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Acetylcholinesterase inhibitors from plants.


Inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is considered as a promising strategy for the treatment of neurological disorders such as Alzheimer's disease, senile dementia, ataxia and myasthenia gravis. A potential source of AChE inhibitors is certainly provided by the abundance of plants in nature. This article aims to provide a comprehensive literature survey of plants that have been tested for AChE inhibitory activity. Numerous phytoconstituents and promising plant species as AChE inhibitors are being reported in this communication.

[c] 2007 Elsevier GmbH. All rights reserved.

Keywords: Plants; Botanicals; Acetylcholinesterase inhibition; Acetylcholine; Alzheimer's disease


Principal role of acetylcholinesterase (AChE) is the termination of nerve impulse transmission at the cholinergic synapses by rapid hydrolysis of acetylcholine (ACh). Inhibition of AChE serves as a strategy for the treatment of Alzheimer's disease (AD), senile dementia, ataxia, myasthenia gravis and Parkinson's disease (Anonymous, 2000; Brenner, 2000; Rahman and Choudhary, 2001). There are a few synthetic medicines, e.g. tacrine, donepezil, and the natural product-based rivastigmine for treatment of cognitive dysfunction and memory loss associated with AD (Oh et al., 2004). These compounds have been reported to have their adverse effects including gastrointestinal disturbances and problems associated with bioavailability (Schulz, 2003; Melzer, 1998), which necessitates the interest in finding better AChE inhibitors from natural resources.

AD is one of the most common forms of dementia affecting so many elderly people. Besides the neuropathologic hallmarks of this disease, namely neurofibrillary tangles and neuritic plaques, it is characterized neurochemically by a consistent deficit in cholinergic neurotransmission, particularly affecting cholinergic neurons in the basal forebrain (Price, 1986; Kasa et al., 1997). The evidence stems from data of several authors that demonstrated the reduction in activity of enzymes involved in the synthesis of acetylcholine, i.e. choline acetyl transferase or excess degradation of ACh by AChE (Davies and Maloney, 1976; Sims et al., 1983; DeKosky et al., 1992). The first AChE inhibitors (AChEIs) specifically approved for the treatment of AD was introduced in 1993 as 1, 2, 3, 4-tetrahydro-9-aminoacridine (tacrine) (Whitehouse, 1993). Currently, several AChE inhibitors, such as donepezil (Kelly et al., 1997), galantamine (Scott and Goa, 2000) and rivastigmine (Gottwald and Rozanski, 1999) are available for the symptomatic treatment of patients with mild-to-moderate AD. Cholinesterase inhibitory therapy may be considered, by its pharmacological nature, as a simple symptomatic short-term intervention. However, data emerging from long-term mostly open label trials is that the maintenance of the clinical effect can be prolonged to at least 1 year. In some clinical studies, the data indicate that beneficial effects can be maintained for up to 36 months; These effects of stabilization of the cognitive status of the patients suggest conceivably a structural effect of the treatment on pathological features of the disease; Giacobini (2002) suggested that the effects may arise from the interaction of these drugs with the amyloid cascade, influencing the expression and/or the metabolic processing of the amyloid precursor protein (APP) and slowing down one of the major pathological steps of the disease process. In traditional practices of numerous plants have been used to treat cognitive disorders, including neurodegenerative diseases and different neuropharmacological disorders. Ethnopharmacological approach and bioassay-guided isolation have provided a lead in identifying potential AChE inhibitors from plant sources, including those for memory disorders. This article highlights on the plants and/or their active constituents so far reported to have AChE inhibitory activity.

Several methods for screening of AChE inhibitory activity from natural resources has been reported based on Ellman's reactions (Ellman et al., 1961). Moreover, Spectrophotometric determination thin-layer chromatography method (Ingkaninan et al., 2000; Marston et al., 2002) and micro-plate assay (Ingkaninan et al., 2000, Brlihlmann et al., 2004) have been reported to be useful. HPLC method for detection of AChE inhibition on immobilized AChE column (Andrisano et al., 2001) and HPLC with on-line coupled UV-MS-biochemical detection for AChE inhibitory activity (Ingkaninan et al., 2000) have also been reported.

