2-Hydroxy-4-methoxybenzaldehyde	AChE	47.0			[78]
66	4-Hydroxy-3-methoxybenzaldehyde	AChE	37.0			[78]
67	Methyl syringate	AChE		5.50		[95]
68	p-Hydroxyphenylpyruvic acid	AChE		5.84		[95]
69	Salicylic acid	AChE		6.07		[95]
70	p-Hydroxyphenylacetic acid	AChE		6.24		[95]
71	Homovanillic acid	AChE		6.45		[95]
72	Nordihydroguaiaretic acid	AChE		6.47		[95]
73	Protocatechuic acid	AChE		6.50		[95]
74	m-Hydroxybenzoic acid	AChE		6.68		[95]
75	Vanillic acid	AChE	923	6.79		[95, 102]
76	Syringic acid	AChE		6.96		[95]
77	Homogentisic acid	AChE		7.16		[95]
78	Gentisic acid	AChE		8.02		[95]
79	Gallic acid	AChE		9.32		[95]
80	Ethyl-p-hydroxybenzoate	AChE		31.38		[95]
81	Ethyl vanillate	AChE		34.19		[95]
82	Dihydroconiferyl dihydro-p-coumarate	AChE	357.9			[96]
83	Gigantol	AChE	> 1,000			[96]
84	Olivetol	AChE	0.005			[98]
84	Olivetol	BuChE	0.006			[98]
85	3,5-Dihydroxybenzoic acid	AChE	> 1,000			[102]
86	Hydroquinone	AChE	260			[102]
87	Thymohydroquinone	AChE	240.6			[103, 104]
88	Carvacrol	AChE	419.4			[103, 104]
89	Thymol	AChE	> 1,000			[103, 104]
90	3,3'-Di-O-methylellagic acid	AChE	141.6			[105]
90	3,3'-Di-O-methylellagic acid	BuChE	152.8			[105]
91	3,3',4'-Tri-O-methylellagic acid-4-O-β-D-xylopyranoside	AChE	128.6			[105]
91	3,3',4'-Tri-O-methylellagic acid-4-O-β-D-xylopyranoside	BuChE	> 200			[105]
92	3,3',4'-Tri-O-methylellagic acid-4-O-β-D-glucopyranoside	AChE	118.0			[105]
92	3,3',4'-Tri-O-methylellagic acid-4-O-β-D-glucopyranoside	BuChE	148.5			[105]
93	3,3'-Di-O-methylellagic acid-4-O-β-D-glucopyranoside	AChE	129.1			[105]
93	3,3'-Di-O-methylellagic acid-4-O-β-D-glucopyranoside	BuChE	182.4			[105]
94	Anisacanthin	AChE	0.09			[106]
95	Pinoresinol	AChE	0.292			[106]
96	Epipinoresinol	AChE	0.242			[106]
97	Phillyrin	AChE	0.279			[106]
98	Pinoresinol-4-O-β-D-glucoside	AChE	0.64			[106]
99	Tannic acid	AChE	0.12			[107]
99	Tannic acid	BuChE	0.09			[107]
100	Salvianolic acid B	AChE	> 150			[109]
100	Salvianolic acid B	BuChE	14.6			[109]
101	Salvianolic acid A	AChE	> 150			[109]
101	Salvianolic acid A	BuChE	97.7			[109]
102	Carnosic acid	AChE	95.8			[109]
102	Carnosic acid	BuChE	12.4			[109]
103	Carnosol	AChE	33.7			[109]
103	Carnosol	BuChE	11.9			[109]
104	Danshensu salt	AChE	NA			[109]
104	Danshensu salt	BuChE	109.8			[109]
105	Eugenol	AChE	8.69			[112]
105	Eugenol	BuChE	8.86			[112]
106	Butylated hydroxyl toluene	AChE	9.16			[112]
106	Butylated hydroxyl toluene	BuChE	9.00			[112]
107	Martinoside	AChE	> 100			[113]
107	Martinoside	BuChE	> 100			[113]
108	Cinnamic acid	AChE	78.5			[113]
108	Cinnamic acid	BuChE	> 100			[113]
109	Isoacteoside	AChE	21.9			[113]
109	Isoacteoside	BuChE	29.7			[113]
110	Decaffeoylverbascoside	AChE	16.1			[113]
110	Decaffeoylverbascoside	BuChE	46.0			[113]
111	Lavandulifolioside	AChE	301.0			[114]
112	Lapathoside B	AChE	> 100			[115]
112	Lapathoside B	BuChE	10.9			[115]
113	Vanicoside B	AChE	32.3			[115]
113	Vanicoside B	BuChE	7.5			[115]
114	Lapathoside A	AChE	30.6			[115]
114	Lapathoside A	BuChE	2.7			[115]
115	Smilaside J	AChE	56.0			[115]
115	Smilaside J	BuChE	10.1			[115]
116	Smilaside G	AChE	> 100			[115]
116	Smilaside G	BuChE	17.1			[115]
117	4-O-caffeoyl quinic acid	AChE	80.2			[116]
118	4,5-Di-O-caffeoyl quinic acid	AChE	62.6			[116]
119	Isocorilagin	AChE	0.49			[117]
119	Isocorilagin	BuChE	4.20			[117]

