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Abstract Title:

Synergistic Effects of Curcumin and Piperine as Potent Acetylcholine and Amyloidogenic Inhibitors With Significant Neuroprotective Activity in SH-SY5Y CellsComputational Molecular Modeling andAssay.

Abstract Source:

Front Aging Neurosci. 2019 ;11:206. Epub 2019 Aug 27. PMID: 31507403

Abstract Author(s):

Aimi Syamima Abdul Manap, Amelia Cheng Wei Tan, Weng Hhin Leong, Adeline Yoke Yin Chia, Shantini Vijayabalan, Aditya Arya, Eng Hwa Wong, Farzana Rizwan, Umesh Bindal, Shajan Koshy, Priya Madhavan

Article Affiliation:

Aimi Syamima Abdul Manap

Abstract:

Hallmarks of Alzheimer's disease (AD) pathology include acetylcholine (ACh) deficiency and plaque deposition. Emerging studies suggest that acetylcholinesterase (AChE) may interact with amyloidβ (Aβ) to promote aggregation of insoluble Aβ plaques in brains of patients. Current therapeutic options available for AD patients, such as AChE inhibitors, provide only symptomatic relief. In this study, we screened four natural compounds believed to harbor cognitive benefits-curcumin, piperine,bacoside A, and chebulinic acid. In the first section, preliminary screening through computational molecular docking simulations gauged the suitability of the compounds as novel AChE inhibitors. From here, only compounds that met theselection criteria were selected for the second section throughinvestigations, including AChE enzyme inhibition assay, 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTT) assay, Thioflavin T (ThT) assay, and biochemical analysisa neuronal cell line model. Of the four compounds screened, only curcumin (-9.6 kcal/mol) and piperine (-10.5 kcal/mol) showed favorable binding affinities and interactions towards AChE and were hence selected.AChE inhibition demonstrated that combination of curcumin and piperine showed greater AChE inhibition with an ICof 62.81± 0.01 μg/ml as compared to individual compounds, i.e., ICof curcumin at 134.5± 0.06 μg/ml and ICof piperine at 76.6± 0.08 μg/ml. In the SH-SY5Y cell model, this combination preserved cell viability up to 85%, indicating that the compounds protect against Aβ-induced neuronal damage (<0.01). Interestingly, our results also showed that curcumin and piperine achieved a synergistic effect at 35μM with an synergism quotient (SQ) value of 1.824. Synergistic behavior indicates that the combination of these two compounds at lower concentrations may provide a better outcome than singularly used for Aβ proteins. Combined curcumin and piperine managed to inhibit aggregation (reduced ThT intensity at 0.432 a.u.;<0.01) as well as disaggregation (reduced ThT intensity at 0.532 a.u.;<0.01) of fibrillar Aβ42. Furthermore, combined curcumin and piperine reversed the Aβ-induced up-regulation of neuronal oxidative stress (<0.01). In conclusion, curcumin and piperine demonstrated promising neuroprotective effects, whereas bacoside A and chebulinic acid may not be suitable lead compounds. These results are hoped to advance the field of natural products research as potentially therapeutic and curative AD agents.

Study Type : In Vitro Study

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Sayer Ji
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