Plants as a source of acetylcholinesterase inhibitors

A variety of plants has been reported to show AChE inhibitory activity and so may be relevant to the treatment of neurodegenerative disorders such as AD. A list of plants reported to have significant AChE inhibitory activity is shown in Table 1.

Bacopa monniera and Ginkgo biloba are well-known cognitive enhancers in Indian and Chinese traditional medicine systems. Standardized extracts of Bacopa monniera and G. biloba both showed a dose-dependent inhibitory effect on AChE activity (Das et al., 2002). Eighty percent methanolic extract of Myricaria elegans Royle was found to have significant AChE inhibitory activity (Ahmad et al., 2003).

Methanolic extracts of seven herbs Acorus calamus, Acorus gramineus, Bupleurm facaltum, Dioscorea batatas, Epimedium koreanum, Poria cocos and Zizyphi jujuba, used in traditional Korean medicine for improvement of memory and cognition in old age have been tested for cholinesterase inhibitory properties and significant inhibition of the enzyme was shown by extracts from Acorus calamus and E. koreanum (Oh et al., 2004). Ingkaninan et al. (2000, 2003) screened the methanolic extracts of 32 plants used in Thai traditional rejuvenating and neurotonic remedies, for inhibitory activity on AChE and found that the extracts from roots of Stephania suberosa and Tabernaemontana divaricata showed significant inhibitory activity.

The chloroform:methanol (1:1) extracts of a number of the plant species namely Corydalis solida (L.) Swartz subsp. solida and Glaucium corniculatum (L.) J. H. Rudolph (Papaveraceae), Rhododendron ponticum L. subsp. ponticum and Rhododendron luteum Sweet. (Ericaceae), Buxus sempervirens L. (Buxaceae), Vicia faba L. (Fabaceae), Robinia pseudoacacia L. (Caeselpiniaceae), Tribulus terrestris L. and Zygophyllum fabago L. (Zygophyllaceae), Lycopodium clavatum L. (Lycopodiaceae), Fumaria vaillantii Lois., Fumaria capreolata L., Fumaria kralikii Jordan, Fumaria asepala Boiss., Fumaria densiflora DC., Fumaria flabellata L., Fumaria petteri Reichb. subsp. thuretii (Boiss.) Pugsley, Fumaria macrocarpa Boiss. ex Hausskn., Fumaria cilicica Hauskkn., Fumaria parviflora Lam. and Fumaria judaica Boiss. (Fumariaceae) were screened for their anti-cholinesterase activity (Orhan et al., 2004). The extracts of Rhododendron ponticum, Rhododendron luteum, Corydalis solida, Glaucium corniculatum, and Buxus sempervirens showed remarkable inhibitory activity above 50% inhibition rate at 1 mg/ml.

Amongst plants that have been investigated for dementia therapy, Salvia is one of the most numerous genera within the family Lamiaceae and grows in many parts of the world. It causes inhibition of AChE as well as nicotinic activity (Perry et al., 2000, 2001).

Phytoconstituents having acetylcholinesterase inhibitory activity

Work on new bioactive compounds from medicinal plants has led to the isolation and structure elucidation of a number of exciting new pharmacophores. A list of phytoconstituents having significant AChE inhibitory activity is provided in Table 2 and structures of these compounds are shown in Fig. 1. Physostigma venenosum was used traditionally in Africa as a ritual poison, claimed to determine the guilt or innocence of person accused of a crime. Treatment with the indole alkaloid physostigmine [1], an AChE inhibitor isolated from P. venenosum, has improved cognitive function in several in vivo studies. Physostigmine, a short-acting reversible AChE inhibitor, is also reported to have shown significant cognitive benefits in both normal and AD patients, but clinical use may be limited by its short half-life, which would require multiple daily dosing (Da-Yuan et al, 1996; Mukherjee, 2001).

Chemical structure of physostigmine has provided a template for the development of rivastigmine [2], an AChE inhibitor that is licensed for use in the UK for the symptomatic treatment of mild-to-moderately severe AD (Foye et al., 1995). Rivastigmine is reported to inhibit AChE in the cortex and hippocampus, brain areas involved in cognition. Thus, it is apparent that plant-derived alkaloid AChE inhibitors may be important for the development of more appropriate drug candidates for the treatment of AD (Foye et al., 1995).