Return to article view

NE: not evaluated; NA: not active

Declarations

Author contributions

JM: Writing—original draft, Writing—review & editing, Visualization, Conceptualization.

Conflicts of interest

The author declares no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Hampl R, Bicíková M. Neuroimmunomodulatory steroids in Alzheimer dementia. J Steroid Biochem Mol Biol. 2010;119:97–104. [DOI] [PubMed]

Noori T, Dehpour AR, Sureda A, Sobarzo-Sanchez E, Shirooie S. Role of natural products for the treatment of Alzheimer’s disease. Eur J Pharmacol. 2021;898:173974. [DOI] [PubMed]

Patil P, Thakur A, Sharma A, Flora SJS. Natural products and their derivatives as multifunctional ligands against Alzheimer’s disease. Drug Dev Res. 2020;81:165–83. [DOI] [PubMed]

Isik AT. Late onset Alzheimer’s disease in older people. Clin Interv Aging. 2010;5:307–11. [DOI] [PubMed] [PMC]

Bekris LM, Yu C, Bird TD, Tsuang DW. Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol. 2010;23:213–27. [DOI] [PubMed] [PMC]

Anand P, Singh B, Singh N. A review on coumarins as acetylcholinesterase inhibitors for Alzheimer’s disease. Bioorg Med Chem. 2012;20:1175–80. [DOI] [PubMed]

Macauley SL, Holtzman DM. Recent Advances from the Bench Toward the Bedside in Alzheimer’s Disease. EBioMedicine. 2015;2:94–5. [DOI] [PubMed] [PMC]

Takashima A. Tau aggregation is a therapeutic target for Alzheimer’s disease. Curr Alzheimer Res. 2010;7:665–9. [DOI] [PubMed]

Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2019;15;321–87. [DOI]

10.

Lima E, Medeiros J. Terpenes as Potential Anti-Alzheimer’s Disease Agents. Appl Sci. 2024;14:3898. [DOI]

11.

Martin L, Latypova X, Wilson CM, Magnaudeix A, Perrin M, Yardin C, et al. Tau protein kinases: involvement in Alzheimer’s disease. Ageing Res Rev. 2013;12:289–309. [DOI] [PubMed]

12.

Citron M. Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov. 2010;9:387–98. [DOI] [PubMed]

13.

Li G, Yin H, Kuret J. Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J Biol Chem. 2004;279:15938–45. [DOI] [PubMed]

14.

Llorach-Pares L, Nonell-Canals A, Avila C, Sanchez-Martinez M. Kororamides, Convolutamines, and Indole Derivatives as Possible Tau and Dual-Specificity Kinase Inhibitors for Alzheimer’s Disease: A Computational Study. Mar Drugs. 2018;16:386. [DOI] [PubMed] [PMC]

15.

Jain P, Karthikeyan C, Moorthy NSHN, Waiker DK, Jain AK, Trivedi P. Human CDC2-like kinase 1 (CLK1): a novel target for Alzheimer's disease. Curr Drug Targets. 2014;15:539–50. [DOI] [PubMed]

16.

Tell V, Hilgeroth A. Recent developments of protein kinase inhibitors as potential AD therapeutics. Front Cell Neurosci. 2013;7:189. [DOI] [PubMed] [PMC]

17.

