Botanics: a potential source of new therapies for Alzheimer's disease?

Figures & data

Figure 1 Mechanism of generation of toxic Aβ peptide and the fibril formation.

Note: Major targets for plant-derived natural compounds are indicated.
Abbreviation: Aβ, amyloid beta.

Figure 2 Role of oxidative stress and acetylcholinesterase in neurodegeneration.

Abbreviations: Aβ, amyloid beta; ACh, acetylcholine; AChE, acetylcholinesterase; GSH, glutathione; GSSG, glutathione disulfide; SOD, superoxide dismutase.

Table 1 Plants with potential AChE inhibitory activity

Serial number	Plant	Family	Extract/active compound	References
1	Angelica archangelica L.	Apiaceae	Unknown	Howes et al^Citation46
2	Coptis Chinensis Franch	Ranunculaceae	Berberine, palmatine	Howes et al^Citation46
3	Evodia rutaecarpa (Juss.)	Tetradium	Dehydroevodiamine	Howes et al^Citation46
4	Polygala tenuifoila willd.	Polygalaceae	Root extract	Howes et al^Citation46
5	Salvia officinalis L.	Labiatae	Ethanolic extract	Howes et al^Citation46
6	Salvia lavandulaefolia vahl.	Labiatae	1,8-cineole and α-pinene	Howes et al^Citation46
7	Withania somnifera (L.) Dunal	Solanaceae	Sitoindosides	Howes et al^Citation46
8	Andrographis paniculata Nees	Acanthaceae	Hydroalcohol extract	Mukherjee et al^Citation47
9	Nardostachys jatamansi (D. Don) DC.	Valerianaceae	Hydroalcohol extract	Mukherjee et al^Citation47
10	Nelumbo nucifera Gaertn	Nymphaeaceae	Hydroalcohol extract	Mukherjee et al^Citation47
11	Myristica fragrans Houtt	Myristicaceae	Hydroalcohol extract	Mukherjee et al^Citation47
12	Evalvulus alsinoides L.	Convolvulaceae	Hydroalcohol extract	Mukherjee et al^Citation47
13	Scoparia dulcis L.	Scrophulariaceae	Chloroform extract	Coulibaly et al^Citation48
14	Centella asiatica (L.) Urban	Umbelliferae	α-pinene, β-pinene, γ-terpinene	Miyazawa et al^Citation49
14	Bacopa monniera wettst.	Plantaginaceae	Ethanolic extract	Ahirwar et al^Citation50
15	Lippia stoechadifolia H. B.	Verbenaceae	Pulegone-1, 2-epoxide	Grundy and Still^Citation51
16	Magnolia officinalis Rehder & Wilson	Magnoliaceae	Honokiol	Hou et al^Citation52
17	Melissa officinalis L.	Lamiaceae	Essential oil fraction	Ferreira et al^Citation53
18	Huperzia serrata Brehn.	Lycopodiaceae	Huperzine A	Wang et al^Citation54
19	Salvia miltiorrhiza Bunge.	Lamiaceaea	Dihydrotanshinone, cryptotanshinone	Ren et al^Citation55
20	Desmodium pulchellum (L.) Benth	Papilionaceae	β-carbolines	Ghosal et al^Citation56
21	Prosopis juliflora (Sw.) DC	Papilionaceae	Juliflorine	Choudhary et al^Citation57
22	Sarcococca saligna (D. Don)	Buxaceae	Salignenamides-C, -E and -F, axillarine- C, saligcinnamide, vaganine-A, 5,6-dehydrosarconidine, 2-hydroxysalignarine-E, salignamine, 2-hydroxysalignamine-E, epipachysamine-D, dictyophlebine, iso-N- formylchonemorphine and axillaridine-A	Khalid et al^Citation58
23	Narcissus pseudonarcissus L.	Amaryllidaceae	Lycorine	Acqua^Citation59
24	Cocculus pendulus (J. R. and G. Frost.) Diels	Menispermaceae	kurramine-2′-β-N-oxide and kurramine- 2′-α-N-oxide	Atta-Ur-Rahman^Citation60
25	Otostegia limbata (Benth.)	Lamiaceae	cis-clerodane	Ahmad et al^Citation61
26	Cynanchum atratum Bunge.	Asclepiadaceae	Cynatroside B	Lee et al^Citation62
27	Buxus papillosa C.K. Schneider	Buxaceae	Buxamines B and C	Khalid et al^Citation63
28	Tabernaemontana australis (Müell. Arg)	Apocynaceae	Coronaridine, voacangine, voacangine hydroxyindolenine and rupicoline	Andrade et al^Citation64
29	Evodia rutaecarpa Juss.	Rutaceae	Dehydroevodiamine	Park et al^Citation65
30	Origanum majorana L.	Lamiaceae	Ursolic acid	Chung et al^Citation66
31	Lycopodium clavatum L.	Lycopodiaceae	α-onocerin	Orhan et al^Citation67
32	Citrus junos Siebold ex. Tanaka	Rutaceae	Naringenin	Heo et al^Citation68

Abbreviation: AChE, acetylcholinesterase.

Table 2 List of plant-derived compounds that are FDA-approved and in clinical trials against AD

Drugs	Brand name	Plant source	FDA-approved	Clinical trials	Targets	Reference
Rivastigmine	Exelon	Physostigma venensosum Balf. (Leguminosae)	2000	–	Inhibits AChE in the cortex and hippocampal region	Polinsky^Citation123
Galantamine	Razadyne	Lycoris radiata (L’Hér.) Herb (Amaryllidaceae) and Galanthus nivalis L.	2001	–	Reversible inhibition of AChE and allosteric potentiation of nicotinic ACh receptors	Razay and Wilcock;^Citation124 Maelicke et al^Citation125
Huperzine A	–	Huperzia serrata (Thumb) Trevis (Lycopodiaceae)	–	Phase III	Restores cognitive deficits by reversibly inhibiting AChE	Ha et al^Citation126
Curcumin	Longvida®	Curcuma longa L. (Zingiberaceae)	–	Phase II	Anti-amyloidogenic, anti-inflammatory, anti-ChE, anti-β-secretase	Rajakrishnan et al^Citation127
Resveratrol	–	Vitis vinifera L. (Vitaceae)	–	Phase III	Prevents cognitive impairments and associated oxidative stress by reducing plaque formation	Karuppagounder et al;^Citation128 Williams et al^Citation129

Notes: Exelon (Novartis Pharmaceutical Corporation, East Hanover, NJ, USA); Razadyne (Janssen pharmaceuticals, Inc., Titusville, NJ, USA); Longvida^® (Verdure Sciences, Noblesville, IN, USA).

Abbreviations: ACh, acetylcholine; AChE, acetylcholinesterase; AD, Alzheimer’s disease; ChE, cholinesterase; FDA, Food and Drug Administration.

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