Galanthus nivalis was used traditionally in Bulgaria and Turkey for neurological conditions. Galantamine [3] is an Amaryllidaceae alkaloid obtained from Galanthus nivalis L. Galantamine is reported to be more selective for AChE than butyrylcholinesterase, and provides complete oral bioavailability. It is licensed in Europe for AD treatment, was well tolerated and significantly improved cognitive function when administered to AD patients, in multi-center randomized-controlled trials (Lopez et al., 2002). Initially derived from extracts of snowdrop and daffodil bulbs, this phenanthrene alkaloid is now synthetically produced. It is a reversible competitive AChE inhibitor that also allosterically modulates nicotinic receptors (this effect is probably independent of its cholinesterase inhibition). It has an elimination half-life of about 6h. Metabolism produces four compounds, one of which is more active as a cholinesterase inhibitor than galantamine itself. Over 2000 patients have been involved in double-blind placebo-controlled trials of galantamine where positive effects on cognitive symptoms have been associated with significant benefits in activities of daily living (Da-Yuan et al, 1996). Other Amaryllidaceae alkaloids such as assoanine [4], epinorgalantamine [5], oxoassoanine [6], sanguinine [7], 11-hydroxygalantamine [8] have also been reported to possess AChE activity (Lopez et al., 2002).

The lycopodium alkaloid huperzine A [9] related to the quinolizidines, is a potent, yet reversible, inhibitor of AChE and is used in China for treating patients with myasthenia gravis and AD. The source of huperzine A is Huperzia serrata, a moss that has been used for treating contusions, strains, hematuria and swelling in Chinese folk medicine (Wang and Tang, 1998). It improved memory retention processes in cognitively impaired aged and adult rats (Raves et al., 1997). In a multicenter, double blind trial, huperzine A significantly improved memory and behavior in AD patients, and was reported to be more selective for AChE than butyrylcholinesterase and less toxic than the synthetic AChE inhibitors donepezil and tacrine. It may also have potential in the attenuation of memory deficits and neuronal damage that occurs after ischemia, so may therefore is beneficial in the treatment of cerebrovascular-type dementia (Raves et al., 1997).

Numerous essential oils and their monoterpene constituents have been investigated for their effects on AChE, and have shown weak inhibitory activity. For example, the essential oils from Melissa officinalis and Rosmarinus officinalis have been reported to inhibit erythrocyte AChE in vitro (Howes et al., 2003a, b). Other monoterpenes that are reported to inhibit AChE include geraniol, 3-carene, [alpha]-caryophyllene and limonene. The structural diversity of the active anticholinesterase terpenoids complicates the prediction of potential structure-activity relationships. One feature associated with AChE inhibition is a hydrophobic ligand. The hydrophobic active site of AChE is reported to be susceptible to hydrophobic interactions. Monoterpenes consist of a hydrocarbon skeleton, which may contribute to their anti-cholinesterase activity. Monoterpenes may be cyclic (e.g. 1,8-cineole and [alpha]-pinene) or acyclic (e.g. geraniol and linalool), a feature that may also influence anti-cholinesterase activity. Further investigations may determine if a cyclic component or particular functional group favors AChE inhibition. Considering the relatively weak anti-cholinesterase activity of terpenoids reported to date, it is unlikely that they may be used therapeutically for cognitive disorders. However, analogues of active terpenoid compounds may be developed to enhance efficacy.

More recently, the stilbene oligomer viniferin [10] from Caragana chamlague, has also been identified as reversible and non-competitive inhibitor of AChE (Da-Yuan et al, 1996). Structure-activity relationship suggested that the nitrogen substituents at C-3 and/or C-20 of steroidal skeleton and the hydrophobic properties of the pregnane skeleton are the key structural features contributed to the inhibitory potency of pregnane-type steroidal alkaloids against AChE (Khalid et al., 2004).