Dolan PJ, Johnson GVW. The role of tau kinases in Alzheimer’s disease. Curr Opin Drug Discov Devel. 2010;13:595–603. [PubMed] [PMC]

18.

Stotani S, Giordanetto F, Medda F. DYRK1A inhibition as potential treatment for Alzheimer’s disease. Future Med Chem. 2016;8:681–96. [DOI] [PubMed]

19.

Branca C, Shaw DM, Belfiore R, Gokhale V, Shaw AY, Foley C, et al. Dyrk1 inhibition improves Alzheimer’s disease-like pathology. Aging Cell. 2017;16:1146–54. [DOI] [PubMed] [PMC]

20.

Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer’s disease. J Neurochem. 2008;104:1433–9. [DOI] [PubMed] [PMC]

21.

Llorens-Martín M, Jurado J, Hernández F, Avila J. GSK-3β, a pivotal kinase in Alzheimer disease. Front Mol Neurosci. 2014;7:46. [DOI] [PubMed] [PMC]

22.

Hernández F, de Barreda EG, Fuster-Matanzo A, Lucas JJ, Avila J. GSK3: a possible link between beta amyloid peptide and tau protein. Exp Neurol. 2010;223:322–5. [DOI] [PubMed]

23.

Hernandez F, Lucas JJ, Avila J. GSK3 and tau: two convergence points in Alzheimer’s disease. J Alzheimers Dis. 2013;33 Suppl 1:S141–4. [DOI] [PubMed]

24.

Martins M, Silva R, Pinto MMM, Sousa E. Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease. Pharmaceuticals (Basel). 2020;13:242. [DOI] [PubMed] [PMC]

25.

Lima E, Medeiros J. Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents. Mar Drugs. 2022;20:75. [DOI] [PubMed] [PMC]

26.

Coman H, Nemes B. New therapeutic targets in Alzheimer’s disease. Int J Gerontol. 2017;11:2–6. [DOI]

27.

Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14:463–77. [DOI] [PubMed]

28.

Schain M, Kreisl WC. Neuroinflammation in Neurodegenerative Disorders-a Review. Curr Neurol Neurosci Rep. 2017;17:25. [DOI] [PubMed]

29.

Barbalace MC, Malaguti M, Giusti L, Lucacchini A, Hrelia S, Angeloni C. Anti-Inflammatory Activities of Marine Algae in Neurodegenerative Diseases. Int J Mol Sci. 2019;20:3061. [DOI] [PubMed] [PMC]

30.

Salter MW, Stevens B. Microglia emerge as central players in brain disease. Nat Med. 2017;23:1018–27. [DOI] [PubMed]

31.

Cowan M, Petri WA Jr. Microglia: Immune Regulators of Neurodevelopment. Front Immunol. 2018;9:2576. [DOI] [PubMed] [PMC]

32.

Hansen DV, Hanson JE, Sheng M. Microglia in Alzheimer’s disease. J Cell Biol. 2018;217:459–72. [DOI] [PubMed] [PMC]

33.

Colonna M, Butovsky O. Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annu Rev Immunol. 2017;35:441–68. [DOI] [PubMed] [PMC]

34.

Dong Y, Li X, Cheng J, Hou L. Drug Development for Alzheimer’s Disease: Microglia Induced Neuroinflammation as a Target? Int J Mol Sci. 2019;20:558. [DOI] [PubMed] [PMC]

35.

Liu C, Wang X, Liu C, Zhang H. Pharmacological Targeting of Microglial Activation: New Therapeutic Approach. Front Cell Neurosci. 2019;13:514. [DOI] [PubMed] [PMC]

36.

Lima E, Rauter AP, Medeiros J. Flavonoids as Promising Multitarget Agents in Alzheimer’s Disease Therapy. Appl Sci. 2023;13:4651. [DOI]

37.

Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer’s disease: Targeting the Cholinergic System. Curr Neuropharmacol. 2016;14:101–15. [DOI] [PubMed] [PMC]

38.

Wang T, Liu X, Guan J, Ge S, Wu M, Lin J, et al. Advancement of multi-target drug discoveries and promising applications in the field of Alzheimer’s disease. Eur J Med Chem. 2019;169:200–23. [DOI] [PubMed]

39.

