Journal
PROTEIN JOURNAL
Volume 40, Issue 1, Pages 78-86Publisher
SPRINGER
DOI: 10.1007/s10930-020-09946-5
Keywords
Anti-amyloidogenic; Hen egg-white lysozyme (HEWL); Molecular docking; Piperine; Phytocompounds; Thioflavin T (ThT)
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Funding
- Guru Gobind Singh Indraprastha University
- Indian Council of Medical Research
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The study found that piperine showed significant anti-amyloidogenic activity, inhibiting amyloid formation effectively as validated through a series of experiments. It interacts with key residues involved in amyloidogenesis, including those in the amyloidogenic region and Trp62.
Amyloidosis is the process of fibril formation responsible for causing several diseases in the human being that involve protein aggregation such as Alzheimer's, Parkinson's, Huntington's disease, and type II diabetes. Natural phytocompounds such as curcumin shown promising anti-amyloidogenic activity. In the present study, selective phytocompounds such as piperine, cinnamaldehyde, eugenol, and cuminaldehyde present in Piper nigrum L, Cinnamomum zeylanicum Blume, Eugenia caryophyllus Thumb, and Cuminum cyminum L, respectively were analyzed for anti-amyloidogenic activity using hen egg white-lysozyme (HEWL) as a model system. Out of the selected phytocompounds, piperine showed the most significant anti-amyloidogenic activity, as evident from in vitro assays that were validated by in silico molecular docking study. Piperine showed 64.7 +/- 3.74% inhibition of amyloid formation at 50 mu M concentration, as observed by Thioflavin T assay. Subsequently, the anti-amyloidogenic activity of piperine was further validated by congo red, intrinsic fluorescence assay, and transmission electron microscopy analysis. The in silico molecular binding interaction showed piperine with the highest docking score and glide energy. Piperine was found to be interacting with amyloidogenic region residues and Trp62, the most important residue involved in the amyloidogenesis process. In conclusion, piperine can be used as a positive lead for a potential therapeutic role in targeting diseases involved amyloidogenesis.
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