Bioassay-guided fractionation of the methanolic extract resulted in the isolation of three furanocoumarins, isoimperatorin, imperatorin and oxypeucedanin as active principles from the methanolic extract of the roots of Angelica dahurica, which inhibited AChE activity in a dose-dependent manner (Kim et al., 2002). In a bioassay-guided search for AChE inhibitors four isoquinoline alkaloids, corynoxidine, protopine, palmatine and berberine have been isolated from the methanolic extract of the aerial parts of Corydalis speciosa (Kim et al., 2004). Bioassay-directed phytochemical investigations on a number of medicinal plants of Pakistan and Iran have led to the isolation of AChE inhibitors such as buxamine B [11], N, N-dimethyl buxapapine [12], sarsalignone [13] and vaganine [14] (Rahman and Choudhary, 2001). Indole alkaloids coronaridine [15], voacangine [16], voacangine hydroxyindolenine and rupicoline [17] isolated from the chloroform extract of stalk of Tabernaemontana australis showed anti-cholinesterasic activity at the same concentration as the reference compounds physostigmine and galantamine, by thin-layer chromatography assay using the modified Ellman's method (Andrade et al., 2005). Ursolic acid [18] obtained from Origanum majorana has also been reported to possess AChE inhibitory activity (Chung et al., 2001).




Acetylcholinesterase (AchE) inhibitors have therapeutic applications in Alzheimer's disease (AD), senile dementia, ataxia, myasthenia gravis and Parkinson's disease. Central cholinergic system is considered as the most important neurotransmitter system involved in the regulation of cognitive functions. Cholinergic neuronal loss in hippocampal area is the major feature of AD and enhancement of central cholinergic activity by use of anti-cholinesterase is presently the mainstay of the pharmacotherapy of senile dementia of Alzheimer type (Enz et al., 1993; Siddiqui and Levey, 1999). The search for plant derived inhibitors of AChE has accelerated in view of the benefits of these drugs not only in the treatment of AD but in other forms of dementia, such as dementia with Lewy bodies (Perry et al., 1994), vascular dementia (Erkinjuntti et al., 2002) and Down's syndrome (Kishnani et al., 1999). Along with the prototype inhibitor of AChE physostigmine, obtained from the plant Physostigma venenosum, other molecules with highly significant anti-cholinesterase activity are huper-zine-A, galantamine, [alpha]-viniferin and ursolic acid obtained from Huperzia serrata, Galanthus nivalis and Narcissus sp., Caragana chamlague and Origanum majorana, respectively.

Majority of studies have focused on the anticholinesterase alkaloids, such as physostigmine and galantamine. So far, more than 35 alkaloids have been reported to have AChE inhibitory activity. The other major classes of compound reported to have such activity are the terpenoids, glycosides and coumarins. Plants belonging to families Acanthaceae, Apocynaceae, Amaryllidaceae, Angelicae, Araceae, Asclepiadaceae, Berberidaceae, Buxaceae, Combretaceae, Compositae, Coniferae, Cyperaceae, Ebenaceae, Ericaceae, Euphorbiaceae, Fumariaceae, Gentianaceae, Guttiferae, Lamiaceae, Leguminosae, Lilliaceae, Lycopodiaceae, Malvaceae, Magnoliaceae, Menispermaceae, Mollugi-naceae, Moraceae, Musaceae, Nelumbonaceae, Papaveraceae, Piperaceae, Rubiaceae, Rutaceae, Sapotaceae, Solanaceae and Tamaricaceae have been reported to have AChE inhibitory potential. For many of the plants and compounds that have demonstrated activities anti-cholinesterase activity relevant to AD therapy, the clinical data are very limited. Clinical efficacy and potential toxicity of active plants and compounds in larger trials requires further assessment, before recommendations concerning their routine use can be identified.


The authors wish to express their gratitude to the Commonwealth Scholarship Commission, Association of Commonwealth Universities, UK, for the Commonwealth Academic Staff Fellowship Award to Dr. Pulok K. Mukherjee through the selection made from the University Grants Commission (UGC), India. Thanks are also due to the Department of Biotechnology (DBT), Government of India for providing financial assistance through research project to the School of Natural Product Studies, Jadavpur University.


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Pulok K. Mukherjee (a,b,*), Venkatesan Kumar (b), Mainak Mal (b), Peter J. Houghton (a)

(a) Department of Pharmacy, Pharmacognosy Research Laboratories, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK

(b) School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India

*Corresponding author. School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Tel./fax: +91 33 24146046.