Zagoskina NV, Zubova MY, Nechaeva TL, Kazantseva VV, Goncharuk EA, Katanskaya VM, et al. Polyphenols in Plants: Structure, Biosynthesis, Abiotic Stress Regulation, and Practical Applications (Review). Int J Mol Sci. 2023;24:13874. [DOI] [PubMed] [PMC]

40.

Badria FA, Blumenberg M. Phenolic compounds: chemistry, synthesis, diversity, non-conventional industrial, pharmaceutical, and therapeutic applications. In: Badria FA. Biochemistry. IntechOpen;2022. [DOI]

41.

Goodwin TW, Mercer EI. Introduction to Plant Biochemistry. 2nd ed. New York: Pergamon Press; 1990.

42.

Verma M. A Textbook of Plant Physiology Biochemistry and Biotechnology. 6th ed. New Delhi: Chand & Co Ltd; 2007.

43.

Ono K, Hirohata M, Yamada M. Ferulic acid destabilizes preformed beta-amyloid fibrils in vitro. Biochem Biophys Res Commun. 2005;336:444–9. [DOI] [PubMed]

44.

Yanagisawa D, Taguchi H, Morikawa S, Kato T, Hirao K, Shirai N, et al. Novel curcumin derivatives as potent inhibitors of amyloid β aggregation. Biochem Biophys Rep. 2015;4:357–68. [DOI] [PubMed] [PMC]

45.

Taguchi R, Hatayama K, Takahashi T, Hayashi T, Sato Y, Sato D, et al. Structure-activity relations of rosmarinic acid derivatives for the amyloid β aggregation inhibition and antioxidant properties. Eur J Med Chem. 2017;138:1066–75. [DOI] [PubMed]

46.

Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem. 2005;280:37377–82. [DOI] [PubMed]

47.

Panche AN, Chandra S, Diwan AD. Multi-Target β-Protease Inhibitors from Andrographis paniculata: In Silico and In Vitro Studies. Plants (Basel). 2019;8:231. [DOI] [PubMed] [PMC]

48.

Miyamae Y, Kurisu M, Murakami K, Han J, Isoda H, Irie K, et al. Protective effects of caffeoylquinic acids on the aggregation and neurotoxicity of the 42-residue amyloid β-protein. Bioorg Med Chem. 2012;20:5844–9. [DOI] [PubMed]

49.

Clifford MN, Wu W, Kirkpatrick J, Kuhnert N. Profiling the chlorogenic acids and other caffeic acid derivatives of herbal chrysanthemum by LC-MSn. J Agric Food Chem. 2007;55:929–36. [DOI] [PubMed]

50.

Kurata R, Adachi M, Yamakawa O, Yoshimoto M. Growth suppression of human cancer cells by polyphenolics from sweetpotato (Ipomoea batatas L.) leaves. J Agric Food Chem. 2007;55:185–90. [DOI] [PubMed]

51.

Merfort I. Caffeoylquinic acids from flowers of Arnica montana and Arnica chamissonis. Phytochemistry. 1992;31:2111–3. [DOI]

52.

Mishima S, Inoh Y, Narita Y, Ohta S, Sakamoto T, Araki Y, et al. Identification of caffeoylquinic acid derivatives from Brazilian propolis as constituents involved in induction of granulocytic differentiation of HL-60 cells. Bioorg Med Chem. 2005;13:5814–8. [DOI] [PubMed]

53.

Wan H, Ge L, Xiao L, Li J, Wu W, Peng S, et al. 3,4,5-Tri-O-caffeoylquinic acid methyl ester isolated from Lonicera japonica Thunb. Flower buds facilitates hepatitis B virus replication in HepG2.2.15 cells. Food Chem Toxicol. 2020;138:111250. [DOI] [PubMed]

54.

Santos SAO, Freire CSR, Domingues MRM, Silvestre AJD, Neto CP. Characterization of phenolic components in polar extracts of Eucalyptus globulus Labill. bark by high-performance liquid chromatography-mass spectrometry. J Agric Food Chem. 2011;59:9386–93. [DOI] [PubMed]

55.

