Extracts from Traditional Chinese Medicinal Plants Inhibit Acetylcholinesterase, a Known Alzheimer's Disease Target - PubMed (original) (raw)

Extracts from Traditional Chinese Medicinal Plants Inhibit Acetylcholinesterase, a Known Alzheimer's Disease Target

Dorothea Kaufmann et al. Molecules. 2016.

Abstract

Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer's Disease (AD). In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM) plants were tested for their in vitro anti-acetylcholinesterase activity based on Ellman's colorimetric assay. All three extracts of Berberis bealei (formerly Mahonia bealei), Coptis chinensis and Phellodendron chinense, which contain numerous isoquinoline alkaloids, substantially inhibited AChE. The methanol and aqueous extracts of Coptis chinensis showed IC50 values of 0.031 µg/mL and 2.5 µg/mL, therefore having an up to 100-fold stronger AChE inhibitory activity than the already known AChE inhibitor galantamine (IC50 = 4.33 µg/mL). Combinations of individual alkaloids berberine, coptisine and palmatine resulted in a synergistic enhancement of ACh inhibition. Therefore, the mode of AChE inhibition of crude extracts of Coptis chinensis, Berberis bealei and Phellodendron chinense is probably due to of this synergism of isoquinoline alkaloids. All extracts were also tested for their cytotoxicity in COS7 cells and none of the most active extracts was cytotoxic at the concentrations which inhibit AChE. Based on these results it can be stated that some TCM plants inhibit AChE via synergistic interaction of their secondary metabolites. The possibility to isolate pure lead compounds from the crude extracts or to administer these as nutraceuticals or as cheap alternative to drugs in third world countries make TCM plants a versatile source of natural inhibitors of AChE.

Keywords: Alzheimer’s; Coptis; Traditional Chinese Medicine; acetylcholinesterase; acetylcholinesterase inhibitor; berberine; coptisine; isoquinoline alkaloids; natural products; palmatine.

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Conflict of interest statement

The Authors declare that they have no conflicts of interest to disclose. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Figures

Figure 1

Figure 1

HPLC-MS total ion current chromatogram of a methanol extract of Coptis chinensis. Peaks: 1: Tetradehydroscoulerine / tetrahydrocheilanthifolinium (m/z = 322); 2: columbamine (m/z = 338); 3: epiberberine (m/z = 336); 4: coptisine (m/z = 320); 5: palmatine (m/z = 352); 6: berberine (m/z = 336).

Figure 2

Figure 2

AChE inhibitory effect and synergistic effects of berberine in combination with coptisine and palmatine. The combination of berberine with other alkaloids inhibits ACh stronger than berberine alone (top); The combination index (CI) increases with higher concentrations of berberine (bottom). Data is shown as mean ± SD from three individual experiments, each carried out in triplicates.

Figure 3

Figure 3

Alkaloids contained in Coptis chinensis.

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References

    1. Alzheimer’s Disease International World Alzheimer Report 2015. [(accessed on 10 August 2016)]. Available online: https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf.
    1. Czech C., Tremp G., Pradier L. Presenilins and Alzheimer’s disease: Biological functions and pathogenic mechanisms. Prog. Neurobiol. 2000;60:363–384. doi: 10.1016/S0301-0082(99)00033-7. - DOI - PubMed
    1. Cummings J.L. Cognitive and behavioral heterogeneity in Alzheimer’s disease: Seeking the neurobiological basis. Neurobiol. Aging. 2000;21:845–861. doi: 10.1016/S0197-4580(00)00183-4. - DOI - PubMed
    1. Bartus R.T., Dean R.L., 3rd, Beer B., Lippa A.S. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217:408–414. doi: 10.1126/science.7046051. - DOI - PubMed
    1. Perry E.K., Perry R.H., Blessed G., Tomlinson B.E. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol. Appl. Neurobiol. 1978;4:273–277. doi: 10.1111/j.1365-2990.1978.tb00545.x. - DOI - PubMed

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