E-mail address: (P.K. Mukherjee).
Table 1. Plants with acetylcholinesterase inhibitory activity

Plant Family used Type of extract

Abutilon indicum Linn. Malvaceae Whole Methanolic
Acanthus ebracteatus Vahl. Acanthaceae Aerial Methanolic
Aegle marmelos (Linn.) Rutaceae Fruit Methanolic
 Correa ex Roxb. pulp
Albizia procera (Roxb.) Leguminosae Bark Methanolic
Bacopa monniera Linn. Scrophulariaceae Whole Ethanolic
Butea superba Roxb. Leguminosae Root Methanolic
Buxus sempervirens Linn. Buxaceae Whole Chloroform:
 methanol (1:1)
Carthamus tinctorius Linn. Compositae Flower Methanolic
Cassia fistula Linn. Leguminosae Roots Methanolic
Corydalis solida Linn. Papaveraceae Whole Chloroform:
 methanol (1:1)
Cyperus rotundus Linn. Cyperaceae Whole Methanolic
Euphorbia antiquorum Linn. Euphorbiaceae Stem Methanolic
Fumaria vaillantii Lois. Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria capreolata Linn. Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria kralikii Jordan Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria asepala Boiss. Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria densiflora DC. Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria flabellate Linn. Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria petteri Reichb Fumariaceae Whole Chloroform:
 subsp. thuretii (Boiss.) methanol (1:1)
Fumaria macrocarpa Boiss. Fumariaceae Whole Chloroform:
 ex Hausskn. methanol (1:1)
Fumaria cilicica Hausskn. Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria parviflora Lam. Fumariaceae Whole Chloroform:
 methanol (1:1)
Fumaria judaica Boiss. Fumariaceae Whole Chloroform:
 methanol (1:1)
Ginkgo biloba Linn. Coniferae Whole Ethanolic
Glaucium corniculatum Papaveraceae Whole Chloroform:
 (Linn.) J.H. Rudolph. methanol (1:1)
Lycopodium clavatum Linn. Lycopodiaceae Whole Chloroform:
 methanol (1:1)
Mammea harmandii Kosterm. Guttiferae Flower Methanolic
Melissa officinalis Linn. Lamiaceae Aerial Volatile oil
Michelia champaca Linn. Magnoliaceae Leaf Methanolic
Mimosa pudica Linn. Leguminosae Whole Methanolic
Mimusops elengi Linn. Sapotaceae Flower Methanolic
Musa sapientum Linn. Musaceae Fruit Methanolic
Myricaria elegans Royle Tamaricaceae Aerial Methanolic
Nelumbo nucifera Gaertn. Nelumbonaceae Stamen Methanolic
Paederia linearis Hook. f. Rubiaceae Whole Methanolic
Piper interruptum Opiz Piperaceae Stems Methanolic
Piper nigrum Linn. Piperaceae Seeds Methanolic
Plumbago indica Linn. Plumbaginaceae Root Methanolic
Ptychopetalum olacoides Olacaceae Root Ethanol
Rhododendron luteum Sweet. Ericaceae Whole Chloroform:
 methanol (1:1)
Rhododendron ponticum Ericaceae Whole Chloroform:
 Linn. subsp. Ponticum methanol (1:1)
Rhodiola rosea Linn. Crassulaceae Root Methanol
Salvia lavandulaefolia Lamiaceae Whole Steam distilled
 Vahl. oil
Salvia officinalis Linn. Lamiaceae Whole Ethanol 95%
 Steam distilled
Stephania suberosa Forman. Menispermaceae Roots Methanolic
Streblus asper Lour. Moraceae Seed Methanolic
Tabernaemontana divaricata Apocynaceae Roots Methanolic
 (Linn.) R. Br. Ex
Terminalia bellirica Combretaceae Fruit Methanolic
 (Gaertn.) Roxb.
Tiliacora triandra Menispermaceae Root Methanolic
 (Colebr.) Diel
Vicia faba Linn. Fabaceae Whole Chloroform:
 methanol (1:1)