Kweon MH, Hwang HJ, Sung HC. Identification and antioxidant activity of novel chlorogenic acid derivatives from bamboo (Phyllostachys edulis). J Agric Food Chem. 2001;49:4646–55. [DOI] [PubMed]

56.

Kidachi E, Kurisu M, Miyamae Y, Hanaki M, Murakami K, Irie K, et al. Structure-activity relationship of phenylethanoid glycosides on the inhibition of amyloid β aggregation. Heterocycles. 2016;92:1976–82. [DOI]

57.

Muralidharan A, Josyula VR, Hariharapura RC. Exploring the potential of marine microbes in clinical management of Alzheimer’s disease: A road map for bioprospecting and identifying promising isolates. Life Sci. 2018;208:149–60. [DOI] [PubMed]

58.

Lee S, Ryu H, Whang W. Development of simultaneous analysis method for multi-compounds content of new shilajit using HPLC-UV and the cognitive enhancing effect: mongolian shilajit. Nat Prod Commun. 2021;16:1–10. [DOI]

59.

Zhang L, Xie Q, Li X. Esculetin: A review of its pharmacology and pharmacokinetics. Phytother Res. 2022;36:279–98. [DOI] [PubMed]

60.

Kashima Y, Miyazawa M. Structure-activity relationships for bergenin analogues as β-secretase (BACE1) inhibitors. J Oleo Sci. 2013;62:391–401. [DOI] [PubMed]

61.

Vidya Chauhan V, Rawat P, Chauhan N. Review on compilation of ethnopharmacological properties of Bergenia ciliata: the medicinal herb of Himalayas. Plant Arch. 2021;21:401–10. [DOI]

62.

Lee SH, Tanaka T, Nonaka GI, Nishioka I. Tannins and related compounds, CV. Monomeric and dimeric hydrolysable tannins having a dehydrohexahydroxydiphenoyl group, spinanin, euphorscopin, euphorhelin and jokianin from Euphorbia species. Chem Pharm Bull. 1991;39:630–8. [DOI]

63.

Jun M, Lee SH, Choi SH, Bae KH, Seong YH, Lee KB, et al. Plant phenolics as β-secretase (BACE1) inhibitors. Food Sci Biotechnol. 2006;15:617–24.

64.

Kim JA, Choi JY, Son AR, Park SH, Xu GH, Lee JG, et al. Inhibitory effect of some natural polyphenols isolated from Euphorbiaceae plants on melanogenesis. Korean J Pharmacogn. 2004;35:157–63.

65.

Lee SH, Tanaka T, Nonaka GI, Nishioka I, Zhang B. Allose gallates from Euphorbia fischeriana. Phytochemistry. 1991;30:1251–3. [DOI]

66.

Lin JH. Studies on tannins from the bark of Macaranga sinensis (Baill.) Muell.-Arg. J Food Drug Anal. 1994;2:Article 2. [DOI]

67.

Pawlowska AM, De Leo M, Braca A. Phenolics of Arbutus unedo L. (Ericaceae) fruits: identification of anthocyanins and gallic acid derivatives. J Agric Food Chem. 2006;54:10234–8. [DOI] [PubMed]

68.

Wang MM, Yeh Y, Shih Y, Tzen JT. Relative content of gallic acid over 5-galloylquinic acid as an index for the baking intensity of oolong teas. J Food Drug Anal. 2018;26:609–19. [DOI] [PubMed] [PMC]

69.

Noviany N, Hadi S. The isolation of α-viniferin, a trimer stilbene, from Shorea ovalis Blume. Mod Appl Sci. 2009;3:45–51. [DOI]

70.

Olas B. Cardioprotective Potential of Berries of Schisandra chinensis Turcz. (Baill.), Their Components and Food Products. Nutrients. 2023;15:592. [DOI] [PubMed] [PMC]

71.

Cornejo A, Sandoval FA, 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;32:945–53. [DOI] [PubMed] [PMC]

72.

Yi-Ming L, Zhuo-Lun Z, Yong-Fu H. New Phenolic Derivatives from Galeola faberi. Planta Med. 1993;59:363–5. [DOI] [PubMed]

73.

Zeng YQ, Gu JH, Chen L, Zhang T, Zhou XF. Gastrodin as a multi-target protective compound reverses learning memory deficits and AD-like pathology in APP/PS1 transgenic mice. J Funct Foods. 2021;77:104324. [DOI]

74.

Zhang Y, Yu S, Guo X, Wang L, Yu L, Wang P. Therapeutic potential of salidroside in preserving rat cochlea organ of corti from gentamicin-induced injury through modulation of NRF2 signaling and GSK3β/NF-κB pathway. PLoS One. 2024;19:e0298529. [DOI] [PubMed] [PMC]

75.

Conforti F, Rigano D, Formisano C, Bruno M, Loizzo MR, Menichini F, et al. Metabolite profile and in vitro activities of Phagnalon saxatile (L.) Cass. relevant to treatment of Alzheimer’s disease. J Enzyme Inhib Med Chem. 2010;25:97–104. [DOI] [PubMed]

76.

Garni HAA, El-Halawany AM, Koshak AE, Malebari AM, Alzain AA, Mohamed GA, et al. Potential antioxidant, α-glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of major constituents isolated from Alpinia officinarum hance rhizomes: computational studies and in vitro validation. SAR QSAR Environ Res. 2024;35:391–410. [DOI] [PubMed]

77.

Alotaibi JAM, Sirwi A, El-Halawany AM, Esmat A, Mohamed GA, Ibrahim SRM, et al. α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies. Saudi Pharm J. 2024;32:102106. [DOI] [PubMed] [PMC]

78.

Kundu A, Mitra A. Flavoring extracts of Hemidesmus indicus roots and Vanilla planifolia pods exhibit in vitro acetylcholinesterase inhibitory activities. Plant Foods Hum Nutr. 2013;68:247–53. [DOI] [PubMed]

79.

Leu Y, Wang Y, Huang S, Shi L. Chemical constituents from roots of Taraxacum formosanum. Chem Pharm Bull (Tokyo). 2005;53:853–5. [DOI] [PubMed]

80.

Aguilar-Méndez ED, Monribot-Villanueva JL, Guerrero-Analco JA, De-la-Peña C. Chlorophyll deficiency in Agave angustifolia Haw.: unveiling the impact on secondary metabolite production. Planta. 2024;260:77. [DOI] [PubMed]

81.

Haj-Zaroubi M, Mattar N, Awabdeh S, Sweidan R, Markovics A, Klein JD, et al. Willow (Salix acmophylla Boiss.) leaf and branch extracts inhibit in vitro sporulation of Coccidia (Eimeria spp.) from goats. Agriculture. 2024;14:648. [DOI]

82.

Papadopoulos G, Boskou D. Antioxidant effect of natural phenols on olive oil. J Am Oil Chem Soc. 1991;68:669–71. [DOI]

83.

Hoberg E, Meier B, Sticher O. An analytical high performance liquid chromatographic method for the determination of agnuside and p-hydroxybenzoic acid contents in Agni-casti fructus. Phytochem Anal. 2000;11:327–9. [DOI]

84.

Botes L, van der Westhuizen FH, Loots du T. Phytochemical contents and antioxidant capacities of two Aloe greatheadii var. davyana extracts. Molecules. 2008;13:2169–80. [DOI] [PubMed] [PMC]

85.

Arteaga S, Andrade-Cetto A, Cárdenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. J Ethnopharmacol. 2005;98:231–9. [DOI] [PubMed]

86.

Alemika TE, Onawunmi GO, Olugbade TO. Antibacterial phenolics from Boswellia dalzielii. Niger J Nat Prod Med. 2006;10:108–10.

87.

Cavalcante MA, Oliveira JS, Barreto MSS, Pinheiro LP, Cantuária PC, Borges WL, et al. An HPLC method to determine phenolic compounds of plant extracts: application to Byrsonima crassifolia and Senna alata leaves. Pharmacogn Res. 2022;14:395–404. [DOI]

88.

Lassed S, Deus CM, Djebbari R, Zama D, Oliveira PJ, Rizvanov AA, et al. Protective Effect of Green Tea (Camellia sinensis (L.) Kuntze) against Prostate Cancer: From In Vitro Data to Algerian Patients. Evid Based Complement Alternat Med. 2017;2017:1691568. [DOI] [PubMed] [PMC]

89.