 Activity (% inhibition)
Plant (concentration) References

Abutilon indicum Linn. 30.66[+ or -]1.06 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Acanthus ebracteatus Vahl. 36.19[+ or -]8.00 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Aegle marmelos (Linn.) 44.65[+ or -]3.04 Ingkaninan et al.
 Correa ex Roxb. (0.1 mg/ml) (2003)
Albizia procera (Roxb.) 40.71[+ or -]0.46 Ingkaninan et al.
 Benth. (0.1 mg/ml) (2003)
Bacopa monniera Linn. 42.9[+ or -]1.2 Das et al, (2002)
 (0.1 mg/ml)
Butea superba Roxb. 55.87[+ or -]5.83 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Buxus sempervirens Linn. 61.76[+ or -]0.76 Orhan et al. (2004)
 (1 mg/ml)
Carthamus tinctorius Linn. 30.33[+ or -]9.22 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Cassia fistula Linn. 54.13[+ or -]3.90 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Corydalis solida Linn. 87.56[+ or -]1.24 Orhan et al. (2004)
 (1 mg/ml)
Cyperus rotundus Linn. 44.19[+ or -]2.27 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Euphorbia antiquorum Linn. 42.31[+ or -]9.10 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Fumaria vaillantii Lois. 94.23[+ or -]0.47 Orhan et al. (2004)
 (1 mg/ml)
Fumaria capreolata Linn. 96.89[+ or -]0.17 Orhan et al. (2004)
 (1 mg/ml)
Fumaria kralikii Jordan 84.98[+ or -]1.07 Orhan et al. (2004)
 (1 mg/ml)
Fumaria asepala Boiss. 91.99[+ or -]0.70 Orhan et al. (2004)
 (1 mg/ml)
Fumaria densiflora DC. 93.42[+ or -]0.92 Orhan et al. (2004)
 (1 mg/ml)
Fumaria flabellate Linn. 92.14[+ or -]1.01 Orhan et al. (2004)
 (1 mg/ml)
Fumaria petteri Reichb 89.45[+ or -]0.86 Orhan et al. (2004)
 subsp. thuretii (Boiss.) (1 mg/ml)
Fumaria macrocarpa Boiss. 93.43[+ or -]0.64 Orhan et al. (2004)
 ex Hausskn. (1 mg/ml)
Fumaria cilicica Hausskn. 88.03[+ or -]0.65 Orhan et al. (2004)
 (1 mg/ml)
Fumaria parviflora Lam. 87.02[+ or -]0.31 Orhan et al. (2004)
 (1 mg/ml)
Fumaria judaica Boiss. 96.47[+ or -]0.63 Orhan et al. (2004)
 (1 mg/ml)
Ginkgo biloba Linn. 50% (268.33 [micro]g) Das et al. (2002)
 Perry et al.
Glaucium corniculatum 86.55[+ or -]0.67 Orhan et al. (2004)
 (Linn.) J.H. Rudolph. (1 mg/ml)
Lycopodium clavatum Linn. 49.85[+ or -]1.33 Orhan et al. (2004)
 (1 mg/ml)
Mammea harmandii Kosterm. 33.63[+ or -]8.00 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Melissa officinalis Linn. -- Perry et al. (1998)
Michelia champaca Linn. 34.88[+ or -]4.56 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Mimosa pudica Linn. 21.40[+ or -]6.68 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Mimusops elengi Linn. 32.81[+ or -]5.36 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Musa sapientum Linn. 29.14[+ or -]4.73 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Myricaria elegans Royle 74.8% (0.2 Ahmad et al. (2003)
Nelumbo nucifera Gaertn. 23.77[+ or -]2.83 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Paederia linearis Hook. f. 29.31[+ or -]6.39 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Piper interruptum Opiz 65.16[+ or -]8.13 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Piper nigrum Linn. 58.02[+ or -]3.83% Ingkaninan et al.
 (0.1 mg/ml) (2003)
Plumbago indica Linn. 30.14[+ or -]3.28 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Ptychopetalum olacoides Dose dependent activity Siqueira et al.
 Benth. at doses of 50 and (2003)
 100 mg/kg, i.p.
Rhododendron luteum Sweet. 76.32[+ or -]0.58 Orhan et al.
 (1 mg/ml) (2004)
Rhododendron ponticum 93.03[+ or -]1.12 Orhan et al.
 Linn. subsp. Ponticum (1 mg/ml) (2004)
Rhodiola rosea Linn. 42.00[+ or -]3.20 Hillhouse et al.
 (10 g/1) (2004)
Salvia lavandulaefolia 63.0[+ or -]3.7 Perry et al. (1996,
 Vahl. (0.1 [micro]g/ml) 2000, 2001)
Salvia officinalis Linn. 68.2[+ or -]15.6 Perry et al. (1996,
 (2.5 mg/ml) 2000, 2001)
 52.4[+ or -]0.8
 (0.1 [micro]g/ml)
Stephania suberosa Forman. 91.93[+ or -]10.80 Ingkaninan et al.
 (0.1 mg/ml) (2003)
Streblus asper Lour. 30.51[+ or -]4.21 Ingkaninan et al.
 (0.1 [micro]g/ml) (2003)
Tabernaemontana divaricata 93.50[+ or -]0.37 Ingkaninan et al.
 (Linn.) R. Br. Ex (0.1 mg/ml) (2003)
Terminalia bellirica 39.68[+ or -]8.15 Ingkaninan et al.
 (Gaertn.) Roxb. (0.1 mg/ml) (2003)
Tiliacora triandra 42.29[+ or -]2.89 Ingkaninan et al.
 (Colebr.) Diel (0.1 mg/ml) (2003)
Vicia faba Linn. 45.23[+ or -]1.03 Orhan et al. (2004)
 (1 mg/ml)