Phadungkit M, Luanratana O. Anti-Salmonella activity of constituents of Ardisia elliptica Thunb. Nat Prod Res. 2006;20:693–6. [DOI] [PubMed]

90.

Pramisandi A, Kurnia K, Chrisnayanti E, Bernawati P, Dobashi K, Mori M, et al. Gentisyl alcohol and homogentisic acid: Plasmodium falciparum dihydroorotate dehydrogenase inhibitors isolated from fungi. J Gen Appl Microbiol. 2021;67:114–7. [DOI] [PubMed]

91.

Tian R, Pan Q, Zhan J, Li J, Wan S, Zhang Q, et al. Comparison of phenolic acids and flavan-3-ols during wine fermentation of grapes with different harvest times. Molecules. 2009;14:827–38. [DOI] [PubMed] [PMC]

92.

Dróżdż P, Pyrzynska K. Assessment of polyphenol content and antioxidant activity of oak bark extracts. Eur J Wood Prod. 2018;76:793–5. [DOI]

93.

Choi HS, Cho J, Kim S, Ham K, Moon J. New lignan tyramide, phenolics, megastigmanes, and their glucosides from aerial parts of New Zealand spinach, Tetragonia tetragonoides. Food Sci Biotechnol. 2019;29:599–608. [DOI] [PubMed] [PMC]

94.

Blazević I, Radonić A, Mastelić J, Zekić M, Skocibusić M, Maravić A. Hedge mustard (Sisymbrium officinale): chemical diversity of volatiles and their antimicrobial activity. Chem Biodivers. 2010;7:2023–34. [DOI] [PubMed]

95.

Budryn G, Majak I, Grzelczyk J, Szwajgier D, Rodríguez-Martínez A, Pérez-Sánchez H. Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies. Nutrients. 2022;14:2476. [DOI] [PubMed] [PMC]

96.

Ahammed S, Afrin R, Uddin N, Al-Amin Y, Hasan K, Haque U, et al. Acetylcholinesterase Inhibitory and Antioxidant Activity of the Compounds Isolated from Vanda roxburghii. Adv Pharmacol Pharm Sci. 2021;2021:5569054. [DOI] [PubMed] [PMC]

97.

Stojanovic IZ, Radulovic NS, Mitrovic TL, Stamenkovic SM, Stojanovic GS. Volatile constituents of selected Parmeliaceae lichens. J Serb Chem Soc. 2011;76:987–94. [DOI]

98.

Taslimi P, Gulçin I. Antioxidant and anticholinergic properties of olivetol. J Food Biochem. 2018;42:e12516. [DOI]

99.

Jakovljević MR, Grujičić D, Stanković M, Milošević-Djordjević O. Artemisia vulgaris L., Artemisia alba Turra and their constituents reduce mitomycin C-induced genomic instability in human peripheral blood lymphocytes in vitro. Drug Chem Toxicol. 2024;47:156–65. [DOI] [PubMed]

100.

Zhao C, Jia Y, Lu F. Angelica Stem: A Potential Low-Cost Source of Bioactive Phthalides and Phytosterols. Molecules. 2018;23:3065. [DOI] [PubMed] [PMC]

101.

Joval E, Kroeger P, Towers N. Hydroquinone: the toxic compound of Agaricus hondensis. Planta Med. 1996;62:185. [DOI] [PubMed]

102.

Işık M, Beydemir Ş. The impact of some phenolic compounds on serum acetylcholinesterase: kinetic analysis of an enzyme/inhibitor interaction and molecular docking study. J Biomol Struct Dyn. 2021;39:6515–23. [DOI] [PubMed]

103.

Jukic M, Politeo O, Maksimovic M, Milos M, Milos M. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother Res. 2007;21:259–61. [DOI] [PubMed]

104.

Khazdair MR. The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity. J Toxicol. 2015;2015:841823. [DOI] [PubMed] [PMC]

105.

Feunaing RT, Tamfu AN, Gbaweng AJY, Kucukaydin S, Tchamgoue J, Lannang AM, et al. In Vitro and Molecular Docking Evaluation of the Anticholinesterase and Antidiabetic Effects of Compounds from Terminalia macroptera Guill. & Perr. (Combretaceae). Molecules. 2024;29:2456. [DOI] [PubMed] [PMC]

106.