Table 2. Phytoconstituents having acetylcholinesterase inhibitory

Name of alkaloid Class Sources

Assoanine Steroidal alkaloid Narcissus assoanus
Buxamine B Steroidal alkaloid Bucus hyrcana Bucus
Coronaridine Indole alkaloid Tabernaemontana australis
Corynoline Isoquinoline alkaloid Corydalis incisa
N, N-dimethyl Steroidal alkaloid Bucus papillosa
Epinorgalantamine Steroidal alkaloid Narcissus confuses N.
 Narcissus leonensis N.
 legionensis Narcissus
Galantamine Steroidal alkaloid Galanthus nivalis
 Narcissus confuses
 Lycorus radiate
(-)-Huperzine A Quinolizidine alkaloid Huperzia serrata Huperzia
11-Hydroxygalantamine Steroidal alkaloid Narcissus poeticus
Oxoassoanine Steroidal alkaloid Narcissus assoanus
Palmatine Isoquinoline alkaloid Corydalis speciosa
Physostigmine Indole alkaloid Physostigma venenosum
Protopine Isoquinoline alkaloid Corydalis speciosa
Rupicoline Indole alkaloid Tabernaemontana australis
Sanguinine Steroidal alkaloid Eucharis grandiflora
Sarsalignone Steroidal alkaloid Sarcococca saligna
[alpha]-Solanine Glycoalkaloid Solanum tuberosum
Vaganine Steroidal alkaloid Sarcococca saligna
Voacangine Indole alkaloid Tabernaemontana australis
Voacangine Indole alkaloid Tabernaemontana australis

Name of glycoside Class Sources
Cynatroside A Pregnane glycoside Cynanchum atratum
Cynatroside B Pregnane glycoside Cynanchum atratum
Norswertianolin Bellidin 8-O-[beta]- Gentiana cambpestris
Swertianolin Bellidifolin Gentiana cambpestris

Flavonoids, Xanthones, Stilbene oligomers and others
Name of compound Class Sources
(+)-[alpha]-Viniferin Stilbene oligomer Caragana chamlague
Bellidin Xanthone Gentiana cambpestris
Bellidifolin Xanthone Gentiana cambpestris
Ursolic acid Hydroxy-heptamethyl- Origanum majorana
 carboxylic acid