Orabi MAA, Abdelhamid RA, Elimam H, Elshaier YAMM, Ali AA, Aldabaan N, et al. Furofuranoid-Type Lignans and Related Phenolics from Anisacanthus virgularis (Salisb.) Nees with Promising Anticholinesterase and Anti-Ageing Properties: A Study Supported by Molecular Modelling. Plants (Basel). 2024;13:150. [DOI] [PubMed] [PMC]

107.

Türkan F, Taslimi P, Saltan FZ. Tannic acid as a natural antioxidant compound: Discovery of a potent metabolic enzyme inhibitor for a new therapeutic approach in diabetes and Alzheimer’s disease. J Biochem Mol Toxicol. 2019;33:e22340. [DOI] [PubMed]

108.

Rahman MM, Rahaman MS, Islam MR, Rahman F, Mithi FM, Alqahtani T, et al. Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects. Molecules. 2021;27:233. [DOI] [PubMed] [PMC]

109.

Kocakaya SO, Ertas A, Yener I, Ercan B, Oral EV, Akdeniz M, et al. Selective in-vitro Enzymes’ Inhibitory Activities of Fingerprints Compounds of Salvia Species and Molecular Docking Simulations. Iran J Pharm Res. 2020;19:187–98. [DOI] [PubMed] [PMC]

110.

Mallavarapu GR, Ramesh S, Chandrasekhara RS, Rao BRR, Kaul PN, Bhattacharya AK. Investigation of the essential oil of cinnamon leaf grown at Bangalore and Hyderabad. Flavour Fragr J. 1995;10:239–42. [DOI]

111.

Babu B, Wu J. Production of Natural Butylated Hydroxytoluene as an Antioxidant by Freshwater Phytoplankton¹. J Phycol. 2008;44:1447–54. [DOI] [PubMed]

112.

Adefegha SA, Okeke BM, Oboh G. Antioxidant properties of eugenol, butylated hydroxylanisole, and butylated hydroxyl toluene with key biomolecules relevant to Alzheimer’s diseases-In vitro. J Food Biochem. 2021;45:e13276. [DOI] [PubMed]

113.

Bae YH, Cuong TD, Hung TM, Kim JA, Woo MH, Byeon JS, et al. Cholinesterase inhibitors from the roots of Harpagophytum procumbens. Arch Pharm Res. 2014;37:1124–9. [DOI] [PubMed]

114.

Nugroho A, Choi JS, Hong JP, Park HJ. Anti-acetylcholinesterase activity of the aglycones of phenolic glycosides isolated from Leonurus japonicus. Asian Pac J Trop Biomed. 2017;7:849–54. [DOI]

115.

Wu Y, Su X, Lu J, Wu M, Yang SY, Mai Y, et al. In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease. Front Pharmacol. 2022;13:905708. [DOI] [PubMed] [PMC]

116.

Zhang XD, Liu XQ, Kim YH, Whang WK. Chemical constituents and their acetyl cholinesterase inhibitory and antioxidant activities from leaves of Acanthopanax henryi: potential complementary source against Alzheimer’s disease. Arch Pharm Res. 2014;37:606–16. [DOI] [PubMed]

117.

Koay Y, Basiri A, Murugaiyah V, Chan K. Isocorilagin, a cholinesterase inhibitor from Phyllanthus niruri. Nat Prod Commun. 2014;9:515–7. [PubMed]

118.

Cavalli A, Bolognesi ML, Minarini A, Rosini M, Tumiatti V, Recanatini M, et al. Multi-target-directed ligands to combat neurodegenerative diseases. J Med Chem. 2008;51:347–72. [DOI] [PubMed]

119.

Zhou J, Jiang X, He S, Jiang H, Feng F, Liu W, et al. Rational Design of Multitarget-Directed Ligands: Strategies and Emerging Paradigms. J Med Chem. 2019;62:8881–914. [DOI] [PubMed]

120.

Prati F, Uliassi E, Bolognesi ML. Two diseases, one approach: Multitarget drug discovery in Alzheimer’s and neglected tropical diseases. Med Chem Comm. 2014;5:853–61. [DOI]