Name of alkaloid Plant family Activity

Assoanine Amaryllidaceae 50% inhibition at
 3.87[+ or -]0.24 [micro]M
Buxamine B Buxaceae 50% inhibition at
 7.56[+ or -]0.008 [micro]M
Coronaridine Apocynaceae Minimum concentration of
 25 [micro]M to produce
 detectable spot in TLC
Corynoline Papaveraceae 50% inhibition at 30.6 [micro]M
N, N-dimethyl Buxaceae 50% inhibition at
 buxapapine 7.28[+ or -]0.06 [micro]M
Epinorgalantamine Amaryllidaceae 50% inhibition at
 9.60[+ or -]0.65 [micro]M
Galantamine Amaryllidaceae 50% inhibition at
 1.07[+ or -]0.18 [micro]M
(-)-Huperzine A Lycopodiaceae 50% inhibition at
 [10.sup.-4] [micro]M
11-Hydroxygalantamine Amaryllidaceae 50% inhibition at
 1.61[+ or -]0.21 [micro]M
Oxoassoanine Amaryllidaceae 50% inhibition at
 47.21[+ or -]1.13 [micro]M
Palmatine Papaveraceae 50% inhibition at 5.8 [micro]M
Physostigmine Leguminosae 50% inhibition at 6 x
 [10.sup.-4] [micro]M
Protopine Papaveraceae 50% inhibition at 16.1 [micro]M
Rupicoline Apocynaceae Minimum concentration of
 25 [micro]M to produce
 detectable spot in TLC
Sanguinine Amaryllidaceae 50% inhibition at
 0.10[+ or -]0.01 [micro]M
Sarsalignone Buxaceae 50% inhibition at
 7.028[+ or -]0.007 [micro]M
[alpha]-Solanine Solanaceae 44.3% inhibition at 10 [micro]M
Vaganine Buxaceae 50% inhibition at
 8.59[+ or -]0.155 [micro]M
Voacangine Apocynaceae Minimum concentration of
 25 [micro]M to produce
 detectable spot in TLC
Voacangine Apocynaceae Minimum concentration of
 hydroxyindolenine 25 [micro]M to produce
 detectable spot in TLC

Name of glycoside Plant family Activity
Cynatroside A Asclepiadaceae 50% inhibition at 6.4 [micro]M
Cynatroside B Asclepiadaceae 50% inhibition at 3.6 [micro]M
Norswertianolin Coniferae Minimum concentration of
 1.20 [micro]M to produce
 detectable spot in TLC
Swertianolin Coniferae Minimum concentration of
 0.18 [micro]M to produce
 detectable spot in TLC

Flavonoids, Xanthones, Stilbene oligomers and others
Name of compound Plant family Activity
(+)-[alpha]-Viniferin Leguminosae 50% inhibition at 2.0 [micro]M
Bellidin Coniferae Minimum concentration of
 0.03 [micro]M to produce
 detectable spot in TLC
Bellidifolin Coniferae Minimum concentration of
 0.15 [micro]M to produce
 detectable spot in TLC
Ursolic acid Lamiaceae 50% inhibition at 7.5 [micro]M

Name of alkaloid References

Assoanine Lopez et al. (2002)
Buxamine B Rahman and Choudhary (2001)
Coronaridine Andrade et al. (2005)
Corynoline Kim (2002)
N, N-dimethyl Rahman and Choudhary (2001)
Epinorgalantamine Lopez et al. (2002)
Galantamine Rhee et al. (2001); Rizzi et al. (1999);
 Ingkaninan et al. (2003); Lopez et al. (2002)
(-)-Huperzine A Tang et al. (1994) Orhan et al. (2004); Ashani et
 al. (1994)
11-Hydroxygalantamine Lopez et al. (2002)
Oxoassoanine Lopez et al. (2002)
Palmatine Kim et al. (2004)
Physostigmine Karczmar (1998)
Protopine Kim et al. (2004)
Rupicoline Andrade et al. (2005)
Sanguinine Lopez et al. (2002)
Sarsalignone Rahman and Choudhary (2001)
[alpha]-Solanine Roddick (1989) Me Gehee et al. (2000)
Vaganine Rahman and Choudhary (2001)
Voacangine Andrade et al. (2005)
Voacangine Andrade et al. (2005)

Name of glycoside References
Cynatroside A Lee et al (2003)
Cynatroside B Lee et al (2003)
Norswertianolin Urbain et al. (2004)
Swertianolin Urbain et al. (2004)

Flavonoids, Xanthones, Stilbene oligomers and others
Name of compound References
(+)-[alpha]-Viniferin Sung et al. (2002)
Bellidin Urbain et al. (2004)
Bellidifolin Urbain et al. (2004)
Ursolic acid Chung et al. (2001)
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Author:Mukherjee, Pulok K.; Kumar, Venkatesan; Mal, Mainak; Houghton, Peter J.
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Date:Apr 1, 2007
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